Bio

Clinical Focus


  • Cancer > Thoracic Oncology
  • Lung Cancer
  • Medical Oncology
  • Thoracic Oncology

Academic Appointments


Professional Education


  • Board Certification: Medical Oncology, American Board of Internal Medicine (2010)
  • Medical Education:Feinberg School of Medicine - Northwestern University (05/2004) IL
  • Fellowship:Dana-Farber Cancer Institute (08/2010) MA
  • Residency:Beth Israel Deaconess Medical Center (06/2007) MA
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2007)

Research & Scholarship

Current Research and Scholarly Interests


Non-small cell lung cancer (NSCLC) has historically been treated with combination chemotherapy. Over the last few years, molecular testing of NSCLC has revealed the presence of driving oncogenic mutations in a subset of tumors of adenocarcinoma histology, including EGFR, KRAS, and ALK. While chemotherapy is still effective for these patients, targeted therapies appear to be more specific with fewer side effects. For example, erlotinib treatment of EGFR mutant tumors results in better response rates and progression-free survival times than chemotherapy, and the investigational drug crizotinib is targeted against tumors harboring ALK translocations. My clinical and research interest is to apply evolving technologies to the diagnosis, characterization, and individualized treatment of NSCLC.

Clinical Trials


  • A Phase II Study of Amrubicin in Relapsed or Refractory Thymic Malignancies Recruiting

    Primary Objectives: Assessment of efficacy Secondary Objectives: Assessment of toxicity

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  • Pemetrexed Disodium or Observation in Treating Patients With Malignant Pleural Mesothelioma Without Progressive Disease After First-Line Chemotherapy Recruiting

    RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This randomized phase II trial is studying how well pemetrexed disodium or observation works in treating patients with malignant pleural mesothelioma without progressive disease after first-line chemotherapy.

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  • LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib Not Recruiting

    A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd will continue until the patient experiences unacceptable toxicity that precludes further treatment, discontinues treatment at the discretion of the investigator or patient, starts a new anti-cancer therapy and/or dies. LDK378 may be continued beyond RECIST-defined PD as assessed by the investigator if, in the judgment of the investigator, there is evidence of clinical benefit. In these patients tumor assessment should continue as per the schedule of assessments until treatment with LDK378 is permanently discontinued. Patients who discontinue the study medication in the absence of progression will continue to be followed for tumor assessment until the time of PD as assessed by the investigator

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo , 650-724-1388.

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  • Phase IIa Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors Recruiting

    Intrapatient dose escalation of desipramine. Start at 75 mg daily. Increase by 75 mg weekly to maximum of 450 mg daily. Taper desipramine upon disease progression, unacceptable toxicity or patient withdrawal from study.

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  • An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene Not Recruiting

    This is a Phase 2 trial that will evaluate the safety and efficacy of PF-02341066 in patients with advanced non-small cell lung cancer with a specific gene profile involving the ALK gene. This trial will also allow patients from a Phase 3 trial who received standard of care chemotherapy (Study A8081007) to receive PF-02341066.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo, (650) 724 - 1388.

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  • Phase I Vorinostat Concurrent With Stereotactic Radiosurgery (SRS) in Brain Metastases From Non-Small Cell Lung Cancer Recruiting

    The purpose of this study is to determine the maximum tolerated dose (MTD) of vorinostat given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLCA) brain metastases in patient with 1-4 lesions.

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  • A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab (Avastin) Plus Platinum And Paclitaxel or With Pemetrexed Plus Platinum in Patients With Non-Squamous Non-Small Cell Lung Cancer Not Recruiting

    This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of RO5490258 (MetMab) in combination with either of two backbone chemotherapy regimens in the first-line setting in patients with incurable Stage IIIB or IV non-squamous non-small cell lung cancer. In Cohort 1, patients will be randomized to receive 4 cycles of bevacizumab (Avastin) 15 mg/kg iv, paclitaxel 200 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMab 15 mg/kg iv or placebo on Day 1 of each 21-day cycle. In Cohort 2, patients will be randomized to receive pemetrexed 500 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMAb 15 mg/m2 iv or placebo on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will be offered maintenance therapy with their assigned treatment of bevacizumab plus either MetMAb or placebo (Cohort 1) or pemetrexed plus either MetMAb or placebo (Cohort 2). Anticipated time on st! udy treatment is until disease progression or unacceptable toxicity occurs.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie SanPedro-Salcedo, (650) 724 - 1388.

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  • BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery Recruiting

    RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. 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 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. Giving vaccine therapy together with bevacizumab after chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving BLP25 liposome vaccine together with bevacizumab after chemotherapy and radiation therapy in treating patients with newly diagnosed stage IIIA or stage IIIB non-small cell lung cancer that cannot be removed by surgery.

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  • Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer Recruiting

    RATIONALE: 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. Bevacizumab may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more effective in treating non-squamous non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium alone or in combination after induction therapy to see how well they work in treating patients with advanced non-squamous non-small cell lung cancer.

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  • Study to Evaluate Safety, Pharmacokinetics, and Efficacy of CO-1686 in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients Recruiting

    The purpose of this study is to characterize safety, PK and preliminary efficacy of CO-1686 in patients with mutant EGFR Non-Small Cell Lung Cancer.

