Bio

Clinical Focus


  • Cervix Cancer - Gynecologic Oncology
  • Gynecology
  • Cervix Cancer
  • Female & Gynecologic Cancers
  • Ovarian Cancer - Gynecologic Oncology
  • Gynecologic Cancers - Medical Oncology
  • Melanoma - Gynecologic Oncology
  • Melanoma
  • Vaginal Cancer - Gynecologic Oncology
  • Vaginal Cancer
  • Gestational Trophoblastic Disease - Gynecologic Oncology
  • Urethral Cancer
  • Uterine Cancer
  • Fallopian Tube - Gynecologic Oncology
  • Ovarian Cancer
  • Endometrial Cancer - Gynecologic Oncology
  • Gestational Trophoblastic Disease
  • Germ Cell Tumors - Gynecologic Oncology
  • Endometrial Cancer
  • Cancer > Gynecologic Cancer
  • Gynecologic Cancers
  • Urethral Cancer - Gynecologic Oncology
  • Fallopian Tube
  • Germ Cell Tumors
  • Uterine Cancer - Gynecologic Oncology
  • Gynecologic Oncology
  • Gynecologic Cancers - Gynecologic Oncology

Academic Appointments


Professional Education


  • Residency:UCLA Medical Center (1981) CA
  • Fellowship:Stanford University School of Medicine (1984) CA
  • Board Certification: Gynecologic Oncology, American Board of Obstetrics and Gynecology (1987)
  • Board Certification: Obstetrics and Gynecology, American Board of Obstetrics and Gynecology (1985)
  • Internship:UCLA Medical Center (1978) CA
  • Medical Education:University Of Miami - School of Medicine (1977) FL

Research & Scholarship

Current Research and Scholarly Interests


Gynecologic Malignancies
Immunotherapy
Biologic Response Modifiers
New Drug Development
Antigenic specificities of human antibodies encoded by the VH4-34 gene

Clinical Trials


  • Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma Not Recruiting

    This study is designed to assess the effectiveness of the combination of Panobinostat plus Bortezomib and Dexamethasone in patients with relapsed and bortezomib refractory Multiple Myeloma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer Not Recruiting

    This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating patients with stage I, stage II, stage III, or stage IVA endometrial cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether carboplatin and paclitaxel are more effective with or without cisplatin and radiation therapy in treating patients with endometrial cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Ovarian Cancer Vaccine for Patients in Remission Not Recruiting

    The purpose of this study is to determine the safety and efficacy of an investigational therapeutic agent (Cvac)in ovarian cancer patients in first or second remission and to determine its ability to prevent cancer from returning.

    Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.

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  • Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries Not Recruiting

    RATIONALE: Zoledronate may prevent bone loss in patients who are undergoing surgery to remove the ovaries. PURPOSE: This randomized phase II trial is studying zoledronate to see how well it works compared to observation in maintaining bone mineral density in patients who are undergoing surgery to remove both ovaries.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Trabectedin in Treating Patients With Advanced, Persistent, or Recurrent Leiomyosarcoma of the Uterus Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well trabectedin works in treating patients with advanced, persistent, or recurrent leiomyosarcoma of the uterus.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Second Curettage in Treating Patients With Persistent Non-Metastatic Gestational Trophoblastic Tumor Not Recruiting

    RATIONALE: A second curettage may be effective in treating persistent gestational trophoblastic tumor. PURPOSE: This phase II trial is studying how well a second curettage works in treating patients with persistent non-metastatic gestational trophoblastic tumor.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Overcoming Obstacles to Clinical Trials Enrollment Through a Navigator Program Not Recruiting

    Pilot study for assessing the effectiveness of a Navigator program to aid in clinical trial participation amongst the Chinese demographic

    Stanford is currently not accepting patients for this trial. For more information, please contact Mei-Chin Kuo, (650) 736 - 1977.

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  • Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer Not Recruiting

    To compare the efficacy of olaparib in combination with paclitaxel and carboplatin when compared with carboplatin and paclitaxel alone in patients with advanced ovarian cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Fitzsimmons, (650) 724 - 3155.

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  • Clinical Trial for Ovarian Cancer (OvaRex®) Not Recruiting

    This study will compare the time to disease relapse between OvaRex® MAb-B43.13-treated patients and placebo-treated patients. This study will also compare assessments of survival, quality of life, immune response and safety between active and placebo groups.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jim Batterson, (650) 725 - 5974.

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  • Veliparib in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Not Recruiting

    Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial studies how well veliparib works in treating patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Pelvic Radiation Therapy or Vaginal Implant Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Stage I or Stage II Endometrial Cancer Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Implant radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether pelvic radiation therapy is more effective than vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with endometrial cancer. PURPOSE: This randomized phase III trial is studying pelvic radiation therapy to see how well it works compared with vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or stage II endometrial cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Carboplatin, Paclitaxel and Gemcitabine With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Not Recruiting

    This randomized phase III trial is studying giving carboplatin, paclitaxel and gemcitabine together with or without bevacizumab after surgery to see how well it works in treating patients with recurrent ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab after surgery in treating patients with recurrent ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sharanya Ramasubramanian, 650-723-0622.

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  • Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Not Recruiting

    This randomized phase III trial is studying bevacizumab and intravenous chemotherapy to see how well they work compared with bevacizumab and intraperitoneal chemotherapy in treating patients with stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving bevacizumab together with intravenous chemotherapy is more effective than giving bevacizumab together with intraperitoneal chemotherapy in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer Not Recruiting

    This phase III clinical trial is studying two different dose schedules of paclitaxel to see how well they work in combination with carboplatin with or without bevacizumab in treating patients with stage II, III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. It is not yet known whether giving paclitaxel once every three weeks is more effective than giving paclitaxel once a week.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Cetuximab in Treating Patients With Persistent or Recurrent Cervical Cancer Not Recruiting

    This phase II trial is studying cetuximab to see how well it works in treating patients with persistent or recurrent cervical cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer Not Recruiting

    This study was designed to find the most effective and safest doses of both HYCAMTIN and CARBOPLATIN that can be given for the treatment of ovarian cancer. This study may allow researchers to determine the effectiveness of combining HYCAMTIN and CARBOPLATIN.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tine Bjornlund, (650) 725 - 9167.

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  • A Study of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Ovary, Peritoneal, or Fallopian Tube Carcinoma Not Recruiting

    This is a placebo-controlled, randomized, multicenter Phase III study evaluating the safety and efficacy of bevacizumab, administered in combination with carboplatin with gemcitabine in women with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Charlesworth, (650) 796 - 0344.

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  • Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritorium Cavity Cancer Not Recruiting

    This randomized phase III trial is studying giving paclitaxel together with carboplatin to see how well it works compared with giving paclitaxel together with ifosfamide in treating patients with newly diagnosed persistent or recurrent uterine, ovarian, fallopian tube, or peritorium cavity cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether paclitaxel is more effective when given together with carboplatin or ifosfamide in treating patients with uterine, ovarian, fallopian tube, or peritorium cavity cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • OPT-821 With or Without Vaccine Therapy in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in Second or Third Complete Remission Not Recruiting

    RATIONALE: Biological therapies, such as OPT-821, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. It is not yet known whether OPT-821 is more effective with or without vaccine therapy in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer. PURPOSE: This randomized phase III trial is studying OPT-821 and vaccine therapy to see how well they work compared with OPT-821 alone in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer in second or third complete remission.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer Not Recruiting

    This randomized phase III trial is studying the side effects of paclitaxel when given together with cisplatin or topotecan with or without bevacizumab and to compare how well they work in treating patients with stage IVB, recurrent, or persistent cervical cancer. Drugs used in chemotherapy, such as paclitaxel, cisplatin, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether paclitaxel is more effective when given together with cisplatin or topotecan with or without bevacizumab in treating patients with cervical cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal Cancer, or Fallopian Tube Cancer Not Recruiting

    This randomized phase III trial is studying carboplatin, paclitaxel, and bevacizumab to see how well they work compared to carboplatin, paclitaxel, and placebo in treating patients with stage III or stage IV ovarian epithelial, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether carboplatin, paclitaxel, and bevacizumab are more effective than carboplatin, paclitaxel, and placebo in treating ovarian epithelial or primary peritoneal cancer , or fallopian tube cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tine Bjornlund, (650) 725 - 9167.

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  • TRINOVA-1: A Study of AMG 386 or Placebo, in Combination With Weekly Paclitaxel Chemotherapy, as Treatment for Ovarian Cancer, Primary Peritoneal Cancer and Fallopian Tube Cancer Not Recruiting

    The purpose of this study is to determine if treatment with paclitaxel plus AMG 386 is superior to paclitaxel plus placebo in women with recurrent partially platinum sensitive or resistant epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer. AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Temsirolimus With or Without Megestrol and Tamoxifen in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer Not Recruiting

    This randomized phase II trial is studying temsirolimus to see how well it works with or without megestrol and tamoxifen in treating patients with advanced, persistent, or recurrent endometrial cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of endometrial cancer cells. Hormone therapy using megestrol and tamoxifen may fight endometrial cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether temsirolimus is more effective when given alone or together with megestrol and tamoxifen in treating endometrial cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Selumetinib in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer Not Recruiting

    This phase II trial is studying the side effects and how well selumetinib works in treating patients with recurrent low-grade ovarian cancer. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Phase I Stereotactic Body Radiation for Metastatic or Recurrent Platinum-Resistant Ovarian Cancer Not Recruiting

    This phase I trial studies the side effects and the best dose of stereotactic body radiation therapy (SBRT) in treating patients with metastatic or recurrent ovarian cancer or primary peritoneal cancer. SBRT may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

    Stanford is currently not accepting patients for this trial. For more information, please contact Elizabeth A. Kidd, 650-725-2174.

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  • Safety and Efficacy Study of Catumaxomab to Treat Ovarian Cancer After a Complete Response to Chemotherapy Not Recruiting

    The purpose of this study is to determine whether the investigational drug catumaxomab delivered in the planned treatment schedule is a safe and effective treatment for women with advanced ovarian cancer who experience a complete response to chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Fitzsimmons, (650) 724 - 3155.

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  • A Study of GDC-0980 in the Treatment of Recurrent or Persistent Endometrial Carcinoma Not Recruiting

    This is a multicenter, single-arm, open-label Phase II study to evaluate the activity of GDC-0980 in patients with recurrent or persistent endometrial cancer. The safety, tolerability, and pharmacokinetics of GDC-0980 will also be evaluated.

    Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.

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  • Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites Not Recruiting

    The purpose of this study is to determine whether the investigational drug catumaxomab is a safe and effective treatment for recurrent symptomatic malignant ascites.

    Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Fitzsimmons, (650) 724 - 3155.

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  • Efficacy and Safety of MORAb-003 in Subjects With Platinum-sensitive Ovarian Cancer in First Relapse Not Recruiting

    This research is being done to find out if Carboplatin and Taxane works better alone or when given with an experimental drug called MORAb-003(farletuzumab) in subjects with first platinum sensitive relapsed ovarian cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.

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  • Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer Not Recruiting

    This randomized phase III trial is studying cisplatin, radiation therapy, and tirapazamine to see how well they work compared to cisplatin and radiation therapy in treating patients with cervical cancer. Drugs used in chemotherapy, such as cisplatin and tirapazamine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin and tirapazamine may make tumor cells more sensitive to radiation therapy. It is not yet known whether giving cisplatin together with radiation therapy is more effective with or without tirapazamine in treating cervical cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Study of FP-1039 in Subjects With Endometrial Cancers Not Recruiting

    An open-label, non-randomized, single arm study to assess the safety, tolerability, and pharmacokinetics of FP-1039 given by weekly intravenous (IV) administrations in advanced endometrial cancer patients with FGFR2-specific mutations. FP-1039 will be dosed weekly starting at a dose of up to 16 mg/kg.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Combination Chemotherapy in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer Not Recruiting

    RATIONALE: Drugs used in chemotherapy such as doxorubicin, cisplatin, paclitaxel, and carboplatin use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective in treating endometrial cancer. PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens to compare how well they work in treating patients with stage III, stage IV, or recurrent endometrial cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Safety and Efficacy Clinical Study of SNS-595 in Patients With Platinum-Resistant Ovarian Cancer Not Recruiting

    The purpose of this study is to evaluate the objective response rate, safety and identify potential biomarkers in platinum-resistant ovarian cancer patients treated with voreloxin injection given on a 28-day cycle.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.

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  • Efficacy Multicentre Trial of ImmunoTherapy Vaccination With Abagovomab to Treat Ovarian Cancer Patients Not Recruiting

    The purpose of this study is to evaluate the benefit of vaccination with Abagovomab, an experimental immunotherapy in ovarian cancer patients. The benefit will be evaluated in terms of time the remission status is kept as well as prolongation of life expectancy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Fitzsimmons Colleen, (650) 724 - 3155.

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  • Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer Not Recruiting

    This study is being conducted to compare the efficacy and safety of pazopanib in combination with lapatinib with that of lapatinib alone or pazopanib alone in subjects with metastatic cervical cancer

    Stanford is currently not accepting patients for this trial. For more information, please contact Tine Bjornlund, (650) 725 - 9167.

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  • Combination Study Of SB-485232 (Interleukin 18) And Doxil For Advanced Stage Epithelial Ovarian Cancer Not Recruiting

    The purpose of this study is to identify a dose of SB-485232 which is safe, tolerable and biologically active when used in combination with pegylated liposomal doxorubicin (Doxil) in patients with epithelial ovarian cancer. This study will use a standard treatment regimen of pegylated liposomal doxorubicin (Doxil) in combination with rising doses of SB-485232. The dose selected from this study will be used in a future studies to evaluate the efficacy of this combination.

    Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.

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Publications

Journal Articles


  • Taxol-oligoarginine conjugates overcome drug resistance in-vitro in human ovarian carcinoma GYNECOLOGIC ONCOLOGY Wender, P. A., Galliher, W. C., Bhat, N. M., Pillow, T. H., Bieber, M. M., Teng, N. N. 2012; 126 (1): 118-123

    Abstract

    Multidrug resistance is the major cause of failure of many chemotherapeutic agents. While resistance can arise from several factors, it is often dominated by drug efflux mediated by P-glycoprotein (P-gp), a membrane-bound polysubstrate export pump expressed at high levels in resistant cells. While co-administration of pump inhibitors and a drug could suppress efflux, this two-drug strategy has not yet advanced to therapy. We recently demonstrated that the reversible attachment of a guanidinium-rich molecular transporter, polyarginine, to a drug provides a conjugate that overcomes efflux-based resistance in cells and animals. This study is to determine whether this strategy for overcoming resistance is effective against human disease.Tumor samples from ovarian cancer patients, both malignant ascites cells and dissociated solid tumor cells, were exposed to Taxol-oligoarginine conjugates designed to release free drug only after cell entry. Cell viability was determined via propidium-iodide uptake by flow cytometry. To analyze bystander effect, toxicity of the drug conjugates was also tested on peripheral blood leucocytes.Human ovarian carcinoma specimens resistant to Taxol in vitro demonstrated increased sensitivity to killing by all Taxol-transporter conjugates tested. These studies also show that the drug conjugates were not significantly more toxic to normal human peripheral blood leukocytes than Taxol.These studies with human tumor indicate that oligoarginine conjugates of known drugs can be used to overcome the efflux-based resistance to the drug, providing a strategy that could improve the treatment outcomes of patients with efflux-based drug-resistance.

    View details for DOI 10.1016/j.ygyno.2012.03.049

    View details for Web of Science ID 000305878400023

    View details for PubMedID 22484398

  • The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Willingham, S. B., Volkmer, J., Gentles, A. J., Sahoo, D., Dalerba, P., Mitra, S. S., Wang, J., Contreras-Trujillo, H., Martin, R., Cohen, J. D., Lovelace, P., Scheeren, F. A., Chao, M. P., Weiskopf, K., Tang, C., Volkmer, A. K., Naik, T. J., Storm, T. A., Mosley, A. R., Edris, B., Schmid, S. M., Sun, C. K., Chua, M., Murillo, O., Rajendran, P., Cha, A. C., Chin, R. K., Kim, D., Adorno, M., Raveh, T., Tseng, D., Jaiswal, S., Enger, P. O., Steinberg, G. K., Li, G., So, S. K., Majeti, R., Harsh, G. R., van de Rijn, M., Teng, N. N., Sunwoo, J. B., Alizadeh, A. A., Clarke, M. F., Weissman, I. L. 2012; 109 (17): 6662-6667

    Abstract

    CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRP?, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

    View details for DOI 10.1073/pnas.1121623109

    View details for Web of Science ID 000303249100065

    View details for PubMedID 22451913

  • Prox-1, Podoplanin and HPV staining assists in identification of lymphangioma circumscriptum of the vulva and discrimination from vulvar warts HISTOPATHOLOGY Sultan, A., Dadras, S. S., Bay, J. M., Teng, N. N. 2011; 59 (6): 1274-1277
  • Wnt and Hedgehog Gene Pathway Expression in Serous Ovarian Cancer INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER Schmid, S., Bieber, M., Zhang, F., Zhang, M., He, B., Jablons, D., Teng, N. N. 2011; 21 (6): 975-980

    Abstract

    Ovarian cancer has very heterogeneous histological classification, and response to therapy of the same grade and type varies. We studied genes in the Wnt and hedgehog (Hh) pathways, which are essential for embryonic development and which play critical roles in proliferation in a variety of human cancers. Variations in these pathway genes causing proliferation could play a role in the variation in tumor progression and response to therapy.Using real-time polymerase chain reaction, we studied 16 primary grade 3 International Federation of Gynecology and Obstetrics stage III serous ovarian cancer samples for expression of the Wnt pathway gene AXIN2, fibroblast growth factor 9, and Hh pathway gene expressions of glioma-associated oncogene 1, glioma-associated oncogene 2, patched homolog 1, patched homolog 2, Indian Hedgehog (HH), sonic HH, and Smoothened, a G protein-coupled receptor protein. Normal ovary epithelial cell line was used as control.We found wide variation of up-regulation of pathway component and target genes in the primary tumor samples and apparent cross talk between the pathways. AXIN2, a Wnt target gene, showed increased expression in all serous ovarian cancer samples. Fibroblast growth factor 9 was also overexpressed in all tumors with greater than 1000-fold increase in gene expression in 4 tumors. Expression of Hh pathway genes varied greatly. More than half of the tumor samples showed involvement of Hh signaling or pathway activation either by expression of transcription factors and Hh ligands or by overexpression of Indian HH/sonic HH and the receptor-encoding patched homolog 1/patched homolog 2.We found a wide variation in fold expression of genes involved in the Wnt and Hh pathway between patient samples.

    View details for DOI 10.1097/IGC.0b013e31821caa6f

    View details for Web of Science ID 000293169500004

    View details for PubMedID 21666490

  • Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Urban, R. R., Teng, N. N., Kapp, D. S. 2011; 204 (5): E9-E12

    Abstract

    We report a case of uterine cancer and invasive cervical cancer, detected incidentally during the female-to-male sex reassignment surgery. The management of these patients is presented. Such individuals may not be receiving regular gynecologic care appropriate to their remaining genital organs; symptoms of malignant disease may be missed.

    View details for DOI 10.1016/j.ajog.2010.12.057

    View details for Web of Science ID 000290206200003

    View details for PubMedID 21354550

  • The incidence of isolated para-aortic nodal metastasis in completely staged endometrial cancer patients GYNECOLOGIC ONCOLOGY Chiang, A., Yu, K., Chao, K., Teng, N. N. 2011; 121 (1): 122-125

    Abstract

    To describe and review the incidence of para-aortic (PA) nodal metastasis in completely staged endometrial cancer patients who are negative for pelvic nodal metastasis.Using an institutionally maintained database, we identified all patients with endometrial cancer from 2002 to 2006 who had both pelvic and aortic nodal dissections and determined the rate of isolated para-aortic nodal metastasis in non-malignant (i.e. negative) pelvic nodes.201 endometrial cancer patients were surgically treated at our institution from 2002 to 2006. 171 patients had both pelvic and PA nodes removed during surgery, and specimens examined by a pathologist. Only 2 (1.2%) had PA nodes that tested positive for malignance (i.e. positive PA nodes) with pelvic nodes that tested negative for malignance (i.e. negative pelvic nodes). The final International Federation of Gynecology and Obstetrics (FIGO) grade for the endometrial tumor cells in the two patients was "G1" with endometrioid adenocarcinoma and "G3" with endometrioid adenocarcinoma and mucinous differentiation, respectively.Based on the very low incidence of patients inflicted with endometrial cancer that have positive para-aortic lymph nodes (PALNs) with negative pelvic nodes found both in our literature review (1.5%) and in our own study (1.2%), the addition of PA lymphadenectomy in all patients was found to have minimal diagnostic and therapeutic value. At the present, the role of complete PA lymphadenectomy in all patients with endometrial cancer should be re-examined. Individualized algorithms should be developed based on risk factors and status of pelvic nodes.

    View details for DOI 10.1016/j.ygyno.2010.11.026

    View details for Web of Science ID 000288920700021

    View details for PubMedID 21194737

  • Squamous Cell Carcinoma Arising From Mature Cystic Teratoma of the Ovary INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER Chiang, A., La, V., Peng, J., Yu, K., Teng, N. N. 2011; 21 (3): 466-474

    Abstract

    Squamous cell carcinoma (SCC) is the most common type of malignant transformation in mature cystic teratoma (MCT) of the ovary. The SCC is difficult to preoperatively diagnose. We conducted a retrospective study to seek the possible risk/prognostic factors and treatments for SCC arising from MCT of the ovary.Using an institutional database, we identified 3 women treated for SCC arising from an MCT of the ovary at the Kaohsiung Veteran General Hospital. A retrospective chart review was conducted, with information obtained from radiographs, operative reports, pathology reports, and radiation oncology records.A total of 1551 cases of MCT were diagnosed at Kaohsiung Veteran General Hospital from 1990 to 2009, of which, malignant teratoma SCC type was noted in 3 cases (0.19%). The median age of the subjects was 39 years. Abdominal fullness was the most common symptom (3/3 cases). The mean diameter of the ovarian tumor was 17.3 cm, ranging from 16 to 18 cm. All 3 patients received simple right salpingo-oophorectomy or debulking surgery. Two of the patients reached stage IIIC and died.: With our review as basis, we recommend being cautious of the following risk factors: patient age, tumor size, ultrasound characteristics, sonar tumor vessel wave form, computed tomography, and levels of SCC and CA125 tumor markers. We suggest that patients have regular ovarian ultrasound examination. Based on our literature review, stage IA patients who undergo standardized operational procedures do well without adjuvant treatment, but such patients must be confirmed accurately with complete surgical staging to be in stage IA before undergoing conservative management. The optimal approach to the management of patients with advanced stage and recurrent disease is unclear. Surgical cytoreduction with proper staging, adjuvant therapy with platinum-based or paclitaxel-based chemotherapy, and concurrent whole pelvic radiation have been recommended as possible methods of treatment.

    View details for DOI 10.1097/IGC.0b013e31820d3e5b

    View details for Web of Science ID 000288743700008

    View details for PubMedID 21430455

  • Leukemia inhibitory factor downregulates human papillomavirus-16 oncogene expression and inhibits the proliferation of cervical carcinoma cells. Infectious diseases in obstetrics and gynecology Bay, J. M., Patterson, B. K., Teng, N. N. 2011; 2011: 463081-?

