TREATMENT AND MOLECULAR ANALYSIS OF ATYPICAL NEVI

描述：（改编自研究者摘要）总体 该建议的目的是确定是否有系统治疗， 生物制剂干扰素α 2a，将调节分子， 非典型痣的免疫学、组织病理学和临床特征， 是恶性黑色素瘤的已知前体和风险标志物。 在家族性黑色素瘤的背景下，非典型痣的存在是 与70岁时发生原发性黑色素瘤的风险接近100%相关。 同样，在散发性黑色素瘤的情况下，40-60%的黑色素瘤发生于 已经存在的非典型痣 此外，患有临床 原发性黑色素瘤和两个或两个以上非典型痣的病史是 患第二原发性黑色素瘤的风险更大。 因此，根据 黑色素瘤的发病率和死亡率不断上升， 找到并实施有助于治愈患有 转移性疾病，而且还可以防止非典型痣的进展， 恶性黑素瘤 我们最近证明，直接基因靶向 bFGF/FGFR-1在人黑色素瘤中导致其生长停滞和消退， 这是黑色素瘤增殖和肿瘤内血管生成受阻的结果。 此外，我们记录了这两个基因在皮肤中的表达， 非典型痣的痣细胞和基质区室。 最近的结果 临床试验提供证据表明，IFNa具有显著的治疗作用， 对转移性黑色素瘤的影响，导致1995年FDA批准IFNa作为 第一个用于高危黑色素瘤辅助治疗的药物。 虽然IFNa是 已知是有效的抗病毒、抗增殖和免疫调节剂， 代理，最近的研究表明，IFNa也作为一个强大的功能， 阻断bFGF mRNA和蛋白的血管生成抑制剂 恶性肿瘤。 鉴于这些发现，我们建议确定 黑色素瘤前体的生物学、组织病理学和临床特征 病变可以通过用低剂量IFNa-2a全身治疗来调节， 有黑素瘤和多发性非典型痣临床病史的患者。

DESCRIPTION: (adapted from the investigator's abstract) The overall objective of this proposal is to determine whether systemic treatment with the biologic agent, interferon a2a, will modulate the molecular, immunologic, histopathologic, and clinical features of atypical nevi, which are the known precursors and risk markers of malignant melanoma. In the setting of familial melanoma, the presence of atypical nevi is associated with a nearly 100% risk of developing primary melanoma by age 70. Likewise, in the case of sporadic melanomas, between 40-60% of them develop from preexisting atypical nevi. Furthermore, patients with a clinical history of primary melanoma and two or more atypical nevi are at an 8-fold greater risk of developing a second primary melanoma. Thus, in light of the rising incidence and mortality rate of melanoma, it is not only imperative to find and implement strategies that will help cure patients with metastatic disease but also to prevent the progression of atypical nevi to malignant melanoma. We recently demonstrated that direct gene targeting of bFGF/FGFR-1 in human melanomas causes their growth arrest and regression as a result of blocked melanoma proliferation and intratumoral angiogenesis. In addition, we documented expression of these two genes in the dermal nevocytic and stromal compartments of atypical nevi. The results of recent clinical trials provided evidence that IFNa has a significant therapeutic impact on metastatic melanoma, leading in 1995 to an FDA approval of IFNa as the first agent for adjuvant therapy of high-risk melanoma. While IFNa is known to be a potent antiviral, antiproliferative and immunomodulating agent, recent studies have shown that IFNa also functions as a strong angiogenesis inhibitor by blocking bFGF mRNA and protein in human malignancies. Given these findings, we propose to determine whether the biological, histopathological and clinical features of melanoma precursor lesions can be modulated by systemic treatment with low-dose IFNa-2a in patients who have a clinical history of melanoma and multiple atypical nevi.