Human papillomavirus in HIV associated lung cancers
HIV相关肺癌中的人乳头瘤病毒
基本信息
- 批准号:10361530
- 负责人:
- 金额:$ 35.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AIDS related cancerAcquired Immunodeficiency SyndromeAffectAttenuatedBiological ModelsCancer EtiologyCancer PatientCancer cell lineCause of DeathCell Culture TechniquesCellsCessation of lifeClinicalData SetDevelopmentDiseaseDisease ManagementEpithelial CellsEstrogen AntagonistsEstrogen Receptor alphaEstrogensEtiologyExhibitsFeedbackFutureGene ExpressionGeneral PopulationGenetic TranscriptionGenomicsGoalsGrowthHIVHPV-High RiskHighly Active Antiretroviral TherapyHuman CloningHuman Papilloma Virus VaccinationHuman PapillomavirusHuman papilloma virus infectionHuman papillomavirus 16Immune EvasionIncidenceIndividualInformaticsKaposi SarcomaLungMalignant NeoplasmsMalignant neoplasm of cervix uteriMalignant neoplasm of lungMediatingMethodsMicrobeMonitorNon-Hodgkin&aposs LymphomaOncogenesOncogenicOncoproteinsPatient CarePatientsPersonsPhenotypePopulationRegimenResearchRisk FactorsRoleSamplingSensitivity and SpecificitySignal TransductionSmokingSmoking StatusTechnologyTestingTherapeuticTimeTranscriptViralViral OncogeneVirus IntegrationWorkbasecancer riskcircular RNAgene producthuman papilloma virus oncogeneimprovedknock-downlung cancer celllung carcinogenesismalignant phenotypenext generation sequencingnovelpathogenpersonalized medicinepreventsextranscriptometranscriptome sequencingtumortumor-immune system interactionstumorigenesis
项目摘要
SUMMARY
In recent years, the incidence of AIDS-defining cancers has dramatically decreased due to the HAART therapy.
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 HIV(+) population. Although smoking is a key risk factor for HIV associated LCs, HIV(+)
individuals still have a 3-fold increased LC risk after controlling for smoking status, indicating that other factors
are responsible for this increased incidence. Unlike other common HIV associated cancers such as cervical
cancer, non-Hodgkin's lymphoma, and Kaposi's sarcoma, HIV associated LCs do not have a known viral
etiology. To discover any potential oncopathogen for HIV associated LCs, we have utilized our Next-
Generation-Sequencing-based PARSES pipeline to interrogate more than 1,000 LC RNA-seq data sets. We
discovered that human papillomavirus (HPV) is causally associated with LCs in the HIV(+) population. The
overarching goal of this proposal is to determine the involvement of HPV in HIV associated LCs using our well-
established sequencing based informatics approaches as well as newly created HPV(+) HIV associated LC
model systems. We will first examine the hypothesis that there is a causal association between HPV and LCs
in the HIV(+) population but not in the general population. In addition, we will test the hypothesis that HPV
promotes lung oncogenesis by enhancing the estrogen-mediated growth signaling and expressing viral
E5/E6/E7/hpv-circ-880-408 oncogenes in the HIV(+) individuals. We will elucidate the critical roles of HPV
oncogene products including a novel viral circular RNA and estrogen-mediated growth signaling and immune-
evasion in HIV associated lung carcinogenesis. We will simultaneously examine an important concept of being
able to precisely treat HPV(+) HIV associated LCs with anti-estrogen and/or anti-HPV regimens in the era of
personalized medicine. Further, by determining the HPV etiology, our work may help prevent LCs by promoting
HPV vaccination for both sexes. Together, completion of the research will add conceptually to our
understanding of HIV associated LCs and provide potentially unique therapeutic opportunities and ultimately
benefit a subset of HIV(+) LC patients.
总结
近年来,由于HAART治疗,艾滋病定义癌症的发病率急剧下降。
相比之下,非艾滋病定义的癌症(NADC),特别是肺癌(LC)的发病率上升了2.5%。
超过3倍。在美国,LC已成为最常见的NADC,发病率为204例/
十万人年LC也是NADC最常见的死亡原因,占癌症的21%-
艾滋病毒(+)感染者的死亡率。虽然吸烟是HIV相关LC的一个关键风险因素,但HIV(+)
在控制吸烟状况后,个体的LC风险仍增加3倍,表明其他因素
是导致发病率上升的原因与其他常见的艾滋病毒相关癌症(如宫颈癌)不同,
癌症、非霍奇金淋巴瘤和卡波西肉瘤,HIV相关LC没有已知的病毒
病因学为了发现HIV相关LC的任何潜在肿瘤病原体,我们利用了我们的Next-
基于代测序的PARSES管道可询问1,000多个LC RNA-seq数据集。我们
发现人乳头瘤病毒(HPV)与HIV(+)人群中的LC存在因果关系。的
该提案的总体目标是使用我们的良好-
已建立的基于测序的信息学方法以及新创建的HPV(+)HIV相关LC
模型系统我们将首先检验HPV和LC之间存在因果关系的假设
在HIV(+)人群中,但在一般人群中没有。此外,我们还将检验HPV
通过增强雌激素介导的生长信号和表达病毒来促进肺癌发生
HIV(+)个体中E5/E6/E7/hpv-circ-880-408癌基因。我们将阐明HPV的关键作用,
癌基因产物,包括一种新的病毒环状RNA和雌激素介导的生长信号和免疫-
HIV相关肺癌发生中的逃避。我们将同时考察存在的一个重要概念
能够用抗雌激素和/或抗HPV方案精确治疗HPV(+)HIV相关LC,
个性化医疗此外,通过确定HPV病因,我们的工作可能有助于通过促进
HPV疫苗对男女都适用。总之,研究的完成将在概念上增加我们的
了解HIV相关LC,并提供潜在的独特治疗机会,
使HIV(+)LC患者亚组受益。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Zhen Lin', 18)}}的其他基金
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 - 财政年份:2022
- 资助金额:
$ 35.24万 - 项目类别:
Human papillomavirus in HIV associated lung cancers
HIV相关肺癌中的人乳头瘤病毒
- 批准号:
10577760 - 财政年份:2021
- 资助金额:
$ 35.24万 - 项目类别:
Human papillomavirus in HIV associated lung cancers
HIV相关肺癌中的人乳头瘤病毒
- 批准号:
10253590 - 财政年份:2021
- 资助金额:
$ 35.24万 - 项目类别:
Project 3-Human papillomavirus in HIV associated lung cancers
项目3-人类乳头瘤病毒在HIV相关肺癌中的作用
- 批准号:
10223350 - 财政年份:2020
- 资助金额:
$ 35.24万 - 项目类别:
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通过风险评估保护基因隐私
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通过风险评估保护基因隐私
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7287366 - 财政年份:2006
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项目3-人类乳头瘤病毒在HIV相关肺癌中的作用
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