Baylor College of Medicine Cancer Center-Cancer Center Support Grant

贝勒医学院癌症中心-癌症中心支持补助金

• 批准号: 10293866
• 负责人: HELEN E HESLOP
• 金额: $ 24.85万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10293866
• 关键词: Area; Asians; Basic Science; Biology; Breast Cancer therapy; Cancer Burden; Cancer Center; Cancer Center Support Grant; Cancer Model; Catchment Area; Cell Therapy; Cellular Metabolic Process; Child; Chromatin; Cities; Clinic; Clinical; Clinical Data; Clinical Protocols; Clinical Sciences; Clinical Trials; Clinics and Hospitals; Communities; Community Outreach; Comprehensive Cancer Center; Country; County; Diagnosis; Disease; Early Diagnosis; Education and Outreach; Ethnic group; Evaluation; Evolution; Faculty; Funding; Future; Genetic Transcription; Geographic Locations; Goals; Health; Hispanics; Hospitals; Individual; Industry; Information Services; Infrastructure; Institutes; Institution; Interdisciplinary Study; Investments; Laboratories; Lead; Malignant Childhood Neoplasm; Malignant Neoplasms; Medical center; Medicine; Mission; Morbidity - disease rate; NCI-Designated Cancer Center; Nuclear Receptors; Patient Care; Patient-Focused Outcomes; Peer Review; Physicians; Play; Population; Population Growth; Population Heterogeneity; Population Sciences; Process; Recommendation; Research; Research Peer Review; Resource Sharing; Role; Scientific Advances and Accomplishments; Scientist; Signal Transduction; Source; Technology; Texas; Training and Education; Translating; Translational Research; Underserved Population; Uninsured; United States; United States Department of Veterans Affairs; United States National Institutes of Health; Vision; cancer cell; cancer education; cancer prevention; cancer survival; cancer therapy; clinical care; college; community engagement; data management; ethnic minority population; gene therapy; health disparity; implementation science; improved; in vivo; member; metropolitan; mortality; multidisciplinary; next generation; novel strategies; outreach; outreach program; prevent; programs; racial and ethnic; racial minority; recruit

Kaposi sarcoma (KS) is by far the most common malignancy associated with human herpesvirus-8 (HHV-8)/KS-associated herpesvirus (KSHV) infection and ranks among the most common overall childhood cancers in sub-Saharan Africa. Over the past decade, our pediatric HIV malignancy program at the Baylor International Pediatric AIDS Initiative at Texas Children's Hospital/Global HOPE (Hematology-Oncology Pediatric Excellence) Clinical Center of Excellence in Lilongwe, Malawi has cared for over 200 children with KS. Our work has highlighted the clinical characteristics that render childhood KS distinct from adult disease, defined the heterogeneity in disease presentation specific to pediatrics, and established risk-stratified treatment regimens that have improved long-term survival. Long-term complete remission and event-free survival can be achieved, especially in children with lymphadenopathic KS. In stark contrast, patients with advanced visceral or disseminated disease experience high mortality rates despite intensified chemotherapeutic approaches. We have also identified associations between clinical sub-groups and KSHV-mediated mechanisms of KS oncogenesis specific to childhood disease. However, there remains a gap in knowledge concerning the inherent pathogenic mechanisms of KS. The proposed study seeks to define somatic genetic alterations of pediatric KS and determine correlations with clinical and virologic features through analysis of tumor specimens from the largest existing biocohort of childhood KS patients (n=70) from Lilongwe, Malawi. Through improved understanding of the molecular features of pediatric KS, we aim to discover biomarkers and targetable pathways that may inform the development of novel diagnostic, prognostic and therapeutic strategies.

Kaposi肉瘤(KS)是迄今为止与人类疱疹病毒-8(HHV-8)/KS相关疱疹病毒(KSHV)感染有关的最常见的恶性肿瘤，是撒哈拉以南非洲最常见的儿童癌症之一。在过去的十年里，我们在得克萨斯州儿童医院贝勒国际儿科艾滋病倡议/马拉维利隆圭的全球HOPE(血液肿瘤学卓越儿科)卓越临床卓越中心开展的儿童HIV恶性肿瘤项目已经照顾了200多名患有KS的儿童。我们的工作突出了使儿童KS有别于成人疾病的临床特征，定义了儿科特有的疾病表现的异质性，并建立了提高长期存活率的风险分层治疗方案。长期完全缓解和无事件生存是可以实现的，特别是在淋巴结病KS儿童中。与之形成鲜明对比的是，尽管加强了化疗方法，但患有晚期内脏或播散性疾病的患者死亡率很高。我们还确定了临床亚组和KSHV介导的儿童疾病特有的KS肿瘤发生机制之间的关联。然而，对于KS的内在致病机制，人们的认识仍然存在差距。这项拟议的研究试图通过分析马拉维利隆圭现有最大的儿童KS患者生物队列(n=70)的肿瘤标本，来定义儿童KS的体细胞遗传变化，并确定与临床和病毒学特征的相关性。通过改善对儿童KS分子特征的了解，我们的目标是发现生物标记物和靶向通路，为开发新的诊断、预后和治疗策略提供信息。