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  • Manuka Honey in Preventing Esophagitis-Related Pain in Patients Receiving Chemotherapy and Radiation Therapy For Lung Cancer Not Recruiting

    RATIONALE: Manuka honey may prevent or reduce esophagitis-related pain caused by chemotherapy and radiation therapy. It is not yet known whether Manuka honey is more effective than standard care in preventing pain. PURPOSE: This randomized phase II clinical trial is studying Manuka honey to see how well it works in preventing esophagitis-related pain in patients receiving chemotherapy and radiation therapy for lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

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  • Chemotherapy With or Without Bevacizumab in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-Small Lung Cancer That Was Removed By Surgery Not Recruiting

    This randomized phase III trial is studying chemotherapy and bevacizumab to see how well they work compared to chemotherapy alone in treating patients with stage IB, stage II, or stage IIIA non-small cell lung cancer that was removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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 also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective with or without bevacizumab in treating non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Pitsiouni, 650-721-6977.

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  • Radiation Therapy in Treating Patients With Extensive Stage Small Cell Lung Cancer Recruiting

    RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. This may be an effective treatment for extensive stage small cell lung cancer. PURPOSE: This randomized phase II trial is comparing how well radiation therapy to the brain works when given with or without radiation therapy to other areas of the body in treating patients with extensive stage small cell lung cancer.

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  • A Study of HGS1036 in Combination With Chemotherapy in Subjects With Advanced Solid Malignancies Not Recruiting

    The primary purpose of this study is to determine the maximally tolerated dose (MTD) of HGS1036 when used in combination with the standard chemotherapeutic regimens paclitaxel plus carboplatin, cisplatin plus etoposide, or docetaxel.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Vargas, 650-723-0371 .

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  • Study is Designed to Assess the Safety and Tolerability of AZD4547 at Increasing Doses in Patients With Advanced Tumours Not Recruiting

    This study is primarily designed to assess the safety and tolerability of AZD4547 at increasing doses in patients with advanced solid malignancies and for whom no standard medication options are available. It also assesses the blood levels and action of AZD4547 in the body over a period of time.

    Stanford is currently not accepting patients for this trial. For more information, please contact Prachi Nandoskar, 650-725-0438.

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  • A Study of MEHD7945A Versus Cetuximab in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of The Head And Neck Not Recruiting

    This phase II, open-label, randomized study will evaluate the efficacy and safety of MEHD7945A versus cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck who have progressed during or following platinum-based chemotherapy. Patients will be randomized to receive either MEHD7945A 1100 mg intravenously (iv) every 2 weeks or cetuximab 400 mg/m2 iv loading dose followed by 250 mg/m2 iv weekly. Patients treated with cetuximab (Arm B) may cross-over to MEHD7945A (Arm A) upon central confirmation of progressive disease and upon meeting eligibility criteria. Anticipated time on study treatment is until disease progression or intolerable toxicity occurs.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ruth Lira, (650) 723 - 1367.

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  • Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck Cancer Not Recruiting

    This phase I trial studies how well talactoferrin works in treating patients with relapsed or refractory non-small cell lung cancer (NSCLC) or squamous cell head and neck cancer. Biological therapies, such as talactoferrin, may stimulate the immune system in different ways and stop tumor cells from growing

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo, (650) 724 - 1388.

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  • Clinical Study of BYM338 for the Treatment of Unintentional Weight Loss in Patients With Cancer of the Lung or the Pancreas Not Recruiting

    A safety & efficacy clinical study of the investigational medicinal product BYM338 for the treatment of unintentional weight loss in patients with cancer of the lung or the pancreas

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo, (650) 724 - 1388.

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  • A Study of CDX-1127 in Patients With Select Solid Tumor Types or Hematologic Cancers Recruiting

    This is a study of CDX-1127, a therapy that targets the immune system and may act to promote anti-cancer effects. The study enrolls patients with hematologic cancers (certain leukemias and lymphomas), as well as patients with select types of solid tumors.

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  • Study of Positron Emission Tomography and Computed Tomography in Guiding Radiation Therapy in Patients With Stage III Non-Small Cell Lung Cancer Recruiting

    This randomized phase II trial studies how well positron emission tomography (PET)/computed tomography (CT) scan work in guiding radiation therapy compared to standard radiation therapy treatment in patients with stage III non-small cell lung cancer. Imaging procedures, such as PET scan and CT scan, may help doctors plan radiation therapy for patients with non-small cell lung cancer.

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  • Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer Not Recruiting

    The purpose of this study is to evaluate progression-free survival among subjects with KRAS mutation positive Non-Small Cell Lung Cancer (NSCLC) treated with erlotinib plus tivantinib (ARQ 197) compared to single agent chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lei Shura, 650-723-2312.

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  • Identification of Circulating Tumor Cells in the Peripheral Blood of Lung Cancer Patients Recruiting

    The primary aim of this study is to determine whether we can identify human lung cancer tumor cells in the peripheral blood of lung cancer patients.

