TREATMENT AND MOLECULAR ANALYSIS OF ATYPICAL NEVI

描述：(改编自调查人员的摘要)总体 这项建议的目标是确定系统治疗是否有 生物制剂干扰素A2a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先兆和风险标记物。 在家族性黑色素瘤的背景下，不典型痣的存在是 与70岁前患上原发黑色素瘤的风险几乎100%相关。 同样，在散发性黑色素瘤的情况下，40%-60%的黑色素瘤会发生 来自先前存在的非典型痣。此外，有临床症状的患者 原发性黑色素瘤病史和两个或两个以上不典型痣的比例为8倍。 罹患第二种原发黑色素瘤的风险更大。因此，鉴于 黑色素瘤发病率和死亡率的上升，不仅势在必行 寻找并实施有助于治愈患者的策略 转移性疾病还能防止非典型痣的进展 恶性黑素瘤。我们最近证明了直接的基因打靶 碱性成纤维细胞生长因子/FGFR-1在人黑色素瘤中引起生长停滞和消退 黑色素瘤增殖受阻和肿瘤内血管生成受阻。 此外，我们还记录了这两个基因在皮肤中的表达。 非典型痣的嗜中性粒细胞和间质隔膜。最近的结果 临床试验提供的证据表明，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为 高危黑色素瘤辅助治疗的第一剂。虽然IFNA是 已知是一种有效的抗病毒、抗增殖和免疫调节 代理，最近的研究表明，IFNA还发挥着强大的 通过阻断碱性成纤维细胞生长因子的mRNA和蛋白抑制血管生成 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 小剂量IFNA-2a全身治疗可调节皮损 有黑色素瘤临床病史和多发性不典型痣的患者。

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.