    Abstract

    The constitutive proliferation and resistance to differentiation and apoptosis of neoplastic cervical cells depend on sustained expression of human papillomavirus oncogenes. Inhibition of these oncogenes is a goal for the prevention of progression of HPV-induced neoplasias to cervical cancer. SiHa cervical cancer cells were transfected with an HPV-16 promoter reporter construct and treated with leukemia inhibitory factor (LIF), a human cytokine of the interleukin 6 superfamily. SiHa and CaSki cervical cancer cells were also assessed for proliferation by MTT precipitation, programmed cell death by flow cytometry, and HPV E6 and E7 expression by real-time PCR. LIF-treated cervical cancer cells showed significantly reduced HPV LCR activation, reduced levels of E6 and E7 mRNA, and reduced proliferation. We report the novel use of LIF to inhibit viral oncogene expression in cervical cancer cells, with concomitant reduction in proliferation suggesting re-engagement of cell-cycle regulation.

    View details for DOI 10.1155/2011/463081

    View details for PubMedID 21747640

  • INTRAOPERATIVE RADIATION THERAPY FOR LOCALLY ADVANCED AND RECURRENT SOFT-TISSUE SARCOMAS IN ADULTS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Tran, P. T., Hara, W., Su, Z., Lin, H. J., Bendapudi, P. K., Norton, J., Teng, N., King, C. R., Kapp, D. S. 2008; 72 (4): 1146-1153

    Abstract

    To analyze the outcomes of and identify prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for locally advanced and recurrent soft-tissue sarcoma in adults from a single institution.We retrospectively reviewed 50 consecutive patients treated with IORT to 62 sites of disease. Primary sites included retroperitoneum-pelvis (78%), extremity (8%), and other (14%). Seventy percent of patients had recurrent disease failing prior surgery (70%) and/or radiation (32%). Mean disease-free interval (DFI) before IORT was 1.9 years (range, 2 weeks-5.4 years). The IORT was delivered with orthovoltage X-rays using individually sized beveled cone applicators. Clinical characteristics were as follows: mean tumor size, 10 cm (range, 1-25 cm); high-grade histologic subtype (72%); and mean dose, 1,159 cGy (range, 600-1,600 cGy). Postoperative radiation or chemotherapy was administered to 37% of IORT Sites and 32% of patients, respectively. Outcomes measured were infield control (IFC), locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Mean and median follow-up of alive patients were 59 and 35 months, respectively.Kaplan-Meier 5-year IFC, LRC, DMFS, and DSS probabilities for the entire group were 55%, 26%, 51%, and 25%, respectively. Prognostic factors found to be significant (p < 0.05) on multivariate analysis were prior DFI and tumor size for LRC, extremity location and leiomyosarcoma histologic subtype for DMFS, and prior DFI for DSS. Our cohort had five Grade 3/4 complications associated with treatment or a 5-year Kaplan-Meier Grade 3/4 complication-free survival rate of 85%.IORT after tumor reductive surgery is well tolerated and seems to confer IFC in carefully selected patients.

    View details for DOI 10.1016/j.ijrobp.2008.02.012

    View details for Web of Science ID 000260592600026

    View details for PubMedID 18394818

  • Integrative proteomic and cytological analysis of the effects of extracellular Ca2+ influx on Pinus bungeana pollen tube development JOURNAL OF PROTEOME RESEARCH Wu, X., Chen, T., Zheng, M., Chen, Y., Teng, N., Samaj, J., Baluska, F., Lin, J. 2008; 7 (10): 4299-4312

    Abstract

    Ca (2+) is an essential ion in the control of pollen germination and tube growth. However, the control of pollen tube development by Ca (2+) signaling and its interactions with cytoskeletal components, energy-providing pathways, and cell-expansion machinery remain elusive. Here, we used nifedipine (Nif) to study Ca (2+) functions in differential protein expression and other cellular processes in Pinus bungeana pollen tube growth. Proteomics analysis indicated that 50 proteins showed differential expression with varying doses of Nif. Thirty-four of these were homologous to previously reported proteins and were classified into different functional categories closely related to tip-growth machinery. Blocking the L-type Ca (2+) channel with Nif in the pollen tube membrane induced several early alterations within a short time, including a reduction of extracellular Ca (2+) influx and a subsequently dramatic decrease in cytosolic free Ca (2+) concentration ([Ca (2+)] c), concomitant with ultrastructural abnormalities and changes in the abundance of proteins involved in energy production and signaling. Secondary alterations included actin filament depolymerization, disrupted patterns of endocytosis/exocytosis, and cell wall remodeling, along with changes in the proteins involved in these processes. These results suggested that extracellular Ca (2+) influx was necessary for the maintenance of the typical tip-focused [Ca (2+)] c gradient in the P. bungeana pollen tube, and that reduced adenosine triphosphate production (ATP), depolymerization of the cytoskeleton, and abnormal endocytosis/exocytosis, together with enhanced rigidity of cell walls, were responsible for the growth arrest observed in pollen tubes treated with Nif.

    View details for DOI 10.1021/pr800241u

    View details for Web of Science ID 000259784300010

    View details for PubMedID 18715029

  • Ovarian cancer. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Morgan, R. J., Alvarez, R. D., Armstrong, D. K., Boston, B., Chen, L., Copeland, L., Fowler, J., Gaffney, D. K., Gershenson, D., Greer, B. E., Grigsby, P. W., Havrilesky, L. J., Johnston, C., Lancaster, J. M., Lele, S., Matulonis, U., O'Malley, D., Ozols, R. F., Remmenga, S. W., Sabbatini, P., Schink, J., Teng, N. 2008; 6 (8): 766-794

    View details for PubMedID 18926089

  • Natural frequency analysis of tooth stability under various simulated types and degrees of alveolar vertical bone loss. Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine Wang, C. H., Liu, H. W., Ou, K. L., Teng, N. C., Yu, J. J., Huang, H. M. 2008; 222 (6): 983-989

    Abstract

    The aim of this study was to test natural teeth stability under various simulated types and degrees of alveolar vertical bone loss, as well as to assess the role that the surrounding bone played for maintaining tooth stability. A three-dimensional finite element model of the human maxillary central incisor with surrounding tissue, including periodontal ligament, enamel, dentin, pulp, and alveolar bone, was established. One side and multiple vertical bone loss were simulated by means of decreasing the surrounding bone level apically from the cemento-enamel junction in 1 mm steps incrementally downward for 10 mm. Natural frequency values of the incisor model with various types and degrees of bone loss were then calculated. The results showed that, with one-sided bone resorption, the model with labial bone loss had the lowest natural frequency decreasing rates (8.2 per cent). On the other hand, in cases of multiple bone loss, vertical bone resorption at the mesial and distal sides had more negative effects on tooth stability compared to vertical bone losses on facial and lingual sides. These findings suggest that the natural frequency method may be a useful, auxiliary clinical tool for diagnosis of vertical periodontal diseases.

    View details for PubMedID 18935815

  • Prognostic factors and risk of extrauterine metastases in 3867 women with grade 1 endometrioid corpus cancer AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chan, J. K., Kapp, D. S., Cheung, M. K., Shin, J. Y., Stieglitz, D., Husain, A., Teng, N. N., Berek, J. S., Osann, K., Guo, H. 2008; 198 (2)

    Abstract

    The purpose of this study was to evaluate the role of surgical staging in patients with grade 1 endometrioid uterine cancer.Data were extracted from Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Kaplan-Meier and Cox proportional hazards analyses were used to determine predictors for disease-specific survival.Twelve thousand seven hundred and twelve women were reported with endometrioid carcinoma, including 3867 with grade 1 disease, of which 25.5% had stage IC or more advanced disease, 15.4% with disease extending beyond the uterine corpus, 7.3% with extrauterine metastases, and 3.3% with lymph node metastases. On multivariate analysis, younger age and earlier stage remained as significant prognostic factors for improved survival.Since grade 1 endometrioid uterine cancers have a 15.4% risk of extrauterine spread, a complete surgical staging procedure is recommended when clinically feasible. Younger age and earlier stage are significant prognostic factors for improved survival.

    View details for DOI 10.1016/j.ajog.2007.08.028

    View details for Web of Science ID 000253587300026

    View details for PubMedID 18226629

  • Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Ueda, S. M., Kapp, D. S., Cheung, M. K., Shin, J. Y., Osann, K., Husain, A., Teng, N. N., Berek, J. S., Chan, J. K. 2008; 198 (2)

    Abstract

    The purpose of this study was to determine factors responsible for the increasing number of deaths from corpus cancer over three time periods.Data were collected from the Surveillance, Epidemiology and End Results database from 1988-2001. Kaplan-Meier and Cox proportional hazards regression analyses were performed.Of 48,510 women with corpus cancer, there was an increase in the proportion of patients dying from advanced cancers (52.1% to 56.0% to 68.8%; P < .001), grade 3 disease (47.5% to 53.3% to 60.6%; P < .001), serous tumors (14.3% to 18.4% to 16.6%; P < .001), and sarcomas (19.1% to 20.4% to 27.2%; P < .001) over time. On multivariate analysis, older age, African American race, lack of primary staging procedures, advanced-stage, high-grade, and non-endometrioid histology were independent prognostic factors for worse survival.Our data suggest that the increase in mortality in women with corpus cancer over the last 14 years may be related to an increased rate of advanced-stage cancers and high-risk histologies.

    View details for DOI 10.1016/j.ajog.2007.08.075

    View details for Web of Science ID 000253587300027

    View details for PubMedID 18226630

  • Ovarian clear cell carcinoma with papillary features: A potential mimic of serous tumor of low malignant potential AMERICAN JOURNAL OF SURGICAL PATHOLOGY Sangoi, A. R., Soslow, R. A., Teng, N. N., Longacre, T. A. 2008; 32 (2): 269-274

    Abstract

    The differential diagnostic problems usually associated with clear cell carcinoma (CCC) of the ovary have been well characterized and include primitive germ cell tumor, sex cord stromal tumor, and metastasis. Distinction from other types of surface epithelial carcinoma may also pose a diagnostic challenge, but the potential for misdiagnosis of serous tumor of low malignant potential (S-LMP) is not well recognized. We report 13 cases of ovarian CCC with prominent papillary architecture that were initially misdiagnosed as S-LMP or low-grade serous carcinoma either on frozen section or at final diagnosis. The ages of the patients ranged from 39 to 65 years (mean, 52.2 y). All patients presented with a pelvic mass; 1 was undergoing evaluation for infertility. Macroscopically, most were described as unilateral, multilocular cysts with internal papillary structures. On microscopic examination, each tumor had a papillary architecture that accounted for 30% to 95% of the tumor; in 6 cases, the cores of the papillae were hyalinized. The neoplastic cells covering the papillae had clear to granular and eosinophilic cytoplasm. Hobnail cells were focal and often subtle. Most had a low mitotic index (9/13) and/or deceptively bland cytology (8/13); only careful attention to the cytologic features and/or mitotic index allowed correct identification of the tumor type in 5 cases. Six were associated with pelvic/ovarian endometriosis. Ten were Federation of Gynecology and Obstetrics stage I (8 IA, 2 IC), 2 were stage II (1 IIB, 1 IIC), and 1 stage IIIC. CCC with prominent papillary architecture is uncommon, but may pose a challenging differential diagnosis with S-LMP, resulting in inadequate staging and delayed treatment. Features most helpful in distinguishing papillary CCC are unilaterality, nonhierarchical branching, monomorphous cell population, and the presence of more typical CCC patterns elsewhere in the tumor. The presence of endometriosis, although not specific, should also prompt consideration for papillary CCC. Increased numbers of mitotic figures may not be present and high-grade cytologic atypia may be focal, requiring careful examination of multiple tumor sections for detection. As CCC and S-LMP exhibit significantly different immunoreactivity for Wilms' Tumor 1 and estrogen receptor, these markers may also be useful adjunctive tests in problematic cases.

    View details for Web of Science ID 000252759900012

    View details for PubMedID 18223330

  • A novel technique for the enrichment of primary ovarian cancer cells AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chan, J. K., Hamilton, C. A., Anderson, E. M., Cheung, M. K., Baker, J., Husain, A., Teng, N. N., Kong, C. S., Negrin, R. S. 2007; 197 (5)

    Abstract

    Primary cancer cells that are extracted from ovarian tumors can serve as an optimal substrate to study the biologic characteristics of ovarian cancer. We describe an efficient and effective method of enriching ovarian tumor cells from ascitic fluid using an immunomagnetic-based method.Mononuclear cells were isolated from ascites specimens by Ficoll gradient separation. Epithelial ovarian cancer cells were labeled magnetically with monoclonal human epithelial antigen-125 that is conjugated to microbeads. After immunomagnetic separation, the purity of tumor cells before and after purification was quantified by cytologic analysis and confirmed by fluorescence-activated cell sorter analysis.Peritoneal ascites specimens were obtained from 6 patients with ovarian cancer. The median age of our patients was 61.5 years (range, 46-79 years). Three patients had papillary serous carcinoma; 2 patients had clear cell carcinoma, and 1 patient had an undifferentiated adenocarcinoma. The mean tumor purity was only 22.8% +/- 10% (range, 1%-60%) before separation. After enrichment, the purity improved to 82.3% +/- 4.0% (range, 70%-90%). Our enrichment technique increased the tumor purity by 59.5% +/- 8.4%. The mean percent yield after positive enrichment was 30.1% +/- 14.5%.The immunomagnetic cell separation technique is an efficient and effective method for isolating and purifying ovarian tumor cells from ascites. Results from experiments with fresh tumor cells rather than cancer cell lines may be more relevant for clinical application.

    View details for DOI 10.1016/j.ajog.2007.05.006

    View details for Web of Science ID 000250915500021

    View details for PubMedID 17980191

  • Long-term survivors using intraoperative radiotherapy for recurrent gynecologic malignancies INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Tran, P. T., Su, Z., Hara, W., Husain, A., Teng, N., Kapp, D. S. 2007; 69 (2): 504-511

    Abstract

    To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution.We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. The mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications.The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p

    View details for DOI 10.1016/j.ijrobp.2007.03.021

    View details for Web of Science ID 000249796100026

    View details for PubMedID 17560736

  • Acute postoperative thrombotic thrombocytopenic purpura following hysterectomy and lymphadenectomy for endometrial cancer GYNECOLOGIC ONCOLOGY Hamilton, C. A., Kao, J. M., Coutre, S. E., Teng, N. N. 2007; 106 (2): 423-426

    Abstract

    Thrombotic thrombocytopenic purpura (TTP) in the acute postoperative setting is a recently recognized syndrome that, similar to classic or idiopathic TTP, presents variably with microangiopathic hemolytic anemia, thrombocytopenia, fever, renal failure, and mental status changes. Though most reports of postoperative TTP are in conjunction with cardiac or vascular surgery, it has also been reported following orthopedic and abdominal surgeries.We present a case of a 53 year-old female diagnosed with metastatic poorly differentiated endometrial cancer who developed TTP the day following her cytoreductive cancer surgery.To our knowledge, this represents the first reported case of postoperative TTP following gynecologic cancer surgery. Because the presentation can be confused with other early postoperative complications, awareness of this syndrome is essential as initiation of plasmapheresis can be life-saving.

    View details for DOI 10.1016/j.ygyno.2007.04.005

    View details for Web of Science ID 000248585700023

    View details for PubMedID 17499845

  • The potential therapeutic role of lymph node resection in epithelial ovarian cancer: a study of 13,918 patients BRITISH JOURNAL OF CANCER Chan, J. K., Urban, R., Hu, J. M., Shin, J. Y., Husain, A., Teng, N. N., Berek, J. S., Osann, K., Kapp, D. S. 2007; 96 (12): 1817-1822

    Abstract

    The aim of the study is to determine the role of lymphadenectomy in advanced epithelial ovarian cancer. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) program reported between 1988 and 2001. Kaplan-Meier estimates and Cox proportional hazards regression models were used for analysis. Of 13 918 women with stage III-IV epithelial ovarian cancer (median age: 64 years), 87.9% were Caucasian, 5.6% African Americans, and 4.4% Asians. A total of 4260 (30.6%) underwent lymph node dissections with a median number of six nodes reported. For all patients, a more extensive lymph node dissection (0, 1, 2-5, 6-10, 11-20, and >20 nodes) was associated with an improved 5-year disease-specific survival of 26.1, 35.2, 42.6, 48.4, 47.5, and 47.8%, respectively (P<0.001). Of the stage IIIC patients with nodal metastases, the extent of nodal resection (1, 2-5, 6-10, 11-20, and >20 nodes) was associated with improved survivals of 36.9, 45.0, 47.8, 48.7, and 51.1%, respectively (P=0.023). On multivariate analysis, the extent of lymph node dissection and number of positive nodes were significant independent prognosticators after adjusting for age, year at diagnosis, stage, and grade of disease. The extent of lymphadenectomy is associated with an improved disease-specific survival of women with advanced epithelial ovarian cancer.

    View details for DOI 10.1038/sj.bjc.6603803

    View details for Web of Science ID 000247218100007

    View details for PubMedID 17519907

  • Lymphadenectomy in endometrioid uterine cancer staging - How many lymph nodes are enough? A study of 11,443 patients CANCER Chan, J. K., Urban, R., Cheung, M. K., Shin, J. Y., Husain, A., Teng, N. N., Berek, J. S., Walker, J. L., Kapp, D. S., Osann, K. 2007; 109 (12): 2454-2460

    Abstract

    The purpose of the current study was investigate the association between the number of lymph nodes examined and the probability of detecting at least a single lymph node involved by metastatic disease in patients with endometrioid corpus cancer.Demographic, clinicopathologic, and surgical information were obtained from the National Cancer Institute between 1990 and 2001. A logistic regression model was used to investigate the relation between the number of lymph nodes identified and the probability of detecting at least a single positive lymph node.Of 11,443 patients, the median age was 64 years (range, 22-74 years). In all, 78.7% had stage I disease, 10.3% had stage II disease, and 11.0% had stage III disease; 31.5% had grade 1 histology, 40.6% had grade 2 histology, and 24.3% had grade 3 histology. The median number of lymph nodes reported was 9 (range, 1-90 lymph nodes). The median number of lymph nodes and the percent of patients with positive lymph nodes have increased from 1988 to 2001. An increasing number of lymph nodes removed was associated with a higher likelihood of identifying those with lymph node metastases. Based on the logistic regression model, the largest increase in probability of detecting at least a single positive lymph node was observed when 21 to 25 lymph nodes were resected (odds ratio [OR] of 1.45; 95% confidence interval [95% CI], 1.08-1.94 [P < .01]). Removing greater than 25 lymph nodes did not improve the statistical probability (OR of 1.23; 95% CI, 0.94-1.61 [P = .13]).The current study data suggest that the removal of 21 to 25 lymph nodes significantly increases the probability of detecting at least 1 positive lymph node in endometrioid uterine cancer. The definition of an adequate lymphadenectomy deserves further investigation.

    View details for DOI 10.1002/cncr.22727

    View details for Web of Science ID 000247113500009

    View details for PubMedID 17503431

  • Influence of the gynecologic oncologist on the survival of ovarian cancer patients OBSTETRICS AND GYNECOLOGY Chan, J. K., Kapp, D. S., Shin, J. Y., Husain, A., Teng, N. N., Berek, J. S., Osann, K., Leiserowitz, G. S., Cress, R. D., O'Malley, C. 2007; 109 (6): 1342-1350

    Abstract

    To estimate the influence of gynecologic oncologists on the treatment and outcome of patients with ovarian cancer.Data were obtained from California Cancer Registry from 1994 to 1996. Kaplan-Meier and Cox proportional hazard methods were used for analyses.Of 1,491 patients, the median age was 65 years (range: 13-100). Only 34.1% received care by gynecologic oncologists (group A) while 65.9% were treated by others (group B). Women in group A were more affluent (P<.001), were more educated (P=.036), were classified as white-collar employees (P=.128), and lived in urban regions (P<.001) compared with group B. Patients who saw gynecologic oncologists were more likely to have surgery as their initial treatment (91.9% versus 69.1%; P<.001), present with advanced (stage III-IV) cancers (78.2% versus 70.5%; P<.001), have more grade 3 tumors (61.7% versus 39.9%; P=.048), and receive chemotherapy (90.0% versus 70.1%; P<.001). Women in group B had a fourfold higher risk of having unstaged cancers (8.0% versus 2.1%; P<.001). The 5-year disease-specific survival of group A patients was 38.6% compared with 30.3% in group B (P<.001). On multivariable analysis, early stage, lower grade, and treatment by gynecologic oncologists were independent prognostic factors for improved survival. After adjusting for surgery and chemotherapy, there was no improvement in survival associated with care by gynecologic oncologists (hazard ratio=0.90, 95% confidence interval 0.78-1.03; P=.133).In this study of 1,491 women, those who were treated by gynecologic oncologists were more likely to undergo primary staging surgery and receive chemotherapy. Stage, grade of disease, and treatment by gynecologic oncologists were important prognosticators.

    View details for Web of Science ID 000247010200013

    View details for PubMedID 17540806

  • Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation GYNECOLOGIC ONCOLOGY Tran, P. T., Su, Z., Lee, P., Lavori, P., Husain, A., Teng, N., Kapp, D. S. 2007; 105 (3): 641-649

    Abstract

    To analyze the results of treatment and identify prognostic factors for primary squamous cell carcinoma (SCCA) of the vagina managed with radiotherapy at a single institution.Seventy-eight patients were analyzed in this retrospective series. Mean characteristics: follow-up 89 months; age 65 years (range 33-99); tumor size 3.8 cm (0.3-10); treatment hemoglobin 12.4 g/dl (range 8.7-14.4); and tumor dose 72 Gy (range 6-127). In addition, 49% of our cohort had a prior hysterectomy. The FIGO stage distribution: I (42%); II (29%); III (17%); and IVA/B (11%). Sixty-two percent of patients were treated with a combination of external beam radiation (EBRT) and brachytherapy, 22% with EBRT alone and 13% with brachytherapy alone.Kaplan-Meier (KM) 5-year pelvic control, distant metastasis free survival and disease specific survival probabilities: stage I, 83%, 100%, and 92%; stage II, 76%, 95%, and 68%; stage III, 62%, 65%, and 44%; and stage IV, 30%, 18%, and 13%. On multivariate analysis: stage; treatment hemoglobin; and prior hysterectomy were prognostic for DSS (p<0.05). The KM 5-year grade 3/4 (G3/4) complication free estimate of our cohort was 84%. G3/4 complications: tumor size and tumor dose were independently predictive (p<0.05).Radiotherapy as a single modality for early stage primary vaginal SCCA produces good results. Advanced stage disease necessitates a combined modality approach and/or new methods. Treatment Hg levels appear to be clinically significant and studies on correction of anemia during treatment are warranted.

