This is a mid-career development award application for Madeleine Duvic, Professor of Medicine and Chief of Dermatology at the MD Anderson Cancer Center. It would support a new program in Cutaneous Oncology and enable her to mentor new Assistant Professors, fellows, residents, and medical students in the field. The applicant has an outstanding track record in conducting patient oriented clinical research and is a leader in developing new therapies for the treatment of Cutaneous T Cell Lymphomas (CTCL). There is an unwavering commitment to the conduct of patient oriented research and mentoring at all levels of career development. The award would free the applicant from half of her current clinical duties, allowing her to spend greater than 60 percent of her time on patient oriented translational retinoid research and mentoring activities. A Clinical Research curriculum, an oncology fellows seminar series, and institutional conferences will enhance further career development of the applicant and students. Two translational research projects are proposed using retinoids for cancer. 1] The loss of a novel class II tumor suppressor, Tazarotene Induced Gene 3 (TIG-3), will be investigated in the development and progression of non-melanoma skin cancers. The finding that TIG-3 is significantly decreased in aggressive versus non-aggressive skin cancer and in basal and squamous carcinomas, compared to paired normal skin will be examined in a larger set of samples and by sequencing cDNAs and by loss of heterozygosity studies. Oral Accutane adjuvant therapy for patients with aggressive tumors may be related to upregulation of TIG-3. 2] Development of molecular markers for Targretin, an experimental RXR selective retinoid, Targretin, will be assessed in the topical and oral treatment of CTCL. Targretin may restore expression of RAR and RXR receptors in epidermis, by altering cytokines and fostering apoptosis of the lymphocytic infiltrates. Patient's skin lesions before and after therapy will be studied using immunohistochemistry and in situ hybridization for retinoid receptors, cytokines, and fas/fas ligand. Genetic basis of large cell progression and gene expression following retinoid therapy will be explored using genomic display and will enhance the training in molecular biology. Understanding the biology of skin cancer and CTCL and the mechanism of novel therapeutic agents should result in the development of better and less toxic therapies for cancer. Young physicians and students who receive advanced training in the proper detection, prevention, and treatment of skin cancers will be a resource and may improve outcomes for patients of the future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24CA086815-04
Application #
6651972
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2000-08-14
Project End
2005-07-31
Budget Start
2003-08-08
Budget End
2004-07-31
Support Year
4
Fiscal Year
2003
Total Cost
$108,141
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Internal Medicine/Medicine
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Talpur, Rakhshandra; Sui, Dawen; Gangar, Pamela et al. (2016) Retrospective Analysis of Prognostic Factors in 187 Cases of Transformed Mycosis Fungoides. Clin Lymphoma Myeloma Leuk 16:49-56
Duvic, Madeleine; Tetzlaff, Michael T; Gangar, Pamela et al. (2015) Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. J Clin Oncol 33:3759-65
Litvinov, Ivan V; Tetzlaff, Michael T; Rahme, Elham et al. (2015) Identification of geographic clustering and regions spared by cutaneous T-cell lymphoma in Texas using 2 distinct cancer registries. Cancer 121:1993-2003
Talpur, Rakhshandra; Singh, Lotika; Daulat, Seema et al. (2012) Long-term outcomes of 1,263 patients with mycosis fungoides and Sézary syndrome from 1982 to 2009. Clin Cancer Res 18:5051-60
Barahmani, N; Lopez, A; Babu, D et al. (2010) Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy. Clin Exp Dermatol 35:409-16
Zhang, Chunlei; Li, Baoqiang; Zhang, Xiang et al. (2010) Curcumin selectively induces apoptosis in cutaneous T-cell lymphoma cell lines and patients' PBMCs: potential role for STAT-3 and NF-kappaB signaling. J Invest Dermatol 130:2110-9
Talpur, Rakhshandra; Vu, Jenny; Bassett, Roland et al. (2009) Phase I/II randomized bilateral half-head comparison of topical bexarotene 1% gel for alopecia areata. J Am Acad Dermatol 61:592.e1-9
Vidulich, Kelley A; Talpur, Rakhshandra; Bassett, Roland L et al. (2009) Overall survival in erythrodermic cutaneous T-cell lymphoma: an analysis of prognostic factors in a cohort of patients with erythrodermic cutaneous T-cell lymphoma. Int J Dermatol 48:243-52
Sun, Grace; Berthelot, Cindy; Li, Yafang et al. (2009) Poor prognosis in non-Caucasian patients with early-onset mycosis fungoides. J Am Acad Dermatol 60:231-5
Talpur, R; Bassett, R; Duvic, M (2008) Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sezary syndrome. Br J Dermatol 159:105-12

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