BIOLOGY OF NONMELANOMA SKIN CANCER GROWTH & PROGRESSION

非黑色素瘤皮肤癌(NMSC)的发病率正在迅速增加，并且 预计还会有进一步的增长。一小部分基本的和 皮肤鳞状细胞癌表现出侵袭性表型， 特点是多次复发，大小超过2厘米，侵犯 肌肉、软骨、骨骼或神经或淋巴转移。国家的状况 德克萨斯州皮肤癌发病率高，死亡率高得异乎寻常 来自NMSC。由于其地理位置和转介模式， 德克萨斯大学医学博士安德森癌症中心治疗了大量 非常激进的NMSC；事实上，在大约100个新的 每年在头颈部就诊的皮肤癌病例 手术表现出攻击性行为，很难通过手术控制 和辐射。 在减少本病发病率、发病率和死亡率方面取得的进展 NMSC需要三管齐下；确定病因和 诱发皮肤癌的遗传因素.测定 皮肤癌的宿主和肿瘤特征 进展；以及开发新的治疗高度直肠癌的方法 积极进取的NMSC。因此，本计划的具体目标是：(1) 加深对导致皮肤癌的分子事件的理解 发展；(2)确定紫外线辐射在发展中的作用 NMSC，包括那些有攻击行为的人，(3)评估贡献 NMSC进展的各种机制；(4)减少发病率和 侵袭性皮肤患者的死亡率与生活质量的改善 癌症。 这些目标将由实验室中的16名关键计划调查人员来解决 P53在紫外线致癌中的作用及临床研究 免疫抑制(项目1)；皮肤癌细胞凋亡的调节 发展(项目2)；皮肤中的DNA修复和染色体不稳定 癌症(项目3)；侵袭性皮肤癌的辅助生物治疗 使用13-顺式维甲酸和干扰素-α(项目5)。这些研究 将由专门用于收集 临床、病理、分子和流行病学数据和 临床标本的采购、维护、加工和分发 以及生物统计分析和实验室与临床的结合 数据。这些努力将得到16名合作者/联合调查员的支持 和8个计划顾问。计划项目将提供有关以下方面的信息 神经间充质干细胞的病因、生物学、发病机制及诱导机制 并生成有价值的临床和流行病学数据库。

The incidence of non-melanoma skin cancer (NMSC) is increasing rapidly, and further increases are expected. A small proportion of these basal and squamous cell carcinomas of the skin exhibit an aggressive phenotype, characterized by multiple recurrences, size more then 2 cm, invasion of muscle, cartilage, bone, or nerves, or lymph node metastasis. The State of Texas has a high incidence of skin cancer and an unusually high death rate from NMSC. Because of its geographic location and referral patterns, the University of Texas M. D. Anderson Cancer Center treats a large number of highly aggressive NMSC; in fact, nearly half of the approximately 100 new cases of skin cancer seen annually in the Department of Head and Neck Surgery exhibit aggressive behavior and are difficult to control by surgery and radiation. Progress toward reducing the incidence of and morbidity and mortality from NMSC requires a 3-pronged approach; Identification of the etiologic and genetic factors that contribute to skin cancer induction; determination of the host and tumor characteristics associated with skin cancer progressions; and development of new approaches for the treatment of highly aggressive NMSC. The specific aims of this Program are therefore, to (1) develop an understanding of the molecular events leading to skin cancer development; (2) ascertain athe role of UV radiation in the development of NMSC, including those with aggressive behavior, (3) assess the contribution of various mechanisms to progression of NMSC; (4) reduce morbidity and mortality and improve the quality of life of patients with aggressive skin cancer. These goals will be addressed by 16 Key Program Investigators in laboratory and clinical investigations on the role of p53 in UV carcinogenesis and immunosuppression (Project 1); regulation of apoptosis in skin cancer development (Project 2); DNA repair and chromosome instability in skin cancers (Project 3); and adjuvant biotherapy of aggressive skin cancers with 13-cis retinoic acid and interferon-alpha (Project 5). These studies will be coordinated and supported by cores devoted to collection of clinical, pathological, molecular, and epidemiological data and procurement, maintenance, processing, and distribution of clinical samples and biostatistical analysis and integration of laboratory and clinical data. These efforts will be supported by 16 collaborators/co-investigators and 8 Program Advisors. The Program Project will provide information on the etiology, biology, pathogenesis, and mechanisms of induction of NMSC and generate valuable clinical and epidemiological databases.