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  • Phase I Erlotinib and Dovitinib (TKI258) in Advanced Non-small Cell Lung Cancer (NSCLC) Not Recruiting

    This phase I trial studies the side effects and best dose of giving erlotinib and dovitinib together to treat patients with metastatic non-small cell lung cancer. Erlotinib blocks the epidermal growth factor receptor (EGFR) and has known activity in non-small cell lung cancer and dovitinib blocks the fibroblast growth factor receptor (FGFR) and other targets which may be important to treat lung cancer. The combination of both drugs may work better than either drug alone, but may also have increased side effects. This trial will look at the side effects of combining the drugs and look for how effective the combination may be.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

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  • A Study of Onartuzumab (MetMAb) Versus Placebo in Combination With Paclitaxel Plus Platinum in Patients With Squamous Non-Small Cell Lung Cancer Not Recruiting

    This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with paclitaxel plus platinum in patients with incurable Stage IIIB or Stage IV squamous non-small cell lung cancer (NSCLC). Patients will be randomized to receive either onartuzumab (MetMAb) 15 mg/kg iv or placebo on Day 1 of each 21-day cycle in combination with 4 cycles of paclitaxel 200 mg/m2 iv and platinum (carboplatin/cisplatin) iv on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will continue with either onartuzumab (MetMAb) or placebo as maintenance therapy until disease progression or unacceptable toxicity occurs.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo, (650) 724 - 1388.

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  • Weekly Docetaxel, Cisplatin, and Cetuximab (TPC) in Palliative Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN) Recruiting

    Docetaxel and cetuximab are FDA approved for the treatment of squamous cell carcinoma of the head and neck. Cisplatin and carboplatin, while not FDA approved for Squamous Cell Carcinoma of the Head and Neck (SCCHN), have been used as standard of care in patients with SCCHN in combination with other drugs. This study will determine if weekly cisplatin and docetaxel, in combination with cetuximab, will be effective in palliative treatment of patients with squamous cell carcinoma of the head and neck. These drugs will be given intravenously weekly, repeated 3 of every 4 weeks until evidence of disease progression or unacceptable adverse events.

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  • Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations Not Recruiting

    The purpose of this research study is to learn if adding hydroxychloroquine (HCQ) to erlotinib helps treat non-small cell lung cancer (NSCLC). Another goal of this research study is to learn more about NSCLC and how it may respond to study treatment. Erlotinib (Tarceva) is a type of drug called a tyrosine kinase inhibitor (TKI). TKIs block a protein called the epidermal growth factor receptor (EGFR). EGFR may control tumor growth and tumor cell survival. However, although TKI drugs can work for some lung cancer patients for a period of time, eventually the tumor finds a way to resist or counteract the TKI treatment and it begins to grow again. Hydroxychloroquine (HCQ) is a drug approved by the FDA for treating malaria, rheumatoid arthritis, and several other diseases. Laboratory research suggests that when HCQ is given with a TKI, it may help delay or prevent TKI resistance from developing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Zeina Babetty, (650) 723 - 2983.

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  • Erlotinib in Patients With Resected, Early Stage NSCLC With Confirmed Mutations in the EGFR Not Recruiting

    In this research study erlotinib will be given to eligible participants whose lung cancer has been removed by surgery. Eligible patients have adenocarcinoma, a type of non-small lung cancer, and must have 1 or more of the following characteristics: be female, be of Asian or Pacific Rim descent and/or be a never smoker. The potential participant's tumor will be examined for Epidermal growth factor (EGFR) mutations. EGFR is a protein that is overexpressed in most non-small cell lung cancers. Some EGFR has been found to have specific mutations and the participant must have one of these mutations in his tumor. Erlotinib blocks this protein and may control tumor growth and increase survival. Previous research has shown that erlotinib is most effective for people who have these specific mutations in the EGFR.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lei Shura, 650-723-2312.

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  • Adjuvant Afatinib in Stage I-III NSCLC With EGFR Mutation Recruiting

    This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied. It also means that the FDA has not yet approved afatinib for use in patients. In this research study the investigators are looking to see if taking afatinib after surgery works better when taken over a short period of time, compared to a long period of time.

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  • A Phase 2 Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Patients With PD-L1 Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer - "FIR" Recruiting

    This multicenter, single-arm study will evaluate the efficacy and safety of MPDL3280A in patients with PD-L1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients will receive an intravenous dose of 1200 mg MPDL3280A on Day 1 of 21-day cycles for a maximum of 16 cycles.

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  • Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or In Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer Recruiting

    This randomized phase II trial studies how well giving erlotinib hydrochloride and cabozantinib-s-malate alone or in combination works as second or third line therapy in treating patient with stage IV non-small cell lung cancer. Erlotinib hydrochloride and cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving erlotinib hydrochloride together with cabozantinib-s-malate is more effective than erlotinib hydrochloride or cabozantinib-s-malate alone in treating non-small cell lung cancer.

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  • Molecular Analysis of Thoracic Malignancies Recruiting

    Primary Objective: To collect detailed clinical information on patients with thoracic malignancies via the electronic medical record and a detailed patient questionnaire, collect blood samples, retrieve paraffin embedded tissue if not collected at Stanford, and perform exploratory molecular analysis of tumor tissues.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • A Case Series of Lengthy Progression-Free Survival With Pemetrexed-Containing Therapy in Metastatic Non-Small-Cell Lung Cancer Patients Harboring ROS1 Gene Rearrangements. Clinical lung cancer Riess, J. W., Padda, S. K., Bangs, C. D., Das, M., Neal, J. W., Adrouny, A. R., Cherry, A., Wakelee, H. A. 2013; 14 (5): 592-595

    View details for DOI 10.1016/j.cllc.2013.04.008

    View details for PubMedID 23810364

  • A Patient With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer With Development of Leptomeningeal Carcinomatosis While on Targeted Treatment With Crizotinib JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Riess, J. W., Nagpal, S., Neal, J. W., Wake, H. A. 2013; 11 (4): 389-394

    Abstract

    Leptomeningeal carcinomatosis (LM) is an infrequent yet morbid and often fatal complication of non-small cell lung cancer (NSCLC). Management of LM is multimodal, often involving systemic chemotherapy, radiotherapy, and a variety of symptom management maneuvers to address elevated intracranial pressure, pain, and mood changes that can accompany the disease. It is increasingly recognized that tumors with actionable mutations in NSCLC, including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations, respond well to systemic therapy with tyrosine kinase inhibitors yet often progress in the central nervous system. More information is needed regarding the natural history and optimal management of LM in specific molecular subtypes of NSCLC. This case report summarizes the management of a patient with ALK-positive NSCLC who developed LM while on targeted treatment with crizotinib within the context of current NCCN Clinical Practice Guidelines in Oncology and recently published studies.

