Vitamin D in viral associated lung cancers

维生素 D 在病毒相关肺癌中的作用

• 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
• 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' 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

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，由于艾滋病的高度活跃，导致艾滋病的癌症发病率急剧下降。 抗逆转录病毒治疗（HAART）。相比之下，非艾滋病定义癌症（NADC）的发病率，尤其是 肺癌 (LC) 增加了 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 也是最常见的 NADC 死亡原因 占人类免疫缺陷病毒 (HIV) 感染人群中癌症相关死亡的 21%。 因此，了解这种致命疾病的根本机制并开发新的药物的需求尚未得到满足。 更有效的治疗策略。与其他常见的与艾滋病毒相关的癌症（例如宫颈癌）不同， 非霍奇金淋巴瘤和卡波西肉瘤、HIV 相关 LC 没有确定的病毒性 病因学。我们的母版 R01 研究 (R01CA261258) 显示人乳头瘤病毒 (HPV) 与 HIV（+）人群中的 LC，这从概念上增加了我们对 HIV 相关 LC 的理解 提供潜在独特的治疗机会。基于双方强有力的初步证据 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 膳食营养素在 HIV（+）人群的肺癌发生中起着至关重要的作用。在本行政 作为补充，我们建议研究 VitD 的抗肿瘤作用和 HIV 相关的治疗潜力 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：逆转 HIV/HAART 引起的 VitD 不足/缺乏通过饮食补充 VitD 可以改善预后 HIV/HPV 相关 LC 的数量。补充工作的顺利完成可以显着提高 母体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 相关的 LC 患者。