Bio

Clinical Focus


  • Clinical Trial
  • Cancer > Cutaneous (Dermatologic) Oncology
  • Epidemiology
  • Skin Cancer
  • Non-melanoma skin cancer
  • Basal Cell Carcinoma
  • Dermatology
  • Cancer Prevention and Control

Academic Appointments


Honors & Awards


  • Scholar-Innovator, Harrington Discovery Center (2014-2016)
  • Clinical Investigator Award, Damon Runyon (July 1 2011 - July 2014)
  • K23 Career Development Award, National Institutes of Health (2009 - 2013)
  • Health Services Investigator Award, American Skin Association (2009)
  • Young Investigator Award, Prevent Cancer Organization (2007-2009)

Professional Education


  • Residency:Stanford University Hospital and Clinics - Dermatology Department (2007) CA
  • Internship:Santa Clara Valley Medical Center (2004) CA
  • Medical Education:Stanford University Hospital and Clinics - Dermatology Department (2003) CA
  • Fellowship:UCSF - Dept of Epidemiology and Biostatistics (2008) CA
  • Board Certification: Dermatology, American Board of Dermatology (2007)
  • Fellow, Univ of Calif, San Francisco, KL2 Clinical Research (2009)
  • Resident, Stanford University, Dermatology (2007)
  • Intern, Santa Clara Valley, Medicine (2004)
  • PhD, Stanford University, Biophysics (2003)
  • MD, Stanford University, Medicine (2003)
  • BA, UC Berkeley, Biochemistry (1995)

Community and International Work


  • Xeroderma Pigmentosum in Underserved Populations, Guatemala City, Guatemala

    Topic

    Skin cancer education, treatment, prevention

    Partnering Organization(s)

    Good Samaritan International

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Research & Scholarship

Current Research and Scholarly Interests


My research focuses on finding new ways to treat and prevent non-melanoma skin cancer. I am committed to bringing laboratory-based insights to benefit our patients. I am interested in these questions:
1. How do we prevent skin cancer?
2. What is the relationship between sunlight, vitamin D, and skin cancer risk?
3. Can we target certain tumor signaling pathways (Hedgehog pathway) to treat basal cell carcinomas - the most common cancer in the US?

Clinical Trials


  • Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients w/ Basal Cell Carcinomas Not Recruiting

    BCCs are the most common human cancer in the US and affect over 1 million people. There is no effective drug to prevent basal cell carcinomas of the skin. We hope to learn if an oral antifungal drug, Itraconazole, might inhibit a marker of proliferation and a biomarker (tumor signaling pathway) of BCC development. Itraconazole is an FDA-approved drug for the treatment of fungal infections of the skin, and has been used for the past 25 years with relatively few side effects. It has been shown in mice to reduce a BCC biomarker and to reduce growth of BCCs. Thus, it could potentially reduce BCC growth in humans.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jean Tang, (650) 721 - 7152.

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  • Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers Not Recruiting

    The purpose of this study is to determine the signaling pathways and changes in gene expression in melanocytes of subjects with a history of non-melanoma skin cancer who are exposed to oral vitamin D. If vitamin D is found to inhibit a signaling pathway involved in the development of melanoma such as BRAF, a protein involved in cell proliferation, then oral vitamin D could be explored further as a chemoprevention for melanoma skin cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Irene Bailey, 650-498-7061.

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  • Arsenic Trioxide in Treating Patients With Basal Cell Carcinoma Not Recruiting

    This pilot clinical trial studies arsenic trioxide in treating patients with basal cell carcinoma. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stop them from dividing

    Stanford is currently not accepting patients for this trial. For more information, please contact Irene Bailey-Healy, 408-892-7261.

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  • A Study of Two Vismodegib Regimens in Patients With Multiple Basal Cell Carcinomas Not Recruiting

    This randomized, double-blind, regimen-controlled, phase II, multicenter study will assess the efficacy and safety of two different vismodegib regimens in patients with multiple basal cell carcinoma. Patients will receive vismodegib 150 mg orally once daily either in an intermittent schedule of 12 weeks vismodegib followed by 8 weeks placebo (Arm A) or as 24 weeks induction followed by an intermittent schedule of 8 weeks placebo followed by 8 weeks vismodegib (Arm B). Anticipated time on study treatment is 72 weeks.

    Stanford is currently not accepting patients for this trial. For more information, please contact Irene Bailey-Healy, 408-892-7261.

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  • Vismodegib in Treating Patients With Basal Cell Carcinoma Not Recruiting

    The purpose of this study is to learn about the effect of vismodegib on sporadic basal cell carcinoma (BCCs) prior to surgical removal.

    Stanford is currently not accepting patients for this trial. For more information, please contact Irene Bailey, 650-721-7149.

    View full details

Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • Network geometry shows evidence sequestration for medical vs. surgical practices: treatments for basal cell carcinoma. Journal of clinical epidemiology Kim, D. D., Tang, J. Y., Ioannidis, J. P. 2014; 67 (4): 391-400

    Abstract

    Basal cell carcinoma (BCC) is the most common cancer with 2 million treatments per year with little evidence-based guidelines for treatment. There are three classes of interventions (surgical, destructive, and topical) for BCC, and this study aimed to determine whether there are preferences or avoidances in comparisons of different types of treatments for BCC in randomized controlled trials (RCTs).PubMed, Cochrane Central Registry of Clinical Trials, and ClinicalTrials.Gov were used to identify eligible published and registered ongoing RCTs.Fifty-five trials (42 published and 13 registered trials) were identified. Only one unpublished registered trial compared a topical vs. a surgical intervention, and only one trial compared a topical vs. a destructive intervention. Conversely, 44 of the 55 trials compared interventions within the same treatment class and 9 of 55 trials compared surgical vs. destructive interventions. In most trials, selection of same-class comparators was not necessitated by the type of BCC lesions (nonaggressive superficial or nodular vs. aggressive, infiltrative, morpheic BCCs, P = 0.155) or their location (face vs. nonfacial, P = 0.137).This is the first time that an evaluation of network geometry is applied to address issues of comparisons between different families of interventions that belong to different specialties and practices (medical vs. surgical). Previous evaluations of homophily have addressed different families of interventions, in which all interventions are medical (drugs) and performed in the same health-care settings. The noncommunicating bodies of evidence between medical and surgical interventions that we document highlight a problem of unnecessary sequestration of the evidence and the corresponding health-care practices.

    View details for DOI 10.1016/j.jclinepi.2013.10.015

    View details for PubMedID 24491794

  • Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma. Journal of clinical oncology Kim, D. J., Kim, J., Spaunhurst, K., Montoya, J., Khodosh, R., Chandra, K., Fu, T., Gilliam, A., Molgo, M., Beachy, P. A., Tang, J. Y. 2014; 32 (8): 745-751

    Abstract

    Itraconazole, a US Food and Drug Administration-approved antifungal drug, inhibits the Hedgehog (HH) signaling pathway, a crucial driver of basal cell carcinoma (BCC) tumorigenesis, and reduces BCC growth in mice. We assessed the effect of itraconazole on the HH pathway and on tumor size in human BCC tumors.Patients with ? one BCC tumor > 4 mm in diameter were enrolled onto two cohorts to receive oral itraconazole 200 mg twice per day for 1 month (cohort A) or 100 mg twice per day for an average of 2.3 months (cohort B). The primary end point was change in biomarkers: Ki67 tumor proliferation and HH activity (GLI1 mRNA). Secondary end points included change in tumor size in a subset of patients with multiple tumors.A total of 29 patients were enrolled, of whom 19 were treated with itraconazole. Itraconazole treatment was associated with two adverse events (grade 2 fatigue and grade 4 congestive heart failure). Itraconazole reduced cell proliferation by 45% (P = .04), HH pathway activity by 65% (P = .03), and reduced tumor area by 24% (95% CI, 18.2% to 30.0%). Of eight patients with multiple nonbiopsied tumors, four achieved partial response, and four had stable disease. Tumors from untreated control patients and from those previously treated with vismodegib showed no significant changes in proliferation or tumor size.Itraconazole has anti-BCC activity in humans. These results provide the basis for larger trials of longer duration to measure the clinical efficacy of itraconazole, especially relative to other HH pathway inhibitors.

    View details for DOI 10.1200/JCO.2013.49.9525

    View details for PubMedID 24493717

  • Tazarotene: randomized, double-blind, vehicle-controlled, and open-label concurrent trials for Basal cell carcinoma prevention and therapy in patients with Basal cell nevus syndrome. Cancer prevention research Tang, J. Y., Chiou, A. S., Mackay-Wiggan, J. M., Aszterbaum, M., Chanana, A. M., Lee, W., Lindgren, J. A., Raphael, M. A., Thompson, B. J., Bickers, D. R., Epstein, E. H. 2014; 7 (3): 292-299

    Abstract

    Sporadic human basal cell carcinomas (BCC) are generally well managed with current surgical modalities. However, in the subset of high-risk patients predisposed to developing large numbers of BCCs, there is an unmet need for effective, low-morbidity chemoprevention. This population includes fair-skinned patients with extensive sun exposure and those with genodermatoses such as the basal cell nevus (Gorlin) syndrome (BCNS). Tazarotene (Tazorac, Allergan) is a topical retinoid with relative specificity for RAR-? and RAR-? receptors. We previously demonstrated tazarotene's robust anti-BCC efficacy in Ptch1(+/-) mice, a murine equivalent of BCNS, and others have found it to have some efficacy against sporadic human BCCs. We report here results of a randomized, double-blind, vehicle-controlled study in patients with BCNS evaluating the efficacy of topically applied tazarotene for BCC chemoprevention (N = 34 subjects), along with an open-label trial evaluating tazarotene's efficacy for chemotherapy of BCC lesions (N = 36 subjects) for a maximum follow-up period of 3 years. We found that only 6% of patients had a chemopreventive response and that only 6% of treated BCC target lesions were clinically cured. Our studies provide no evidence for either chemopreventive or chemotherapeutic effect of tazarotene against BCCs in patients with BCNS. Cancer Prev Res; 7(3); 292-9. ©2014 AACR.