    View details for Web of Science ID 000317543800006

    View details for PubMedID 23584342

  • A Case Series of NSCLC Patients with Different Molecular Characteristics and Choroidal Metastases Improvement in Vision with Treatment Including Pemetrexed and Bevacizumab JOURNAL OF THORACIC ONCOLOGY Riess, J. W., Nagpal, S., Das, M., Neal, J. W., Kim, J. W., Wakelee, H. A. 2013; 8 (2): E17-E18

    View details for DOI 10.1097/JTO.0b013e31827690da

    View details for Web of Science ID 000316204900003

    View details for PubMedID 23328555

  • Aflibercept in lung cancer EXPERT OPINION ON BIOLOGICAL THERAPY Neal, J. W., Wakelee, H. A. 2013; 13 (1): 115-120

    Abstract

    Angiogenesis, the recruitment and growth of blood vessels, is a process central to the growth of solid tumors. One of the key mediators of angiogenesis is the vascular endothelial growth factor (VEGF) family of ligands. An antibody to VEGF-A, bevacizumab, has demonstrated a survival benefit in conjunction with platinum-based doublet chemotherapy in non-small-cell lung cancer (NSCLC). Aflibercept (VEGF Trap) is a recombinant VEGF receptor-antibody protein fusion with higher affinity for VEGF-A than bevacizumab, plus affinity for VEGF-B and placental growth factor (PlGF). AREAS COVERED: This article reviews recent clinical trials investigating the role of aflibercept in the treatment of lung cancer, both published in the literature and those for which preliminary data have been presented at major scientific meetings. EXPERT OPINION: Aflibercept has proven Phase III efficacy in metastatic colorectal cancer, but in lung cancer, large clinical trials have not yielded positive results. There remains hope that identification of biomarkers of response will one day help select patients most likely to benefit from antiangiogenesis therapy.

    View details for DOI 10.1517/14712598.2013.745847

    View details for Web of Science ID 000312219700010

    View details for PubMedID 23199019

  • Targeting fibroblast growth factor receptor and discoidin domain receptor 2 in non-small-cell lung cancer. Journal of thoracic oncology Riess, J. W., Neal, J. W. 2012; 7 (16): S385-6

    View details for DOI 10.1097/JTO.0b013e31826df166

    View details for PubMedID 23160327

  • A Phase I Study of Erlotinib and Hydroxychloroquine in Advanced Non-Small-Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Goldberg, S. B., Supko, J. G., Neal, J. W., Muzikansky, A., Digumarthy, S., Fidias, P., Temel, J. S., Heist, R. S., Shaw, A. T., McCarthy, P. O., Lynch, T. J., Sharma, S., Settleman, J. E., Sequist, L. V. 2012; 7 (10): 1602-1608

    Abstract

    This investigator-initiated study explores the safety, maximum tolerated dose, clinical response, and pharmacokinetics of hydroxychloroquine (HCQ) with and without erlotinib in patients with advanced non-small-cell lung cancer.Patients with prior clinical benefit from an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor were randomized to HCQ or HCQ plus erlotinib in a 3 + 3 dose-escalation schema.Twenty-seven patients were treated, eight with HCQ (arm A) and 19 with HCQ plus erlotinib (arm B). EGFR mutations were detected in 74% of the patients and 85% had received two or more prior therapies. Arm A had no dose-limiting toxicities, but the maximum tolerated dose was not reached as this arm closed early to increase overall study accrual. In arm B, one patient each experienced grade 3 rash, nail changes, skin changes, nausea, dehydration, and neutropenia; one had grade 4 anemia; and one developed fatal pneumonitis, all considered unrelated to HCQ. There were no dose-limiting toxicities, therefore the highest tested dose for HCQ with erlotinib 150 mg was 1000 mg daily. One patient had a partial response to erlotinib/HCQ, for an overall response rate of 5% (95% confidence interval, 1-25). This patient had an EGFR mutation and remained on therapy for 20 months. Administration of HCQ did not alter the pharmacokinetics of erlotinib.HCQ with or without erlotinib was safe and well tolerated. The recommended phase 2 dose of HCQ was 1000 mg when given in combination with erlotinib 150 mg.

