As part of this program project, we have carried out clinical trials using retinoids in human cancers and detected and reported significant activity in mycosis fungoides and advanced squamous/basal cancer of the skin. In addition responses have been observed in head and neck cancer, myelodysplastic syndromes and melanoma. We have also conducted trials in premalignant lesions of the skin and oral cavity. Owing to the potential significance to cancer prevention of treatments capable of reversing preneoplastic lesions, we plan to focus our current efforts in this area. We will expand on the promising results of our previous trial using beta- carotene for the treatment of oral leukoplakia conducted as a part of this program project. In addition, we will develop and evaluate a topical formulation of alpha-difluoramethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, in a phase I trial in actinic keratosis. DFMO is of considerable interest as a prevention agent. However, for skin cancer prevention, a topical preparation would be of immense value for clinical study and use, since it would obviate the need for and toxicity associated with systemic use of this compound. The phase I study will be followed by a randomized, placebo-controlled phase II trial comparing topical DFMO with trans-retinoic acid (Retin-A) in this disease. Although a proposal is not included in this grant, we hope to be able to undertake future studies with topical DFMO in other premalignant lesions of the skin, e.g. dysplastic nevus syndrome. The clinical trials project has enhanced considerably our knowledge of the role of retinoids and carotenoids in preneoplastic and neoplastic conditions and the current proposal will deepen and expand that effort particularly in the area of oral preneoplasia. The leukoplakia study proposed will provide the basis for use of beta-carotene in this disease and the prevention of head and neck cancer. The actinic keratosis study will result in a topical, therefore, less toxic and more acceptable, preparation of DFMO suitable for clinical study in this disease and available for testing in other conditions.
| 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 |
| 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 |
| 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 |
| 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 |
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