    View details for DOI 10.1158/1940-6207.CAPR-13-0305

    View details for PubMedID 24441673

  • Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women The Women's Health Initiative CANCER Gamba, C. A., Swetter, S. M., Stefanick, M. L., Kubo, J., Desai, M., Spaunhurst, K. M., Sinha, A. A., Asgari, M. M., Sturgeon, S., Tang, J. Y. 2013; 119 (8): 1562-1569

    Abstract

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS).At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders.During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and ? 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ? 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk.Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation.

    View details for DOI 10.1002/cncr.27817

    View details for Web of Science ID 000317618700016

    View details for PubMedID 23483536

  • GLI activation by atypical protein kinase C ?/? regulates the growth of basal cell carcinomas. Nature Atwood, S. X., Li, M., Lee, A., Tang, J. Y., Oro, A. E. 2013; 494 (7438): 484-488

    Abstract

    Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI. Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy. Here we identify atypical protein kinase C ?/? (aPKC-?/?) as a novel GLI regulator in mammals. aPKC-?/? and its polarity signalling partners co-localize at the centrosome and form a complex with missing-in-metastasis (MIM), a scaffolding protein that potentiates HH signalling. Genetic or pharmacological loss of aPKC-?/? function blocks HH signalling and proliferation of BCC cells. Prkci is a HH target gene that forms a positive feedback loop with GLI and exists at increased levels in BCCs. Genome-wide transcriptional profiling shows that aPKC-?/? and SMO control the expression of similar genes in tumour cells. aPKC-?/? functions downstream of SMO to phosphorylate and activate GLI1, resulting in maximal DNA binding and transcriptional activation. Activated aPKC-?/? is upregulated in SMO-inhibitor-resistant tumours and targeting aPKC-?/? suppresses signalling and growth of resistant BCC cell lines. These results demonstrate that aPKC-?/? is critical for HH-dependent processes and implicates aPKC-?/? as a new, tumour-selective therapeutic target for the treatment of SMO-inhibitor-resistant cancers.

    View details for DOI 10.1038/nature11889

    View details for PubMedID 23446420

  • Itraconazole and Arsenic Trioxide Inhibit Hedgehog Pathway Activation and Tumor Growth Associated with Acquired Resistance to Smoothened Antagonists CANCER CELL Kim, J., Aftab, B. T., Tang, J. Y., Kim, D., Lee, A. H., Rezaee, M., Kim, J., Chen, B., King, E. M., Borodovsky, A., Riggins, G. J., Epstein, E. H., Beachy, P. A., Rudin, C. M. 2013; 23 (1): 23-34

    Abstract

    Recognition of the multiple roles of Hedgehog signaling in cancer has prompted intensive efforts to develop targeted pathway inhibitors. Leading inhibitors in clinical development act by binding to a common site within Smoothened, a critical pathway component. Acquired Smoothened mutations, including SMO(D477G), confer resistance to these inhibitors. Here, we report that itraconazole and arsenic trioxide, two agents in clinical use that inhibit Hedgehog signaling by mechanisms distinct from that of current Smoothened antagonists, retain inhibitory activity in vitro in the context of all reported resistance-conferring Smoothened mutants and GLI2 overexpression. Itraconazole and arsenic trioxide, alone or in combination, inhibit the growth of medulloblastoma and basal cell carcinoma in vivo, and prolong survival of mice with intracranial drug-resistant SMO(D477G) medulloblastoma.

    View details for DOI 10.1016/j.ccr.2012.11.017

    View details for Web of Science ID 000313759100005

    View details for PubMedID 23291299

  • Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome NEW ENGLAND JOURNAL OF MEDICINE Tang, J. Y., Mackay-Wiggan, J. M., Aszterbaum, M., Yauch, R. L., Lindgren, J., Chang, K., Coppola, C., Chanana, A. M., Marji, J., Bickers, D. R., Epstein, E. H. 2012; 366 (23): 2180-2188

    Abstract

    Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas.We tested the anti-basal-cell carcinoma efficacy of vismodegib in a randomized, double-blind, placebo-controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011. The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection (surgically eligible) with vismodegib versus placebo after 3 months; secondary end points included reduction in the size of existing basal-cell carcinomas.In 41 patients followed for a mean of 8 months (range, 1 to 15) after enrollment, the per-patient rate of new surgically eligible basal-cell carcinomas was lower with vismodegib than with placebo (2 vs. 29 cases per group per year, P<0.001), as was the size (percent change from baseline in the sum of the longest diameter) of existing clinically significant basal-cell carcinomas (-65% vs. -11%, P=0.003). In some patients, all basal-cell carcinomas clinically regressed. No tumors progressed during treatment with vismodegib. Patients receiving vismodegib routinely had grade 1 or 2 adverse events of loss of taste, muscle cramps, hair loss, and weight loss. Overall, 54% of patients (14 of 26) receiving vismodegib discontinued drug treatment owing to adverse events. At 1 month, vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90% (P<0.001) and diminished tumor-cell proliferation, but apoptosis was not affected. No residual basal-cell carcinoma was detectable in 83% of biopsy samples taken from sites of clinically regressed basal-cell carcinomas.Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of new basal-cell carcinomas in patients with the basal-cell nevus syndrome. The adverse events associated with treatment led to discontinuation in over half of treated patients. (Funded by Genentech and others; ClinicalTrials.gov number, NCT00957229.).

    View details for Web of Science ID 000304863400007

    View details for PubMedID 22670904

  • Alcohol consumption and risk of melanoma and non-melanoma skin cancer in the Women's Health Initiative CANCER CAUSES & CONTROL Kubo, J. T., Henderson, M. T., Desai, M., Wactawski-Wende, J., Stefanick, M. L., Tang, J. Y. 2014; 25 (1): 1-10

    Abstract

    The relationship between alcohol consumption and preference of alcohol type with hazard of melanoma (MM) and risk of non-melanoma skin cancer (NMSC) was examined in the Women's Health Initiative (WHI) Observational Study (OS).A prospective cohort of 59,575 White postmenopausal women in the WHI OS (mean age 63.6) was analyzed. Cox proportional hazards models and logistic regression techniques were used to assess the hazard and risk of physician-adjudicated MM and self-reported NMSC, respectively, after adjusting for potential confounders including measures of sun exposure and skin type.Over 10.2 mean years of follow-up, 532 MM cases and 9,593 NMSC cases occurred. A significant relationship between amount of alcohol consumed and both MM and NMSC was observed, with those who consume 7+ drinks per week having a higher hazard of MM (HR 1.64 (1.09, 2.49), p global = 0.0013) and higher risk of NMSC (OR 1.23 (1.11, 1.36), p global < 0.0001) compared to non-drinkers. Lifetime alcohol consumption was also positively associated with hazard of MM (p = 0.0011) and risk of NMSC (p < 0.0001). Further, compared to non-drinkers, a preference for either white wine or liquor was associated with an increased hazard of MM (HR 1.52 (1.02, 2.27) for white wine; HR 1.65 (1.07, 2.55) for liquor) and risk of NMSC (OR 1.16 (1.05, 1.28) for white wine; OR 1.26 (1.13, 1.41) for liquor).Higher current alcohol consumption, higher lifetime alcohol consumption, and a preference for white wine or liquor were associated with increased hazard of MM and risk of NMSC.

    View details for DOI 10.1007/s10552-013-0280-3

    View details for Web of Science ID 000329351700001

    View details for PubMedID 24173533

  • Eczema and sensitization to common allergens in the United States: a multiethnic, population-based study. Pediatric dermatology Fu, T., Keiser, E., Linos, E., Rotatori, R. M., Sainani, K., Lingala, B., Lane, A. T., Schneider, L., Tang, J. Y. 2014; 31 (1): 21-26

    Abstract

    The relationship between food and environmental allergens in contributing to eczema risk is unclear on a multiethnic population level. Our purpose was to determine whether sensitization to specific dietary and environmental allergens as measured according to higher specific immunoglobulin E (IgE) levels is associated with eczema risk in children. National Health and Nutrition Examination Survey participants ages 1 to 17 years were asked whether they had ever received a diagnosis of eczema from a physician (n = 538). Total and specific serum IgE levels for four dietary allergens (egg, cow's milk, peanut, and shrimp) and five environmental allergens (dust mite, cat, dog, Aspergillus, and Alternaria) were measured. Logistic regression was used to examine the association between eczema and IgE levels. In the United States, 10.4 million children (15.6%) have a history of eczema. Eczema was more common in black children (p < 0.001) and in children from families with higher income and education (p = 0.01). The median total IgE levels were higher in children with a history of eczema than in those without (66.4 vs 50.6 kU/L, p = 0.004). In multivariate analysis adjusted for age, race, sex, family income, household education, and physician-diagnosed asthma, eczema was significantly associated with sensitization to cat dander (odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.05, 1.4, p = 0.009) and dog dander (OR = 1.5, 95% CI, 1.2, 1.7, p < 0.001). After correction for multiple comparisons, only sensitization to dog dander remained significant. U.S. children with eczema are most likely to be sensitized to dog dander. Future prospective studies should further explore this relationship.

