Vitamin D in viral associated lung cancers

总结 近年来，艾滋病定义癌症的发病率急剧下降，这是由于高活性的 抗逆转录病毒疗法（HAART）。与此相反，非艾滋病定义癌症（NADC）的发病率，特别是 肺癌（LC）的发病率上升了3倍多。在美国，LC已成为最常见的NADC， 发病率为每10万人年204例。LC也是NADC最常见的死亡原因， 在人类免疫缺陷病毒（HIV）感染人群中，占癌症相关死亡的21%。 因此，了解这种致命疾病的潜在机制并开发 更有效的治疗策略。与其他常见的艾滋病毒相关癌症如宫颈癌不同， 非霍奇金淋巴瘤和卡波西肉瘤，HIV相关的LC没有确定的病毒 病因学我们的母研究R 01（R 01 CA 261258）显示，人乳头瘤病毒（HPV）与 与HIV（+）人群中的LC相关，这在概念上增加了我们对HIV相关LC的理解， 提供了潜在的独特治疗机会。根据双方的初步证据， 根据已发表的文献和我们新的实验数据，我们现在假设维生素D（VitD）作为一种重要的 膳食营养素在HIV（+）人群的肺癌发生中起着关键作用。本行政 补充，我们建议调查维生素D的抗肿瘤作用和治疗HIV相关的潜力， LC使用我们独特的动物模型系统。我们将研究一个重要的概念， HIV/HAART引起的VitD不足/缺乏通过膳食补充VitD可改善预后 HIV/HPV相关的LC。成功完成补充工作可以大大提高 通过进一步阐明这种致命疾病的潜在机制并最终受益于亲本R 01研究 许多HIV相关的LC患者。

SUMMARY In recent years, the incidence of AIDS-defining cancers has dramatically decreased due to the highly active antiretroviral therapy (HAART). In contrast, the incidence of the non-AIDS-defining cancers (NADC), especially lung cancer (LC) has risen by more than 3 fold. In the U.S., LC has become the most common NADC with an incidence rate of 204 cases per 100,000 person-years. LC is also the most common NADC cause of death and accounts for 21% of cancer-related death in the human immunodeficiency virus (HIV)-infected population. Thus, there is an unmet need to understand the underlying mechanism of this deadly disease and develop more effective therapeutic strategy. Unlike other common HIV associated cancers such as cervical cancer, non-Hodgkin's lymphoma, and Kaposi's sarcoma, HIV associated LCs do not have an established viral etiology. Our parent R01 study (R01CA261258) shows that human papillomavirus (HPV) is causally associated with LCs in the HIV(+) population, which adds conceptually to our understanding of HIV associated LCs and provides potentially unique therapeutic opportunities. Based on strong preliminary evidence from both published literatures and our new experimental data, we now hypothesize that Vitamin D (VitD) as an important dietary nutrient plays a critical role in lung carcinogenesis in the HIV(+) population. In this administrative supplement, we propose to investigate VitD's anti-tumorigenic role and therapeutic potential for HIV associated LCs using our unique animal model system. We will examine an important concept of reversing the HIV/HAART-induced VitD insufficiency/deficiency by dietary VitD supplementation can improve the prognosis of HIV/HPV associated LCs. Successful completion of the supplement work can significantly enhance the parent R01 study by further elucidating the underlying mechanism of this lethal disease and ultimately benefit many HIV associated LC patients.