    View details for DOI 10.1097/JTO.0b013e318262de4a

    View details for Web of Science ID 000308919400023

    View details for PubMedID 22878749

  • Complex Role of Histone Deacetylase Inhibitors in the Treatment of Non-Small-Cell Lung Cancer JOURNAL OF CLINICAL ONCOLOGY Neal, J. W., Sequist, L. V. 2012; 30 (18): 2280-2282

    View details for DOI 10.1200/JCO.2011.41.0860

    View details for Web of Science ID 000305413200022

    View details for PubMedID 22508823

  • Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non-Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study JOURNAL OF CLINICAL ONCOLOGY Lynch, T. J., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., Sebastian, M., Neal, J., Lu, H., Cuillerot, J., Reck, M. 2012; 30 (17): 2046-2054

    Abstract

    Ipilimumab, which is an anti-cytotoxic T-cell lymphocyte-4 monoclonal antibody, showed a survival benefit in melanoma with adverse events (AEs) managed by protocol-defined guidelines. A phase II study in lung cancer assessed the activity of ipilimumab plus paclitaxel and carboplatin.Patients (N = 204) with chemotherapy-naive non-small-cell lung cancer (NSCLC) were randomly assigned 1:1:1 to receive paclitaxel (175 mg/m(2)) and carboplatin (area under the curve, 6) with either placebo (control) or ipilimumab in one of the following two regimens: concurrent ipilimumab (four doses of ipilimumab plus paclitaxel and carboplatin followed by two doses of placebo plus paclitaxel and carboplatin) or phased ipilimumab (two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimumab plus paclitaxel and carboplatin).Treatment was administered intravenously every 3 weeks for ? 18 weeks (induction). Eligible patients continued ipilimumab or placebo every 12 weeks as maintenance therapy. Response was assessed by using immune-related response criteria and modified WHO criteria. The primary end point was immune-related progression-free survival (irPFS). Other end points were progression-free survival (PFS), best overall response rate (BORR), immune-related BORR (irBORR), overall survival (OS), and safety.The study met its primary end point of improved irPFS for phased ipilimumab versus the control (hazard ratio [HR], 0.72; P = .05), but not for concurrent ipilimumab (HR, 0.81; P = .13). Phased ipilimumab also improved PFS according to modified WHO criteria (HR, 0.69; P = .02). Phased ipilimumab, concurrent ipilimumab, and control treatments were associated with a median irPFS of 5.7, 5.5, and 4.6 months, respectively, a median PFS of 5.1, 4.1, and 4.2 months, respectively, an irBORR of 32%, 21% and 18%, respectively, a BORR of 32%, 21% and 14%, respectively, and a median OS of 12.2, 9.7, and 8.3 months. Overall rates of grade 3 and 4 immune-related AEs were 15%, 20%, and 6% for phased ipilimumab, concurrent ipilimumab, and the control, respectively. Two patients (concurrent, one patient; control, one patient) died from treatment-related toxicity.Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipilimumab in NSCLC.

    View details for DOI 10.1200/JCO.2011.38.4032

    View details for Web of Science ID 000305159200009

    View details for PubMedID 22547592

  • First-line treatment of EGFR-mutant non-small-cell lung cancer: the role of erlotinib and other tyrosine kinase inhibitors. Biologics : targets & therapy Nguyen, K. H., Neal, J. W. 2012; 6: 337-345

    Abstract

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) were initially established as second- or third-line treatment of advanced non-small-cell lung cancer (NSCLC). Subsequent studies, including IPASS, OPTIMAL, and EURTAC, have demonstrated that these TKIs are effective first-line therapeutic options in patients with tumors harboring activating mutations in the EGFR gene. The TKIs are better tolerated than conventional chemotherapy, with frequent yet mild side effects such as rash and diarrhea, and rarely interstitial lung disease. Because most patients on TKIs develop resistance due to a variety of mechanisms, the use of TKIs in the acquired-resistance setting and in the setting of earlier-staged cancers is being extensively studied. Here we review the major trials leading to the established use of EGFR TKIs in NSCLC, followed by discussion of recently completed and ongoing trials using the next-generation EGFR inhibitor afatinib.

    View details for DOI 10.2147/BTT.S26558

    View details for PubMedID 23055691

  • Current Management of Small Cell Lung Cancer CLINICS IN CHEST MEDICINE Neal, J. W., Gubens, M. A., Wakelee, H. A. 2011; 32 (4): 853-?

    Abstract

    Confined to one side of the chest, limited stage small cell lung cancer is treated with a combination of chemotherapy and radiotherapy, yet has a long-term survival rate of only 15%. Extensive stage disease has initial response rates to chemotherapy exceeding 70%. However, the disease almost invariably progresses and becomes fatal. Many recent clinical trials have failed to show superiority of newer chemotherapeutics or targeted therapies compared with the standard chemotherapy backbone of platinum plus etoposide. Numerous promising targeted therapies and other agents are still in development.

    View details for DOI 10.1016/j.ccm.2011.07.002

    View details for Web of Science ID 000297822700017

    View details for PubMedID 22054891

  • Targeting FGFR, Ephrins, Mer, MET, and PDGFR-alpha in Non-small Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Riess, J. W., Neal, J. W. 2011; 6 (11): S1797-S1798
  • One Allele's Loss Is Another's Gain: Alterations of NKX2-8 in Non-Small Cell Lung Cancer CLINICAL CANCER RESEARCH Neal, J. W., Shaw, A. T. 2011; 17 (4): 638-639

    Abstract

    Large-scale genetic changes such as loss or gain of chromosomes are important drivers of solid tumor carcinogenesis. Recent technological advances in genomic profiling have allowed quantitative detection of gene copy numbers, leading to identification of the 14q13.3 gene locus as functionally important in non-small cell lung cancers.