    View details for DOI 10.1111/pde.12237

    View details for PubMedID 24283549

  • The Use of Vismodegib to Shrink Keratocystic Odontogenic Tumors in Patients With Basal Cell Nevus Syndrome. JAMA dermatology Ally, M. S., Tang, J. Y., Joseph, T., Thompson, B., Lindgren, J., Raphael, M. A., Ulerio, G., Chanana, A. M., Mackay-Wiggan, J. M., Bickers, D. R., Epstein, E. H. 2014

    Abstract

    IMPORTANCE Keratocystic odontogenic tumors (KCOTs) of the jaw affect more than 65% of patients with basal cell nevus syndrome (BCNS). Surgery frequently causes facial disfigurement and is not always curative. Most BCNS-related and some sporadic KCOTs have malignant activation of the Hedgehog signaling pathway. OBSERVATIONS We examined the effect of vismodegib (an oral Hedgehog pathway inhibitor) on KCOT size in patients with BCNS enrolled in a clinical trial testing vismodegib for basal cell carcinoma prevention (NCT00957229), using pretreatment and posttreatment magnetic resonance imaging. Four men and 2 women had pretreatment KCOTs (mean longest diameter, 2.0 cm; range, 0.7-3.3 cm), occurring primarily in the mandible. Patients were treated with vismodegib, 150 mg/d, for a mean (SD) of 18.0 (4.8) months (range, 11-24 months). Four patients experienced a size reduction and 2 had no change. Vismodegib reduced the mean longest diameter of KCOTs in all patients by 1.0 cm (95% CI, 0.03-1.94; P?=?.02) or 50% from baseline. We observed no enlargement of existing KCOTs or new KCOT development. CONCLUSIONS AND RELEVANCE Vismodegib shrinks some KCOTs in patients with BCNS and may offer an alternative to surgical therapy. These effects were maintained for at least 9 months after drug cessation in 1 patient. Further studies assessing long-term efficacy and optimal maintenance regimens should be performed.

    View details for DOI 10.1001/jamadermatol.2013.7444

    View details for PubMedID 24623282

  • Quantifying Soft Tissue Loss in Facial Aging: A Study in Women Using Magnetic Resonance Imaging DERMATOLOGIC SURGERY Wysong, A., Joseph, T., Kim, D., Tang, J. Y., Gladstone, H. B. 2013; 39 (12): 1895-1902

    Abstract

    Facial aging involves changes in the facial skeleton and soft tissues. There is limited quantitative data on soft tissue aging of the face.Magnetic resonance imaging (MRI) was used to quantify and compare facial soft tissue loss over time.Two thousand thirty-seven MRI scans from 58 women divided into young, middle-aged, and older groups were screened. A blinded radiologist used MRI to measure the temporal, infraorbital, and medial and lateral cheek areas.The mean thickness of the subcutaneous tissue in the temporal area was 12.3, 8.4, and 8.9 mm in the young, middle-aged, and older groups, respectively (p < .001). A mean difference of 1.6 mm was seen between the young and middle-aged groups and 2.2 mm between the young and older group (p < .001) in the infraorbital area, 3.3 mm between the young and middle-aged groups and 3.2 mm between the young and older group in the medial cheeks (p < .001), and 2.4 mm between the young and middle-aged groups and 2.4 mm between the young and older group in the lateral cheeks (p = .01).Facial soft tissue undergoes significant deterioration over time, with the most dramatic changes between the ages of 30 and 60 in the temporal, infraorbital, and lateral and medial cheek areas. Soft tissue augmentation and volume correction in these areas may be an effective strategy for facial rejuvenation.

    View details for DOI 10.1111/dsu.12362

    View details for Web of Science ID 000327556600018

    View details for PubMedID 24238002

  • Lower Skin Cancer Risk in Women with Higher Body Mass Index: The Women's Health Initiative Observational Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Tang, J. Y., Henderson, M. T., Hernandez-Boussard, T., Kubo, J., Desai, M., Sims, S. T., Aroda, V., Thomas, F., McTiernan, A., Stefanick, M. L. 2013; 22 (12): 2412-2415

    Abstract

    The unclear relationship of obesity to incident melanoma and nonmelanoma skin cancer (NMSC) risks was evaluated in the large, geographically diverse longitudinal, prospective Women's Health Initiative (WHI) observational study. Risks of melanoma and NMSC in normal weight women were compared with risks in overweight [body mass index (BMI) = 25-29.0 kg/m(2)] and obese (BMI ? 30 kg/m(2)) women, using Cox proportional hazards models for melanoma and logistic regression for NMSC. Over a mean 9.4 years of follow-up, there were 386 melanoma and 9,870 NSMC cases. Risk of melanoma did not differ across weight categories (P = 0.86), whereas in fully adjusted models, NMSC risk was lower in overweight [OR, 0.93; 95% confidence interval (CI), 0.89-0.99] and obese (OR, 0.85; 95% CI, 0.80-0.91) women (P < 0.001). Excess body weight was not associated with melanoma risk in postmenopausal women but was inversely associated with NMSC risk, possibly due to lower sun exposure in overweight and obese women. This supports previous work demonstrating the relationship between excess body weight and skin cancer risk. Cancer Epidemiol Biomarkers Prev; 22(12); 2412-5. ©2013 AACR.

    View details for DOI 10.1158/1055-9965.EPI-13-0647

    View details for PubMedID 24042260

  • Role of aspirin and non-aspirin NSAIDs in preventing melanoma. Future oncology Ally, M. S., Swetter, S. M., Tang, J. Y. 2013; 9 (11): 1671-1674

    View details for DOI 10.2217/fon.13.112

    View details for PubMedID 23731359

  • Comment on basal cell carcinoma rebound after cessation of vismodegib in an individual with basal cell nevus syndrome. Dermatologic surgery Ally, M. S., Wysong, A., Tang, J. Y., Aasi, S. 2013; 39 (9): 1413-1414

    View details for DOI 10.1111/dsu.12250

    View details for PubMedID 23682843

  • Low-Fat Diet and Skin Cancer Risk: The Women's Health Initiative Randomized Controlled Dietary Modification Trial CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Gamba, C. S., Stefanick, M. L., Shikany, J. M., Larson, J., Linos, E., Sims, S. T., Marshall, J., Van Horn, L., Zeitouni, N., Tang, J. Y. 2013; 22 (9): 1509-1519

    Abstract

    Background: Large cohort studies have reported no relationship between dietary fat and nonmelanoma skin cancer (NMSC), although a low-fat diet intervention reduced NMSC risk in a small clinical trial. In animal studies, skin tumor development has been reduced by low-fat diet. We evaluated the effect of a low-fat dietary pattern on NMSC and melanoma in the Women's Health Initiative Dietary Modification trial. Methods: Postmenopausal women aged 50 to 79 years (N=48,835) were randomly assigned to the low-fat dietary pattern intervention (N=19,541) or comparison group (N=29,294). The intervention goals included decreasing fat intake to ?20% of calories, increasing vegetable and fruit intake, and increasing grain intake. Self-reported incident NMSC (N=4,907) and physician-adjudicated incident melanoma (N=279) were ascertained every 6 months. Results: Over 8.1 years of follow-up, the low-fat diet intervention did not affect overall incidence of NMSC (hazard ratio [HR] 0.98, 95% confidence interval [CI]: 0.92-1.04) or melanoma (HR 1.04, 95% CI: 0.82-1.32). In subgroup analyses of melanoma risk, baseline fat intake interacted significantly with group assignment (Pinteraction=0.006). Among women with higher baseline fat intake, the dietary intervention significantly increased risk (HR 1.48; 95% CI: 1.06-2.07), whereas, among women with lower baseline fat intake, the intervention tended to reduce melanoma risk (HR 0.72, 95% CI: 0.50-1.02). Conclusions: In this large randomized trial, a low-fat dietary pattern did not affect overall incidence of NMSC or melanoma. Impact: A low-fat diet does not reduce incidence of NMSC, but an interaction between baseline fat intake and dietary intervention on melanoma risk warrants further investigation.

    View details for DOI 10.1158/1055-9965.EPI-13-0341

    View details for Web of Science ID 000324674500004

    View details for PubMedID 23697610

  • Cutaneous human papillomavirus infection and Basal cell carcinoma of the skin. journal of investigative dermatology Ally, M. S., Tang, J. Y., Arron, S. T. 2013; 133 (6): 1456-1458

    Abstract

    Human papillomavirus (HPV) is ubiquitous in skin and has been associated with nonmelanoma skin cancer. Iannacone et al. investigate the role of HPV in basal cell carcinoma (BCC) by assessing the presence of HPV antibodies, HPV DNA in tumors, and the relationship between these two markers and BCC. In contrast to squamous cell carcinoma (SCC), there is no association between HPV and BCC.

    View details for DOI 10.1038/jid.2013.46

    View details for PubMedID 23673499

  • The use of aprepitant in brachioradial pruritus. JAMA dermatology (Chicago, Ill.) Ally, M. S., Gamba, C. S., Peng, D. H., Tang, J. Y. 2013; 149 (5): 627-628

    View details for DOI 10.1001/jamadermatol.2013.170

    View details for PubMedID 23677105

  • Update on metastatic Basal cell carcinoma: a summary of published cases from 1981 through 2011. JAMA dermatology (Chicago, Ill.) Wysong, A., Aasi, S. Z., Tang, J. Y. 2013; 149 (5): 615-616

    View details for DOI 10.1001/jamadermatol.2013.3064

    View details for PubMedID 23677097

  • Nonmelanoma Skin Cancer Visits and Procedure Patterns in a Nationally Representative Sample: National Ambulatory Medical Care Survey 1995-2007 DERMATOLOGIC SURGERY Wysong, A., Linos, E., Hernandez-Boussard, T., Arron, S. T., Gladstone, H., Tang, J. Y. 2013; 39 (4): 596-602

    Abstract

    The rising incidence of nonmelanoma skin cancer (NMSC) is well documented, but data are limited on the number of visits and treatment patterns of NMSC in the outpatient setting.To evaluate practice and treatment patterns of NMSC in the United States over the last decade and to characterize differences according to sex, age, race, insurance type, and physician specialty.Adults with an International Classification of Diseases, Ninth Revision, diagnosis of NMSC were included in this cross-sectional survey study of the National Ambulatory Medical Care Survey between 1995 and 2007. Primary outcomes included population-adjusted NMSC visit rates and odds ratios of receiving a procedure for NMSC using logistic regression.Rates of NMSC visits increased between 1995 and 2007. The number of visits was significantly higher in men, particularly those aged 65 and older. Fifty-nine percent of NMSC visits were associated with a procedure, and the individuals associated with that visit were more likely to be male, to be seen by a dermatologist, and to have private-pay insurance.Nonmelanoma skin cancer visit rates increased from 1995 to 2007 and were higher in men than women. Visits to a dermatologist are more likely to be associated with a procedure for NMSC, and there may be discrepancies in treatment patterns based on insurance type and sex.

