THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANT

蒂施癌症研究所 - 癌症中心支持拨款

基本信息

批准号：
10293870
负责人：
Ramon E Parsons
金额：
$ 25万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10293870
关键词：
Academic Medical Centers Access to Information Administrator Affect Award Bioinformatics Biometry Cancer Burden Cancer Center Support Grant Cancer Control Cancer Patient Cancer Research Project Caring Catchment Area Clinical Clinical Investigator Clinical Trials Communities Community Networks Development Disease Doctor of Philosophy Equipment Faculty Family Flow Cytometry Shared Resource Focus Groups Fostering Foundations Funding Health Personnel Human Immunologic Monitoring Incidence Individual Informatics Information Technology Infrastructure Institutes Leadership Malignant Neoplasms Microscopy Mission Morbidity - disease rate Neighborhoods New York City Pathology Patients Peer Review Pilot Projects Prevention Principal Investigator Protocols documentation Research Research Infrastructure Research Personnel Scientist Side Site Strategic Planning Students Training and Education Translating Translations United States National Institutes of Health Work anticancer research biobank biomedical data science cancer clinical trial cancer prevention cancer risk cancer therapy cancer type clinical investigation design early phase trial experience first responder improved improved outcome innovation medical schools meetings mortality mouse genetics next generation sequencing novel novel therapeutics population health prevent programs public health relevance screening training opportunity tumor immunology

项目摘要

Anal cancer causes significant morbidity as the second most common solid malignancy in People with HIV (PWH) with >2,000 new cases per year. Our data show that anal cancer incidence is rapidly growing in the US. This trend is even more pronounced in HIV infected men who have sex with men where the lifetime risk is 10% and is projected to increase despite advances in early detection and prevention. Anal Cancer is more prevalent in PWH above 50 years of age compared to those under 50. Prevention of anal cancer centers around identification and ablation of high-grade squamous intraepithelial lesions (HSIL), the immediate precursors of carcinoma. HSIL are highly aggressive in PWH, with 1% per year progressing to invasive carcinoma. Treatment efficacy is limited for PWH, however, as 50% of patients with treated HSIL will have high-grade lesions detected in the same anatomic quadrant. There are indications that treatment failure rates increase with age, but the data is limited and biomarkers for predicting treatment failure are needed and may be age dependent. Objective: The goal of this project is to understand whether age disparities are associated with HSIL aggressiveness and to identify biomarkers of aggressiveness. Specific Aims: (1) To determine the failure rate of treatment with increasing age; (2) and to determine the extent of clonality in anal high-grade squamous intraepithelial lesions (HSIL) across age groups and test the association of clonality with lesion aggressiveness in people with HIV. Study Design: We propose to study and sequence HSIL from a tissue bank of >2,000 specimens from an ethnically diverse cohort of PWH harboring HPV-associated HSIL. We will first determine the frequency of lesions found in the same anatomic quadrant after ablation in people above 50 years of age and those below 50. This will establish if treatment is failing with age and if it is correlated to the number of recurrent lesions. We will randomly select 200 HSIL unselected to outcome by age to use for the prediction of HSIL that will recur after ablation to improve risk stratification.

肛门癌导致艾滋病毒（PWH）患者的第二大最常见的固体恶性肿瘤引起明显的发病率，每年> 2,000例新病例。我们的数据表明，在美国，肛门癌发病率正在迅速增长。这种趋势在与男性发生性关系的艾滋病毒感染男性中更加明显，尽管终生风险为10％，并且尽管早期发现和预防进展，但预计仍会增加。与50岁以下的PWH相比，肛门癌在50岁以上的PWH中更为普遍。预防肛门癌中心围绕鉴定和消融高级鳞状上皮内病变（HSIL），这是癌的直接前体。 HSIL在PWH中具有很高的侵略性，每年1％的侵入性癌。但是，PWH的治疗功效受到限制，但是，在同一解剖象限中，治疗的HSIL患者中有50％的患者将患有高级病变。有迹象表明，治疗失败率随着年龄的增长而增加，但是数据是有限的，并且需要预测治疗失败的生物标志物，并且可能依赖于年龄。目的：该项目的目的是了解年龄差异是否与HSIL侵略性相关并确定侵略性的生物标志物。具体目的：（1）确定年龄增长的治疗失败率；（2）并确定肛门高级鳞状上皮内病变（HSIL）的克隆性程度，并在HIV患者中测试克隆性与病变侵略性的关联。研究设计：我们建议从具有HPV相关的HSIL的PWH组中的> 2,000个标本的组织库进行研究和序列HSIL。我们将首先确定在50岁以上的人和50岁以下的人消融后在同一解剖象限中发现的病变频率。这将确定治疗是否随着年龄的增长而失败，并且是否与复发性病变的数量相关。我们将随机选择未选择的200 HSIL以按年龄进行结果，以预测HSIL，这将在消融后重复出现以改善风险分层。