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， 预计还会进一步增加。 其中一小部分基础和 皮肤的鳞状细胞癌表现出侵袭性表型， 特征为多发性复发，大小超过2 cm， 肌肉、软骨、骨或神经，或淋巴结转移。 的状态 德克萨斯州皮肤癌发病率高，死亡率也异常高 关于NMSC 由于其地理位置和转诊模式， 德克萨斯大学M. D.安德森癌症中心治疗了大量的 非常积极的NMSC;事实上，大约100个新的NMSC中有近一半 头颈部每年出现的皮肤癌病例 外科手术表现出攻击性行为，并且难以通过外科手术控制 和辐射。 在减少儿童死亡率和发病率方面取得的进展 NMSC需要三管齐下的方法;病原学和 导致皮肤癌诱发的遗传因素; 与皮肤癌相关的宿主和肿瘤特征 发展新的方法来治疗高度 攻击性NMSC。 因此，本方案的具体目标是：（1） 了解导致皮肤癌的分子事件 （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 NMSC进展的各种机制;（4）降低发病率， 提高侵袭性皮肤病患者的生活质量 癌 这些目标将由16名关键项目研究人员在实验室完成 p53在紫外线致癌作用中的作用， 免疫抑制（项目1）;皮肤癌细胞凋亡调控 发育（项目2）;皮肤中的DNA修复和染色体不稳定性 癌症（项目3）;以及侵袭性皮肤癌的辅助生物疗法 与13-顺式视黄酸和干扰素-α（项目5）。 这些研究 将由专门收集 临床、病理、分子和流行病学数据， 临床样本的采购、维护、处理和分发 生物统计分析和实验室与临床的整合 数据 这些努力将得到16名合作者/共同调查员的支持 8名项目顾问。 该计划将提供以下信息： NMSC的病因学、生物学、发病机制和诱导机制 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.