    View details for DOI 10.1016/j.ygyno.2007.01.033

    View details for Web of Science ID 000246815700014

    View details for PubMedID 17363046

  • Effects of human monoclonal antibody 216 on B-progenitor acute lymphoblastic leukemia in vitro PEDIATRIC BLOOD & CANCER Bieber, M. M., Twist, C. J., Bhat, N. M., Teng, N. N. 2007; 48 (4): 380-386

    Abstract

    Human monoclonal antibody (mAb) 216 is a naturally occurring IgM cytotoxic mAb that binds to a glycosylated epitope on the surface of B-lymphocytes. This study investigated if this mAb could bind and kill acute lymphoblastic leukemia (ALL) B-progenitor lymphoblasts in vitro. ALL cell lines were used to determine if combining mAb 216 with chemotherapeutic drugs would enhance killing and cell lines were used to measure cytotoxicity by mAb 216 with human complement.Expression of cell surface markers and mAb 216 epitope on fresh and banked ALL bone marrow samples was determined by flow cytometry. Fresh lymphoblasts were incubated for 20 hr with mAb 216 without complement to measure cytotoxicity. Cytotoxicity of ALL cell lines incubated with mAb 216 and vincristine (VCR) or human complement was determined using flow cytometry.Pre-B-ALL cells but not T-ALL cells are bound and killed by mAb 216. The combination of mAb 216 and VCR at sub-therapeutic levels demonstrated enhanced cytotoxicity beyond that observed for either agent alone. Incubation of mAb 216 with human complement increased cytotoxicity of ALL cell lines.This increased cytotoxicity with chemotherapy and the functional ability of mAb 216 to use multiple pathways to induce cell death identify mAb 216 as a potentially novel therapeutic tool in the treatment of B-progenitor ALL. Based on the results from this preclinical study, a Phase I clinical trial with mAb 216 for the treatment of patients with relapsed or refractory B-lineage ALL is ongoing.

    View details for DOI 10.1002/pbc.20770

    View details for Web of Science ID 000244611500004

    View details for PubMedID 16421902

  • Safety and efficacy of lenalidomide (Revlimid((R))) in recurrent ovarian and primary peritoneal carcinoma GYNECOLOGIC ONCOLOGY Zhang, M. M., Chan, J. K., Husain, A., Guo, H., Teng, N. N. 2007; 105 (1): 194-198

    Abstract

    To conduct a phase I trial to determine the safety and toxicity profile of a novel immunomodulatory drug, lenalidomide, in recurrent ovarian and primary peritoneal cancer. The secondary objective is to evaluate the efficacy profile and quality of life (QOL) parameters in patients receiving this treatment.Patients with recurrent ovarian or peritoneal cancer who received standard staging surgery and at least one prior platinum-based chemotherapy regimen were treated with single-agent oral lenalidomide 25 mg daily for 21 days of a 28-day cycle. Toxicities were monitored by patient report, physical exam, and laboratories. Response was assessed by imaging, physical exam, and CA-125. Therapy was discontinued with disease progression and/or unacceptable toxicity.20 patients with recurrent ovarian or peritoneal cancer were enrolled and received 70 completed 28-day cycles and 10 partial cycles of lenalidomide therapy. The majority of adverse events were grades 1-2, including fatigue (25/80 cycles), nausea/vomiting (23/80), constipation (13/80), abdominal pain (17/80), rash (12/80), neutropenia (12/80), and anemia (12/80). Grade 3 toxicities occurred in 12 of 80 cycles (14%) and no grade IV toxicities were observed. Eleven patients completed > or = 2 cycles and were evaluable for response. Nine achieved stable disease (SD) of at least 3 months, with four patients maintaining SD for > 6 months. The mean time to progression was 5.8 months (range 2-12 months).Overall, oral lenalidomide was well tolerated and may have some activity as a single agent in this heavily pre-treated population. Further studies combining lenalidomide with cytotoxic treatments may be warranted in this disease setting.

    View details for DOI 10.1016/j.ygyno.2006.11.026

    View details for Web of Science ID 000245559000030

    View details for PubMedID 17257661

  • Prognostic factors for uterine cancer in reproductive-aged women OBSTETRICS AND GYNECOLOGY Lee, N. K., Cheung, M. K., Shin, J. Y., Husain, A., Teng, N. N., Berek, J. S., Kapp, D. S., Sann, K., Chan, J. K. 2007; 109 (3): 655-662

    Abstract

    To determine the prognostic factors that influence the survival of younger women diagnosed with uterine cancer.Demographic and clinico-pathologic data were collected from the National Cancer Institute database between 1988 and 2001. Data were analyzed with Kaplan-Meier methods and Cox proportional hazards regression.Of the 51,471 women diagnosed with uterine cancer in the study period, 2,076 (4.0%) patients were aged 40 years or younger, and 49,395 (96.0%) were older than 40. The mean age in the younger group was 35.6 years, compared with 65.2 years of the older group. The overall distribution by stage was stage I 75.4%, II 8.1%, III 6.7%, and IV 9.8%. Younger patients were more likely to be nonwhite (42.4% versus 18.3%, P<.001) and have stage I disease (79.2% versus 75.3%, P<.001), grade 1 lesions (47.6% versus 35.6%, P<.001), and sarcomas (15.9% versus 8.2%, P<.001) compared with their older counterparts. The overall 5-year disease-specific survival for younger patients was significantly better than that of older women (93.2% versus 86.4%, P<.001). On multivariable analysis, younger age, earlier stage, lower grade, nonblack race, endometrioid histology, and surgical treatment remained as significant independent prognostic factors for improved survival.This large population-based study demonstrates that patients 40 years and younger have an overall survival advantage compared with women older than 40 years, independent of other clinico-pathologic prognosticators.III.

    View details for Web of Science ID 000246771200011

    View details for PubMedID 17329517

  • Prognostic factors responsible for survival in sex cord stromal tumors of the ovary- An analysis of 376 women GYNECOLOGIC ONCOLOGY Zhang, M., Cheung, M. K., Shin, J. Y., Kapp, D. S., Husain, A., Teng, N. N., Berek, J. S., Osann, K., Chan, J. K. 2007; 104 (2): 396-400

    Abstract

    To evaluate prognostic factors that impact on the survival of women with ovarian sex cord stromal tumors (SCST).Data including age at diagnosis, stage, histology, grade, treatment, and survival were extracted from the 1988-2001 Surveillance, Epidemiology, and End Results Program. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival.376 women (median age: 51) with ovarian sex cord stromal cell tumors were identified, including 339 with granulosa cell and 37 with Sertoli-Leydig cell tumors. 265 (71%) patients had stage I, 39 (10%) stage II, 40 (11%) stage III, and 32 (8%) had stage IV disease. Women with stage I-II disease had a 5-year disease-specific survival of 95% compared to 59% in those with stage III-IV cancers (p<0.001). Patients50 years (93% vs. 84%, p<0.001). This age-associated survival advantage was observed for early (97% vs. 92%, p=0.003), but not for advanced-staged (68% vs. 53%, p=0.09) patients. 110 patients with stage I-II disease underwent conservative surgery without hysterectomy. The survival for this group was similar to patients who underwent a standard surgery including a hysterectomy (94.8% and 94.9%, p=0.38). On multivariate analysis, age

    View details for DOI 10.1016/j.ygyno.2006.08.032

    View details for Web of Science ID 000244101200021

    View details for PubMedID 17030354

  • Association of lymphadenectomy and survival in stage I ovarian cancer patients OBSTETRICS AND GYNECOLOGY Chan, J. K., Munro, E. G., Cheung, M. K., Husain, A., Teng, N. N., Berek, J. S., Osann, K. 2007; 109 (1): 12-19

    Abstract

    To estimate the survival impact of lymphadenectomy in women diagnosed with clinical stage I ovarian cancer.Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology and End Results Program between 1988 and 2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression.A total of 6,686 women had clinical stage I ovarian cancer (median age 54 years, range 1-99). Of this total, 75.9% of patients were Caucasian, 8.3% were Hispanic, 5.8% were African American, and 7.3% were Asian. Epithelial tumors were present in 85.8% of the women, and 2,862 (42.8%) patients underwent lymphadenectomy. Patients aged 50 years or more were less likely to undergo lymphadenectomy compared with their younger cohorts (39.8% compared with 60.2%, P<.001). Only 32.7% of African-American women had lymphadenectomy compared with 42.7% of Caucasian women, 47.2% of Hispanics, and 48.8% of Asians (P<.001). Lymphadenectomy was associated with improved 5-year disease-specific survival of all patients from 87.0% to 92.6% (P<.001). More specifically, lymphadenectomy improved the survival in those with non-clear cell epithelial ovarian cancer (85.9% to 93.3%, P<.001) but not in those with clear cell carcinoma, germ cell tumors, sex cord stromal tumors, and sarcomas. Moreover, the extent of lymphadenectomy (0 nodes, less than 10 nodes, and 10 or more nodes) increased the survival rates from 87.0% to 91.9% to 93.8%, respectively (P<.001). On multivariable analysis, the extent of lymphadenectomy was a significant prognostic factor for improved survival, independently of other factors such as age, stage, histology, and grade of disease.Our data suggest that women with stage I non-clear cell ovarian cancers who underwent lymphadenectomy had a significant improvement in survival.II.

    View details for Web of Science ID 000246771500003

    View details for PubMedID 17197582

  • Disruption of actin filaments by latrunculin B affects cell wall construction in Picea meyeri pollen tube by disturbing vesicle trafficking PLANT AND CELL PHYSIOLOGY Chen, T., Teng, N., Wu, X., Wang, Y., Tang, W., Samaj, J., Baluska, F., Lin, J. 2007; 48 (1): 19-30

    Abstract

    The involvement of actin filaments (AFs) in vesicle trafficking, cell wall construction and tip growth was investigated during pollen tube development of Picea meyeri. Pollen germination and tube elongation were inhibited in a dose-dependent manner by the latrunculin B (LatB) treatment. The fine AFs were broken down into disorganized fragments showing a tendency to aggregate. FM4-64 labeling revealed that the dynamic balance of vesicle trafficking was perturbed due to F-actin disruption and the fountain-like cytoplasmic pattern changed into disorganized Brownian movement. The configuration and/or distribution of cell wall components, such as pectins, callose and cellulose, as well as arabinogalactan proteins changed in obvious ways after the LatB application. Fourier transform infrared (FTIR) analysis further established significant changes in the chemical composition of the wall material. Our results indicate that depolymerization of AFs affects the distribution and configuration of cell wall components in Picea meyeri pollen tube by disturbing vesicle trafficking.

    View details for DOI 10.1093/pcp/pc1036

    View details for Web of Science ID 000243993900004

    View details for PubMedID 17118947

  • Mesonephric adenocarcinoma of the cervix: A case report and review of the literature GYNECOLOGIC ONCOLOGY Yap, O. W., Hendrickson, M. R., Teng, N. N., Kapp, D. S. 2006; 103 (3): 1155-1158

    Abstract

    Malignant mesonephric tumor arising in the uterine cervix is an exceedingly uncommon variant of cervical adenocarcinoma with only 30 well-documented cases in the literature.We present a case of a 54-year-old woman with postmenopausal vaginal bleeding who was found to have a stage IB mesonephric adenocarcinoma of the cervix.At present there is no consensus on a standardized treatment protocol for malignant mesonephric tumors of the cervix. The present case suggests that a favorable outcome may be achieved for patients with stage IB tumors with aggressive initial therapy.

    View details for DOI 10.1016/j.ygyno.2006.08.031

    View details for Web of Science ID 000242809500065

    View details for PubMedID 17023031

  • The benefit of adjuvant radiation therapy in single-node-positive squamous cell vulvar carcinoma GYNECOLOGIC ONCOLOGY Parthasarathy, A., Cheung, M. K., Osann, K., Husain, A., Teng, N. N., Berek, J. S., Kapp, D. S., Chan, J. K. 2006; 103 (3): 1095-1099

    Abstract

    To determine if adjuvant radiotherapy improves the survival of women with invasive squamous cell carcinoma of the vulva involving one inguinal node.Demographic, pathologic, and treatment information was obtained on patients with vulvar cancers from the Surveillance, Epidemiology, and End Results database between 1988 and 2001. Kaplan-Meier estimates and Cox-proportional hazards model were used for analyses.Of the 490 patients with stage III, node-positive vulvar cancers, 208 had a single positive inguinal node. The median age of this group was 71 years (range: 29-100). 82.2% of patients were White, 7.2% were Hispanic, 7.7% were Black, 1.4% were Asian, and 1.4% were Others. 91.8% of patients underwent a radical vulvectomy with a unilateral or bilateral inguinal lymphadenectomy. The median number of lymph nodes resected was 13 (range: 1-34). 102 women underwent adjuvant radiotherapy, while 106 did not receive any radiation treatment. Women who received adjuvant radiotherapy had a 5-year disease-specific survival of 77.0% compared to 61.2% in those without radiotherapy (p=0.02). After stratifying the study group based on the extent of lymphadenectomy, we found that radiation treatment improved the survival of those with

    View details for DOI 10.1016/j.ygyno.2006.06.030

    View details for Web of Science ID 000242809500053

    View details for PubMedID 16889821

  • Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma GYNECOLOGIC ONCOLOGY Chan, J. K., Manuel, M. R., Ciaravino, G., Cheung, M. K., Husain, A., Teng, N. N. 2006; 103 (3): 919-923

    Abstract

    Thalidomide is an anti-angiogenesis agent that has shown activity in some solid tumors. We performed a phase I clinical trial to determine the toxicity and potential efficacy of Thalidomide in recurrent epithelial ovarian carcinoma.Patients with recurrent ovarian cancer were evaluated between 1998 and 2000. Data were evaluated using Kaplan-Meier and logistic regression analyses.17 heavily pretreated patients with recurrent epithelial ovarian cancer received oral Thalidomide starting at 100 mg/day, with dose escalations of 100 mg/day every 2 weeks, up to 1200 mg/day as tolerated. The median number of courses was four (range: 1-18 courses), and median dose was 200 mg/day (range: 100-600 mg/day). Treatment duration ranged from 2 to 48 months. Common grade 1 or 2 side effects included constipation (76%), neuropathy (71%), and fatigue (65%) with few grade 3 or 4 events. Three (18%) patients had partial responses, and six (35%) had stabilization of disease after 6 months. After 1 year of treatment, six of the nine patients with an initial partial response (n=2) or stable disease (n=4) remained in these response categories. Median time to progression was 10 months. Forty-seven percent of patients had a 50-70% decrease in CA125 levels. Using logistic regression and repeated measures analyses, CA125 levels decreased by 62 units/ml per month (p=0.07).Our study demonstrates the safety, tolerability, and potential efficacy of Thalidomide in recurrent and refractory epithelial ovarian cancers. Additional clinical trials are warranted.

    View details for DOI 10.1016/j.ygyno.2006.05.035

    View details for Web of Science ID 000242809500024

    View details for PubMedID 16828852

  • Ovarian cancer in younger vs older women: a population-based analysis BRITISH JOURNAL OF CANCER Chan, J. K., Urban, R., Cheung, M. K., Osann, K., Husain, A., Teng, N. N., Kapp, D. S., Berek, J. S., Leiserowitz, G. S. 2006; 95 (10): 1314-1320

    Abstract

    To compare the clinico-pathologic prognostic factors and survival of younger vs older women diagnosed with epithelial ovarian cancer. Demographic, clinico-pathologic, treatment, and surgery information were obtained from patients with ovarian cancer from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001 and analysed using Kaplan-Meier estimates. Of 28 165 patients, 400 were <30 years (very young), 11 601 were 30-60 (young), and 16 164 were >60 (older) years of age. Of the very young, young, and older patients, 261 (65.3%), 4664 (40.2%), and 3643 (22.5%) had stage I-II disease, respectively (P<0.001). Across all stages, very young women had a significant survival advantage over the young and older groups with 5-year disease-specific survival estimates at 78.8% vs 58.8 and 35.3%, respectively (P<0.001). This survival difference between the age groups persists even after adjusting for race, stage, grade, and surgical treatment. Reproductive age (16-40 years) women with stage I-II epithelial ovarian cancer who received uterine-sparing procedures had similar survivals compared to those who underwent standard surgery (93.3% vs 91.5%, P=0.26). Younger women with epithelial ovarian cancer have a survival advantage compared to older patients.

    View details for DOI 10.1038/sj.bjc.6603457

    View details for Web of Science ID 000242046700002

    View details for PubMedID 17088903

  • The effect of adjuvant chemotherapy versus whole abdominopelvic radiation on the survival of patients with advanced stage uterine papillary serous carcinoma GYNECOLOGIC ONCOLOGY Hamilton, C. A., Cheung, M. K., Osann, K., Balzer, B., Berman, M. L., Husain, A., Teng, N. N., Kapp, D. S., Chan, J. K. 2006; 103 (2): 679-683

    Abstract

    To compare the outcomes of stage III and IV uterine papillary serous carcinoma (UPSC) patients treated with platinum-based chemotherapy (PC) versus whole abdominopelvic irradiation (WAPI) after optimal cytoreductive surgery.Surgically staged patients with advanced stage UPSC diagnosed between 1981 and 2002 were identified from tumor registry databases at four hospitals. Survival analyses and predictors of outcome were analyzed using Kaplan-Meier methods.Of the 40 patients with advanced UPSC (median age: 64.5), 84% were Caucasian, 8% were African American, and 8% were Asian. The majority of patients (85%) presented with vaginal bleeding. Twenty-seven had stage III and 13 had stage IV disease. All patients were optimally debulked; 21 patients received adjuvant PC while 19 underwent WAPI. The median follow-up was 27 months (range: 5-209). The 3-year overall survival (OS) and progression-free survival (PFS) for the patients with stage III disease were 49% and 37% compared to 37% and 31% in those with stage IV disease (P = 0.23 for OS; P = 0.41 for PFS). Women who received PC had a 3-year OS and PFS of 43% and 31% compared to 45% and 41% in those receiving WAPI, respectively (P = 0.40 for OS; P = 0.84 for PFS).Platinum-based chemotherapy or whole abdominopelvic irradiation resulted in similar survival in this series of women with optimally cytoreduced UPSC. Given the overall poor prognosis of these patients, new treatment modalities are warranted.

    View details for DOI 10.1016/j.ygyno.2006.05.005

    View details for Web of Science ID 000241759600053

    View details for PubMedID 16793126

  • Therapeutic role of lymph node resection in endometrioid corpus cancer - A study of 12,333 patients CANCER Chan, J. K., Cheung, M. K., Huh, W. K., Osann, K., Husain, A., Teng, N. N., Kapp, D. S. 2006; 107 (8): 1823-1830

    Abstract

    The purpose of the current study was to determine the potential therapeutic role of lymphadenectomy in women with endometrioid corpus cancer.Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program between 1988-2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression.In all, 12,333 women (median age, 64) underwent surgical staging with lymph node assessment, including 9,009, 1,211, 1,223, and 890 with Stage I-IV disease. Over the time intervals 1988-1992, 1993-1997, and 1998-2001, the percentage of patients undergoing lymph node staging increased from 22.6%, 29.6%, to 40.9% (P < .001). In the intermediate/high-risk patients (Stage IB, Grade 3; Stage IC and II-IV, all grades), a more extensive lymph node resection (1, 2-5, 6-10, 11-20, and >20) was associated with improved 5-year disease-specific survivals across all 5 groups at 75.3%, 81.5%, 84.1%, 85.3%, and 86.8%, respectively (P < .001). For Stage IIIC-IV patients with nodal disease, the extent of node resection significantly improved the survival from 51.0%, 53.0%, 53.0%, 60.0%, to 72.0%, (P < .001). However, no significant benefit of lymph node resection in low-risk patients could be demonstrated (Stage IA, all grades; Stage IB, Grades 1 and 2 disease; P = .23). In multivariate analysis, a more extensive node resection remained a significant prognostic factor for improved survival in intermediate/high-risk patients after adjusting for other factors including age, year of diagnosis, stage, grade, adjuvant radiotherapy, and the presence of positive nodes (P < .001).The findings of the current study suggest that the extent of lymph node resection improves the survival of women with intermediate/high-risk endometrioid uterine cancer.

    View details for DOI 10.1002/cncr.22185

    View details for Web of Science ID 000241171300011

    View details for PubMedID 16977653

  • Ovarian cancer. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Morgan, R. J., Alvarez, R. D., Armstrong, D. K., Chen, L., Copeland, L., Fowler, J., Gaffney, D. K., Gershenson, D., Greer, B. E., Johnston, C., Lancaster, J. M., Lele, S., Matulonis, U., Ozols, R. F., Remmenga, S. W., Sabbatini, P., Soper, J., Teng, N. 2006; 4 (9): 912-939

    View details for PubMedID 17020669

  • Outcomes of women with metachronous breast and ovarian carcinomas GYNECOLOGIC ONCOLOGY Liou, W., Hamilton, C. A., Cheung, M. K., Osann, K., Longacre, T. A., Teng, N. N., Husain, A., Dirbas, F. M., Chan, J. K. 2006; 103 (1): 190-194

    Abstract

    Women with a history of breast cancer have a significantly increased risk of developing a second primary ovarian cancer and vice versa. We proposed to determine the characteristics and outcomes of women diagnosed with metachronous breast and ovarian cancer.Patients were identified from the Surveillance, Epidemiology, and End Results program database between 1988 and 2001. Kaplan-Meier and Cox proportional hazards regression tests were used to determine survival outcomes.Of 704 women, 526 developed breast cancer then ovarian cancer (B-O) and 178 developed ovarian cancer then breast cancer (O-B). The mean age at diagnosis of the first cancer in the B-O versus O-B group was 60.3 versus 58.9 years, respectively (P = 0.23). Twenty-five percent of women in the B-O group had stage I-II ovarian cancer versus 63% in the O-B group (P < 0.001). The percentage of those with stage I-II breast cancer was 94% and 91% in the B-O versus O-B group, respectively (P = 0.13). Women in the B-O group had more high grade of ovarian cancer compared to those in the O-B group (P < 0.001). The mean time interval between diagnoses of breast then ovarian versus ovarian then breast cancer was 58 versus 56 months, respectively (P = 0.42).In the largest series to date, we found that women diagnosed with ovarian cancer first had significantly more early stage and lower grade ovarian cancers with better survival compared to those with breast cancer followed by ovarian cancer. Since half of the women had their second cancer beyond 5 years, continued surveillance of these high risk patients is recommended.

    View details for DOI 10.1016/j.ygyno.2006.02.022

    View details for Web of Science ID 000240887100036

    View details for PubMedID 16569424

  • Breast cancer followed by corpus cancer: Is there a higher risk for aggressive histologic subtypes? GYNECOLOGIC ONCOLOGY Chan, J. K., Manuel, M. R., Cheung, M. K., Osann, K., Husain, A., Teng, N. N., Rao, A., Carlson, R. W., Whittemore, A. S. 2006; 102 (3): 508-512

    Abstract

    To analyze corpus cancer patients with a breast cancer history for risk of developing aggressive uterine histologic types.Corpus cancer patients with a history of breast cancer were identified from the Surveillance Epidemiology and End Results database from 1988 to 2001. Demographics, clinico-pathologic, and survival data were analyzed using Kaplan-Meier and logistic regression analyses.Of 52,109 women diagnosed with corpus cancer, 1922 had a history of breast cancer. Women with a history of breast cancer had a significantly higher proportion of uterine papillary serous carcinomas (UPSC) and sarcomas compared to those without a breast cancer history (9.4% vs. 6.3% for UPSC and 10.3% vs. 8.4% for sarcoma; P < 0.001). Patients with endometrioid or sarcoma of the uterus after breast cancer had significantly worse 5-year survivals than patients without a breast cancer history (84.4% vs. 90.5%; P < 0.001 and 49.0% vs. 63.6%, P < 0.001, respectively). Older age, advanced stage, lack of surgery and radiation treatment, poor histologic types, and history of breast cancer were independent prognostic factors for poorer survival.In this study, the proportional incidence of UPSC and sarcoma was significantly higher in women with a breast cancer history. These findings highlight the association of breast cancer and high-risk corpus cancer subtypes.

