Skin cancers are the most common malignancies in humans and have become a major health problem, particularly in the Southwestern region of the United States. More than 600,000 basal and squamous cell skin cancers, and approximately 32,000 melanomas were diagnosed in the United States in 1991. The near epidemic rates of skin cancer Incidence are expected to increase even more dramatically In the mid-1990s due to the accelerated loss of ozone from the earth's outer atmosphere. According to NASA officials the levels of chlorine monoxide are high enough to destroy ozone in the Northern hemisphere at the rate of 1-2% per day during late winter 1992, leading to depletion of the Northern ozone layer by 30-40%. Estimates released last february (1992) by the United Nations Environment Program predict a 26% rise in the incidence of non-melanoma skin cancers worldwide if the overall ozone levels drop 10%. Even though the mortality rate from basal cell and squamous cell skin cancers is relatively low, they are the source of considerable morbidity and rapidly Increasing health care costs. Additionally, melanoma prognosis continues to be poor with mortality rates increasing yearly. Because of the extreme Importance of these public health problems in Arizona, we have selected as our overall objective to examine the mechanisms of skin carcinogenesis and develop effective chemoprevention strategies for melanoma and non-melanoma skin cancer. Using specialized research projects, various chemopreventive strategies are being tested In order to design and optimize laboratory-based clinical trials in patients with actinic keratoses and resected squamous and basal cell skin cancers. This integrated approach to patients with established and precancerous skin lesions has led to the structure of this Program Project which utilizes novel intermediate markers of skin cancer risk (e.g., bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) labeling Indices, mutant Ha-ras gene and p53 gene copy numbers, PGE2 and polyamines in actinic keratoses and tissue fatty acids), unique chemopreventive agents (e.g., human melanotropin analogs, epigallocatechin gal late or green tea and topically administered agents such as DFMO and moderately high doses of retinyl palmitate), and Innovative biostatistically-based clinical trial designs. The Program Project includes: * Three basic science projects which evaluate immunologic, oxidative and genetic mechanisms of skin carcinogenesis. * An epidemiology project which examines unique prognostic factors combined with the extent of UV-B exposure and utilizes up-to-date biologic and chemical marker endpoints. * Three clinical projects which evaluate primary, secondary and tertiary chemopreventive strategies in normal subjects and patients with actinic keratosis and resected non-melanoma skin cancers.
| Blohm-Mangone, Karen; Burkett, Nichole B; Tahsin, Shekha et al. (2018) Pharmacological TLR4 Antagonism Using Topical Resatorvid Blocks Solar UV-Induced Skin Tumorigenesis in SKH-1 Mice. Cancer Prev Res (Phila) 11:265-278 |
| Knights-Mitchell, Shellie S; Romanowski, Marek (2018) Near-Infrared Activated Release of Doxorubicin from Plasmon Resonant Liposomes. Nanotheranostics 2:295-305 |
| Roh, Eunmiri; Lee, Mee-Hyun; Zykova, Tatyana A et al. (2018) Targeting PRPK and TOPK for skin cancer prevention and therapy. Oncogene 37:5633-5647 |
| Chen, Yin; Vasquez, Monica M; Zhu, Lingxiang et al. (2017) Effects of Retinoids on Augmentation of Club Cell Secretory Protein. Am J Respir Crit Care Med 196:928-931 |
| Yamamoto, Hiroyuki; Ryu, Joohyun; Min, Eli et al. (2017) TRAF1 Is Critical for DMBA/Solar UVR-Induced Skin Carcinogenesis. J Invest Dermatol 137:1322-1332 |
| Zykova, Tatyana A; Zhu, Feng; Wang, Lei et al. (2017) The T-LAK Cell-originated Protein Kinase Signal Pathway Promotes Colorectal Cancer Metastasis. EBioMedicine 18:73-82 |
| Einspahr, Janine G; Curiel-Lewandrowski, Clara; Calvert, Valerie S et al. (2017) Protein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light. NPJ Precis Oncol 1: |
| Gao, Ge; Zhang, Tianshun; Wang, Qiushi et al. (2017) ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK. Mol Cancer Ther 16:1843-1854 |
| Glazer, Evan S; Bartels, Peter H; Lian, Fangru et al. (2016) Quantitative histopathology identifies patients with thin melanomas who are at risk for metastases. Melanoma Res 26:261-6 |
| Franklin, Stephen J; Younis, Usir S; Myrdal, Paul B (2016) Estimating the Aqueous Solubility of Pharmaceutical Hydrates. J Pharm Sci 105:1914-1919 |
Showing the most recent 10 out of 395 publications
