Vitamin D in viral associated lung cancers

维生素 D 在病毒相关肺癌中的作用

基本信息

批准号：
10604870
负责人：
Zhen Lin
金额：
$ 16.72万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10604870
关键词：
AIDS related cancer Acquired Immunodeficiency Syndrome Administrative Supplement Animal Cancer Model Animal Model Attenuated Biological Models Blood group antibody D Cancer Etiology Cancer Patient Cause of Death Cessation of life Data Development Dietary Supplementation Disease Etiology Goals HIV HIV Infections Highly Active Antiretroviral Therapy Human Papillomavirus Human papilloma virus infection Incidence Inflammation Inflammatory Interleukin-17 Kaposi Sarcoma Lead Link Literature Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of lung Malnutrition Non-Hodgkin&apos s Lymphoma Nutrient Parents Persons Play Population Production Prognosis Publishing Role Testing Therapeutic Viral Vitamin D Vitamin D Deficiency Vitamin D supplementation Vitamin Deficiency Work base cytokine dietary improved lung carcinogenesis novel prevent therapeutically effective tumor tumorigenic

AIDS related cancer Acquired Immunodeficiency Syndrome Administrative Supplement Animal Cancer Model Animal Model Attenuated Biological Models Blood group antibody D Cancer Etiology Cancer Patient Cause of Death Cessation of life Data Development Dietary Supplementation Disease Etiology Goals HIV HIV Infections Highly Active Antiretroviral Therapy Human Papillomavirus Human papilloma virus infection Incidence Inflammation Inflammatory Interleukin-17 Kaposi Sarcoma Lead Link Literature Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of lung Malnutrition Non-Hodgkin&apos s Lymphoma Nutrient Parents Persons Play Population Production Prognosis Publishing Role Testing Therapeutic Viral Vitamin D Vitamin D Deficiency Vitamin D supplementation Vitamin Deficiency Work base cytokine dietary improved lung carcinogenesis novel prevent therapeutically effective tumor tumorigenic

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项目摘要

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.

概括近年来，由于高度活跃，定义艾滋病癌症的发生率显着下降抗逆转录病毒疗法（HAART）。相反，非辅助定义癌症（NADC）的发生率，尤其是肺癌（LC）的增长超过3倍。在美国，LC已成为最常见的NADC 每100,000人年的发病率为204例。 LC也是最常见的NADC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，没有必要了解这种致命疾病的基本机制并发展更有效的治疗策略。与其他常见的HIV相关癌症（例如宫颈癌）不同，非霍奇金的淋巴瘤和Kaposi的肉瘤，HIV相关的LCS没有既定病毒病因。我们的家长R01研究（R01CA261258）表明人乳头瘤病毒（HPV）是有因果关系的艾滋病毒（+）人群中的LCS，从概念上增加了我们对艾滋病毒相关的LC和提供潜在独特的治疗机会。基于两者的强有力的初步证据已发表的文献和我们的新实验数据，我们现在假设维生素D（VITD）是重要的饮食营养素在HIV（+）种群中在肺癌发生中起关键作用。在此管理中补充说，我们建议研究VITD的抗肿瘤性作用和与HIV相关的治疗潜力 LCS使用我们独特的动物模型系统。我们将研究一个逆转的重要概念 HIV/HAART引起的VITD不足/缺乏饮食的VITD补充可以改善预后 HIV/HPV相关的LCS。成功完成补充工作可以显着增强父母R01研究通过进一步阐明这种致命疾病的基本机制，并最终受益许多HIV相关的LC患者。