    View details for DOI 10.1016/j.ygyno.2006.01.014

    View details for Web of Science ID 000240871000017

    View details for PubMedID 16483640

  • Patterns and progress in ovarian cancer over 14 years OBSTETRICS AND GYNECOLOGY Chan, J. K., Cheung, M. K., Husain, A., Teng, N. N., West, D., Whittemore, A. S., Berek, J. S., Osann, K. 2006; 108 (3): 521-528

    Abstract

    To estimate the change in survival rates of women with ovarian cancer during the past 14 years.Women diagnosed with epithelial, germ cell, sarcomas, and sex-cord stromal ovarian tumors were identified from the Surveillance Epidemiology and End Results Database. Demographic and clinicopathologic factors, and survival information were extracted and tested using chi 2 and Kaplan-Meier and Cox regression analyses.A total of 30,246 women were diagnosed with ovarian cancer, including 26,753 non-clear cell epithelial, 1,411 clear cell, 818 sarcoma, 778 germ cell, and 486 sex-cord stromal tumors. The 5-year disease-specific survival rate across 1988-1992 and 1993-1997 improved from 45.4% to 48.6% (P < .001). The corresponding estimates show increases for non-clear cell epithelial carcinoma from 42.5% to 45.8% (P < .001), and for sarcomas from 33.5% to 38.8% (P = .07). However, improvements were not observed in those with clear cell, 64.3% to 63.9% (P = .82), and sex-cord stromal, 89.7% to 85.7% (P = .18), tumors of the ovary. In multivariable analyses, younger age, early stage, favorable histologic cell types, low-grade tumors, standard surgery, and recent time interval from 1993-1997 were independent prognostic factors for improved survival.In this large population-based study, there has been some improvement in the overall survival of women with ovarian cancers during a 14-year period. However, new treatment strategies are warranted for those with epithelial cancer and sarcomas of the ovary, given their overall poor prognosis. These results from our updated analyses might help to counsel women diagnosed with ovarian cancers.

    View details for Web of Science ID 000246769000008

    View details for PubMedID 16946210

  • Uterine cancers. Journal of the National Comprehensive Cancer Network Greer, B. E., Koh, W., Abu-Rustum, N., Bookman, M. A., Bristow, R. E., Campos, S., Cho, K. R., Copeland, L., Eifel, P., Jaggernauth, W., Jhingran, A., Kapp, D. S., Kavanagh, J., Lipscomb, G. H., Lurain, J. R., Morgan, R. J., Nag, S., Partridge, E. E., Powell, C. B., Remmenga, S. W., Reynolds, R. K., Small, W., Soper, J., Teng, N. 2006; 4 (5): 438-462

    View details for PubMedID 16687093

  • Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: A preclinical study CLINICAL CANCER RESEARCH Chan, J. K., Hamilton, C. A., Cheung, M. K., Karimi, M., Baker, J., Gall, J. M., Schulz, S., Thorne, S. H., Teng, N. N., Contag, C. H., Lum, L. G., Negrin, R. S. 2006; 12 (6): 1859-1867

    Abstract

    Cytokine-induced killer (CIK) cells are ex vivo activated and expanded CD8+ natural killer T cells that have been shown to have antitumor activity. This is the first study exploring cell killing of primary ovarian carcinoma cells with and without bispecific antibodies. Primary cancer cells and autologous CIK cells were collected from women with epithelial ovarian cancer. Bispecific antibodies against cancer antigen-125 (BSAbxCA125) and Her2 (BSAbxHer2) were developed using chemical heteroconjugation. On fluorescence-activated cell sorting analysis, the expansion of CIK cells resulted in a significant increase of CD3+CD8+ and CD3+CD56+ T cells. With enhancement by bispecific antibodies, the mean percent lysis in a 51Cr release assay of fresh ovarian cancer cells exposed to autologous CIK cells increased from 21.7 +/- 0.3% to 89.4 +/- 2.1% at an E:T ratio of 100:1 (P < 0.001). Anti-NKG2D antibodies attenuated the CIK activity by 56.8% on primary cells (P < 0.001). In a xenograft severe combined immunodeficient mouse model, real-time tumor regression and progression was visualized using a noninvasive in vivo bioluminescence imaging system. Four hours after CIK cell injection, we were able to visualize CD8+NKG2D+ CIK cells infiltrating Her2-expressing cancer cells on fluorescence microscopy. Mice that underwent adoptive transfer of CIK cells redirected with BSAbxCA125 and BSAbxHer2 had significant reduction in tumor burden (P < 0.001 and P < 0.001) and improvement in survival (P = 0.05 and P = 0.006) versus those treated with CIK cells alone. Bispecific antibodies significantly enhanced the cytotoxicity of CIK cells in primary ovarian cancer cells and in our in vivo mouse model. The mechanism of cytolysis seems to be mediated in part by the NKG2D receptor.

    View details for DOI 10.1158/1078-0432.CCR-05-2019

    View details for Web of Science ID 000236458800028

    View details for PubMedID 16551871

  • Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers BRITISH JOURNAL OF CANCER Hamilton, C. A., Cheung, M. K., Osann, K., Chen, L., Teng, N. N., Longacre, T. A., Powell, M. A., Hendrickson, M. R., Kapp, D. S., Chan, J. K. 2006; 94 (5): 642-646

    Abstract

    To compare the survival of women with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC) to those with grade 3 endometrioid uterine carcinoma (G3EC). Demographic, pathologic, treatment, and survival information were obtained from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Data were analysed using Kaplan-Meier and Cox proportional hazards regression methods. Of 4180 women, 1473 had UPSC, 391 had CC, and 2316 had G3EC cancers. Uterine papillary serous carcinoma and CC patients were older (median age: 70 years and 68 vs 66 years, respectively; P<0.0001) and more likely to be black compared to G3EC (15 and 12% vs 7%; P<0.0001). A higher proportion of UPSC and CC patients had stage III-IV disease compared to G3EC patients (52 and 36% vs 29%; P<0.0001). Uterine papillary serous carcinoma, CC and G3EC patients represent 10, 3, and 15% of endometrial cancers but account for 39, 8, and 27% of cancer deaths, respectively. The 5-year disease-specific survivals for women with UPSC, CC and G3EC were 55, 68, and 77%, respectively (P<0.0001). The survival differences between UPSC, CC and G3EC persist after controlling for stage I-II (74, 82, and 86%; P<0.0001) and stage III-IV disease (33, 40, and 54; P<0.0001). On multivariate analysis, more favourable histology (G3EC), younger age, and earlier stage were independent predictors of improved survival. Women with UPSC and CC of the uterus have a significantly poorer prognosis compared to those with G3EC. These findings should be considered in the counselling, treating and designing of future trials for these high-risk patients.

    View details for DOI 10.1038/sj.bjc.6603012

    View details for Web of Science ID 000235868700007

    View details for PubMedID 16495918

  • Improved survival of Asians with corpus cancer compared with whites - An analysis of underlying factors OBSTETRICS AND GYNECOLOGY Zhang, M. M., Cheung, M. K., Osann, K., Lee, M. M., Gomez, S. S., Whittemore, A. S., Husain, A., Teng, N. N., Chan, J. K. 2006; 107 (2): 329-335

    Abstract

    To compare the clinicopathologic prognosticators and survival of Asians and whites with corpus cancer.Demographic, clinicopathologic, and survival data were obtained from the 1992-2001 Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed by Kaplan-Meier methods and Cox proportional hazards model.A total of 2,144 Asians and 32,999 whites with corpus cancer were identified. The age-adjusted incidence of uterine cancer in Asians compared with whites was 16.8 compared with 26.1 per 100,000. Asians presented at a younger age (mean 58.4 years compared with 65.1; P < .01) and with more advanced stage disease than whites (21.5% compared with 15.4%; P < .01). The 5-year survival rate for Asians was 79.4% compared with 75.2% for whites (P < .01). Asians with stage I-II and III-IV cancers had 5-year survival rates of 89.3% and 41.2% compared with 82.3% and 34.0% for the whites, respectively (P < .01, early stage; P < .01, advanced stage). The survival advantage of Asians persists in endometrioid (P < .01) and uterine papillary serous carcinomas (P < .01), but not in clear cell carcinoma (P = .62) or sarcomas (P = .78). In multivariate analysis, younger age (P < .01), earlier stage (P < .01), favorable histology (P < .01), and lower grade (P < .01) remained as significant independent prognosticators for improved survival. However, race was not an important prognosticator.The overall survival advantage experienced by Asians with uterine cancer is attributable to their younger age at diagnosis. Because Asian women present at a younger age with more advanced disease, physicians should have an increased index of suspicion for malignancy in young Asian women with suspicious symptoms and consider a lower age threshold for biopsy in this group.II-2.

    View details for Web of Science ID 000241295400019

    View details for PubMedID 16449120

  • Elevated CO2 induces physiological, biochemical and structural changes in leaves of Arabidopsis thaliana NEW PHYTOLOGIST Teng, N., Wang, J., Chen, T., Wu, X., Wang, Y., Lin, J. 2006; 172 (1): 92-103

    Abstract

    Leaves of Arabidopsis thaliana grown under elevated or ambient CO2 (700 or 370 micromol mol(-1), respectively) were examined for physiological, biochemical and structural changes. Stomatal characters, carbohydrate and mineral nutrient concentrations, leaf ultrastructure and plant hormone content were investigated using atomic absorption spectrophotometry, transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA). Elevated CO2 reduced the stomatal density and stomatal index of leaves, and also reduced stomatal conductance and transpiration rate. Elevated CO2 increased chloroplast number, width and profile area, and starch grain size and number, but reduced the number of grana thylakoid membranes. Under elevated CO2, the concentrations of carbohydrates and plant hormones, with the exception of abscisic acid, increased whereas mineral nutrient concentrations declined. These results suggest that the changes in chloroplast ultrastructure may primarily be a consequence of increased starch accumulation. Accelerated A. thaliana growth and development in elevated CO2 could in part be attributed to increased foliar concentrations of plant hormones. The reductions in mineral nutrient concentrations may be a result of dilution by increased concentrations of carbohydrates and also of decreases in stomatal conductance and transpiration rate.

    View details for DOI 10.1111/j.1469-8137.2006.01818.x

    View details for Web of Science ID 000239988100011

    View details for PubMedID 16945092

  • Intraoperative radiation therapy in recurrent ovarian cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Yap, O. W., Kapp, D. S., Teng, N. N., Husain, A. 2005; 63 (4): 1114-1121

    Abstract

    To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT).A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications.Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments.In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.

    View details for DOI 10.1016/j.ijrobp.2005.04.007

    View details for Web of Science ID 000232943900020

    View details for PubMedID 15964710

  • Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hamilton, C. A., Liou, W. S., Osann, K., Berman, M. L., Husain, A., Teng, N. N., Kapp, D. S., Chan, J. K. 2005; 63 (3): 839-844

    Abstract

    To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma.Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods.Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival.Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.

    View details for DOI 10.1016/j.ijrobp.2005.03.028

    View details for Web of Science ID 000232411600025

    View details for PubMedID 16199314

  • A modified technique for insertion of intraperitoneal port for chemotherapy JOURNAL OF SURGICAL ONCOLOGY Liou, W. S., Teng, N. N., Chan, J. K. 2005; 90 (4): 247-248

    Abstract

    The clinical and pharmacological rationale of using intraperitoneal (IP) chemotherapy has been demonstrated in randomized clinical trials. However, IP chemotherapy is often discontinued secondary to catheter-related complications such as blockage, leakage, infection, and access difficulties. An effective method that provides a reliable access to the IP cavity is needed. In this report, we describe a novel technique of IP port placement that may prevent access problems and decrease patient discomfort.

    View details for DOI 10.1002/jso.20255

    View details for Web of Science ID 000229453300006

    View details for PubMedID 15906367

  • Cervical cancer guidelines. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Teng, N., Abu-Rustum, N. R., Bahador, A., Bookman, M. A., Bristow, R. E., Campos, S., Cho, K. R., Copeland, L., Eifel, P., Fiorica, J., Greer, B. E., Kapp, D. S., Kavanagh, J., Koh, W., Kuettel, M., Lurain, J. R., Molpus, K. L., Nag, S., Partridge, E. E., Powell, C. B., Reynolds, R. K., Small, W., Soper, J., Tillmanns, T. D. 2004; 2 (6): 612-630

    View details for PubMedID 19780304

  • Detection of pelvic lymph node micrometastasis in stage IA2-IB2 cervical cancer by immunohistochemical analysis GYNECOLOGIC ONCOLOGY Juretzka, M. M., Jensen, K. C., Longacre, T. A., Teng, N. N., Husain, A. 2004; 93 (1): 107-111

    Abstract

    The objectives of this study were to (1) determine the incidence of lymph node micrometastasis in cervical cancer by immunohistochemical analysis and (2) determine if the presence of micrometastasis is a poor prognostic feature in early cervical cancer.We retrospectively reviewed the medical records of 62 patients who underwent radical hysterectomy and lymphadenectomy for FIGO stage IA2-IB2 cervical cancer at Stanford University Hospital from 1990 to 2000. Forty-nine patients with negative lymph nodes were identified. A total of 976 formalin-fixed paraffin-embedded pelvic lymphadenectomy specimens were serially sectioned and stained with anti-cytokeratin antibodies AE1 and AE1/CAM5.2.Six patients had stage IA2 disease, 37 had stage IB1, and 6 had IB2. The mean age of the patients was 44 years (range, 24-76). Seventy-one percent had squamous cell carcinomas, 22% had adenocarcinomas, and 6% had other types. Lymph node micrometastases were immunohistochemically detected in 4 of the 49 (8.1%) patients, comprising 4 of 976 (0.41%) pelvic lymph nodes examined. Twelve of 45 (15.6%) patients with negative nodes had lymph-vascular space invasion (LVSI) whereas 3 of 4 (75%) patients with micrometastases had LVSI. At a mean follow-up time of 39.4 months, 2 of 4 (50%) patients with micrometastasis had recurrent disease, while 3 of 45 (6.7%) patients without micrometastasis developed recurrent disease.These preliminary data suggest that immunohistochemical detection of pelvic lymph nodes is more frequent in patients with LVSI and may identify patients needing adjuvant chemoradiation.

    View details for DOI 10.1016/j.ygyno.2003.11.033

    View details for Web of Science ID 000220850800016

    View details for PubMedID 15047221

  • Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: Who benefits? CANCER Zang, R. Y., Li, Z. T., Tang, J., Cheng, X., Cai, S. M., Zhang, Z. Y., Teng, N. N. 2004; 100 (6): 1152-1161

    Abstract

    This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval > or = 3 months.One hundred seventeen patients with relapsed EOC after a clinical complete remission duration > or = 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model.The median patient age at the time of relapse was 53 years (range, 20-78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to > or = 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured < or = 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. < or = 1 cm [P = 0.1211], < or = 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1-2 cycles vs. 3-5 cycles [P = 0.0144]; 1-2 cycles vs. > or = 6 cycles [P < 0.0001]; and 3-5 cycles vs. > or = 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106).SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted > or = 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy.

    View details for DOI 10.1002/cncr.20106

    View details for Web of Science ID 000220195200007

    View details for PubMedID 15022281

  • B cell lymphoproliferative disorders and VH4-34 gene encoded antibodies. Human antibodies Bhat, N. M., Bieber, M. M., Yang, Y., Leu, Y., Van Vollenhoven, R. F., Teng, N. N. 2004; 13 (3): 63-68

    Abstract

    The VH4-34 represents an unusual Ig heavy chain variable region gene given that it is conserved and overexpressed despite its autoreactivity. Besides RBC 'I/i' recognition, a subset of VH4-34 encoded Igs bind and kill human B-lymphocytes via interaction with a cytoskeletally-associated ligand similar in structure to the cord RBC 'i' antigen. In vivo, secretion of VH4-34 gene encoded antibodies is minimal in healthy individuals. The turn on signal occurs in few clinical conditions such as, systemic lupus erythematosus, AIDS and infectious mononucleosis. Here we show that secretion of VH4-34 Abs is also switched on in hepatitis C and nasopharyngeal carcinoma; but not in diseases such as HPV-associated cervical carcinoma, multiple sclerosis and sarcoidosis. All syndromes with increased VH4-34 Igs appear to be associated with B cell hyperproliferation and B cell lymphotropic viruses, particularly EBV. The significance of the tightly controlled secretion of an autoreactive, conserved Ig gene is discussed.

    View details for PubMedID 15598986

  • Differential expression of CD40 and CD95 in ovarian carcinoma EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY Ciaravino, G., Bhat, M., Manbeian, C. A., Teng, N. N. 2004; 25 (1): 27-32

    Abstract

    The role of CD95 (Fas) as a mediator of apoptosis has been well documented. CD40 ligation has been recently shown to initiate apoptosis and modulate CD95 mediated apoptosis in normal and some neoplastic tissues. Here we report the expression of CD95 and CD40 in cryopreserved cell suspensions from ovarian cancer associated ascites, fresh primary and recurrent ovarian carcinoma (OVCA) specimens, and ten established ovarian cancer cell lines. The effect of CD95 and CD40 receptor binding on apoptosis is described in two cell lines.Ascites specimens, fresh primary and recurrent OVCA specimens were dissociated to single cell suspensions. Expression of CD95 and CD40 was analyzed using flow cytometry. Apoptosis was determined via annexin uptake by flow cytometry following incubation with anti-CD95 antibody, CH11 and trimeric CD40L.Ascites showed the highest expression of both CD95 and CD40. Recurrent OVCA, in contrast, expressed low levels of CD95 and CD40. Primary OVCA showed moderate expression of both receptors. CD40 expression in ascites was significantly greater when compared to solid specimens (p < 0.05). Both CD40 and CD95 were strongly expressed in eight of ten cell lines studied. Binding of CD40L did not influence CD95 mediated apoptosis.CD40 is ubiquitously expressed in ovarian carcinomas and expression differs between ascites and solid tumor. There may be differential expression of both CD40 and CD95 in recurrent vs primary ovarian carcinoma, which may contribute to increased clinical malignancy of recurrent disease. In contrast to other epithelial malignancies, CD40 ligation does not appear to modulate CD95 mediated apoptosis.

    View details for Web of Science ID 000189378400004

    View details for PubMedID 15053058

  • Epoxidation of chiral camphor N-enoylpyrazolidinones with methyl(trifluoromethyl)dioxirane and urea hydrogen peroxide/acid anhydride: Reversal of stereoselectivity JOURNAL OF ORGANIC CHEMISTRY Fan, C. L., Lee, W. D., Teng, N. W., Sun, Y. C., Chen, K. M. 2003; 68 (25): 9816-9818

    Abstract

    Both diastereomeric isomers of epoxides with high optical purity are obtained when camphor N-methacryloylpyrazolidinone (1a) and N-tigloylpyrazolidinone (1b) are treated with a urea hydrogen peroxide/TFAA and methyl(trifluoromethyl)dioxirane, respectively.

    View details for DOI 10.1021/jo034807w

    View details for Web of Science ID 000187016700037

    View details for PubMedID 14656113

  • Modification of the vertical rectus abdominis musculocutaneous (VRAM) flap for functional reconstruction of complex vulvoperineal defects ANNALS OF PLASTIC SURGERY Hui, K., Zhang, F., Pickus, E., Rodriguez, L. F., Teng, N., Lineaweaver, W. C. 2003; 51 (6): 556-560

    Abstract

    Radical vulvoperineal ablations present challenging reconstructive dilemmas, especially when local metastatic spread requires distal vaginal and anal resection. Despite advances in vaginal salvage and sphincteroplasty, surface recontouring remains elusive because of the necessity to resurface a large, complex area that includes the mons, vulva, and fourchette. We describe a modification of the inferior-based vertical rectus abdominis musculocutaneous (VRAM) flap where the superior portion is split longitudinally to produce "tongue" flaps, which can resurface complex vulvoperineal wounds. By splitting the flap, one can resurface the vulva, provide an edge to reattach the vaginal cuff, and recreate the fourchette and line the anoderm after anoplasty. This musculocutaneous flap provides adequate contour and protection against radiation injury. Splitting of the flap is based on the vascular territory of the superior epigastric branches and their perforators and can be carried down to the level of their anastomosis, with the inferior system at the level of the umbilicus. The split VRAM flap has been used successfully in 3 patients with complex perineal wounds with excellent results and maintenance of vaginal patency.

    View details for DOI 10.1097/01.sap.0000096444.59573.87

    View details for Web of Science ID 000187178600005

    View details for PubMedID 14646647

  • Gene expression patterns in ovarian carcinomas MOLECULAR BIOLOGY OF THE CELL Schaner, M. E., Ross, D. T., Ciaravino, G., Sorlie, T., Troyanskaya, O., Diehn, M., Wang, Y. C., Duran, G. E., Sikic, T. L., Caldeira, S., Skomedal, H., Tu, I. P., Hernandez-Boussard, T., Johnson, S. W., O'Dwyer, P. J., Fero, M. J., Kristensen, G. B., Borresen-Dale, A. L., Hastie, T., Tibshirani, R., van de Rijn, M., Teng, N. N., Longacre, T. A., Botstein, D., Brown, P. O., Sikic, B. I. 2003; 14 (11): 4376-4386

    Abstract

    We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers.

    View details for Web of Science ID 000186738300005

    View details for PubMedID 12960427

  • Preoperative CT diagnosis of primary fallopian tube carcinoma in a patient with a history of total abdominal hysterectomy JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Santana, P., Desser, T. S., Teng, N. 2003; 27 (3): 361-363

    Abstract

    Fallopian tube carcinoma is an unusual gynecologic malignancy that is rarely diagnosed preoperatively. We report a case of fallopian tube carcinoma occurring in a patient who had undergone a hysterectomy many years previously, in whom findings on computed tomography and ultrasound were highly suggestive of the diagnosis.

    View details for Web of Science ID 000183746200011

    View details for PubMedID 12794600

  • Liposomal doxorubicin for treatment of metastatic chemorefractory vulvar adenocarcinoma GYNECOLOGIC ONCOLOGY Huang, G. S., Juretzka, M., Ciaravino, G., Kohler, S., Teng, N. N. 2002; 87 (3): 313-318

    Abstract

    Primaryadenocarcinoma of the vulva is a rare entity, and for widely metastatic vulvar adenocarcinoma, no effective treatment has been established.A 65-year-old woman was diagnosed with regionally advanced vulvar adenocarcinoma, with bulky involvement of bilateral groin lymph nodes, and associated extramammary Paget's disease. Initial therapy consisted of multiagent chemotherapy and vulvar and groin irradiation, followed by radical vulvectomy with groin and pelvic lymph node dissection. She subsequently developed widely metastatic disease including brain, pulmonary, hepatic, osseus, and subcutaneous lesions. Treatment with liposomal doxorubicin (Doxil) resulted in dramatic regression of metastatic lesions and marked improvement in quality-of-life. She remains clinically well, greater than 1 year since initiating Doxil treatment for widely metastatic vulvar adenocarcinoma, and has surpassed 5 years of survival since her initial diagnosis.We report the first case of Doxil used for the treatment of metastatic chemorefractory vulvar adenocarcinoma. We observed that Doxil was a well-tolerated and effective agent for this gynecologic malignancy, and warrants further investigation.