    View details for DOI 10.1111/dsu.12092

    View details for Web of Science ID 000317018200010

    View details for PubMedID 23331766

  • New Onset of Keratoacanthomas After Vismodegib Treatment for Locally Advanced Basal Cell Carcinomas: A Report of 2 Cases JAMA DERMATOLOGY Aasi, S., Silkiss, R., Tang, J. Y., Wysong, A., Liu, A., Epstein, E., Oro, A. E., Chang, A. L. 2013; 149 (2): 242-243
  • Factors affecting sunscreen use and sun avoidance in a US national sample of organ transplant recipients BRITISH JOURNAL OF DERMATOLOGY Mihalis, E. L., Wysong, A., Boscardin, W. J., Tang, J. Y., Chren, M. M., Arron, S. T. 2013; 168 (2): 346-353

    Abstract

    Organ transplant recipients have an increased risk of nonmelanoma skin cancers due to immunosuppressive therapy following transplantation. Use of sunscreen has been shown to reduce this risk.To identify patient and healthcare factors associated with sun-protective behaviours in organ transplant recipients after transplantation with the goal of increasing overall sunscreen use.This study utilized a cross-sectional, retrospective survey from a national sample of 198 organ transplant recipients in the U.S.A. from 2004 to 2008 with no prior diagnosis of skin cancer. The main outcome measures were sunscreen use and sun avoidance before and after transplantation. Frequency of sunscreen use and sun exposure was obtained by self-report on Likert scales ranging from never to always, and these responses were converted to a numerical scale from 0 to 4.Overall sunscreen use increased after transplantation (from a score of 1·4 to 2·1, P < 0·001). Sex, Fitzpatrick skin type, receiving advice to avoid sun from a healthcare provider, and pretransplantation sunscreen use were significantly associated with frequency of post-transplantation sunscreen use in multivariate models. Pretransplantation sun exposure, advice to avoid sun and pretransplantation sunscreen use were significantly associated with sun avoidance post-transplantation.Both patient features and clinician advice are associated with sun-protective behaviours after organ transplantation. These results will help physicians target expanded sun-protection counselling to those patients most in need of such intervention.

    View details for DOI 10.1111/j.1365-2133.2012.11213.x

    View details for Web of Science ID 000314470600021

    View details for PubMedID 22880814

  • The Evolving Conception and Management Challenges of Malignant Fibrous Histiocytoma DERMATOLOGIC SURGERY Hollmig, S. T., Kirkland, E. B., Henderson, M. T., Tang, J. Y., Gladstone, H. B. 2012; 38 (12): 1922-1929

    Abstract

    Malignant fibrous histiocytoma (MFH) is a rare and aggressive tumor. Mohs micrographic surgery (MMS) has been reported as an effective treatment, although most cases were published before advances in cytopathologic techniques led to reclassification of many tumors.To evaluate a contemporary cohort of individuals with MFH and analyze management practices.We reviewed all cases of MFH diagnosed at our institution from January 1995 to December 2010, evaluating 839 records to identify 36 patients undergoing management of tumors of the head and neck.Seventeen of the total 36 patients (47%; mean age 67) experienced tumor recurrence, and 10 (28%) developed metastases. Seven of nine patients initially treated with MMS (78%), and 10 of 24 (42%) treated with WLE experienced recurrence (p = .06). Patients treated with MMS had smaller tissue defects after surgery. The mean contemporary recurrence rate of MFH treated with MMS is significantly higher (58.8%) than the cumulative recurrence rate reported before 2000 (7.4%) (p < .001).Our study is consistent with reports of MFH as an aggressive neoplasm and describes the largest population treated with MMS in 3 decades. The changing conception of MFH, along with a propensity for in-transit metastases, may explain higher contemporary recurrence rates.

    View details for DOI 10.1111/j.1524-4725.2012.02538.x

    View details for Web of Science ID 000312217900003

    View details for PubMedID 22882717

  • Is Tanning Bed Exposure Associated With Aggressive Basal Cell Carcinoma? JOURNAL OF CLINICAL ONCOLOGY Gamba, C. A., Wysong, A., Million, L., Aasi, S., Kim, J., Tang, J. Y. 2012; 30 (32): E333-E336

    View details for DOI 10.1200/JCO.2012.42.1008

    View details for Web of Science ID 000310914800006

    View details for PubMedID 23008324

  • Vitamin D in cutaneous carcinogenesis Part II JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Tang, J. Y., Fu, T., Lau, C., Oh, D. H., Bikle, D. D., Asgari, M. M. 2012; 67 (5)
  • Vitamin D in cutaneous carcinogenesis Part I JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Tang, J. Y., Fu, T., Lau, C., Oh, D. H., Bikle, D. D., Asgari, M. M. 2012; 67 (5)

    Abstract

    Skin cancer is the most common cancer in the United States. Exposure to ultraviolet radiation is a known risk factor for skin cancer but is also the principal means by which the body obtains vitamin D. Several studies have suggested that vitamin D plays a protective role in a variety of internal malignancies. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar protective effect. These noncalcemic actions of vitamin D have called into question whether the current recommended intake of vitamin D is too low for optimal health and cancer prevention. Part I will review the role of vitamin D in the epidermis; part II will review the role of vitamin D in keratinocyte-derived tumors to help frame the discussion on the possible role of vitamin D in the prevention of skin cancer.

    View details for DOI 10.1016/j.jaad.2012.05.044

    View details for Web of Science ID 000310776600037

    View details for PubMedID 23062903

  • Does a History of Eczema Predict a Future Basal Cell Carcinoma? JOURNAL OF INVESTIGATIVE DERMATOLOGY Gamba, C. A., Tang, J. Y. 2012; 132 (11): 2497-2499

    Abstract

    Dyer et al. (this issue) assess the risk of new basal cell carcinoma (BCC) in the Veterans Affairs topical tretinoin chemoprevention trial, which included individuals with a history of at least two prior keratinocyte carcinomas. In addition to known risk factors for a future BCC, such as number of prior BCCs, a history of eczema and lower education levels were also associated with greater risk.

    View details for DOI 10.1038/jid.2012.323

    View details for Web of Science ID 000309997200005

    View details for PubMedID 23069907

  • Sunscreen use in NCAA collegiate athletes: Identifying targets for intervention and barriers to use PREVENTIVE MEDICINE Wysong, A., Gladstone, H., Kim, D., Lingala, B., Copeland, J., Tang, J. Y. 2012; 55 (5): 493-496

    Abstract

    Ultraviolet radiation is a known risk factor for skin cancer and photoaging. Athletes are at high-risk with frequent sun exposure during peak hours of ultraviolet radiation. The aim of this study was to identify attitudes, personal characteristics, and barriers associated with sunscreen use among a high-risk athlete population.A cross-sectional survey study conducted in 290 collegiate athletes from April 2010 to June 2011 at Duke and Stanford Universities.The average athlete spent 4h per day and 10 months per year training outdoors. While 96% agreed that sunscreen helps prevent skin cancer, over 50% never used sunscreen and 75% used sunscreen 3 or fewer days/week. Having a coach or athletic administrator discuss photoprotection was significantly associated with sunscreen use. Predictors of sunscreen use were female gender, sunburns in the last year, belief at risk for skin cancer, knowing someone with skin cancer, and being worried about wrinkles, sun burns, or skin cancer.Continued identification of characteristics and barriers to sunscreen use can lead to targeted interventions and education in this high-risk group of collegiate athletes with early and elevated total lifetime ultraviolet exposure.

