Vitamin D in viral associated lung cancers

摘要 近年来，由于艾滋病的高度活跃，定义为艾滋病的癌症的发病率大幅下降。 抗逆转录病毒疗法(HAART)。相比之下，非艾滋病定义癌症(NADC)的发病率，特别是 肺癌(LC)的发病率增加了3倍以上。在美国，LC已成为最常见的NADC，具有 发病率为每10万人年204例。LC也是NADC最常见的死亡原因和 占人类免疫缺陷病毒(HIV)感染人群癌症相关死亡的21%。 因此，有一种尚未得到满足的需求，即了解这种致命疾病的潜在机制并发展 更有效的治疗策略。与宫颈癌等其他常见的艾滋病毒相关癌症不同， 非霍奇金淋巴瘤和卡波西肉瘤，HIV相关LC没有既定的病毒 病因学。我们的母公司R01研究(R01CA261258)表明，人乳头瘤病毒(HPV)与 在HIV(+)人群中发现LCS，这从概念上增加了我们对HIV相关LCS和 提供潜在独特的治疗机会。基于来自两个国家的强有力的初步证据 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)是一种重要的 在HIV(+)人群中，饮食营养在肺癌的发生中起着关键作用。在这个管理部门中 补充，我们建议研究维生素D的抗肿瘤作用和治疗艾滋病毒相关的潜力 LCS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，即扭转 饮食补充维生素D可改善HIV/HAART所致维生素D不足/缺乏的预后 HIV/HPV相关LC。成功完成补充工作可大大提高 亲本R01研究通过进一步阐明这种致命疾病的潜在机制并最终受益 许多HIV相关性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.