    View details for DOI 10.1006/gyno.2002.6830

    View details for Web of Science ID 000179842700015

    View details for PubMedID 12468332

  • VH4-34 encoded antibody in systemic lupus erythematosus: Effect of Isotype JOURNAL OF RHEUMATOLOGY Bhat, N. M., Lee, L. M., Van Vollenhoven, R. F., Teng, N. N., Bieber, M. M. 2002; 29 (10): 2114-2121

    Abstract

    To determine the clinical significance of elevated serum levels of VH4-34 encoded IgM and IgG antibodies with respect to the clinical characteristics of systemic lupus erythematosus (SLE).VH4-34 encoded IgM and IgG immunoglobulin was measured in 95 patients with SLE by ELISA using antiidiotype monoclonal antibody (Mab) 9G4. SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Presence of VH4-34 encoded antibodies on patients' B lymphocytes was analyzed by flow cytometry using Mab 9G4.Fifty-two of 95 patients with SLE had elevated levels of VH4-34 encoded antibodies of IgG isotype; 17 patients with VH4-34 IgG had elevated VH4-34 of the IgM isotype. Forty-three of the 95 patients had normal levels of VH4-34 encoded antibodies. When disease severity was correlated to VH4-34 isotype, patients with circulating VH4-34 IgG but without IgM had significantly more severe disease compared to patients who had VH4-34 of both isotypes. Eighty-six percent of patients with SLE nephritis and 100% of those with central nervous system (CNS) lupus had VH4-34 IgG without IgM. In vivo, VH4-34 encoded antibodies were found to bind autologous B lymphocytes.Presence of VH4-34 IgG in the absence of VH4-34 IgM was the finding most strongly associated with severe SLE, nephritis, and CNS lupus, suggesting that isotype switching of VH4-34 encoded antibodies or loss of VH4-34 IgM encoded antibodies may influence the progression of disease in SLE.

    View details for Web of Science ID 000178374000015

    View details for PubMedID 12375320

  • A new approach to enhancement of bone formation by electrically polarized hydroxyapatite JOURNAL OF DENTAL RESEARCH Teng, N. C., Nakamura, S., Takagi, Y., Yamashita, Y., Ohgaki, M., Yamashita, K. 2001; 80 (10): 1925-1929

    Abstract

    An electrical field may affect osteogenesis. Since we found that hydroxyapatite (HA) ceramics may be polarizable, we hypothesized that electrically polarized HA may foster production of new bone in vivo. Both polarized and non-polarized HA ceramics were inserted into the subperiosteum spaces at the parietal bone area of rats. After 2, 4, and 8 weeks, the implant sites were examined histologically. Morphometric analysis revealed that new bone formation was accelerated on the negatively charged surface of the polarized HA (N-surface) at 2 weeks. The newly formed bone approached maturation at 4 weeks and was thicker on the N-surface than in the controls. By 8 weeks, newly formed bone in the controls was almost the same as that on the N-surface. These findings suggest that polarized HA is biocompatible and that bone formation on the N-surface is enhanced in the early stage of bone healing.

    View details for Web of Science ID 000174684300012

    View details for PubMedID 11706953

  • Effect of 17 beta-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH da Paz, L. H., De Falco, V., Teng, N. C., dos Reis, L. M., Pereira, R. M., Jorgetti, V. 2001; 34 (8): 1015-1022

    Abstract

    The objective of the present study was to evaluate the effect of 17beta-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17beta-estradiol at a dose of 30 microg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17beta-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass.

    View details for Web of Science ID 000170731800007

    View details for PubMedID 11471040

  • Treatment of high-risk uterine cancer with whole abdominopelvic radiation therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Smith, R. S., Kapp, D. S., Chen, Q., Teng, N. N. 2000; 48 (3): 767-778

    Abstract

    To evaluate the treatment outcomes in patients with optimally debulked Stage III and IV endometrial adenocarcinoma (ACA) or Stages I-IV uterine papillary serous (UPSC) or clear cell (CCC) carcinoma of the uterus, treated postoperatively with whole abdominopelvic irradiation (WAPI).Between 1979 and 1998, 48 patients received postoperative WAPI at our institution. Twenty-two patients had FIGO Stage III or Stage IV ACA and 26 patients had FIGO Stages I-IV UPSC or CCC. The median dose was 30 Gy to the upper abdomen and 49.8 Gy to the pelvis. Mean follow-up was 37 months (2.4-135 months).The 3-year estimated disease-free survival (DFS) and overall survival (OS) rates for the entire group were 60% and 77%, respectively. Patients with ACA had 3-year DFS and OS of 79% and 89%, respectively, compared with 47% and 68% in the UPSC/CCC group. Early-stage patients (I and II) with UPSC/CCC had 3-year DFS and OS of 87% compared with 32% and 61% in those with advanced (Stage III and IV) disease. The 3-year actuarial major complication rate was 7%, with no treatment-related deaths. All 4 failures in the ACA group were extra-abdominal and 6 of the 11 in the UPSC/CCC group had an extra-abdominal component. Age and UPSC/CCC histology were significant prognostic factors for DFS and OS. In addition, stage and number of extrauterine sites of disease were significant predictors for DFS in UPSC/CCC.WAPI is a safe, effective treatment for patients with optimally debulked advanced-stage uterine ACA or early-stage UPSC/CCC. Survival was significantly worse in advanced-stage UPSC/CCC patients. We recommend future trials of WAPI with concurrent, or subsequent systemic therapy in patients with advanced-stage UPSC or CCC.

    View details for Web of Science ID 000089822600019

    View details for PubMedID 11020574

  • Recognition of auto- and exoantigens by V4-34 gene encoded antibodies SCANDINAVIAN JOURNAL OF IMMUNOLOGY Bhat, N. M., Bieber, M. M., Spellerberg, M. B., Stevenson, F. K., Teng, N. N. 2000; 51 (2): 134-140

    Abstract

    The antigenic specificities of 24 V4-34-encoded monoclonal antibodies were compared with the amino acid sequence. The specificities were divided into three categories, red blood cells, B lymphocytes and auto/exoantigens. Six anti-I monoclonal antibodies, with multiple substitutions in their VH region, did not bind B lymphocytes or auto/exoantigens. Reactivity to these two antigens segregated with the 16 anti-i monoclonal antibodies, which were derived from the near germline V4-34 gene. All anti-i monoclonal antibodies bound B lymphocytes, albeit with varying intensities. B-cell binding correlated with basic amino acids in the VH-CDR3. Reactivity to auto/exoantigens was demonstrated only by a subset anti-i monoclonal antibodies and did not correlate with B-lymphocyte or i-antigen binding. These anti-ssDNA reactive monoclonal antibodies had basic amino acids in the VH-CDR3, strongly supporting the suggested role of arginine in DNA binding. However, an arginine-rich CDR3 was not enough to ensure DNA reactivity, since six other anti-i monoclonal antibodies that fulfilled this criteria did not bind ssDNA. Thus it is possible that the anti-DNA reactivity of V4-34-encoded monoclonal antibodies is mediated by the classic antigen-binding groove generated by the CDRs of the heavy/light chains. In contrast, anti-B-cell/i-antigen reactivity is mediated, unconventionally, by the V4-34 protein with a dominant influence of the VH-CDR3.

    View details for Web of Science ID 000085609000004

    View details for PubMedID 10652159

  • Primary leiomyosarcoma of the vagina. A case report and literature review. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society Ciaravino, G., Kapp, D. S., Vela, A. M., Fulton, R. S., Lum, B. L., Teng, N. N., Roberts, J. A. 2000; 10 (4): 340-347

    Abstract

    Primary vaginal leiomyosarcoma is a rare tumor. We report a unique case of a 27-year-old woman with stage I, high-grade primary leiomyosarcoma of the vagina treated with surgical resection and adjuvant radiation therapy. She returned within 6 months with an abdominal-pelvic recurrence and lung metastases. The patient died of disease 9 months after diagnosis. A comprehensive review of primary vaginal leiomyosarcoma was performed and factors affecting survival were analyzed. A Medline search of the English-language literature revealed 66 previously reported cases. Forty-eight of these had follow-up data. Survival probabilities were calculated using the Kaplan-Meier method, and the effects of age, stage, grade, tumor location, and treatment modality were analyzed. Stage III and IV data were combined. The overall 5-year survival rate was 43%. Patients more than 50 years of age had a 5-year survival rate of 26% compared with 51% for those less than 40 years. Five-year survival for stage I and II tumors was 55% and 44%, respectively. Patients with stage III/IV disease had 25% survival at 18 months. No patient treated primarily with chemotherapy or radiation therapy survived beyond 36 months. In contrast, patients treated primarily with surgery had a 5-year survival rate of 57%. Only stage remained an independent predictor of survival on Cox regression analysis. We continue to recommend surgical resection as primary treatment. Exenteration may be an option for select patients, but ultimately management should continue on a case-by-case basis.

    View details for PubMedID 11240697

  • Malignant granular cell tumor of the vulva in a 17-year-old: Case report and literature review. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society Ramos, P. C., Kapp, D. S., Longacre, T. A., Teng, N. N. 2000; 10 (5): 429-434

    Abstract

    Granular cell tumors are uncommon soft tissue tumors. Although the majority of these tumors are benign, a rare malignant variant exists which is aggressive, with local recurrence rates up to 70% and 3-year survival rates of less than 50%. We present a case of malignant granular cell tumor of the vulva in a 17-year-old, the sixth such case to be reported at this site. She was treated with a left hemivulvectomy and ipsilateral groin node dissection followed by postoperative radiation therapy. She remains free of disease at 16 months. Patients with malignant granular cell tumor or granular cell tumor of malignant potential are best managed with wide local excision and regional lymph node dissection.

    View details for PubMedID 11240710

  • VH4-34 encoded antibodies in systemic lupus erythematosus: A specific diagnostic marker that correlates with clinical disease characteristics JOURNAL OF RHEUMATOLOGY van Vollenhoven, R. F., Bieber, M. M., Powell, M. J., Gupta, P. K., Bhat, N. M., Richards, K. L., Albano, S. A., Teng, N. N. 1999; 26 (8): 1727-1733

    Abstract

    To determine the clinical significance of elevated serum levels of VH4-34 encoded antibodies (VH4-34 Ab) with respect to the diagnosis and clinical characteristics of systemic lupus erythematosus (SLE).Ninety-five patients with SLE and 344 controls were studied. The controls included 34 healthy individuals, 282 patients with nonautoimmune diseases, and 28 patients with autoimmune diseases other than SLE. VH4-34 Ab levels were measured by inhibition ELISA using anti-idiotope monoclonal antibody (9G4). SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.Fifty-two of 95 patients with SLE had elevated levels of VH4-34 Ab compared to 18 of 344 controls (5%), giving a sensitivity of 55% and a specificity of 95% for elevated VH4-34 Ab as a serologic test for SLE. The positive predictive value of elevated VH4-34 under these conditions was 74-85%. In this study, anti-dsDNA was not VH4-34 encoded. Significant correlations between VH4-34 and disease activity and severity indices were observed (r = 0.29-0.50). The relative risk for severe disease in SLE patients with VH4-34 antibody level in the highest tertile compared to the lowest tertile was 5.25. Twenty-five of 29 patients with lupus nephritis and 6 of 6 patients with central nervous system (CNS) lupus had elevated VH4-34 Ab.With a specificity of 94-95%, the VH4-34 antibody assay may prove valuable as a confirmatory diagnostic test for SLE. In patients with known SLE, serum VH4-34 Ab levels correlate with overall disease severity and activity, but not damage, and with nephritis and CNS lupus.

    View details for Web of Science ID 000081725000015

    View details for PubMedID 10451069

  • Clinical practice guidelines in the management of gynecologic malignancies HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Winn, R. J., Teng, N. N. 1999; 13 (1): 63-?

    Abstract

    The need for guidelines in managing gynecologic cancer is addressed in the first part of this article. Second, the guideline development process that enables the practitioner to judge the validity and usefulness of proffered guidelines is detailed. An important element in this discussion is an exploration of the shortcomings, either real or perceived, of the process. The last section focuses on issues relating to the implementation of guidelines and some of the obstacles that one may encounter as the programs evolve.

    View details for Web of Science ID 000079144800005

    View details for PubMedID 10080070

  • Cytotoxicity of murine B lymphocytes induced by human VH4-34 (VH4.21) gene-encoded monoclonal antibodies CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY Bhat, N. M., Bieber, M. M., Teng, N. N. 1997; 84 (3): 283-289

    Abstract

    We have previously described specific binding and cytotoxicity of human B lymphocytes by VH4-34 gene-derived anti-i cold agglutinin (CA) mAbs. Here we demonstrate that the carbohydrate ligand recognized by human VH4-34 anti-i CA mAbs is also expressed on murine B lymphocytes. Similar to human B cells, binding of murine B lymphocytes by VH4-34-derived anti-i CA mAbs leads to rapid cytotoxicity of target cells as tested both in vitro and in vivo. Moreover, the mechanism leading to murine B cell death is also similar to human B cells, since morphologically identical membrane pores were detected within 15 min of mAb exposure by scanning electron microscopy. The conservation of the carbohydrate ligand across species provides an ideal system to study the function of human VH4-34 gene derived Abs in immune regulation.

    View details for Web of Science ID A1997XV88200007

    View details for PubMedID 9281387

  • Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies .2. CLINICAL AND EXPERIMENTAL IMMUNOLOGY Bhat, N. M., Bieber, M. M., Hsu, F. J., Chapman, C. J., Spellerberg, M., Stevenson, F. K., Teng, N. N. 1997; 108 (1): 151-159

    Abstract

    We have previously described complement-independent killing of human B lymphocytes by two IgM MoAbs derived from the VH4-34 (VH4.21) gene. Analysis of 17 independently derived VH4-34-encoded MoAbs shows that B cell toxicity is not limited to the two described MoAbs, but is a general property shared by a subset of MoAbs derived from the VH4-34 gene. As observed by two independent microscopy techniques, giant membrane pores were formed on target B cells within 10-15 min of exposure to cytotoxic VH4-34-derived MoAbs. Toxicity by individual MoAb correlated directly to its B cell binding intensity measured by FACS, i.e. stronger the binding greater the killing. Sequence analysis showed that V(H) region in germ-line or in near germ-line configuration was necessary but not sufficient for B cell binding. In addition, a particular sequence motif enriched in basic amino acids in the CDR3 may be required to supplement the reactivity mediated by the V(H) region of the MoAb molecule. VH4-34-encoded antibodies that fulfil the above sequence requirements have cold agglutinin activity towards the i antigen of cord erythrocytes. In vivo, such anti-i/anti-B cell antibodies are rarely detected in healthy adults, but serum levels are dramatically elevated in selective pathological conditions, such as systemic lupus erythematosus and infectious mononucleosis. This strict regulation may be related to the novel and rapid mechanism of human B cell toxicity demonstrated by antibodies encoded by a single human V(H) gene.

    View details for Web of Science ID A1997WR92700022

    View details for PubMedID 9097924

  • Heavy chain variable gene usage by human B-1 lymphocytes and polyreactive autoantibodies. Human antibodies Bhat, N. M., Bieber, M. M., Teng, N. N. 1997; 8 (3): 146-150

    Abstract

    To evaluate the role of B-1 cells and polyreactive autoantibodies in the development of adult immune repertoire, it is necessary to assess their immunoglobulin heavy chain variable-gene usage. We thus screened 28 independently derived human polyreactive MAbs from fetal and adult splenic B lymphocytes for their VH-region usage. We demonstrate that the polyreactivity of the IgM antibodies secreted by B-1 cells is not the result of the expression of particular variable region gene families. All six VH families are represented roughly in proportion to their estimated family size. Furthermore, the representation of the six families appears similar in polyreactive MAbs derived from fetal or adult lymphocytes.

    View details for PubMedID 9322085

  • V(H)4-34(V(H)4.21) gene expression in the chronic arthritides of childhood: Studies of associations with anti-lipid a antibodies, HLA antigens, and clinical features JOURNAL OF RHEUMATOLOGY Miller, J. J., Bieber, M. M., Levinson, J. E., Zhu, S. L., Tsou, E., Teng, N. N. 1996; 23 (12): 2132-2139

    Abstract

    To determine if the germ line gene VH4-34 (VH4.21) encodes the antimonophosphoryl lipid A (MPL) polyspecific antibodies found in oligoarticular arthritis of childhood.Sera from a range of rheumatic diseases of childhood were assayed for VH4-34 derived antibodies by ELISA using the antiidiotype monoclonal antibody 9G4. Results were compared to assays for anti-MPL antibodies, C4d, and Bb, and for HLA type, joint count, and sedimentation rate.VH4-34 derived antibodies were elevated in all diseases studied except rheumatoid factor positive polyarticular disease. In oligoarticular arthritis, VH4-34 gene expression correlated with C4d concentration, and VH4-34 encoded globulins were more concentrated in synovial fluid than in blood. No association was found with HLA type. An association between VH4-34 expression and IgG anti-MPL was found in sera from patients from Cincinnati but not from Stanford. No other evidence supported a direct association between VH4-34 derived and anti-MPL antibodies in these children.The expression of VH4-34 is increased in several rheumatic diseases of childhood, but, as in adults, not in rheumatoid arthritis. VH4-34 expression is not associated with HLA type. The polyspecific autoantibody nature of some VH4-34 derived antibodies may explain the wide range of the unusual antibodies found in oligoarticular arthritis.

    View details for Web of Science ID A1996VX84300022

    View details for PubMedID 8970052

  • Lymphangioleiomyomatosis of the uterus simulating high-stage endometrial stromal sarcoma GYNECOLOGIC ONCOLOGY Longacre, T. A., Hendrickson, M. R., Kapp, D. S., Teng, N. N. 1996; 63 (3): 404-410

    Abstract

    Symptomatic uterine lymphangioleiomyomatosis (LAM) simulating high-stage uterine sarcoma in a patient with tuberous sclerosis complex is reported. A 49-year-old female presented with abdominal pain and anemia. Preoperative workup revealed a uterine mass and a large amount of peritoneal free fluid and possible metastatic implant along the lateral edge of the liver. The patient also had a large right pleural effusion. A fungating anterior uterine fundal mass with apparent perforation and intraabdominal hemorrhage was found on laparotomy. A portion of the mass was excised and initially interpreted as an endometrial stromal sarcoma. Microscopic examination revealed multiple vascular epithelioid smooth muscle proliferations in the uterus and serosal surface of the fallopian tube and periaortic lymph node lymphangioleiomyomas. The uterine, fallopian tube, and nodal lesions were positive for smooth muscle actin, desmin, and HMB-45, findings characteristic of LAM. Additional examination of the patient revealed stigmata of tuberous sclerosis complex. Although uterine LAM is uncommon, it may be associated with pelvic and/or abdominal symptoms and may simulate a primary uterine mesenchymal neoplasm.

    View details for Web of Science ID A1996VY31800021

    View details for PubMedID 8946880

  • NCCN Ovarian Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology (Williston Park, N.Y.) Morgan, R. J., Copeland, L., Gershenson, D., Locker, G., McIntosh, D., Ozols, R., Teng, N. 1996; 10 (11): 293-310

    View details for PubMedID 8953610

  • Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies CLINICAL AND EXPERIMENTAL IMMUNOLOGY Bhat, N. M., Bieber, M. M., Stevenson, F. K., Teng, N. N. 1996; 105 (1): 183-190

    Abstract

    We have previously described two human cold agglutinin MoAbs 216 and A6(H4C5), that are derived from the VH4-34 (VH4.21) gene that bind specifically to a cell surface ligand on human B lymphocytes. In this study, we report that binding of 216 and A6(H4C5) leads to rapid killing of target B cells. This complement-independent cytotoxicity was measured by three independent assays, cell viability dye uptake on FACS, 3H-thymidine uptake, and the 3(4,5)-dimethylthiazol-2,5-diphenyl tetrazolium bromide (MTT) assay. Cytotoxicity was specific for CD20+ mononuclear cells in human spleen and peripheral blood. The MoAbs were also cytotoxic to human B cell lines Nalm-6, OCI-LY8, Arent and SUP-B8, but not to T cell lines HuT 78 and PEER. As observed by scanning electron microscopy, membrane pores were formed within 15 min of exposure to the MoAbs. Cytotoxic activity was dependent on MoAb concentration and temperature of exposure. Killing with greater at 4 degrees C than 37 degrees C. Sodium azide and EDTA did not block the cytotoxic activity. No DNA fragmentation typical of apoptosis was observed. This rapid cytotoxic activity, independent of physiologic cellular process and independent of complement, suggests a novel mechanism of all death via membrane perturbations.

    View details for Web of Science ID A1996UU85000029

    View details for PubMedID 8697629

  • Phase 1 trial of intraperitoneal AD-32 in gynecologic malignancies GYNECOLOGIC ONCOLOGY Markman, M., Homesley, H., Norberts, D. A., Schink, J., Abbas, F., Miller, A., Soper, J., Teng, N., Hammond, N., Muggia, F., Israel, M., Sweatman, T. 1996; 61 (1): 90-93

    Abstract

    AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, was examined for intraperitoneal (ip) administration in a phase 2 trial involving 25 patients with advanced gynecologic malignancies. At an AD-32 dose of 600 mg/m2, the limiting toxicity was grade 4 neutropenia (64% of patients), while severe abdominal pain was relatively uncommon (12%). Intraperitoneal AD-32 administration was associated with a 200-fold pharmacokinetic advantage for cavity exposure, compared to the systemic compartment. At the 600 mg/m2 dose level, 4 of 9 patients (44%) with ascites experienced control of malignant fluid reaccumulation. Based on the results of this phase 1 trial, further exploration of a possible role for the ip administration of AD-32 in individuals with gynecological malignancies appears indicated, particularly in patients with either small volume residual disease after initial systemic chemotherapy or in those with intractable ascites.

    View details for Web of Science ID A1996UC96100017

    View details for PubMedID 8626124

  • Operative laparoscopy in the management of ovarian cancer SURGICAL LAPAROSCOPY & ENDOSCOPY Amara, D. P., Nezhat, C., Teng, N. N., Nezhat, F., Nezhat, C., Rosati, M. 1996; 6 (1): 38-45

    Abstract

    Advances in operative laparoscopic techniques have made possible the extension of this technology to the treatment of women with ovarian cancer. We present a detailed case series of eight patients with ovarian cancer who underwent a total of 11 operative laparoscopies for treatment of ovarian cancer ranging in stage from IA to IIIC. Three patients underwent initial laparoscopic staging and therapeutic debulking procedures. In three other cases that were incompletely staged via laparotomy, laparoscopy was used to complete the staging. Interval laparoscopic tumor debulking combined with second-look laparoscopy was performed in four cases. We describe our experience with these new applications of evolving techniques with particular regard to potential advantages, disadvantages, and complications. This detailed preliminary case series suggests the need for prospective clinical studies to establish the safety and efficacy of the approach.

    View details for Web of Science ID A1996TR44000010

    View details for PubMedID 8808559

  • The female genital tract. Pathology (Philadelphia, Pa.) Longacre, T. A., Teng, N. N., Hendrickson, M. R. 1996; 3 (2): 427-492

    View details for PubMedID 8795830

  • HUMAN CD5+ B-LYMPHOCYTES (B-1 CELLS) DECREASE IN PERIPHERAL-BLOOD DURING PREGNANCY JOURNAL OF REPRODUCTIVE IMMUNOLOGY Bhat, N. M., Mithal, A., Bieber, M. M., Herzenberg, L. A., Teng, N. N. 1995; 28 (1): 53-60

    Abstract

    Pregnancy is a unique immunologic state where a natural homeostasis exists between antigenically different tissues. Several earlier studies have addressed the fluctuations in the number and/or function of lymphocytes, including B cells during pregnancy, but changes within the subsets of B lymphocytes, conventional (CD5-) and B-1 (CD5+), have not been addressed. Here we demonstrate that the frequency of B-1 cells decreases dramatically during pregnancy, whereas the frequency of conventional B cells remains relatively constant. The missing B-1 cells return to pre-pregnancy levels 8-10 weeks after parturition. The polyreactive autoantibodies secreted by B-1 cells have been implicated in autoimmunity and immune regulation. The possible role of B-1 cells during pregnancy will be discussed in that context.