    View details for DOI 10.1016/j.ypmed.2012.08.020

    View details for Web of Science ID 000311061100029

    View details for PubMedID 22975268

  • Nanoelectroablation therapy for murine basal cell carcinoma BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Nuccitelli, R., Kevin Tran, K., Athos, B., Kreis, M., Nuccitelli, P., Chang, K. S., Epstein, E. H., Tang, J. Y. 2012; 424 (3): 446-450

    Abstract

    When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1(+/-)K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology [2,20] and in response to drug therapy [19]. We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 ± 5 (SEM) mm(3) shrunk by 76 ± 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

    View details for DOI 10.1016/j.bbrc.2012.06.129

    View details for Web of Science ID 000307618800014

    View details for PubMedID 22771794

  • Pachyonychia congenita patients with mutations in KRT6A have more extensive disease compared with patients who have mutations in KRT16 BRITISH JOURNAL OF DERMATOLOGY Spaunhurst, K. M., Hogendorf, A. M., Smith, F. J., Lingala, B., Schwartz, M. E., Cywinska-Bernas, A., Zeman, K. J., Tang, J. Y. 2012; 166 (4): 875-878

    Abstract

    Pachyonychia congenita (PC) is an autosomal dominant, very rare keratin disorder caused by mutations in any of at least four genes (KRT6A, KRT6B, KRT16 or KRT17), which can lead to hypertrophic nail dystrophy and palmoplantar keratoderma, among other manifestations. Classically, patients with mutations in KRT6A and KRT16 have been grouped to the PC-1 subtype (Jadassohn-Lewandowsky type) and KRT6B and KRT17 to PC-2 (Jackson-Lawler type).To describe clinical heterogeneity among patients with PC who have genetic mutations in KRT6A and KRT16.In 2004, the Pachyonychia Congenita Project established the International PC Research Registry (IPCRR) for patients with PC. All patients reporting here underwent genetic testing and responded to a standardized, validated survey about their PC symptoms. We report results from 89 patients with KRT6A mutations and 68 patients with KRT16 mutations.Patients with PC who have KRT6A and KRT16 mutations display distinct phenotypic differences. Patients with PC-K6a experience earlier onset, more extensive nail disease and more substantial disease outside palms and soles, as they reported a higher prevalence of oral leucokeratosis (P < 0·001), cysts (P < 0·001) and follicular hyperkeratosis (P < 0·001) compared with their PC-K16 counterparts.Phenotypic differences between patients with KRT6A and KRT16 mutations support adoption of a new classification system based on the mutant gene (PC-6a, PC-16) rather than the PC-1 nomenclature.

    View details for DOI 10.1111/j.1365-2133.2011.10745.x

    View details for Web of Science ID 000302013100099

    View details for PubMedID 22098151

  • Ulcers and stellate scars on bilateral ankles. Archives of dermatology Spaunhurst, K. M., Wysong, A., Kim, J., Tang, J. Y. 2012; 148 (3): 385-390

    View details for DOI 10.1001/archdermatol.2011.2923

    View details for PubMedID 22431781

  • Vitamin D in cutaneous carcinogenesis: part II. Journal of the American Academy of Dermatology Tang, J. Y., Fu, T., Lau, C., Oh, D. H., Bikle, D. D., Asgari, M. M. 2012; 67 (5): 817.e1-11; quiz 827-8

    Abstract

    The role of vitamin D in health maintenance and disease prevention in fields ranging from bone metabolism to cancer is currently under intensive investigation. A number of epidemiologic studies have suggested that vitamin D may have a protective effect on cancer risk and cancer-associated mortality. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar risk reducing effect. Potential mechanisms of action include inhibition of the hedgehog signaling pathway and upregulation of nucleotide excision repair enzymes. The key factor complicating the association between vitamin D and skin cancer is ultraviolet B radiation. The same spectrum of ultraviolet B radiation that catalyzes the production of vitamin D in the skin also causes DNA damage that can lead to epidermal malignancies. Part II of this continuing medical education article will summarize the literature on vitamin D and skin cancer to identify evidence-based optimal serum levels of vitamin D and to recommend ways of achieving those levels while minimizing the risk of skin cancer.

    View details for PubMedID 23062904

  • Sun protective behaviors and vitamin D levels in the US population: NHANES 2003-2006 CANCER CAUSES & CONTROL Linos, E., Keiser, E., Kanzler, M., Sainani, K. L., Lee, W., Vittinghoff, E., Chren, M., Tang, J. Y. 2012; 23 (1): 133-140

    Abstract

    Sun protection is recommended for skin cancer prevention, yet little is known about the role of sun protection on vitamin D levels. Our aim was to investigate the relationship between different types of sun protective behaviors and serum 25(OH)D levels in the general US population.Cross-sectional, nationally representative survey of 5,920 adults aged 18-60 years in the US National Health and Nutrition Examination Survey 2003-2006. We analyzed questionnaire responses on sun protective behaviors: staying in the shade, wearing long sleeves, wearing a hat, using sunscreen and SPF level. Analyses were adjusted for multiple confounders of 25(OH)D levels and stratified by race. Our primary outcome measures were serum 25(OH)D levels (ng/ml) measured by radioimmunoassay and vitamin D deficiency, defined as 25(OH)D levels <20 ng/ml.Staying in the shade and wearing long sleeves were significantly associated with lower 25(OH)D levels. Subjects who reported frequent use of shade on a sunny day had -3.5 ng/ml (p (trend) < 0.001) lower 25(OH)D levels compared to subjects who reported rare use. Subjects who reported frequent use of long sleeves had -2.2 ng/ml (p (trend) = 0.001) lower 25(OH)D levels. These associations were strongest for whites, and did not reach statistical significance among Hispanics or blacks. White participants who reported frequently staying in the shade or wearing long sleeves had double the odds of vitamin D deficiency compared with those who rarely did so. Neither wearing a hat nor using sunscreen was associated with low 25(OH)D levels or vitamin D deficiency.White individuals who protect themselves from the sun by seeking shade or wearing long sleeves may have lower 25(OH)D levels and be at risk for vitamin D deficiency. Frequent sunscreen use does not appear to be linked to vitamin D deficiency in this population.

    View details for DOI 10.1007/s10552-011-9862-0

    View details for Web of Science ID 000297757400013

    View details for PubMedID 22045154

  • Reliability and prevalence of digital image skin types in the United States: Results from National Health and Nutrition Examination Survey 2003-2004 JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Keiser, E., Linos, E., Kanzler, M., Lee, W., Sainani, K. L., Tang, J. Y. 2012; 66 (1): 163-165

    View details for DOI 10.1016/j.jaad.2011.02.044

    View details for Web of Science ID 000298712100031

    View details for PubMedID 22177642

  • Emerging Treatments and Signaling Pathway Inhibitors SEMINARS IN CUTANEOUS MEDICINE AND SURGERY Tang, J. Y., Marghoob, A. A. 2011; 30 (4): S14-S18

    Abstract

    A number of therapies that target components of the Hedgehog signaling pathway currently are in clinical trials. The specific molecules that seem most promising in basal cell carcinoma and a number of other cancers are those that target the Smoothened transmembrane protein. The pivotal phase II trials have been completed on the Smoothened inhibitor known as GDC-0449; five other agents (BMS-833923, LDE225, LEQ506, IPI926, and TAK-441) have also shown promise in animal studies and early clinical trials and have shown some efficacy in a variety of cancers that are affected by the Hedgehog signaling pathway.

    View details for DOI 10.1016/j.sder.2011.11.002

    View details for Web of Science ID 000298710300004

    View details for PubMedID 22177102

  • Elucidating the Role of Molecular Signaling Pathways in the Tumorigenesis of Basal Cell Carcinoma SEMINARS IN CUTANEOUS MEDICINE AND SURGERY Tang, J. Y. 2011; 30 (4): S6-S9

    Abstract

    The Hedgehog signaling pathway has been identified as fundamentally important to normal embryonic development in living organisms ranging from fruit flies to mammals. Postdevelopmentally, it remains active in hair and skin cells. Abnormal activation of components of the Hedgehog pathway--specifically, resulting from mutations in the Patched 1 gene--is associated with the development of basal cell carcinoma, as well as several other cancers, including medulloblastoma. Patched 1 gene mutation has also been identified as the underlying mechanism in most cases of Gorlin syndrome (also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome). Research that resulted in the current understanding of the Hedgehog signaling pathway, in turn, led to multiple lines of investigation to discover mechanisms for halting abnormal signaling, in the hope that agents could be developed that could beneficially stop this pathway. To date, several agents have been developed-and some are in clinical trials-that hold promise for improved nonsurgical treatments for patients with Gorlin syndrome and those with locally advanced/metastatic BCCs.

    View details for DOI 10.1016/j.sder.2011.11.001

    View details for Web of Science ID 000298710300002

    View details for PubMedID 22177103

  • Correlates of low bone mass in children with generalized forms of epidermolysis bullosa JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Bruckner, A. L., Bedocs, L. A., Keiser, E., Tang, J. Y., Doernbrack, C., Arbuckle, H. A., Berman, S., Kent, K., Bachrach, L. K. 2011; 65 (5): 1001-1009

    Abstract

    Epidermolysis bullosa (EB) is a family of rare, heterogeneous, genetic disorders characterized by fragility of the skin and mucous membranes. Reduced bone mass and fractures have been recognized as complications of generalized forms of EB.We sought to describe the range and to estimate the prevalence of low bone mass in children with generalized EB, and to identify correlates of low bone mass in this population.This was a prospective, observational study of 24 patients with generalized EB. Each patient completed a history, physical examination, laboratory studies, bone age, and x-rays of the lumbar spine. Those aged 6 years and older underwent dual energy x-ray absorptiometry scans of the lumbar spine. Primary outcomes were areal bone mineral density (aBMD) based on chronologic age, bone age, and adjusted for height Z-score. Descriptive statistics were used to summarize results, and linear regression was used to determine factors associated with low aBMD.Mean lumbar spine aBMD Z-scores ± SD were: -2.6 ± 1.4 for chronologic age, -1.7 ± 1.3 for bone age, and -1.0 ± 1.2 after adjusting for height Z-score. aBMD Z-scores were less than or equal to -2 in 64% for chronologic age, 50% for bone age, and 28% after adjusting for height Z-score. aBMD correlated with height Z-score, weight Z-score, extensive blistering, immobility, albumin, hemoglobin, iron, erythrocyte sedimentation rate, and c-reactive protein values.Small sample size was a limitation.Children with severe, generalized recessive dystrophic EB have low aBMD for age. Deficits in aBMD were reduced after adjusting for delayed skeletal maturation and small body size.