    View details for DOI 10.1158/1078-0432.CCR-10-3081

    View details for Web of Science ID 000287913200002

    View details for PubMedID 21163872

  • The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell lung cancer FUTURE ONCOLOGY Neal, J. W. 2010; 6 (12): 1827-1832

    Abstract

    The first-line treatment of advanced non-small-cell lung cancer (NSCLC) generally consists of a maximum of six cycles of platinum-based doublet chemotherapy followed by surveillance for disease progression. Recently, the strategy of starting second-line treatment immediately following the completion of chemotherapy, known as 'maintenance' chemotherapy, has been investigated. The use of maintenance pemetrexed improves both progression-free and overall survival, while the use of maintenance docetaxel did not significantly improve overall survival. The Sequential Tarceva in Unresectable NSCLC (SATURN) study investigated the use of maintenance erlotinib following the completion of first-line chemotherapy. It demonstrated a significant improvement in overall survival from 11.1 months in the placebo group to 12.3 months in patients receiving maintenance erlotinib, with the important caveat that only 21% of patients in the placebo group ever received erlotinib. A subset of patients whose tumors had EGF receptor mutations had a higher magnitude of benefit from maintenance treatment. Therefore, maintenance erlotinib should be considered in the treatment of patients with NSCLC.

    View details for DOI 10.2217/FON.10.156

    View details for Web of Science ID 000297100400007

    View details for PubMedID 21142856

  • Cetuximab monotherapy in patients with advanced non-small cell lung cancer after prior epidermal growth factor receptor tyrosine kinase inhibitor therapy. Journal of thoracic oncology Neal, J. W., Heist, R. S., Fidias, P., Temel, J. S., Huberman, M., Marcoux, J. P., Muzikansky, A., Lynch, T. J., Sequist, L. V. 2010; 5 (11): 1855-1858

    Abstract

    Therapeutic agents directed against the epidermal growth factor receptor (EGFR) signaling pathway have been effective in the treatment of non-small cell lung cancer (NSCLC). Cetuximab is a monoclonal antibody against the EGFR receptor with antitumor activity in NSCLC. This study evaluated the efficacy of cetuximab monotherapy after prior treatment with an oral EGFR tyrosine kinase inhibitor (TKI).Eligible patients had stage IIIB, IV, or recurrent NSCLC with progression on the oral EGFR TKIs gefitinib or erlotinib. Cetuximab was administered intravenously at 400 mg/m on day 1 and then 250 mg/m weekly until disease progression or unacceptable toxicity. The primary end point was response rate.Eighteen patients were enrolled. Patients were heavily pretreated with chemotherapy and TKIs (average number of treatments = 4.2). The response rate was 0/18 (0%), and 28% of patients had confirmed stable disease. Median progression-free survival was 1.8 months (95% confidence interval, 1.6-5.4 months), and median overall survival was 7.5 months (95% confidence interval, 2.2-19 months). Three patients harbored activating EGFR mutations, and one of them had stable disease for nearly 6 months on cetuximab. Common toxicities were mild and included fatigue, skin rash, and nausea/vomiting. Two patients developed interstitial lung disease, life threatening in one case.Cetuximab monotherapy administered after prior EGFR TKI treatment in patients with advanced NSCLC does not yield clinical responses.

    View details for DOI 10.1097/JTO.0b013e3181f0bee0

    View details for PubMedID 20975380

  • AMG-386, a selective angiopoietin-1/-2-neutralizing peptibody for the potential treatment of cancer CURRENT OPINION IN MOLECULAR THERAPEUTICS Neal, J., Wakelee, H. 2010; 12 (4): 487-495

    Abstract

    The VEGF/VEGFR and angiopoietin/Tie-2 signaling pathways are important in the process of vascular endothelial growth (angiogenesis) and in the maintenance of tumor-associated blood vessels. While there are several agents targeting the VEGF/VEGFR signaling pathway, there are none available that target the angiopoietin/Tie-2 signaling pathway. The first such agent to reach clinical trials is AMG-386 (2xCon4C), being developed by Amgen Inc and licensed in Japan to Takeda Bio Development Center Ltd. AMG-386 is an anti-angiopoietin peptibody comprising a peptide with angiopoietin-binding properties that is fused to the Fc (crystallizable fragment) region of an antibody and inhibits the interaction between the ligands angiopoietin-1 and angiopoietin-2 with the Tie-2 receptor. AMG-386 significantly inhibited the growth of tumors in a variety of mouse xenograft models. In phase I trials of AMG-386 as a monotherapy or in combination with chemotherapy in patients with advanced solid tumors, AMG-386 demonstrated only mild toxicities, and one complete response and several partial responses were achieved in patients. Phase II trials of AMG-386 in combination with chemotherapy were ongoing in a variety of solid tumors, including breast, ovarian, colorectal, gastric and renal cell cancers. If safe and effective, AMG-386 could be an exciting addition to other antiangiogenic therapies in solid tumors.

    View details for Web of Science ID 000280507000013

    View details for PubMedID 20677100

  • Exciting New Targets in Lung Cancer Therapy: ALK, IGF-1R, HDAC, and Hh CURRENT TREATMENT OPTIONS IN ONCOLOGY Neal, J. W., Sequist, L. V. 2010; 11 (1-2): 36-44

    Abstract

    The anaplastic lymphoma kinase (ALK) inhibitor crizotinib will become an integral addition to the treatment of patients with non-small cell lung cancer (NSCLC) harboring genetic ALK translocations. The insulin-like growth factor receptor (IGF-1R) monoclonal antibody figitumumab, while initially promising, appears to increase toxicity and death in combination with chemotherapy in the treatment of patients with NSCLC of squamous histology; therefore, clinical development of this class of agents will need to proceed with caution. The histone deacetylation (HDAC) inhibitor vorinostat did not demonstrate an improvement in overall survival (OS) compared with placebo in a large randomized trial, but other agents in this class may have greater selectivity and efficacy. Inhibitors of the hedgehog (Hh) signaling pathways have some early clinical promise in both NSCLC and small cell lung cancer (SCLC), and larger studies using these agents are eagerly anticipated.