    View details for Web of Science ID A1995QH79400005

    View details for PubMedID 7537825

  • THE ROLE OF LAPAROSCOPY IN THE MANAGEMENT OF GYNECOLOGIC MALIGNANCY SEMINARS IN SURGICAL ONCOLOGY Nezhat, C., Nezhat, F., Teng, N. N., Edraki, B., Nezhat, C. H., BURRELL, M. O., Benigno, B. B., Ramirez, C. E. 1994; 10 (6): 431-439

    Abstract

    With the advent of minimally invasive laparoscopic techniques, most gynecologic procedures for benign conditions can be performed in an outpatient setting. However, the role of such techniques in gynecologic oncology is not well defined. By reviewing the literature and presenting some new data, we attempt to elucidate the applications of operative videolaparoscopy in gynecologic oncology. Advanced laparoscopic techniques are utilized for the management of cervical cancer as well as the staging and treatment of endometrial and ovarian cancers. Such techniques are used in performing radical hysterectomy for early stage cervical cancer, pelvic and paraaortic lymphadenectomy, and second look laparoscopy following chemotherapy for ovarian cancer. Even though preliminary data are encouraging, large prospective controlled studies with long-term follow-up are necessary to better define the role and limitations of laparoscopy in the treatment of gynecologic malignancies.

    View details for Web of Science ID A1994QH21200010

    View details for PubMedID 7855480

  • FACS ANALYSIS OF PERITONEAL LYMPHOCYTES IN OVARIAN-CANCER AND CONTROL PATIENTS IMMUNOBIOLOGY Reijnhart, R. M., Bieber, M. M., Teng, N. N. 1994; 191 (1): 1-8

    Abstract

    In this study different lymphocyte populations in the malignant ascites of 10 patients with ovarian carcinoma and in the peritoneal fluid of 8 control patients (tubal ligation and benign conditions) were analyzed. A panel of monoclonal antibodies against the CD markers of lymphocytes was used to stain different populations and the cells were analyzed on a FACS II (fluorescence-activated cell sorter). The mean percentage of B lymphocytes in the peritoneal cavity of the OVCA patients was 0.18 +/- 0.5% and in the control patients 0.05 +/- 0.07%. There was no significant difference between the two groups. In the OVCA group and in the controls the percentage of T lymphocytes (CD5+) was 23.5% and 17.1% respectively with no significant difference between the groups. These results indicate that B lymphocytes are not present in the human peritoneal cavity. The small numbers of B cells found in this study could be due to contamination with peripheral blood. The human peritoneal cavity contains a cell population which differs from that present in peripheral blood. Significant numbers of B lymphocytes have been reported in the peritoneal cavity of mice. The difference between the lymphocyte population of the human peritoneal cavity and that of rodents implies that data on characterization and function of B lymphocytes in the mouse peritoneal cavity would not be applicable to humans.

    View details for Web of Science ID A1994PE02100001

    View details for PubMedID 7806256

  • HUMAN ANTILIPID A MONOCLONAL-ANTIBODIES BIND TO HUMAN B-CELLS AND THE I-ANTIGEN ON CORD RED-BLOOD-CELLS JOURNAL OF IMMUNOLOGY Bhat, N. M., Bieber, M. M., Chapman, C. J., Stevenson, F. K., Teng, N. N. 1993; 151 (9): 5011-5021

    Abstract

    We describe two independently derived human mAb, A6(H4C5) and 216, initially selected for their reactivity to the lipid A domain of bacterial LPS, which also react with the following Ag: the i Ag present on cord RBC, a ligand on human B lymphocytes, and to certain autoantigens, defining these mAb as polyreactive. Both mAb have specific affinity for a carbohydrate epitope consisting minimally of a disaccharide with an acyl substitution at the 2-carbon position. Structural examination of the diverse Ag recognized by the two antibodies reveals the presence of this carbohydrate structure required for antibody binding. A6(H4C5) and 216 are IgM in isotype, but differ in their L chain expression. Molecular analysis shows that both the mAb are encoded by a highly conserved VH4 gene, designated VH4-21. This gene encodes a number of autoantibodies, particularly cold agglutinins. Specific recognition of lipid A and of a carbohydrate epitope on B lymphocytes by the two human mAb suggests a dual function for the highly conserved VH4-21 gene in antibacterial response and in B cell development and regulation.

    View details for Web of Science ID A1993MD34900061

    View details for PubMedID 7691963

  • PERITONEAL IMPLANT ELIMINATION DURING CYTOREDUCTIVE SURGERY FOR OVARIAN-CANCER - IMPACT ON SURVIVAL GYNECOLOGIC ONCOLOGY Eisenkop, S. M., NALICK, R. H., Wang, H. J., Teng, N. N. 1993; 51 (2): 224-229

    Abstract

    A case-control study was performed to evaluate the potential benefit of peritoneal and serosal implant elimination (PIE) during primary cytoreductive surgery for patients with Stage IIIC epithelial ovarian cancer. Peritoneal implant excision and/or ablation was accomplished with electrocautery, CO2 laser, sharp dissection, argon beam coagulator, and cavitron ultrasonic surgical aspirator. Three groups of patients were compared: Group A (7 patients); macroscopically disease-free after cytoreduction without needing PIE; Group B (26 patients); macroscopically disease-free after cytoreduction, including PIE; Group C (34 patients); macroscopic disease < or = 1 cm remaining exclusively on peritoneal surfaces with PIE not attempted. Each group had statistically equivalent mean ages, estimated blood loss, extent of disease, and variety of cytoreductive operations performed. Group B had a longer mean operating time than that of A or C (4.0 vs 2.8 hr P = 0.002). No serious morbidity occurred from PIE. Comparison of survival by log rank analysis and Cox proportional hazards regression shows a survival advantage for patients rendered free of macroscopic peritoneal implants (Group B vs Group C; P = 0.003). The result suggests that complete elimination of all visible peritoneal metastases might be of benefit during surgical cytoreduction for ovarian cancer if this renders the patient macroscopically disease-free. We also suggest the need of a randomized, prospective study to clarify the clinical role of PIE.

    View details for Web of Science ID A1993MQ99300017

    View details for PubMedID 8276298

  • DOCUMENTATION OF COMPLETE RESOLUTION OF GESTATIONAL CHORIOCARCINOMA IN THE OOPHORECTOMIZED PATIENT GYNECOLOGIC ONCOLOGY OHANLAN, K. A., Wu, T. F., Teng, N. N. 1993; 51 (2): 261-265

    Abstract

    A 39-year-old woman with choriocarcinoma metastatic to the lungs and parametrium underwent total abdominal hysterectomy/bilateral salpingo-oophorectomy and follow-up chemotherapy with regression of the hCG assay, plateauing at 9 mIU/ml. Spinal fluid hCG assay was negative. An LH assay was performed which was 135 mIU/ml (2nd IRP-HMG). A quantitative hCG assay was performed on two sources of purified LH at varying concentrations to determine the contribution of LH cross-reactivity. When corrected for the LH contribution, the quantitative hCG was zero. Chemotherapy was discontinued. At 12-months follow-up the patient has remained in complete chemical remission and has an excellent performance status. Whenever a patient is oophorectomized, LH cross-reactivity should be ruled out as a cause for persistent low titers of hCG.

    View details for Web of Science ID A1993MQ99300024

    View details for PubMedID 8276305

  • LIPOPOLYSACCHARIDE AND PEPTIDOGLYCAN SHARE BINDING-SITES ON HUMAN PERIPHERAL-BLOOD MONOCYTES JOURNAL OF INFECTIOUS DISEASES Rabin, R. L., Bieber, M. M., Teng, N. N. 1993; 168 (1): 135-142

    Abstract

    p73, a binding site for lipopolysaccharide (LPS) on human peripheral blood monocytes was identified using the radiolabeled photoaffinity cross-linker sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD). The 125I-labeled conjugate of SASD and LPS (125I-labeled ASD-LPS) was bound to monocytes and UV cross-linked, and the cellular extracts were analyzed with two-dimensional SDS-PAGE and autoradiography. In addition to the major binding site on human monocytes at 73 kDa, isoelectric point 5.95, there were multiple minor binding sites that recognized both smooth and rough LPS. Binding of 125I-labeled ASD-LPS to monocytes is concentration dependent, decreased in the absence of calcium and magnesium, and inhibited by either excess LPS or the low-molecular-weight soluble isolate of bacterial cell wall peptidoglycan (sPGN). However, sPGN only minimally stimulates tumor necrosis factor (TNF) secretion by human peripheral blood mononuclear cells. In contrast, the relatively insoluble high-molecular-weight peptidoglycan significantly stimulates TNF secretion.

    View details for Web of Science ID A1993LH88000020

    View details for PubMedID 8515100

  • LONG-TERM SURVIVAL WITH ADJUVANT WHOLE ABDOMINOPELVIC IRRADIATION FOR UTERINE PAPILLARY SEROUS CARCINOMA CANCER Mallipeddi, P., Kapp, D. S., Teng, N. N. 1993; 71 (10): 3076-3081

    Abstract

    The optimum management of uterine papillary serous carcinoma (UPSC), a clinically aggressive histologic variant of endometrial adenocarcinoma, is a controversial issue.Ten patients with UPSC were reviewed who received whole abdominopelvic irradiation (WAP) as adjuvant therapy after a staging laparotomy and debulking surgery.Nine patients had clinical Stage I disease; the tumors in eight of them were upstaged based on laparotomy findings. There was greater than a 50% invasion of the myometrium in four of the hysterectomy specimens, and vascular space invasion was noted in seven patients. Peritoneal washings were positive in three of the nine specimens obtained; two others showed atypical cells. Five patients are alive with no evidence of disease at 102-133 months. Four patients are dead, and one patient is alive with disease. All recurrences were observed within 30 months of the initial diagnosis and were more common in the presence of deep myometrial invasion and vascular space involvement. Three of the four patients who died had pleural effusions that did not respond to hormonal and/or chemotherapy. Local irradiation produced long-term control of recurrences in two patients, including one with supraclavicular lymph node metastases who had no evidence of disease 117 months after radiation treatment to the involved nodes.These findings suggest that WAP be considered as an adjuvant therapy in the management of UPSC. The patients with the greatest benefit were those with early disease by surgical staging with or without positive peritoneal cytologic findings. For patients at high risk for pleural effusions and pulmonary metastasis, additional adjuvant therapy, such as innovative chemotherapy or low-dose lung irradiation, needs to be considered.

    View details for Web of Science ID A1993LD04100029

    View details for PubMedID 8490835

  • ONE-STEP ENRICHMENT OF NUCLEATED RED-BLOOD-CELLS - A POTENTIAL APPLICATION IN PERINATAL DIAGNOSIS JOURNAL OF IMMUNOLOGICAL METHODS Bhat, N. M., Bieber, M. M., Teng, N. N. 1993; 158 (2): 277-280

    Abstract

    We describe a discontinuous triple density gradient to obtain a 25-fold enrichment of nucleated red blood cells from mononuclear cells, granulocytes, and mature red blood cells in a single centrifugation step.

    View details for Web of Science ID A1993KK44400016

    View details for PubMedID 8094088

  • Adenocarcinoma-reactive human monoclonal antibody MS2B6 defines an antigen in simple glandular epithelium. Human antibodies and hybridomas Glasky, M. S., Yin, A., Smith, L. H., Bieber, M., Teng, N. N. 1992; 3 (3): 114-122

    Abstract

    A human monoclonal antibody (MAb), MS2B6, produced from splenocytes isolated from a patient with advanced papillary serous cystadenocarcinoma of the ovary, defines a unique human tumor-associated antigen. This antigen, EA2B6 (epithelial antigen 2B6), is expressed in a tissue-restricted manner on cultured and fresh human adenocarcinomas and some normal glandular epithelial tissues. EA2B6 is a 38-48 kD protein antigen that co-fractionates with the nuclear matrix-intermediate filament scaffold of simple glandular epithelial tissues. EA2B6 is a molecule with restricted solubility, and in vitro antigen-antibody binding is dependent on the antigen being presented on a solid support. To determine if EA2B6 is a cytokeratin, competition studies were undertaken with several cytokeratin-specific murine monoclonal antibodies. None of these antibodies inhibited the binding of human MAb MS2B6 to partially purified EA2B6. Less than 1% of HT29 colon adenocarcinoma cells and fresh ovarian adenocarcinoma ascites cells express EA2B6 on their surface. The majority of EA2B6 is intracellular. Because of the restricted tissue distribution of this antigen and stability of the antibody, we believe MS2B6 is a good candidate for MAb-mediated diagnosis and therapy of human adenocarcinomas.

    View details for PubMedID 1382650

  • HUMAN MONOCLONAL-ANTIBODY RECOGNIZING AN ANTIGEN ASSOCIATED WITH OVARIAN AND OTHER ADENOCARCINOMAS AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Smith, L. H., Yin, A., Glasky, M. S., Tyler, N., Robles, M., Foster, C. A., Bieber, M., Teng, N. N. 1992; 166 (2): 634-645

    Abstract

    MS2B6, a human monoclonal antibody derived from a patient with advanced ovarian cancer, has been used to study the distribution and characteristics of its target antigen. The MS2B6 antigen was detected by immunoperoxidase studies in 41 of 41 epithelial ovarian cancers and in the majority of nonovarian adenocarcinomas. Among normal tissues the MS2B6 antigen was found in the adult epithelia of the fallopian tube, endometrium, endocervix, colon, bronchus, breast, sweat duct, and large renal ducts. No detectable antigen was found in peritoneal epithelia, tissue stromal cells, spleen, thymus, or blood-borne cells. Immunoblotting analysis showed that the MS2B6 epitope resides on polypeptides of 38, 44, and 60 kd. The cellular location of the MS2B6 antigen was studied with immunoperoxidase and immunofluorescent staining and immunoelectronmicroscopy of ovarian cancer ascites tumor cells. The results suggest that in ascites tumor cells the MS2B6 antigen is located in a layer of the peripheral cytoplasm beginning just below the cell membrane. MS2B6 may be useful as an imaging or therapeutic agent.

    View details for Web of Science ID A1992HE65600038

    View details for PubMedID 1371375

  • THE ONTOGENY AND FUNCTIONAL-CHARACTERISTICS OF HUMAN B-1 (CD5+B) CELLS INTERNATIONAL IMMUNOLOGY Bhat, N. M., Kantor, A. B., Bieber, M. M., STALL, A. M., Herzenberg, L. A., Teng, N. N. 1992; 4 (2): 243-252

    Abstract

    We demonstrate that, on average, greater than 90% of B lymphocytes in fetal spleen express CD5 at gestational ages of 17-23 weeks. Similarly, CD5+ B cells (B-1 cells) are the major B cell subset in umbilical cord blood. These findings depend on the optimization of fluorochrome conjugated anti-CD5 reagents for multiparameter fluorescent-activated cell sorter (FACS) analysis. From infancy through childhood the percentage of B-1 cells gradually diminishes in both spleen and peripheral blood. Stable adult levels, 25-35% of the total B cell population, are reached in late adolescence. The decrease in the percentage of B-1 cells in spleen is accompanied by an increase in conventional (CD5-) B cells, keeping the percentage of total B cells per mononuclear cells relatively constant. In contrast, in peripheral blood, the concentration of both B-1 cells and total B cells decreases, while T cells increase. At the functional level, we show that polyreactive IgM autoantibodies are produced by FACS-sorted CD5high B cells, but not by CD5- B cells from adolescent spleen. In contrast, fetal splenic CD5high and CD5- B cells appear functionally uniform, both producing IgM autoantibodies that are typical of B-1 cells. The apparent level of CD5- B cells in fetal spleen, on average 10% of total B cells, may still result from limitations of our reagent. The prominence of B-1 cells in fetal spleen and cord blood, the gradual reduction of B-1 cells with increasing age, and its characteristic repertoire, all suggest a role for this cell type in immunologically immature hosts.

    View details for Web of Science ID A1992HF01700016

    View details for PubMedID 1377947

  • CRITICAL REASSESSMENT OF 2ND LOOK EXPLORATORY LAPAROTOMY FOR EPITHELIAL OVARIAN-CARCINOMA - MINIMAL DIAGNOSTIC AND THERAPEUTIC VALUE IN PATIENTS WITH PERSISTENT CANCER CANCER Miller, D. S., Spirtos, N. M., Ballon, S. C., Cox, R. S., SORIERO, O. M., Teng, N. N. 1992; 69 (2): 502-510

    Abstract

    From 1979 to 1984, 88 women with epithelial ovarian cancer were treated with surgery and chemotherapy, achieved a clinical complete response, and then had "second-look" exploratory laparotomy to assess the pathologic status of their disease. Persistent cancer was found in 50 (57%) patients: 34 of 50 (68%) had gross tumor, which was larger than 2 cm in 12 (24%) and smaller than 2 cm in 22 (44%), and 16 (32%) had microscopic disease. Salvage therapy was as follows for these patients: whole abdominal irradiation, 29 (58%); chemotherapy, 17 (34%); intraperitoneal chromic phosphate, 1 (2%); and no further therapy, 3 (6%). With a follow-up time of 4 to 8 years, 7 (14%) patients are alive without evidence of cancer, 7 (14%) are alive with disease, 35 (70%) are dead of disease, and 1 (2%) has died of treatment complications. At 5 years, the relapse-free rate was 18% and the survival rate was 25%. Seventy-two parameters of suspected prognostic significance and 64 potential sites of tumor involvement were correlated with survival in a univariate analysis. The factors favorably affecting survival included the following: lower grade; microscopic tumor versus gross disease at second-look laparotomy; removal of the uterus; removal of the omentum; pelvic and paraaortic lymph node biopsy; negative results of a right diaphragm biopsy; and radiation therapy at Stanford University Medical Center, Stanford, California. There was no survival advantage for whole abdomen irradiation compared with chemotherapy or for the patients who had their disease successfully debulked at second-look laparotomy. The above factors and others were evaluated by multivariate regression. The best model (P = 0.000004) for predicting survival included largest tumor mass (P = 0.0002), operative blood loss (P = 0.002), perioperative blood transfusion (P = 0.003), and grade (P = 0.004). The detection of persistent ovarian cancer by second-look exploratory laparotomy should identify a subgroup of patients whose conditions can be salvaged by a second-line therapy. Unfortunately, that subgroup is small (8%) and an effective salvage therapy remains to be identified.

    View details for Web of Science ID A1992GY83700037

    View details for PubMedID 1728381

  • MODIFIED POSTERIOR EXENTERATION FOR OVARIAN-CANCER OBSTETRICS AND GYNECOLOGY Eisenkop, S. M., NALICK, R. H., Teng, N. N. 1991; 78 (5): 879-885

    Abstract

    The operative description of a modified posterior exenteration along with operative findings, other operative procedures, postoperative course, and follow-up information are presented for 47 patients (37 primary cytoreduction, ten secondary cytoreduction). All had stage IIIC or IV epithelial ovarian cancer with pelvic disease encasing the reproductive organs, pelvic peritoneum, cul-de-sac, and sigmoid colon. In addition to modified posterior exenteration, all patients had multiple other procedures performed as part of the cytoreductive efforts. Forty-five (95.7%) had optimal (less than 2 cm) cytoreduction and 18 (38.3%) had complete cytoreductive surgery. Thirty-four patients were ultimately rendered continent of feces (25 primarily and nine after colostomy reversal). Nine patients (19.1%) had serious morbidity and one (2.1%) died postoperatively. The median follow-up for those undergoing primary cytoreduction was 13.3 months (6-84). Nineteen (51.4%) were alive at the time of writing, 16 (43.2%) were dead, and two (5.4%) were lost to follow-up. Modified posterior exenteration effectively removes all visible pelvic disease with acceptable mortality. Hence, even patients with the most advanced cases of ovarian cancer may attain optimal cytoreduction and become ideal candidates for adjunctive therapy, with improved survival or a chance for cure.

    View details for Web of Science ID A1991GL66900033

    View details for PubMedID 1923216

  • QUANTITATIVE PROTEIN-CHANGES IN METASTATIC VERSUS PRIMARY EPITHELIAL OVARIAN-CARCINOMA GYNECOLOGIC ONCOLOGY Lawson, S. R., LATTER, G., Miller, D. S., Goldstein, D., NAPS, M., BURBECK, S., Teng, N. N., Zuckerkandl, E. 1991; 41 (1): 22-27

    Abstract

    Primary and metastatic ovarian carcinomas from six patients were obtained during primary exploratory laparotomy. Tumor cells were synthetically radiolabeled with [35S]methionine. Radiolabeled cellular proteins of the primary and metastatic cells were examined by two-dimensional polyacrylamide gel electrophoresis followed by autoradiography. Computer assisted analysis of the resultant autoradiograms revealed that the amounts of only two proteins, p35 and p36, were consistently and significantly decreased in the metastatic tumor cells. No other consistent differences in protein synthesis between primary and metastatic tumors were detected.

    View details for Web of Science ID A1991FN28400003

    View details for PubMedID 2026354

  • TREATMENT OF GRAM-NEGATIVE BACTEREMIA AND SEPTIC SHOCK WITH HA-1A HUMAN MONOCLONAL-ANTIBODY AGAINST ENDOTOXIN - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL NEW ENGLAND JOURNAL OF MEDICINE Ziegler, E. J., Fisher, C. J., Sprung, C. L., Straube, R. C., Sadoff, J. C., Foulke, G. E., Wortel, C. H., Fink, M. P., Dellinger, R. P., Teng, N. N., Allen, I. E., Berger, H. J., Knatterud, G. L., LoBuglio, A. F., Smith, C. R. 1991; 324 (7): 429-436

    Abstract

    HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia.To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol.Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected.HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

    View details for Web of Science ID A1991EX36300001

  • Gynecologic factors in sexual dysfunction of the older woman. Clinics in geriatric medicine Goldstein, M. K., Teng, N. N. 1991; 7 (1): 41-61

    Abstract

    Older women may experience sexual dysfunction due to many different causes. Some problems related to menopausal hormonal change may be easily treated with estrogen supplements. Other problems involve intricate interpersonal relations between the woman and her sexual partner and may require a combination of medical therapy and sexual counseling. Gynecologic cancer and cancer treatments are often accompanied by problems in sexual functioning. These problems may then impair relations and self-image, leading to a vicious circle of deteriorating social function. Some recommendations for the clinician follow. The clinician should maintain an attitude of openness to the possibility of sexual concerns in older women. Such concerns should be taken seriously and should not be dismissed as part of aging. Routine periodic health examinations can include a question such as "Do you have any concerns about your sexual life that you would like to discuss?" In follow-up visits for procedures with a high likelihood of causing sexual dysfunction, questions that would open the door to a discussion of sexuality should be asked. Sexual dysfunction should be recognized as a couple-oriented phenomenon. A woman's anxiety about her appearance, postoperative depression, or dyspareunia may be perceived by her partner as a sexual rejection and may initiate a cycle of decreasing contact or may even lead to erectile dysfunction. Sexual counseling should include both partners. When a surgical procedure that will probably have an impact on sexual function is contemplated, provide the patient and her partner with advance counseling. Descriptions of surgery should not be simply a statement of body parts to be removed but should specifically address the anticipated sexual effects. Counseling should include a description of basic anatomy and function of the genital organs. Illustrations and appropriate demonstration during the physical examination should be used to ensure the patient's understanding. Descriptions should be accurate without being either frightening or falsely reassuring. The patient should be counseled about the benefits of including her partner in discussions. Then, when possible, the sexual partner of the patient should be invited to sessions of advance counseling on contemplated procedures. Clinicians should remain open to the possibility that the sexual partner will be a nontraditional one, e.g., an unmarried male partner or another woman. The clinician should be alert to remediable causes of dysfunction. For example, decreased vaginal lubrication may be managed with use of water-soluble lubricants.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for PubMedID 2004290

  • WOMEN WITH PREECLAMPSIA HAVE HIGHER PLASMA ENDOTHELIN LEVELS THAN WOMEN WITH NORMAL PREGNANCIES JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Taylor, R. N., Varma, M., Teng, N. N., ROBERTS, J. M. 1990; 71 (6): 1675-1677

    Abstract

    Endothelin, a newly discovered endothelium-derived peptide, has potent vasoactive properties in vivo and in vitro. The actions of endothelin in clinical conditions of hypertension have not yet been defined. This study examined the possible role of endothelin in the vasospasm and hypertension associated with a well-defined syndrome of gestational hypertension, preeclampsia. Our results indicate that the concentration of immunoreactive endothelin is elevated significantly in plasma obtained from women with preeclampsia and rapidly returns to a normal pregnancy value within 48 hours of delivery, as predicted by the prompt clinical resolution of this disorder. The findings suggest that endothelin may contribute to the vasospasm associated with this syndrome and lend further support to the involvement of endothelial cells in the pathophysiology of preeclampsia.