    View details for DOI 10.1016/j.jaad.2010.08.028

    View details for Web of Science ID 000296268000011

    View details for PubMedID 21550693

  • Menopausal Hormone Therapy and Risks of Melanoma and Nonmelanoma Skin Cancers: Women's Health Initiative Randomized Trials JOURNAL OF THE NATIONAL CANCER INSTITUTE Tang, J. Y., Spaunhurst, K. M., Chlebowski, R. T., Wactawski-Wende, J., Keiser, E., Thomas, F., Anderson, M. L., Zeitouni, N. C., Larson, J. C., Stefanick, M. L. 2011; 103 (19): 1469-1475

    Abstract

    Case-control studies have reported that exogenous estrogen use is associated with increased risk of skin cancer. The effects of menopausal hormone therapy on incidence of nonmelanoma skin cancer and melanoma were evaluated in post hoc analyses of the Women's Health Initiative randomized placebo-controlled hormone therapy trials of combined estrogen plus progestin (E + P) and estrogen only (E-alone).Postmenopausal women aged 50-79 years were randomly assigned to conjugated equine estrogen (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo in the E + P trial if they had an intact uterus (N = 16,608) or to conjugated equine estrogen alone or placebo in the E-alone trial if they had a hysterectomy (N = 10,739); the mean follow-up was 5.6 and 7.1 years, respectively. Incident nonmelanoma skin cancers (n = 980 [E + P trial]; n = 820 [E-alone trial]) and melanomas (n = 57 [E + P trial]; n =38 [E-alone trial]) were ascertained by self-report. Incident cases of cutaneous malignant melanoma were confirmed by physician review of medical records. Incidences of nonmelanoma skin cancer and melanoma were compared between the two randomization groups within each trial using hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) and Wald statistic P values from Cox proportional hazards models. All statistical tests were two-sided.Rates of incident nonmelanoma skin cancer and melanoma were similar between the active hormone (combined analysis of E + P and E-alone) and placebo groups (nonmelanoma skin cancer: HR = 0.98, 95% CI = 0.89 to 1.07; melanoma: HR = 0.92, 95% CI = 0.61 to 1.37). Results were similar for the E + P and E-alone trials when analyzed individually.Menopausal hormone therapy did not affect overall incidence of nonmelanoma skin cancer or melanoma. These findings do not support a role of menopausal estrogen, with or without progestin, in the development of skin cancer in postmenopausal women.

    View details for DOI 10.1093/jnci/djr333

    View details for Web of Science ID 000295683800011

    View details for PubMedID 21878677

  • Subcutaneous Nodules in an Elderly Patient Necrobiotic xanthogranuloma ARCHIVES OF DERMATOLOGY Fu, T., Zwerner, J., Kim, J., Tang, J. 2011; 147 (10): 1215-1220

    View details for Web of Science ID 000295944300022

    View details for PubMedID 22006142

  • Calcium Plus Vitamin D Supplementation and the Risk of Nonmelanoma and Melanoma Skin Cancer: Post Hoc Analyses of the Women's Health Initiative Randomized Controlled Trial JOURNAL OF CLINICAL ONCOLOGY Tang, J. Y., Fu, T., Leblanc, E., Manson, J. E., Feldman, D., Linos, E., Vitolins, M. Z., Zeitouni, N. C., Larson, J., Stefanick, M. L. 2011; 29 (22): 3078-3084

    Abstract

    In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial.Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Women's Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication.Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; P(interaction) = .038), which was not observed in women without history of NMSC.Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation.

    View details for DOI 10.1200/JCO.2011.34.5967

    View details for Web of Science ID 000293222200029

    View details for PubMedID 21709199

  • Hat, shade, long sleeves, or sunscreen? Rethinking US sun protection messages based on their relative effectiveness CANCER CAUSES & CONTROL Linos, E., Keiser, E., Fu, T., Colditz, G., Chen, S., Tang, J. Y. 2011; 22 (7): 1067-1071

    Abstract

    Sun protection messages in the United States emphasize sunscreen use, although its efficacy in skin cancer prevention remains controversial.We used data from NHANES 2003-2006, restricted to adult whites (n = 3,052) to evaluate how Americans protect themselves from the sun. Participants completed questionnaires on the frequency with which they used sunscreen, wore a hat, long sleeves, or stayed in the shade, in addition to the number of sunburns in the past year.Although using sunscreen is the most common sun protective behavior (30%), frequent sunscreen use was not associated with fewer sunburns. However, the odds of multiple sunburns were significantly lower in individuals who frequently avoided the sun by seeking shade (OR = 0.70, p < 0.001) or wearing long sleeves (OR = 0.73, p = 0.01).Our findings suggest that shade and protective clothing may be more effective than sunscreen, as typically used by Americans.

    View details for DOI 10.1007/s10552-011-9780-1

    View details for Web of Science ID 000291742700014

    View details for PubMedID 21637987

  • Targeting Superficial or Nodular Basal Cell Carcinoma with Topically Formulated Small Molecule Inhibitor of Smoothened CLINICAL CANCER RESEARCH Tang, T., Tang, J. Y., Li, D., Reich, M., Callahan, C. A., Fu, L., Yauch, R. L., Wang, F., Kotkow, K., Chang, K. S., Shpall, E., Wu, A., Rubin, L. L., Marsters, J. C., Epstein, E. H., Caro, I., de Sauvage, F. J. 2011; 17 (10): 3378-3387

    Abstract

    Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened.In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in Ptch1 (+/-) K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days.In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study.Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent.

    View details for DOI 10.1158/1078-0432.CCR-10-3370

    View details for Web of Science ID 000290610000030

    View details for PubMedID 21558397

  • Genotype-Phenotype Correlations among Pachyonychia Congenita Patients with K16 Mutations JOURNAL OF INVESTIGATIVE DERMATOLOGY Fu, T., Leachman, S. A., Wilson, N. J., Smith, F. J., Schwartz, M. E., Tang, J. Y. 2011; 131 (5): 1025-1028

    Abstract

    Pachyonychia congenita (PC) is a rare, autosomal dominant keratin disorder caused by mutations in four genes (KRT6A, KRT6B, KRT16, or KRT17). The International PC Research Registry is a database with information on patients' symptoms as well as genotypes. We sought to describe the heterogeneity of clinical symptoms and to investigate possible genotype-phenotype correlations in patients with two types of K16 mutations, p.Asn125 and p.Arg127, causing the PC-16 subtype of PC. We found that clinical symptoms depended on the type of amino-acid substitution. Patients with p.Asn125Asp and p.Arg127Pro mutations exhibited more severe disease than patients carrying p.Asn125Ser and p.Arg127Cys mutations in terms of age of onset of symptoms, extent of nail involvement, and impact on daily quality of life. We speculate that amino-acid substitutions causing larger, more disruptive changes to the K16 protein structure, such as a change in amino-acid charge in the p.Asn125Asp mutation or a bulky proline substitution in the p.Arg127Pro mutation, may also lead to more severe disease phenotypes. The variation in phenotypes seen with different substitutions at the same mutation site suggests a genotype-phenotype correlation. Knowledge of the exact gene defect is likely to assist in predicting disease prognosis and clinical management.

    View details for DOI 10.1038/jid.2010.373

    View details for Web of Science ID 000289789900009

    View details for PubMedID 21160496

  • Vitamin D3 Inhibits Hedgehog Signaling and Proliferation in Murine Basal Cell Carcinomas CANCER PREVENTION RESEARCH Tang, J. Y., Xiao, T. Z., Oda, Y., Chang, K. S., Shpall, E., Wu, A., So, P., Hebert, J., Bikle, D., Epstein, E. H. 2011; 4 (5): 744-751

    Abstract

    Constitutive Hedgehog (HH) signaling underlies several human tumors, including basal cell carcinoma (BCC). Recently, Bijlsma and colleagues reported a new biologic function for vitamin D3 in suppressing HH signaling in an in vitro model system. On the basis of that work, we have assessed effects of vitamin D3 on HH signaling and proliferation of murine BCCs in vitro and in vivo. We find that indeed in BCC cells, vitamin D3 blocks both proliferation and HH signaling as assessed by mRNA expression of the HH target gene Gli1. These effects of vitamin D3 on Gli1 expression and on BCC cell proliferation are comparable to the effects of cyclopamine, a known inhibitor of the HH pathway. These results are specific for vitamin D3, because the precursor 7-dehydrocholesterol and the downstream products 25-hydroxy vitamin D3 [25(OH)D] and 1,25-dihydroxy vitamin D3 [1,25(OH)(2)D] are considerably less effective in reducing either Gli1 mRNA or cellular proliferation. Moreover, these effects seem to be independent of the vitamin D receptor (VDR) because short hairpin RNA knockdown of VDR does not abrogate the anti-HH effects of D3 despite reducing expression of the VDR target gene 24-hydroxylase. Finally, topical vitamin D3 treatment of existing murine BCC tumors significantly decreases Gli1 and Ki67 staining. Thus, topical vitamin D3 acting via its HH inhibiting effect may hold promise as an effective anti-BCC agent.

    View details for DOI 10.1158/1940-6207.CAPR-10-0285

    View details for Web of Science ID 000290201100015

    View details for PubMedID 21436386

  • Association of facial skin aging and vitamin D levels in middle-aged white women CANCER CAUSES & CONTROL Chang, A. L., Fu, T., Amir, O., Tang, J. Y. 2010; 21 (12): 2315-2316

    Abstract

    To investigate the relationship between UV-induced skin photodamage and 25(OH) vitamin D levels, we performed a cross-sectional study in 45 female subjects aged >40. Menopausal status, smoking status, skin cancer history, oral supplement use, and season of blood draw were recorded and serum 25(OH)D measured. A single-blinded, dermatologist evaluated standardized digital facial images for overall photodamage, erythema/telangiectasias, hyperpigmentation, number of lentigines, and wrinkling. Adjusting for age and season of blood collection, women with lower photodamage scores were associated with a 5-fold increased odds of being vitamin D insufficient (OR 5.0, 95% CI: 1.1, 23). Low scores for specific photodamage parameters including erythema/telangiectasias, hyperpigmentation, and wrinkling were also significantly associated with vitamin D insufficiency. Our results suggest an association between skin aging and 25(OH)D levels.