    View details for DOI 10.1007/s11864-010-0120-6

    View details for Web of Science ID 000281247200004

    View details for PubMedID 20676809

  • Targeted therapies: optimal first-line therapy for NSCLC with EGFR mutations. Nature reviews. Clinical oncology Neal, J. W., Sequist, L. V. 2010; 7 (2): 71-72

    View details for DOI 10.1038/nrclinonc.2009.191

    View details for PubMedID 20118973

  • First-line use of EGFR tyrosine kinase inhibitors in patients with NSCLC containing EGFR mutations. Clinical advances in hematology & oncology : H&O Neal, J. W., Sequist, L. V. 2010; 8 (2): 119-126

    Abstract

    While the small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib have modest clinical benefit in unselected patients with non-small cell lung cancer after platinum-based chemotherapy, an emerging and potentially more elegant strategy is to move these agents to the frontline setting for select patients. Those with somatic mutations in EGFR respond dramatically to EGFR inhibitors, and mounting evidence from recent clinical trials, particularly the Iressa Pan-Asia Study (IPASS) trial, confirms superior response rates, progression-free survival, and tolerability with this targeted therapy compared with conventional chemotherapy. Here, we review the studies supporting the use of EGFR tyrosine kinase inhibitors in the frontline setting in patients with EGFR mutations.

    View details for PubMedID 20386533

  • Induction of FucT-VII by the Ras/MAP kinase cascade in Jurkat T cells BLOOD Barry, S. M., Zisoulis, D. G., Neal, J. W., Clipstone, N. A., Kansas, G. S. 2003; 102 (5): 1771-1778

    Abstract

    Induction of the alpha1,3-fucosyltransferase FucT-VII in T lymphocytes is crucial for selectin ligand formation, but the signaling and transcriptional pathways that govern FucT-VII expression are unknown. Here, using a novel, highly phorbol myristate acetate (PMA)-responsive variant of the Jurkat T-cell line, we identify Ras and downstream mitogen-activated protein (MAP) kinase pathways as essential mediators of FucT-VII gene expression. PMA induced FucT-VII in only a subset of treated cells, similar to expression of FucT-VII in normal activated CD4 T cells. Introduction of constitutively active Ras or Raf by recombinant retroviruses induced FucT-VII expression only in that subset of cells expressing the highest levels of Ras, suggesting that induction of FucT-VII required a critical threshhold of Ras signaling. Both PMA treatment and introduction of active Ras led to rolling on E-selectin. Pharmacologic inhibition studies confirmed the involvement of the classic Ras-Raf-MEK-extracellular signal-regulated kinase (Ras-Raf-MEK-ERK) pathway in FucT-VII induction by PMA, Ras, and Raf. These studies also revealed a second, Ras-induced, Raf-1-independent pathway that participated in induction of FucT-VII. Strong activation of Ras represents a major pathway for induction of FucT-VII gene expression in T cells.

    View details for DOI 10.1182/blood-2002-11-3551

    View details for Web of Science ID 000184945200042

    View details for PubMedID 12738675

  • A constitutively active NFATc1 mutant induces a transformed phenotype in 3T3-L1 fibroblasts JOURNAL OF BIOLOGICAL CHEMISTRY Neal, J. W., Clipstone, N. A. 2003; 278 (19): 17246-17254

    Abstract

    The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway is best known for its role in T lymphocyte activation. However, it has become increasingly apparent that this signaling pathway is also involved in the regulation of cell growth and development in a wide variety of different tissues and cell types. Here we have investigated the effects of sustained NFATc1 signaling on the growth and differentiation of the murine 3T3-L1 preadipocyte cell line. Remarkably, we find that expression of a constitutively active NFATc1 mutant (caNFATc1) in these immortalized cells inhibits their differentiation into mature adipocytes and causes them to adopt a transformed cell phenotype, including loss of contact-mediated growth inhibition, reduced serum growth requirements, protection from growth factor withdrawal-induced apoptosis, and formation of colonies in semisolid media. Furthermore, we find that caNFATc1-expressing cells acquire growth factor autonomy and are able to proliferate even in the complete absence of serum. We provide evidence that this growth factor independence is caused by the NFATc1-dependent production of a soluble heat-labile autocrine factor that is capable of promoting the growth and survival of wild type 3T3-L1 cells as well as potently inhibiting their differentiation into mature adipocytes. Finally, we demonstrate that cells expressing caNFATc1 form tumors in nude mice. Taken together, these results indicate that deregulated NFATc1 activity is able to induce the immortalized 3T3-L1 preadipocyte cell line to acquire the well established hallmarks of cellular transformation and thereby provide direct evidence for the oncogenic potential of the NFATc1 transcription factor.