    View details for Web of Science ID A1990EL03300046

    View details for PubMedID 2229324

  • Synthesis and Characterization of Gentiobiose Heptaacetate Conjugate Vaccines That Produce Endotoxin-Neutralizing Antibodies BIOCONJUGATE CHEMISTRY Bhattacharjee, A. K., Sadoff, J. C., Collins, H., Cross, A. S., Khalil, A. H., Bieber, M. M., Wright, C., Teng, N. N. 1990; 1 (6): 375-380

    Abstract

    We have prepared aminoethyl (AE), aminopropyl (AP), and aminopentyl (APT) derivatives of gentiobiose heptaacetate (GH). These spacer compounds (AEGH, APGH, APTGH) have been coupled to succinylated diphtheria toxoid (Suc.DT) to produce conjugate vaccines. These conjugates all bind to the anti-lipid A human monoclonal antibody A6(H4C5) in an ELISA binding assay. Rabbits immunized with the APGH conjugate vaccine in either Freund's complete adjuvant or aluminum hydroxide gel produced antibody levels of 5120 and 3600 ELISA units, respectively, compared to an antibody level of less than 20 ELISA units for the prebleed sera. Sera from mice immunized with either the aminopropyl or the aminopentyl conjugate had antibody levels of 5120 and 2560 ELISA antibody units, respectively. These antibodies neutralized endotoxin in a Limulus lysate neutralization assay. Protection against the local Shwartzman reaction was demonstrated (p less than 0.05) in eight out of nine rabbits immunized with the Suc-DT-APGH conjugate vaccine compared to three out of 10 rabbits immunized with the carrier protein Suc-DT. Passive transfer experiments demonstrated that four out of five rabbits receiving immune serum were protected from Shwartzman reaction compared to one out of five rabbits receiving normal serum (p less than 0.1). These results indicated that epitopes contained in gentiobiose heptaacetate when properly presented as conjugate vaccines were capable of inducing neutralizing antibodies against endotoxin.

    View details for Web of Science ID 000206175400002

    View details for PubMedID 2099185

  • STUDY OF THE SELECTIVE CYTOTOXIC PROPERTIES OF CATIONIC, LIPOPHILIC MITOCHONDRIAL-SPECIFIC COMPOUNDS IN GYNECOLOGIC MALIGNANCIES GYNECOLOGIC ONCOLOGY CHRISTMAN, J. E., Miller, D. S., Coward, P., Smith, L. H., Teng, N. N. 1990; 39 (1): 72-79

    Abstract

    Cationic lipophilic compounds have a unique cytotoxic mechanism of action which is dependent on mitochondrial-specific localization of these fluorescent dyes. We have demonstrated in vitro that carcinoma cells, which have a higher negative mitochondrial membrane potential than normal cells, have an increased accumulation and retention of two of these compounds. The compounds tested were rhodamine 123 and dequalinium (DECA). After the development of a reproducible murine intraperitoneal (ip) human ovarian cancer model, which maintained the biologic characteristics of the parent cell line, we undertook in vivo evaluation of DECA. Mice with intraperitoneal tumor inoculations were treated with cisplatin, and/or DECA. When compared to cisplatin, a chemotherapeutic agent known to be effective in the treatment of clinical ovarian cancer, DECA was significantly more efficacious and seemed less toxic in the murine model. Cisplatin and DECA used together were possibly synergistic. Cationic lipophilic compounds may prove to be an exciting new class of antineoplastic agents which exploit intracellular, mitochondrial differences between normal cells and cancer cells.

    View details for Web of Science ID A1990EF79100011

    View details for PubMedID 2227576

  • ONE-STEP SEPARATION OF HUMAN FETAL LYMPHOCYTES FROM NUCLEATED RED-BLOOD-CELLS JOURNAL OF IMMUNOLOGICAL METHODS Bhat, N. M., Bieber, M. M., Teng, N. N. 1990; 131 (1): 147-149

    View details for Web of Science ID A1990DQ54300020

    View details for PubMedID 2380562

  • DELIVERY OF A NORMAL INFANT FOLLOWING CISPLATIN, VINBLASTINE, AND BLEOMYCIN (PVB) CHEMOTHERAPY FOR MALIGNANT TERATOMA OF THE OVARY DURING PREGNANCY GYNECOLOGIC ONCOLOGY CHRISTMAN, J. E., Teng, N. N., LEBOVIC, G. S., Sikic, B. I. 1990; 37 (2): 292-295

    Abstract

    Pregnancy complicated by an immature teratoma is rare, with a reported incidence of 0.07%. A case report of a grade 3 immature teratoma measuring 18 x 20 cm, with operative intraabdominal rupture (FIGO stage IC), is reported. The poor prognosis of malignant germ cell tumors treated by surgery alone seems to indicate a need for adjunctive chemotherapy. One course of multiagent chemotherapy consisting of cisplatin, vinblastine, and bleomycin (PVB) was initiated during the midtrimester. After an uncomplicated vaginal delivery at term of a normal infant, the planned regimen of chemotherapy was resumed. Subsequent "second-look" laparotomy was negative for malignant disease. The actual risk of PVB chemotherapy in pregnancy cannot be assessed by a single case report. The delivery of a normal infant is encouraging.

    View details for Web of Science ID A1990DE81300025

    View details for PubMedID 1693127

  • INITIAL EVALUATION OF A HUMAN IMMUNOGLOBULIN-M MONOCLONAL-ANTIBODY (HA-1A) IN HUMANS JOURNAL OF BIOLOGICAL RESPONSE MODIFIERS Khazaeli, M. B., Wheeler, R., Rogers, K., Teng, N., Ziegler, E., Haynes, A., Saleh, M. N., Hardin, J. M., BOLMER, S., Cornett, J., Berger, H., LoBuglio, A. F. 1990; 9 (2): 178-184

    Abstract

    A human monoclonal antibody (HA-1A) directed against bacterial endotoxin was administered to 15 patients with incurable malignant disease. No adverse effects were noted following single intravenous infusions of 0.05 to 100 mg. Pharmacokinetics were evaluated in nine patients receiving 10 mg (n = 3), 25 mg (n = 3), and 100 mg (n = 3). Seven of these patients had initial peak serum concentrations greater than 80% of predicted values with plasma disappearance curves fitting a one-compartment system and a plasma half-life of 31.5 h (range of 20.3-44.6 h). The peak serum concentrations and area under the curve values were proportional to the dose of HA-1A administered. One patient had a hypercatabolic state with low levels of serum albumin and IgM. He achieved 65% of the predicted value for peak serum concentration of HA-1A with a plasma half-life of 12.3 h. A second patient had detectable serum HA-1A for only 15 min following infusion without an adequate technical or biologic explanation. We were unable to demonstrate antibody to HA-1A in sera from these nine patients either prior to therapy or during 28 days postinfusion using a "double-antigen" radiometric assay. This study suggests that HA-1A human monoclonal antibody administration is well tolerated by patients. Phase I trials will need to be carried out to characterize further the pharmacokinetics and toxicity of HA-1A in patients with gram-negative sepsis.

    View details for Web of Science ID A1990CZ55400007

    View details for PubMedID 2341860

  • PROSPECTIVE RANDOMIZED TRIAL OF TOPICAL ALPHA-INTERFERON (ALPHA-INTERFERON GELS) FOR THE TREATMENT OF VULVAR INTRAEPITHELIAL NEOPLASIA-3 GYNECOLOGIC ONCOLOGY Spirtos, N. M., Smith, L. H., Teng, N. N. 1990; 37 (1): 34-38

    Abstract

    Twenty-one patients were prospectively randomized into a blinded double-armed crossover study comparing alpha-interferon (alpha-IFN, 10(6) IU in a 3.5% aqueous methylcellulose base) with and without 1% nonoxynol-9. Nine and twelve patients were randomized to arms with (+N) and without (-N) 1% nonoxynol-9, respectively. Patients applied the gel to affected areas every 8 hr and were evaluated biweekly. Including those crossed over, 14 patients were treated with -N. Six of fourteen (43%) achieved complete responses: biopsy proven with at least 1 year follow-up (CR). One patient achieved a partial response with at least a 50% reduction in the total surface area of all lesions present (PR). Similarly, 13 patients were treated with +N. Two patients in this group were found to have invasive cancer and one to have HIV and thus were eliminated from statistical analysis. Of the remaining 10 patients, 3 had CRs (30%), 5 had PRs (50%), and 2 failed to respond. There was no significant difference in responses between the two groups. Overall, 14 of 18 (67%) patients demonstrated some response to alpha-IFN applied topically. These data support the conclusion that alpha-IFN is an active agent in the treatment of vulvar intraepithelial neoplasia III.

    View details for Web of Science ID A1990DA10500008

    View details for PubMedID 2182407

  • A RANDOMIZED COMPARATIVE TRIAL OF CARBOPLATIN AND IPROPLATIN IN ADVANCED SQUAMOUS CARCINOMA OF THE UTERINE CERVIX - A GYNECOLOGIC ONCOLOGY GROUP-STUDY JOURNAL OF CLINICAL ONCOLOGY McGuire, W. P., Arseneau, J., Blessing, J. A., Disaia, P. J., Hatch, K. D., Given, F. T., Teng, N. N., Creasman, W. T. 1989; 7 (10): 1462-1468

    Abstract

    A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.

    View details for Web of Science ID A1989AR88400011

    View details for PubMedID 2674333

  • RADIATION-THERAPY FOR PRIMARY SQUAMOUS-CELL CARCINOMA OF THE VAGINA - STANFORD-UNIVERSITY EXPERIENCE GYNECOLOGIC ONCOLOGY Spirtos, N. M., DOSHI, B. P., Kapp, D. S., Teng, N. 1989; 35 (1): 20-26

    Abstract

    A retrospective analysis of 38 patients with primary squamous cell carcinoma of the vagina seen at Stanford University Medical Center from 1958 to 1984 was undertaken. Patients were analyzed with regard to symptoms, stage, treatment techniques, survival, patterns of failure, and complications. Eighteen patients were classified as FIGO Stage I, 5 as Stage II, 10 as Stage III, and 5 as Stage IV. The 5-year disease-free survival was 94% in Stage I, 80% in Stage II, 50% in Stage III, and 0% in Stage IV. Five patients (13%) had eight major complications secondary to treatment. Only 2 of 23 patients with Stage I or Stage II disease developed a recurrence. There was a significant correlation between dose and response in patients treated with radiotherapy.

    View details for Web of Science ID A1989AT54200004

    View details for PubMedID 2792898

  • DELETION OF HISTO-BLOOD GROUP-A AND GROUP-B ANTIGENS AND EXPRESSION OF INCOMPATIBLE A-ANTIGEN IN OVARIAN-CANCER JOURNAL OF THE NATIONAL CANCER INSTITUTE Metoki, R., Kakudo, K., Tsuji, Y., Teng, N., Clausen, H., Hakomori, S. I. 1989; 81 (15): 1151-1157

    Abstract

    Expression of histo-blood group ABH antigens in 53 cases of ovarian cancer was examined by immunoperoxidase staining of Formalin-fixed as well as frozen histological sections with various monoclonal antibodies, including those defining type 1, 2, 3, and 4 chain A. Findings of major interest were (a) deletion of A and B determinants in tumors from histo-blood group A and B individuals, and a high incidence of H antigen deletion in tumors from group O individuals were observed and (b) strong expression of incompatible A antigen in two of 10 samples from group B patients and in two of nine samples from group O patients was demonstrated. A antigen expression was defined by monoclonal antibody AH21, which reacts with monofucosyl type 1 chain A (ALed), but not by other types of anti-A antibodies directed to difucosyl type 1 chain A (ALeb), mono- or difucosyl type 2 chain A, or type 3 or type 4 chain A. The reactivity of monoclonal antibody AH21 was abolished by alpha-N-acetylgalactosaminidase from chicken liver. These findings clearly identified the specific expression of incompatible A antigen with the structure monofucosyl type 1 chain A (ALed) in tumors from histo-blood group B and O individuals.

    View details for Web of Science ID A1989AH03600005

    View details for PubMedID 2664192

  • EFFECTS OF ANTI-LIPID A HUMAN MONOCLONAL-ANTIBODY ON LIPOPOLYSACCHARIDE-INDUCED TOXICITY TO THE KIDNEY JOURNAL OF UROLOGY Tune, B. M., Hsu, C. Y., Bieber, M. M., Teng, N. N. 1989; 141 (6): 1463-1466

    Abstract

    Studies were done to evaluate the effects of the human monoclonal anti-lipid A IgM antibody A6(H4C5) on several components of the hemodynamic and renal toxicity of the cell wall lipopolysaccharide of E. coli 0111:B4. Antibody (0.25 to four mg./kg. BW) was administered 0.5 hour before, or premixed for one hour with, lipopolysaccharide (0.05 mg./kg., a 14 to 18% lethal dose), and the following measurements made over 0.5 to 3.5 hours of study: systemic arterial blood pressure, renal plasma flow, and glomerular filtration. The proximal tubular cell cytotoxicity of 90 mg./kg. of the cephalosporin cephaloridine was also quantified in similarly treated animals sacrificed 48 hours later. While one mg./kg. of antibody prevented the reduction by the lipopolysaccharide of renal plasma flow, it did not prevent the nephrotoxic synergy with cephaloridine, and four times the antibody dose did not prevent lipopolysaccharide-induced hypotension or reduced glomerular filtration. These amounts of this antibody protect leukopenic rabbits against the lethality of the slow onset bacteremic model of Pseudomonas conjunctivitis. It is suggested that the incompleteness of protection in this study may be the result of the sensitivity of the assay methods used and/or the acute endotoxemia produced in these animals.

    View details for Web of Science ID A1989U850100052

    View details for PubMedID 2657114

  • TOPICAL INTERFERON FOR TREATING CONDYLOMA ACUMINATA IN WOMEN JOURNAL OF INFECTIOUS DISEASES Keay, S., Teng, N., Eisenberg, M., Story, B., SELLERS, P. W., Merigan, T. C. 1988; 158 (5): 934-939

    Abstract

    We conducted a randomized, double-blind, placebo-controlled trial of two forms of topical interferon therapy for condyloma acuminata in women. Gel containing 10(6) IU of leukocyte interferon/g, with or without nonoxynol-9, was compared with treatment with gel base alone. Eighty-nine patients applied the gel three times a day for four weeks and were studied for at least 16 w. Side effects were generally mild and limited to the site of application for all three drugs. Although a transient, statistically significant therapeutic effect was noted early in the course of treatment with both interferon gels as compared with placebo, this effect was lost by the end of the follow-up period, possibly because of a generally high response rate in patients receiving placebo. Hence, there was no overall difference in the number of patients with a partial or complete response to any of the agents by the end of therapy or by the end of the study.

    View details for Web of Science ID A1988Q700100004

    View details for PubMedID 2460568

  • GENERATION OF HUMAN MONOCLONAL-ANTIBODIES TO CANCER-ASSOCIATED ANTIGENS USING LIMITED NUMBERS OF PATIENT LYMPHOCYTES JOURNAL OF IMMUNOLOGICAL METHODS Smith, L. H., Yin, A., Bieber, M., Teng, N. N. 1987; 105 (2): 263-273

    Abstract

    A limiting dilution method for the efficient transformation by Epstein-Barr virus (EBV) of human B lymphocytes has been applied to the production of human monoclonal antibodies to ovarian cancer-associated antigens. Limited numbers (e.g., 2 X 10(5)) of EBV-infected B lymphocytes from ovarian cancer patient spleen, lymph node, tumor, ascites and blood were successfully transformed using this method. An immunofiltration assay system was employed to identify EBV transformants secreting IgM antibody which reacted selectively with ovarian cancer patient ascites tumor cells, but not with a mixture of normal cell types. A miniature Western blot assay was utilized to screen for IgG reactivity to protein species in detergent extracts of ovarian cancer tumor cells. EBV-transformed cells selected after screening were then fused with heteromyeloma fusion partner SHM-D33 resulting in efficient recovery of hybridomas secreting MAb of the desired specificity. Human MAbs which selectively react with antigens associated with ovarian cancer tumor cells were obtained.

    View details for Web of Science ID A1987L481200014

    View details for PubMedID 2826600

  • CARDIOVASCULAR EFFECT OF INTRAVENOUS LIPID-A IN RABBITS CIRCULATORY SHOCK Ali, K. H., Feeley, T. W., Bieber, M., McGrath, B., Teng, N. N. 1987; 23 (4): 285-293

    Abstract

    The in vivo cardiovascular effect of intravenous administration of monophosphoryl lipid A (mp-lipid A) and diphosphoryl lipid A (dp-lipid A) in awake New Zealand white rabbits was investigated. Observed changes were evaluated in comparison to a control group and an endotoxin-treated group. Rabbits given lipid A showed a significant depression in cardiac index (p less than .025), mean arterial pressure (p less than .025, dp-lipid A only), arterial carbon dioxide tension (p less than .025), and total leukocyte count (p less than .05) compared to controls. Animals receiving lipid A tended to respond overall in a manner closely matching that of the endotoxin group. Dosages of lipid A given were approximately 3.5 times larger than the endotoxin dosages with respect to actual number of molecules administered (1.25-2.0 times larger by mass). These results indicate that lipid A is active in producing the cardiovascular and leukopenic effects characteristic of experimental septic shock.

    View details for Web of Science ID A1987L092500006

    View details for PubMedID 3690820

  • SINGLE-DOSE ACTINOMYCIN-D TREATMENT FOR NONMETASTATIC GESTATIONAL TROPHOBLASTIC DISEASE - A PROSPECTIVE PHASE-II TRIAL OF THE GYNECOLOGIC-ONCOLOGY-GROUP CANCER PETRILLI, E. S., Twiggs, L. B., Blessing, J. A., Teng, N. N., Curry, S. 1987; 60 (9): 2173-2176

    Abstract

    The Gynecologic Oncology Group (GOG) conducted a prospective trial of single-dose Actinomycin-D (ACT-D) given intravenously (IV) at 1.25 mg/m2 every 2 weeks to patients with nonmetastatic gestational trophoblastic disease (NMGTD) in order to determine the efficacy of pulse scheduling and the frequency and severity of associated toxicity. Of 31 evaluable patients, 29 (94%) achieved remission after receiving a median of four courses of therapy. Two patients who failed to respond to pulse therapy were subsequently cured by alternative treatment. There were 93 toxic events in 133 cycles of therapy. Ninety-two percent of adverse effects were graded as mild or moderate, and 8% were graded as severe. No life-threatening toxicity occurred. Although single-dose ACT-D efficacy and toxicity is comparable to conventional therapy for NMGTD, the advantages of easier administration, greater patient convenience, and improved cost-effectiveness make it superior to other alternatives. On this basis it is recommended as the treatment of choice for NMGTD.

    View details for Web of Science ID A1987K484400009

    View details for PubMedID 2449942

  • CLINICAL-APPLICATIONS OF MONOCLONAL-ANTIBODIES IN GYNECOLOGIC ONCOLOGY CANCER Smith, L. H., Teng, N. N. 1987; 60 (8): 2068-2074

    Abstract

    The advances of both murine and human monoclonal antibody (MoAb) technology have allowed the development of several antibodies against gynecologic tumors. The goals are to produce effective and specific reagents for both immunodiagnosis and therapy. However, despite an extensive research effort, a clear demonstration of specific cancer-associated antigens in gynecologic malignancies, or of specific immune responses to such antigens has been elusive. Currently, most antibodies found are cross reactive with either oncofetal antigens or some normal adult tissues. Clinical usefulness of these MoAbs as a screening test in radioimaging or in immunotherapy remains to be proven. However, the use of MoAb technology in defined antigens/tumor markers such as beta-human chorionic gonadotropin, and alpha fetal proteins has provided convenient, reproducible and highly specific reagents. More recently, promising antibodies have been shown to detect tumor antigens in serum of patients with ovarian cancer.

    View details for Web of Science ID A1987K299800019

    View details for PubMedID 3308066

  • THE EFFECT OF HUMAN ANTIENDOTOXIN MONOCLONAL-ANTIBODIES ON ENDOTOXIN-INDUCED LUNG INJURY IN THE RAT AMERICAN REVIEW OF RESPIRATORY DISEASE Feeley, T. W., MINTY, B. D., Scudder, C. M., Jones, J. G., Royston, D., Teng, N. N. 1987; 135 (3): 665-670

    Abstract

    A model of endotoxin-induced lung injury was developed in the rat. We found that 24 h after intravenously administered endotoxin (3 mg/kg) there was increased clearance of the isotope 99mTcDTPA from the lung to blood, increased neutrophils in the lung in bronchoalveolar lavage, and increased levels of products of peroxidation of lipids and nucleic acid in the serum. Using this model, we evaluated the effect of pretreatment of rats with a human monoclonal antibody specific to the core glycolipid that is common to all endotoxins. We found that pretreatment prevented the increased clearance of 99mTcDTPA from the lung, as well as the increase in lipid peroxidation products in the serum. The antibody did not prevent increased neutrophil accumulation in the lung. The findings suggest that the administration of human antiendotoxin monoclonal antibodies prior to endotoxemia may prevent some of the changes in the lung associated with endotoxin.

    View details for Web of Science ID A1987G356300029

    View details for PubMedID 3548509

  • EPITHELIAL OVARIAN-CARCINOMA IN PATIENTS WITH INTERSEX DISORDERS - THE ROLE OF PITUITARY GONADOTROPINS IN OVARIAN TUMORIGENESIS GYNECOLOGIC ONCOLOGY Miller, D. S., Teng, N. N., Ballon, S. C. 1986; 24 (3): 299-308

    Abstract

    The common epithelial tumors of the human ovary have rarely been found in the gonads of intersex patients with gonadal dysgenesis or true hermaphroditism. This report describes a patient with ovarian serous cystadenocarcinoma and mixed gonadal dysgenesis (45,X/46,XY) and reviews other reported cases. Intersex patients require early evaluation with treatment based on the karyotypic risk of malignant gonadal transformation. Epithelial ovarian tumors arising in dysgenetic gonads, which lack ova and are incapable of ovulating, provide a unique model for understanding the role of pituitary gonadotropins in ovarian epithelial tumorigenesis.