    View details for DOI 10.1007/s10552-010-9646-y

    View details for Web of Science ID 000288609600041

    View details for PubMedID 20882333

  • High Prevalence of Vitamin D Deficiency in Patients With Basal Cell Nevus Syndrome ARCHIVES OF DERMATOLOGY Tang, J. Y., Wu, A., Linos, E., Parimi, N., Lee, W., Aszterbaum, M., Asgari, M. M., Bickers, D. R., Epstein, E. H. 2010; 146 (10): 1105-1110

    Abstract

    To evaluate vitamin D status in patients with basal cell nevus syndrome (BCNS) who practice photoprotection because of their genetic predisposition to skin cancer and to determine risk factors for deficiency.Retrospective cohort study.Academic medical centers.Forty-one ambulatory patients with BCNS who participated in a 2-year chemoprevention clinical trial. Population-based controls (n = 360) were selected and matched by age, sex, Fitzpatrick skin type, and season/geography.Levels of 25-hydroxyvitamin D (25[OH]D) and vitamin D deficiency (defined as a 25[OH]D level of ?20 ng/mL).Twenty-three patients with BCNS (56%) were vitamin D deficient. Patients with BCNS had mean 25(OH)D levels below those of the general population (-3 ng/mL; P = .02) and were 3 times more likely to be vitamin D deficient (56% vs 18%; P < .001). Levels of 25(OH)D were lower in patients who were overweight (-3.0 ng/mL; P = .04) and who had blood collected in the winter compared with the summer (-7.1 ng/mL; P < .001). Conclusion: Patients with BCNS may be at increased risk for vitamin D deficiency, depending on their adherence to photoprotection practices.

    View details for Web of Science ID 000283087300007

    View details for PubMedID 20956641

  • Novel investigational drugs for basal cell carcinoma EXPERT OPINION ON INVESTIGATIONAL DRUGS So, P., Tang, J. Y., Epstein, E. H. 2010; 19 (9): 1099-1112

    Abstract

    In the United States, the annual incidence of basal cell carcinoma (BCC) is close to 1 million. Ultraviolet radiation exposure is the main risk factor; however, the availability of ever more potent sunscreens and education have not prevented the rise in BCC incidence. Therefore, concerted effects to identify novel preventive and therapeutic strategies are necessary.This article summarizes our current understanding of the etiology and molecular mechanisms of BCC tumorigenesis and discusses the preclinical and clinical studies to identify agents with anti-BCC efficacy.The discovery that hyperactive Hh pathway signaling causes several cancers, including BCC, has spawned the development of many pharmacologic inhibitors of Hh signaling. Early clinical testing of the most advanced, GDC-0449, demonstrated impressive efficacy in patients with advanced BCC. Other promising anti-BCC chemopreventive strategies include drugs that are already FDA-approved for treating other diseases.Preclinical and clinical trials with pre-existing FDA-approved drugs suggest novel uses for BCC chemoprevention and treatment. Also, new chemical entities that inhibit the Hh pathway show promise, and in combination with other drugs may provide a nonsurgical cure for this most common cancer.

    View details for DOI 10.1517/13543784.2010.504714

    View details for Web of Science ID 000281968200007

    View details for PubMedID 20662553

  • Association of Prediagnostic Serum Vitamin D Levels with the Development of Basal Cell Carcinoma JOURNAL OF INVESTIGATIVE DERMATOLOGY Asgari, M. M., Tang, J., Warton, M. E., Chren, M., Quesenberry, C. P., Bikle, D., Horst, R. L., Orentreich, N., Vogelman, J. H., Friedman, G. D. 2010; 130 (5): 1438-1443

    Abstract

    We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and basal cell carcinoma (BCC) risk in a nested case-control study at Kaiser Permanente Northern California (KPNC). A total of 220 case patients with BCC diagnosed after serum collection were matched to 220 control subjects. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression. Fully adjusted models included body mass index (BMI), smoking, education, sun-exposure variables, X-ray exposure, and personal history of cancer. For each measure of serum 25(OH)D (continuous, clinically relevant tertiles, quintiles), we found an increased risk of BCC in unadjusted models (OR=1.03, 95% CI 1.00-1.05, P<0.05; OR=3.98, 95% CI: 1.31-12.31, deficient vs. sufficient, test for trend P-value <0.01; OR=2.32, 95% CI: 1.20-4.50, 1st vs. 5th quintile, test for trend P-value 0.03). In fully adjusted models, the values attenuated slightly (OR=1.02, 95% CI 1.00-1.05, P<0.05; OR=3.61, 95% CI: 1.00-13.10, deficient vs. sufficient, t-trend P=0.03; OR=2.09 1st vs. 5th quintile, 95% CI: 0.95-4.58, t-trend P=0.11). Our findings suggest that higher prediagnostic serum 25(OH)D levels may be associated with increased risk of subsequent BCC. Further studies to evaluate the effect of sun exposure on BCC and serum 25(OH)D levels may be warranted.

    View details for DOI 10.1038/jid.2009.402

    View details for Web of Science ID 000276972300031

    View details for PubMedID 20043012

  • Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth CANCER CELL Kim, J., Tang, J. Y., Gong, R., Kim, J., Lee, J. J., Clemons, K. V., Chong, C. R., Chang, K. S., Fereshteh, M., Gardner, D., Reya, T., Liu, J. O., Epstein, E. H., Stevens, D. A., Beachy, P. A. 2010; 17 (4): 388-399

    Abstract

    In a screen of drugs previously tested in humans we identified itraconazole, a systemic antifungal, as a potent antagonist of the Hedgehog (Hh) signaling pathway that acts by a mechanism distinct from its inhibitory effect on fungal sterol biosynthesis. Systemically administered itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model and does so at serum levels comparable to those in patients undergoing antifungal therapy. Mechanistically, itraconazole appears to act on the essential Hh pathway component Smoothened (SMO) by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation.

    View details for DOI 10.1016/j.ccr.2010.02.027

    View details for Web of Science ID 000276879700010

    View details for PubMedID 20385363

  • Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men CANCER CAUSES & CONTROL Tang, J. Y., Parimi, N., Wu, A., Boscardin, W. J., Shikany, J. M., Chren, M., Cummings, S. R., Epstein, E. H., Bauer, D. C. 2010; 21 (3): 387-391

    Abstract

    To determine the relationship between 25(OH) vitamin D levels and non-melanoma skin cancer (NMSC), we performed a nested case-control study in ambulatory, elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study. Health habit and medical history, including self-reported history of NMSC were recorded and 25(OH)D levels were measured on serum collected at baseline from a random sample of Caucasian MrOS subjects. Mean age (73 +/- 5), BMI, daily vitamin D and calcium intake were similar in the men with (n = 178) and without NMSC (n = 930), but higher levels of 25(OH)D were associated with a decreased risk of having a history of NMSC (P(trend) = 0.04). Men in the highest quintile of 25(OH)D (>30 ng/mL) had 47% lower odds of NMSC (95% CI: 0.30-0.93, p = 0.026) compared to those in the lowest quintile. Our results suggest that a diagnosis of NMSC is not a surrogate for adequate 25(OH)D levels or increased UV exposure, and high 25(OH)D levels may be associated with a reduced risk of NMSC.

    View details for DOI 10.1007/s10552-009-9470-4

    View details for Web of Science ID 000275921300006

    View details for PubMedID 19921445

  • Medical Management of Advanced or Metastatic Basal Cell Carcinomas AccessMedicine from McGraw-Hill Jean Y Tang, Ervin H. Epstein 2010
  • Basal Cell Carcinoma Chemoprevention with Nonsteroidal Anti-inflammatory Drugs in Genetically Predisposed PTCH1(+/-) Humans and Mice CANCER PREVENTION RESEARCH Tang, J. Y., Aszterbaum, M., Athar, M., Barsanti, F., Cappola, C., Estevez, N., Hebert, J., Hwang, J., Khaimskiy, Y., Kim, A., Lu, Y., So, P., Tang, X., Kohn, M. A., McCulloch, C. E., Kopelovich, L., Bickers, D. R., Epstein, E. H. 2010; 3 (1): 25-34

    Abstract

    In vitro and epidemiologic studies favor the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) in preventing skin squamous photocarcinogenesis, but there has been relatively little study of their efficacy in preventing the more common skin basal cell carcinoma (BCC) carcinogenesis. We first compared the relative anti-BCC effects of genetic deletion and NSAID pharmacologic inhibition of cyclooxygenase (COX) enzymes in the skin of Ptch1(+/-) mice. We then assessed the effects of celecoxib on the development of BCCs in a 3-year, double-blinded, randomized clinical trial in 60 (PTCH1(+/-)) patients with the basal cell nevus syndrome. In Ptch1(+/-) mice, genetic deletion of COX1 or COX2 robustly decreased (75%; P < 0.05) microscopic BCC tumor burden, but pharmacologic inhibition with celecoxib reduced microscopic BCCs less efficaciously (35%; P < 0.05). In the human trial, we detected a trend for oral celecoxib reducing BCC burden in all subjects (P = 0.069). Considering only the 60% of patients with less severe disease (<15 BCCs at study entry), celecoxib significantly reduced BCC number and burden: subjects receiving placebo had a 50% increase in BCC burden per year, whereas subjects in the celecoxib group had a 20% increase (P(difference) = 0.024). Oral celecoxib treatment inhibited BCC carcinogenesis in PTCH1(+/-) mice and had a significant anti-BCC effect in humans with less severe disease.