    View details for DOI 10.1074/jbc.M300528200

    View details for Web of Science ID 000182818600107

    View details for PubMedID 12598522

  • Calcineurin mediates the calcium-dependent inhibition of adipocyte differentiation in 3T3-L1 cells JOURNAL OF BIOLOGICAL CHEMISTRY Neal, J. W., Clipstone, N. A. 2002; 277 (51): 49776-49781

    Abstract

    Recent studies have revealed that the calcium-dependent serine/threonine phosphatase calcineurin mediates the effects of intracellular calcium in many different cell types. In this study we investigated the role of calcineurin in the regulation of adipocyte differentiation. We found that the specific calcineurin inhibitors cyclosporin A and FK506 overcame the antiadipogenic effect of calcium ionophore on the differentiation of 3T3-L1 preadipocytes. This finding suggests that calcineurin is responsible for mediating the previously documented Ca(2+)-dependent inhibition of adipogenesis. We further demonstrate that the expression of a constitutively active calcineurin mutant potently inhibits the ability of 3T3-L1 cells to undergo adipocyte differentiation by preventing expression of the proadipogenic transcription factors peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha). This calcineurin-mediated block in adipocyte differentiation is rescued by ectopic expression of PPARgamma1. Finally, we demonstrate that inhibition of endogenous calcineurin activity with either FK506 or a specific calcineurin inhibitory peptide enhances differentiation of 3T3-L1 cells in response to suboptimal adipogenic stimuli, suggesting that endogenous calcineurin activity normally sets a signaling threshold that antagonizes efficient adipocyte differentiation. Collectively, these data indicate that calcineurin acts as a Ca(2+)-dependent molecular switch that negatively regulates commitment to adipocyte differentiation by preventing the expression of critical proadipogenic transcription factors.

    View details for DOI 10.1074/jbc.M207913200

    View details for Web of Science ID 000180028900090

    View details for PubMedID 12351639

  • Glycogen synthase kinase-3 inhibits the DNA binding activity of NFATc JOURNAL OF BIOLOGICAL CHEMISTRY Neal, J. W., Clipstone, N. A. 2001; 276 (5): 3666-3673

    Abstract

    The NFAT family of transcription factors is required for the expression of numerous immunologically important genes and plays a pivotal role in both the initiation and coordination of the immune response. NFAT family members appear to be regulated primarily at the level of their subcellular localization. Here we show that NFATc is additionally regulated at the level of its DNA binding activity. Using gel mobility shift assays, we demonstrate that the intrinsic DNA binding activity of NFATc is negatively regulated by phosphorylation. We found that activation of calcineurin activity in cells and dephosphorylation of NFATc in vitro enhanced NFATc DNA binding activity, whereas phosphorylation of NFATc in vitro inhibited its ability to bind DNA. Through the analysis of NFATc mutants, we identified the conserved Ser-Pro repeat motifs as critical quantitative determinants of NFATc DNA binding activity. In addition, we provide several lines of evidence to suggest that the phosphorylation of the Ser-Pro repeats by glycogen synthase kinase-3 inhibits the ability of NFATc to bind DNA. Taken together, these studies afford new insights into the regulation of NFATc and underscore the potential role of glycogen synthase kinase-3 in the regulation of NFAT-dependent gene expression.

    View details for Web of Science ID 000166784900089

    View details for PubMedID 11063740

  • REGULATION OF THE GLUCOSE-H+ SYMPORTER BY METABOLITE-ACTIVATED ATP-DEPENDENT PHOSPHORYLATION OF HPR IN LACTOBACILLUS-BREVIS JOURNAL OF BACTERIOLOGY Ye, J. J., Neal, J. W., Cui, X. W., Reizer, J., Saier, M. H. 1994; 176 (12): 3484-3492

    Abstract

    Lactobacillus brevis takes up glucose and the nonmetabolizable glucose analog 2-deoxyglucose (2DG), as well as lactose and the nonmetabolizable lactose analoge thiomethyl beta-galactoside (TMG), via proton symport. Our earlier studies showed that TMG, previously accumulated in L. brevis cells via the lactose:H+ symporter, rapidly effluxes from L. brevis cells or vesicles upon addition of glucose and that glucose inhibits further accumulation of TMG. This regulation was shown to be mediated by a metabolite-activated protein kinase that phosphorylase serine 46 in the HPr protein. We have now analyzed the regulation of 2DG uptake and efflux and compared it with that of TMG. Uptake of 2DG was dependent on an energy source, effectively provided by intravesicular ATP or by extravesicular arginine which provides ATP via an ATP-generating system involving the arginine deiminase pathway. 2DG uptake into these vesicles was not inhibited, and preaccumulated 2DG did not efflux from them upon electroporation of fructose 1,6-diphosphate or gluconate 6-phosphate into the vesicles. Intravesicular but not extravesicular wild-type or H15A mutant HPr of Bacillus subtilis promoted inhibition (53 and 46%, respectively) of the permease in the presence of these metabolites. Counterflow experiments indicated that inhibition of 2DG uptake is due to the partial uncoupling of proton symport from sugar transport. Intravesicular S46A mutant HPr could not promote regulation of glucose permease activity when electroporated into the vesicles with or without the phosphorylated metabolites, but the S46D mutant protein promoted regulation, even in the absence of a metabolite. The Vmax but not the Km values for both TMG and 2DG uptake were affected. Uptake of the natural, metabolizable substrates of the lactose, glucose, mannose, and ribose permeases was inhibited by wild-type HPr in the presence of fructose 1,6-diphosphate or by S46D mutant HPr. These results establish that HPr serine phosphorylation by the ATP-dependent, metabolite-activated HPr kinase regulates glucose and lactose permease activities in L. brevis and suggest that other permeases may also be subject to this mode of regulation.

    View details for Web of Science ID A1994NQ76400006

    View details for PubMedID 8206825

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