    View details for Web of Science ID A1986D021200004

    View details for PubMedID 2424810

  • INFLUENCE OF AVIDITY AND IDIOTOPE RECOGNITION ON THE MODULATION OF SURFACE-IMMUNOGLOBULIN ON MALIGNANT HUMAN B-CELLS BY RAT MONOCLONAL ANTIIDIOTYPE ANTIBODIES JOURNAL OF IMMUNOLOGY Campbell, M., Bieber, M., Levy, R., Teng, N. N. 1986; 136 (8): 2983-2988

    Abstract

    Immunoglobulin (Ig) was obtained from the tumor cells of patients with B cell malignancies by somatic cell hybridization to mouse-human heteromyeloma cells. The human Ig secreted by one of these hybridomas was used as an immunogen for the production of rat monoclonal antibodies (mAb). A panel of mAb specific for the idiotype (Id) was produced and characterized. Competitive binding studies that made use of [Se]-labeled anti-Id mAb (MAID) demonstrated several distinct yet topographically related Id on the Id-bearing Ig. These antibodies were shown to have avidities ranging from 0.38 to 45.3 X 10(8) l/mol. Additional studies demonstrated varying degrees of antigenic modulation of surface Id in vitro by MAID. The degree of modulation correlates with antibody avidity.

    View details for Web of Science ID A1986C169100038

    View details for PubMedID 3485677

  • A CRITICAL REASSESSMENT OF 2ND-LOOK LAPAROTOMY IN EPITHELIAL OVARIAN-CARCINOMA CANCER Miller, D. S., Ballon, S. C., Teng, N. N., Seifer, D. B., SORIERO, O. M. 1986; 57 (3): 530-535

    Abstract

    Eighty-eight women with epithelial ovarian carcinoma, treated by first-line chemotherapy, achieved a complete clinical response and underwent second-look laparotomy to assess the true pathologic status of their disease. Persistent tumor was found in 50 patients (57%). Thirty-two of these (36%) had obvious gross tumor, whereas, 16 (18%) had microscopic disease. Thirty-eight patients (43%) had no pathologic evidence of persistent ovarian carcinoma. With a follow-up of 6 to 60 months, 30 of these patients (79%) remain without evidence of recurrence. Multivariate logistic regression analysis revealed three covariates that were independently significant in predicting continued disease-free status. These included: the greatest diameter of the largest residual tumor left at the primary operation; histologic features of the tumor; and the diameter of the largest tumor aggregate found at initial operation. A mathematical model based on the most significant covariates was designed to assess the relative risk of any patient having persistent tumor at second-look laparotomy. A comparison of the predicted to actual outcome revealed a sensitivity of the model of 88%, a specificity of 71%, and an accuracy of 77%. Second-look laparotomy represents the basis on which potentially curative second-line salvage therapy can be initiated. With an increasing period of follow-up and with greater numbers of patients, it can potentially document a complete pathologic response to first-line therapy administered with curative intent, and identify patients for additional, adjunctive therapy, who are at risk of recurrence.

    View details for Web of Science ID A1986AYC4300019

    View details for PubMedID 3942985

  • PROTECTION AGAINST GRAM-NEGATIVE BACTEREMIA AND ENDOTOXEMIA WITH HUMAN MONOCLONAL IGM ANTIBODIES PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Teng, N. N., KAPLAN, H. S., Hebert, J. M., Moore, C., Douglas, H., Wunderlich, A., BRAUDE, A. I. 1985; 82 (6): 1790-1794

    Abstract

    Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the J5 mutant of Escherichia coli, which is deficient in O antigenic side chains. This deficiency exposes the core oligosaccharide, common to LPS of all Gram-negative bacteria. The mAbs cross-reacted strongly with endotoxins from a wide range of unrelated species of Gram-negative bacteria. The mAbs also gave strong protection against LPS in the dermal Shwartzman reaction and against lethal Gram-negative bacteremia in mice. These findings indicate that monoclonal IgM against LPS endotoxin can neutralize its toxicity in vivo and might be valuable for treatment of patients with Gram-negative bacteremia. Analysis of one of the hybridoma clones, A6(H4C5), showed that the IgM mAb is directed against the covalently bound lipid A, which represents the most conservative and least variable structural element of LPS.

    View details for Web of Science ID A1985AED8800046

    View details for PubMedID 3856860

  • ANTIBODIES TO PEPTIDES CORRESPONDING TO A CONSERVED SEQUENCE OF GONOCOCCAL PILINS BLOCK BACTERIAL ADHESION PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rothbard, J. B., Fernandez, R., Wang, L., Teng, N. N., SCHOOLNIK, G. K. 1985; 82 (3): 915-919

    Abstract

    Antisera generated against each of seven synthetic peptides corresponding to constant and variable sequences of the pilin from gonococcal strain MS11 were assayed for their ability to crossreact with intact pili from both homologous and heterologous strains. The peptides elicited roughly equal antipeptide responses but varied substantially in their ability to elicit antisera that crossreacted with intact pili. Of the antisera to peptides corresponding to regions of conserved sequence, antisera directed against residues 69-84 were the most efficient in binding pili from all strains tested in both solid-phase assays and immunoblots. Anti-69-84 also efficiently precipitated a tryptic fragment of pilin known to bind human endocervical cells. Sera against the two peptides (121-134 and 135-151) previously shown to contain strain-specific epitopes crossreacted with MS11 pili equally well, but differed in their ability to bind pili from heterologous strains. Anti-121-134 was strain-specific whereas anti-135-151 bound all pilin tested. Each of the sera was examined for its ability to inhibit bacterial adhesion to a human endometrial carcinoma cell line. Sera generated against residues 41-50 and 69-84 successfully inhibited a heterologous gonococcal strain from binding. These peptides could be important components of an effective vaccine for the prevention of gonorrhea.

    View details for Web of Science ID A1985ADL2400060

    View details for PubMedID 3919385

  • PRODUCTION OF HUMAN MONOCLONAL IGG ANTIBODIES AGAINST RHESUS (D) ANTIGEN PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES Bron, D., Feinberg, M. B., Teng, N. N., KAPLAN, H. S. 1984; 81 (10): 3214-3217

    Abstract

    An Epstein-Barr virus (EBV)-transformed human B-cell line ( LB4r ) producing anti-Rhesus [Rho(D) antigen] antibody was fused with a non-immunoglobulin-producing mouse-human heteromyeloma ( SHM - D33 ) and selected in hypoxanthine/aminopterin/thymidine medium containing 0.5 microM ouabain. Surviving hybrids found to secrete specific anti-Rho(D) antibody were cloned by limiting dilution. Two clones (D4-B2 and E10-C1) producing high levels (12 and 20 micrograms/ml per 10(6) cells per 24 hr, respectively) of monospecific antibody (IgG3, lambda chain) were selected for expansion and further characterization. Compared to the parental cell line ( LB4r ), these hybridoma cell lines presented several advantages: antibody production was increased 10-fold, cloning efficiency was improved, and the EBV genome was not retained. Antibody production has been stable for greater than 8 months. These human monoclonal anti-Rho(D) antibodies have demonstrated utility in routine blood-group typing. They may also prove useful in the biochemical and genetic characterization of the Rh antigen system. Most important, they offer a source of Rh-immune globulin for the prevention of Rh immunization and alloimmune hemolytic disease of the newborn.

    View details for Web of Science ID A1984SU47600056

    View details for PubMedID 6427767

  • PARTIAL HYDATIDIFORM MOLE WITH DIPLOID KARYOTYPE - REPORT OF 3 CASES AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Teng, N. N., Ballon, S. C. 1984; 150 (8): 961-964

    Abstract

    Recent studies suggest that a partial mole with a triploid karyotype has little tendency to invade and metastasize and usually requires no therapy other than evacuation. This report describes three patients with a mole of normal diploid karyotype coexisting with a living fetus. Each patient had persistent elevation of human chorionic gonadotropin. Two patients required chemotherapy; one of these had invasive mole. The partial mole with normal diploid karyotype is a distinct clinical entity with the potential for malignant sequelae. The possibility of twin gestation cannot be excluded.

    View details for Web of Science ID A1984TX04400012

    View details for PubMedID 6507534

  • SOMATIC-CELL HYBRID SELECTION WITH A TRANSFECTABLE DOMINANT MARKER SOMATIC CELL AND MOLECULAR GENETICS RIERA, F. C., BLAM, S. B., Teng, N. N., KAPLAN, H. S. 1984; 10 (2): 123-127

    Abstract

    A recombinant plasmid vector, pSV2-neo, coding for resistance to neomycin and the related antibiotic G-418, was transfected into the mouse myeloma line X63-Ag8.653 by a modification of the protoplast fusion technique. The time interval required to obtain 10(6) G-418 resistant cells was 20 days and the efficiency was 10(-4)-10(-5), which represents a significant advantage over classical methods of selecting mutant cells bearing a dominant selection marker. To investigate the efficiency of this marker in somatic cell hybrid selection, these cells were fused to the human myeloma line U-266 and the hybrids were selected either in HAT + G-418 or HAT + ouabain. The pSV2-neo vector was as efficient as ouabain as a dominant marker with respect to the number of viable hybrid colonies selected and their levels of immunoglobulin secretion. The reciprocal experiment was also performed: HAT-sensitive, mutant U-266 cells were transfected with pSV2-neo, clones selected in G-418 and fused with X63-Ag8.653 cells, and hybrids selected in ouabain plus G-418, yielding HAT-sensitive hybrid "heteromyelomas" that were effective fusion partners with human B lymphocytes.

    View details for Web of Science ID A1984SK09400002

    View details for PubMedID 6324391

  • 2ND-LOOK LAPAROTOMY IN EPITHELIAL OVARIAN-CARCINOMA - PRECISE DEFINITION, SENSITIVITY, AND SPECIFICITY OF THE OPERATIVE PROCEDURE GYNECOLOGIC ONCOLOGY Ballon, S. C., PORTNUFF, J. C., Sikic, B. I., Turbow, M. M., Teng, N. N., SORIERO, O. M. 1984; 17 (2): 154-160

    Abstract

    Twenty-five women treated with chemotherapy for epithelial ovarian carcinoma underwent "second-look" laparotomy after thorough clinical and radiographic examinations failed to detect residual tumor. Chest roentgenogram, barium enema, upper gastrointestinal series with small-bowel follow through, and abdominopelvic CAT scan were obtained in all patients prior to operation. Inspection, palpation, and multiple biopsies were performed in accordance with precise and detailed protocol requirements. Eight patients (32%) had gross tumor found at laparotomy, while 6 (24%) had no suspicion of residual disease at operation but had cytologic or microscopic evidence of tumor found on review of submitted specimens. Eleven patients (44%) had no gross or microscopic evidence of residual ovarian carcinoma. After follow-up of from 4 to 25 months, 1 of these 11 patients (9%) has suffered a recurrence. The maximum sensitivity of "second-look" laparotomy is 85.7%, and the maximum specificity is 90.9% in this series. Any additional recurrences observed over time will decrease both the sensitivity and specificity of the operation. The sites of microscopic disease support rigid adherence to a precise operative procedure which should minimize the false negative rate.

    View details for Web of Science ID A1984SE71100003

    View details for PubMedID 6706223

  • MONOCLONAL VERSUS POLYCLONAL ANTIBODY-RADIOIMMUNOASSAY AGAINST THE BETA-SUBUNIT OF HUMAN CHORIONIC-GONADOTROPIN IN PATIENTS WITH GESTATIONAL TROPHOBLASTIC NEOPLASIA AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Wu, T., Ballon, S. C., Teng, N. N. 1983; 147 (7): 821-825

    Abstract

    The level of human chorionic gonadotropin (hCG) in series of sera from eight patients with gestational trophoblastic neoplasia was measured by monoclonal antibody and polyclonal antibody radioimmunoassay. A comparative analysis was performed. Three commercially available monoclonal anti-beta-subunit of hCG (beta-hCG) antibodies were evaluated and the most specific and sensitive one was chosen to develop a quantitative beta-hCG radioimmunoassay. beta-hCG radioimmunoassay kits from Nuclear Medical Systems, Inc., and Clinical Assays served as polyclonal antibody assays. Results obtained with the monoclonal antibody radioimmunoassays demonstrated a high degree of correlation (r greater than 0.95, p less than 0.01) with those obtained by the polyclonal antibody techniques; however, the sera from one patient continuously demonstrated a low level of hCG in the monoclonal antibody radioimmunoassay while registering undetectable levels in the polyclonal antibody assays. Although the monoclonal antibody radioimmunoassay appears to be specific and fairly sensitive, the results indicate that, with current technology, there is no special advantage to employing this assay to measure hCG in patients with gestational trophoblastic neoplasia.

    View details for Web of Science ID A1983RU08900020

    View details for PubMedID 6196974

  • CONSTRUCTION AND TESTING OF MOUSE HUMAN HETEROMYELOMAS FOR HUMAN MONOCLONAL-ANTIBODY PRODUCTION PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES Teng, N. N., Lam, K. S., RIERA, F. C., KAPLAN, H. S. 1983; 80 (23): 7308-7312

    Abstract

    FU-266, a mutant human myeloma cell line sensitive to hypoxanthine/aminopterin/thymidine (HAT), was transfected by protoplast fusion with DNA of the recombinant plasmid vector pSV2-neoR, thus acquiring a dominant marker conferring resistance to the antibiotic G-418. One of the resultant neoR clones, E-1, was fused to irradiated (500 rads) or unirradiated cells of the HAT-sensitive, G-418-sensitive, nonproducer mouse myeloma line X63-Ag8.653. Hybrid clones were selected in G-418 plus ouabain, thus preserving their HAT sensitivity. Small numbers of human chromosomes were retained in all such hybrids, but most of them ceased secreting human myeloma (IgE(lambda). Selected hybrid clones were then tested as malignant fusion partners in a series of fusions with polyclonally activated human B lymphocytes and with antigen-primed human B lymphocytes, in some instances after transformation of the latter with Epstein-Barr virus. The yield of viable chimeric hybridomas has been consistently high, as has the proportion of hybridomas secreting human immunoglobulin molecules unpermuted with mouse or human myeloma heavy or light chains. Secretion by many subcloned hybridomas has been stable for over 6 months, and several antigen-specific human monoclonal antibodies have been generated. Thus these heteromyeloma cell lines appear to have significant advantages for human monoclonal antibody production.

    View details for Web of Science ID A1983RT73300054

    View details for PubMedID 6316357

  • CHARACTERIZATION OF AN ALPHA-BUNGAROTOXIN BINDING COMPONENT FROM DROSOPHILA - MELANOGASTER JOURNAL OF NEUROCHEMISTRY SCHMIDTNIELSEN, B. K., GEPNER, J. I., Teng, N. N., Hall, L. M. 1977; 29 (6): 1013-1029

    View details for Web of Science ID A1977EE17200009

    View details for PubMedID 413880

  • APPEARANCE OF ACETYLCHOLINE RECEPTORS IN CULTURED MYOBLASTS PRIOR TO FUSION JOURNAL OF SUPRAMOLECULAR STRUCTURE Teng, N. N., Fiszman, M. Y. 1976; 4 (3): 381-387

    Abstract

    The development of the acetylcholine receptors in chick embryo myoblasts from 11-day old embryos was studied in vitro. Using the purified alpha-bungarotoxin labeled with radioactive iodide, a high concentration of acetylcholine receptors was found in the prefusing myoblasts; most of these receptors were located in the interior of the myoblasts. However, upon the completion of myoblasts fusion, the majority of the acetylcholine receptors appeared on the external cell surface of the myotubes.

    View details for Web of Science ID A1976BP46300008

    View details for PubMedID 772316

  • MITOGENICITY OF THROMBIN AND SURFACE ALTERATIONS ON MOUSE SPLENOCYTES EXPERIMENTAL CELL RESEARCH Chen, L. B., Teng, N. N., Buchanan, J. M. 1976; 101 (1): 41-46

    View details for Web of Science ID A1976CE09400005

    View details for PubMedID 986310

  • THROMBIN-SENSITIVE SURFACE PROTEIN OF CULTURED CHICK-EMBRYO CELLS NATURE Teng, N. N., Chen, L. B. 1976; 259 (5544): 578-580

    View details for Web of Science ID A1976BF69500042

    View details for PubMedID 1250403

  • The role of surface proteins in cell proliferation as studied with thrombin and other proteases. Proceedings of the National Academy of Sciences of the United States of America Teng, N. N., Bo Chen, L. 1975; 72 (2): 413-417

    Abstract

    This communication explores the capacity of different proteases to stimulate DNA synthesis in resting chick embryo fibroblasts and to cause the removal of cell membrane proteins previosly postulated as important in the regulation of growth and division of cells. Thrombin, a highly specific protease and a known mitogen, was incubated with chick embryo fibroblasts, and analysis was made of the cell membrane proteins. Of particular interest were a protein of molecular weight 250,000, which is known to be readily removed by the action of trypsin and is not present in most transformed cells, and two other proteins, which are reduced in amount in transformed as compared to confluent resting cell cultures. None of these three proteins was removed by thrombin when the latter was added to confluent cells in concentrations sufficient to cause significant increase in DNA synthesis twelve hours after stimulation by the protease. The presence or absence of these proteins in the membranes of confluent resting or transformed cells of chick embryo fibroblasts does not seem to be directly related to the process of regulation of DNA synthesis and cellular division.

    View details for PubMedID 1054823

  • HISTONES OF CHICK EMBRYONIC LENS NUCLEI DEVELOPMENTAL BIOLOGY Teng, N. N., PIATIGOR, J., Ingram, V. M. 1974; 41 (1): 72-76

    View details for Web of Science ID A1974U648300007

    View details for PubMedID 4474101

  • MECHANISM OF ACTION OF PARA HYDROXYBENZOATE HYDROXYLASE FROM PSEUDOMONAS-PUTIDA .3. ENZYME-SUBSTRATE COMPLEX JOURNAL OF BIOLOGICAL CHEMISTRY Teng, N., KOTOWYCZ, G., Calvin, M., Hosokawa, K. 1971; 246 (17): 5448-?

    View details for Web of Science ID A1971K329400036

    View details for PubMedID 4398470

  • 220-MHZ NUCLEAR MAGNETIC RESONANCE STUDY OF A SOLVENT-INDUCED CONFORMATIONAL CHANGE IN FLAVIN ADENINE DINUCLEOTIDE JOURNAL OF BIOLOGICAL CHEMISTRY KOTOWYCZ, G., Teng, N., Klein, M. P., Calvin, M. 1969; 244 (20): 5656-?

    View details for Web of Science ID A1969E474900029

    View details for PubMedID 5348605

  • [PRELIMINARY STUDIES ON LIGHT ANESTHESIA WITH ETHER]. Zhonghua wai ke za zhi [Chinese journal of surgery] TENG, N. F., Wang, L. H., Chang, K. H. 1963; 11: 802-804

    View details for PubMedID 14110578

  • Poisoning: a four year survey. Texas state journal of medicine DOBSON, H. L., Daeschner, C. W., MONDSHINE, R., Teng, N., PREBLE, H., Knudsen, J. M. 1957; 53 (7): 514-519

    View details for PubMedID 13455566

Conference Proceedings


  • Cervical cancer screening. Partridge, E. E., Abu-Rustum, N., Campos, S., Fahey, P. J., Greer, B. E., Lele, S. M., Lieberman, R. W., Lipscomb, G. H., Morgan, M., Nava, M. E., Reynolds, R. K., Singh, D. K., Smith-McCune, K., Teng, N., Trimble, C. L., Valea, F., Wilczynski, S. 2008: 58-82

    View details for PubMedID 18267060

  • Cervical cancer. Greer, B. E., Koh, W., Abu-Rustum, N., Bookman, M. A., Bristow, R. E., Campos, S., Cho, K. R., Copeland, L., Eifel, P., Huh, W. K., Jaggernauth, W., Kapp, D. S., Kavanagh, J., Lipscomb, G. H., Lurain, J. R., Morgan, M., Morgan, R. J., Powell, C. B., Remmenga, S. W., Reynolds, R. K., Secord, A. A., Small, W., Teng, N. 2008: 14-36

    View details for PubMedID 18267056

  • Susceptibility of B-cell lymphoma to human antibodies encoded by the V4-34 gene Bhat, N. M., Bieber, M. M., Young, L. W., Teng, N. N. ELSEVIER SCIENCE INC. 2001: 59-68

    Abstract

    Our previous studies have shown that mAbs derived from the human V4-34 gene bind and kill human B-lymphocytes via membrane disruption. This study demonstrates the cytotoxicity of two V4-34 encoded mAbs, 216 and Z2D2, towards human B-cell lymphoma. In vitro, 216 and Z2D2 are cytotoxic to a variety of B-cell lymphomas obtained from patient biopsies. In vivo, increased survival was observed with both mAbs in a lymphoma model developed in scid mice with human B-cell line Nalm-6. Studies in mice show that these mAbs are well tolerated with minimum side effects. Since 216 and Z2D2 show increased toxicity towards cycling cells, V4-34 mAb-based therapy can be additive with drugs that block cell-cycle progression. Stem cells that are V4-34 mAb ligand negative would not be depleted. Together, these studies recommend an evaluation of the two completely human mAbs in a phase I trial for B-cell lymphoma.

    View details for Web of Science ID 000169725400007

    View details for PubMedID 11418302

  • ANTIENDOTOXIN HUMAN MONOCLONAL-ANTIBODY A6H4C5 (HA-1A) UTILIZES THE VH4.21 GENE Bieber, M. M., Bhat, N. M., Teng, N. N. UNIV CHICAGO PRESS. 1995: S186-S189

    Abstract

    Human IgM monoclonal antibody A6H4C5 was manufactured by Centocor (Malvern, PA) and used in clinical trials as HA-1A (Centoxin). In vitro, A6H4C6 binds to lipid A and rough-strain, gram-negative bacteria endotoxin. Further analysis of A6H4C5 has shown that it is a polyreactive, cold agglutinin that utilizes the VH4.21 gene segment in germline configuration. It is also a human antibody that binds to human B cells. We have characterized several other independently derived VH4.21 human monoclonal antibodies with the same characteristics as A6H4C5. This group of antibodies may represent a conserved host immune response.

    View details for Web of Science ID A1995RZ52700011

    View details for PubMedID 8845451

  • OPTICAL BIOSENSOR ASSAY (OBA) Tsay, Y. G., Lin, C. I., Lee, J., Gustafson, E. K., APPELQVIST, R., MAGGINETTI, P., Norton, R., Teng, N., Charlton, D. AMER ASSOC CLINICAL CHEMISTRY. 1991: 1502-1505

    Abstract

    We describe a new biosensor immunoassay involving optical diffraction to detect clinically important analytes in human body fluids. A silicon wafer is used as a support for immobilization of antigen or antibody. The protein-coated surface is illuminated through a photo mask to create distinct periodic areas of active and inactive protein. When the surface is incubated with a positive sample, antigen-antibody binding occurs only on the active areas. Upon illumination with a light source such as a laser, the resulting biological diffraction grating diffracts the light. A negative sample does not result in diffraction because no antigen-antibody binding occurs to create the diffraction grating. The presence or absence of a diffraction signal differentiates between positive and negative samples, and the intensity of the signal provides a quantitative measure of the analyte concentration. The technique is demonstrated with a quantitative assay of choriogonadotropin in serum.

    View details for Web of Science ID A1991GF97100007

    View details for PubMedID 1893575

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