    View details for DOI 10.1158/1940-6207.CAPR-09-0200

    View details for Web of Science ID 000273295500006

    View details for PubMedID 20051370

  • Statin use and risk of basal cell carcinoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Asgari, M. A., Tang, J., Epstein, E. H., Chren, M., Warton, E. M., Quesenberry, C. P., Go, A. S., Friedman, G. D. 2009; 61 (1): 66-72

    Abstract

    We examined the association between statin use and basal cell carcinoma (BCC) risk.We identified all members of a large integrated health care delivery system with a diagnosis of a histologically proven BCC in 1997. Subsequent BCCs were identified through 2006 from health plan electronic pathology records. Longitudinal exposure to statins and other lipid-lowering agents was determined from automated pharmacy records. We used extended Cox regression to examine the independent association between receipt of statin therapy (ever vs never, cumulative duration) and risk of subsequent BCC. To minimize confounding by indication, we conducted sensitivity analyses in the subset of individuals considered eligible for lipid-lowering therapy based on national guidelines.Among 12,123 members given a diagnosis of BCC who had no prior statin exposure, 6381 developed a subsequent BCC during follow-up. Neither "ever use of statins" (adjusted hazard ratio 1.02, 95% confidence interval: 0.92-1.12) or cumulative duration of statin (adjusted hazard ratio 1.02/year, 95% confidence interval: 0.99-1.11) was associated with subsequent BCC after adjustment for age, sex, and health care use. Risk estimates did not change appreciably when the analysis was limited to the subset of individuals who met eligibility criteria for initiating statin therapy. There was also no significant association between use of non-statin antilipemics and subsequent BCC (adjusted hazard ratio 1.10, 95% confidence interval: 0.76-1.58).No information was available for BCC risk factors, such as sun sensitivity and sun exposure.Among a large cohort of individuals with BCC, statin therapy was not significantly associated with risk of subsequent BCC.

    View details for DOI 10.1016/j.jaad.2009.02.011

    View details for Web of Science ID 000267325000010

    View details for PubMedID 19464071

  • Novel Hedgehog pathway targets against basal cell carcinoma TOXICOLOGY AND APPLIED PHARMACOLOGY Tang, J. Y., So, P., Epstein, E. H. 2007; 224 (3): 257-264

    Abstract

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence.

    View details for DOI 10.1016/j.taap.2006.12.011

    View details for Web of Science ID 000250639300008

    View details for PubMedID 17276471

  • Xeroderma pigmentosum group C in an isolated region of Guatemala JOURNAL OF INVESTIGATIVE DERMATOLOGY Cleaver, J. E., Feeney, L., Tang, J. Y., Tuttle, P. 2007; 127 (2): 493-496

    View details for DOI 10.1038/sj.jid.5700555

    View details for Web of Science ID 000243732600037

    View details for PubMedID 16990803

  • Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rieger, K. E., Hong, W. J., Tusher, V. G., Tang, J., Tibshirani, R., Chu, G. 2004; 101 (17): 6635-6640

    Abstract

    Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity. The analysis used heterogeneity-associated transformation of the data to account for a clinical outcome arising from more than one underlying cause. To compute the risk of toxicity for each patient, we applied nearest shrunken centroids, a method that identifies and cross-validates predictive genes. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of 14 patients with no false positives among 43 controls (P = 2.2 x 10(-7)). The responses of these nine patients displayed significant heterogeneity. Of the five patients with toxicity and normal responses, two were treated with protocols that proved to be highly toxic. These results may enable physicians to predict toxicity and tailor treatment for individual patients.

    View details for DOI 10.1073/pnas.0307761101

    View details for Web of Science ID 000221107900056

    View details for PubMedID 15096622

  • Interaction between UV-damaged DNA binding activity proteins and the c-Abl tyrosine kinase JOURNAL OF BIOLOGICAL CHEMISTRY Cong, F., Tang, J., Hwang, B. J., Vuong, B. Q., Chu, G., Goff, S. P. 2002; 277 (38): 34870-34878

    Abstract

    The c-Abl tyrosine kinase is activated by some forms of DNA damage, including ionizing radiation, but not UV radiation. The functions of this activation in the damage response pathways remain obscure. To identify potential targets of c-Abl kinase, we utilized the yeast two-hybrid system to screen a murine cDNA library. One c-Abl binding protein of particular interest was the large subunit (DDB1) of the heterodimeric complex with UV-damaged DNA binding activity (UV-DDB). This complex binds with high specificity to DNA damaged by UV, is absent in a subset of xeroderma pigmentosum group E cells, and is required for global genomic repair of UV-induced damage. The association of c-Abl with DDB1 required the kinase domain of c-Abl and preserved the interaction between DDB1 and the small subunit (DDB2) of the UV-DDB complex. Significantly, overexpression of c-Abl increased tyrosine phosphorylation of DDB2 and suppressed UV-DDB activity. Conversely, a dominant negative, kinase-deficient allele of c-Abl decreased tyrosine phosphorylation of DDB2 and dramatically stimulated UV-DDB activity. These results suggest that one role of c-Abl may be to negatively regulate UV-DDB activity by phosphorylation of DDB2.

    View details for DOI 10.1074/jbc.M204416200

    View details for Web of Science ID 000178117000029

    View details for PubMedID 12107171

  • Xeroderma pigmentosum complementation group E and UV-damaged DNA-binding protein DNA REPAIR Tang, J., Chu, G. 2002; 1 (8): 601-616

    Abstract

    UV-damaged DNA-binding protein (UV-DDB) is composed of two subunits, DDB1 (p127) and DDB2 (p48). Mutations in the DDB2 gene inactivate UV-DDB in individuals from complementation group E of xeroderma pigmentosum (XP-E), an autosomal recessive disease characterized by sun sensitivity, severe risk for skin cancer and defective nucleotide excision repair. UV-DDB is also deficient in many rodent tissues, exposing a shortcoming in rodent models for cancer. In vitro, UV-DDB binds to cyclobutane pyrimidine dimers (CPDs), 6-4 photoproducts and other DNA lesions, stimulating the excision of CPDs, and to a lesser extent, of 6-4 photoproducts. In vivo, UV-DDB plays an important role in the p53-dependent response of mammalian cells to DNA damage. When cells are exposed to UV, the resulting accumulation of p53 activates DDB2 transcription, which leads to increased levels of UV-DDB. Binding of UV-DDB to CPDs targets these lesions for global genomic repair, suppressing mutations without affecting UV survival. Apparently, cells are able to survive with unrepaired CPDs because of the activity of bypass DNA polymerases. Finally, there is evidence that UV-DDB may have roles in the cell that are distinct from DNA repair.

    View details for Web of Science ID 000178248700002

    View details for PubMedID 12509284

  • Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis MOLECULAR CELL Tang, J. Y., Hwang, B. J., Ford, J. M., Hanawalt, P. C., Chu, G. 2000; 5 (4): 737-744

    Abstract

    UV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma pigmentosum group E individuals due to mutation of the p48 gene, but its role in DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamster cells, and enhanced removal of cyclobutane pyrimidine dimers (CPDs) from genomic DNA and from the nontranscribed strand of an expressed gene. Expression of p48 suppressed UV-induced mutations arising from the nontranscribed strand, but had no effect on cellular UV sensitivity. These results define the role of p48 in DNA repair, demonstrate the importance of CPDs in mutagenesis, and suggest how rodent models can be improved to better reflect cancer susceptibility in humans.

    View details for Web of Science ID 000086790000014

    View details for PubMedID 10882109

  • INHIBITION OF LECITHIN-CHOLESTEROL ACYLTRANSFERASE AND MODIFICATION OF HDL APOLIPOPROTEINS BY ALDEHYDES ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY McCall, M., Tang, J. Y., Bielicki, J. K., Forte, T. M. 1995; 15 (10): 1599-1606

    Abstract

    Experimental evidence suggests that aldehydes generated as a consequence of lipid peroxidation may be involved in the pathogenesis of atherosclerosis. It is well documented that aldehydes modify LDL: however, less is known concerning the effects of aldehydes on other plasma and interstitial fluid components. In the present study, we investigated the effects of five physiologically relevant aldehydes (acetaldehyde, acrolein, hexanal, 4-hydroxynonenal [HNE], and malondialdehyde [MDA]) on two key constituents of the antiatherogenic reverse cholesterol transport pathway, lecithin-cholesterol acyltransferase (LCAT) and HDL. Human plasma was incubated for 3 hours at 37 degrees C with each one of the five aldehydes at concentrations ranging from 0.16 to 84 mmol/L. Dose-dependent decreases in LCAT activity were observed. The short-chain (acrolein) and long-chain (HNE) alpha,beta-unsaturated aldehydes were the most effective LCAT inhibitors. Micromolar concentrations of these unsaturated aldehydes resulted in significant reductions in plasma LCAT activity. The short- and longer-chain saturated aldehydes acetaldehyde and hexanal and the dialdehyde MDA were considerably less effective at inhibiting LCAT than were acrolein and HNE. In addition to inhibiting LCAT, aldehydes increased HDL electrophoretic mobility and cross-linked HDL apolipoproteins. Cross-linking of apolipoproteins A-I and A-II required higher aldehyde concentrations than inhibition of LCAT. The alpha,beta-unsaturated aldehydes acrolein and HNE were fourfold to eightfold more effective cross-linkers of apolipoproteins A-I and A-II than the other aldehydes studied. These data suggest that products of lipid peroxidation, especially unsaturated aldehydes, may interfere with normal HDL cholesterol transport by inhibiting LCAT and modifying HDL apolipoproteins.

    View details for Web of Science ID A1995RZ86500010

    View details for PubMedID 7583533

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