Safer Approaches to CRC Chemoprevention

更安全的 CRC 化学预防方法

• 批准号: 10260715
• 负责人: Chinthalapally V. Rao
• 金额: $ 21.75万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260715
• 关键词: Adjuvant; Administrative Supplement; African American; Alabama; American Indians; Anti-Inflammatory Agents; Area; Blood; Calories; Cancer Burden; Cancer Center; Cancer Death Rates; Cancer Etiology; Caucasians; Centers for Disease Control and Prevention (U.S.); Cessation of life; Cities; Clinical; Colonic Polyps; Colonoscopy; Colorectal Cancer; Colorectal Neoplasms; Communities; Data; Diet; Disease-Free Survival; Economically Deprived Population; Environment; Environmental Risk Factor; Exposure to; Fatty acid glycerol esters; Gene Expression; Genetic; Genetic Predisposition to Disease; Genomics; Goals; Heavy Metals; Household; Immune Targeting; Incidence; Individual; Inflammation; Inflammatory; Institutes; Laboratories; Low income; Malignant Neoplasms; Marriage; Mediating; Metal exposure; Mutation; Not Hispanic or Latino; Obesity; Oklahoma; Outcome; Outcomes Research; Pesticides; Population; Prevention; Race; Research; Research Personnel; Risk; Risk Factors; Risk Marker; Rural; Sampling; Serum; Smoking; Tissues; Underserved Population; Universities; Variant; base; cancer chemoprevention; cancer health disparity; chemokine; colon cancer patients; colorectal cancer risk; cytokine; experience; high risk; improved; inflammatory marker; insertion/deletion mutation; medically underserved; metabolomics; metropolitan; mortality; novel; transcriptome sequencing; transcriptomics; tribal Nation; underserved area

Abstract/Summary Administrative Supplement toR01 CA213987 “Safer approaches to CRC Chemoprevention” Understanding genomic and metabolomic risk factors of CRC in American Indians Vs Caucasians of Oklahoma. This application responds to the PA-18-842 “Administrative Supplements to Support Cancer Disparity Collaborative Research”, and is focused on colorectal cancer (CRC). The long- term goal is to improve community and clinical CRC-related practice for American Indians (AIs) and African Americans (AAs) compared to that of Caucasians (mainly non-Hispanic whites) in Oklahoma. CRC is the second most common cause of cancer-related deaths in both Oklahomans and the US population as a whole. In general, Oklahomans have higher incidence and mortality for most cancers – this is particularly so for CRC where deaths are >21% greater than the US average CRC death rate. It is particularly concerning that Oklahoman AIs have a staggering 63% greater incidence rates >51% higher mortality rates for CRC than the national rate drawn mostly from Caucasian populations. Oklahoman AAs also have higher incidence (~20%) and mortality (54.9%) compared to overall US mortality rates. At present no in-depth studies have been performed to understand the risk factors that contribute to these CRC incidence and mortality rates in Oklahoma’s AIs and AAs compared to Caucasians. Thus, this collaborative administrative supplement focuses on understanding the genomic and metabolomic risk factors with specific focus on the inflammation in CRC patients of AI, AA and Caucasian descent. Our collaborative team includes laboratory based basic researchers (C.V. Rao, Ph.D; H. Yamada, Ph.D, K. Morris, M.D, C. Xu, Ph.D,) and cancer disparities researchers M. Doescher, M.D, from the Stephenson Cancer Center and Upender Manne, Ph.D, (University of Alabama, at Birmingham) the latter with expertise in AA cancer disparities. Our specific goals in this administrative supplement are to establish whether: i) enhanced genomic mutational burden; ii) altered gene expression; and iii) higher systemic and colonic inflammation are key factors contributing to the higher incidence and mortality of Oklahoman AIs and AAs as compared to Oklahoma Caucasian populations. The outcomes will provide a basis to develop novel anti- inflammatory (R01 213987 specific objective) and immune targeted approaches as adjuvants to improve disease free survival in AI and AA CRC patients.

摘要/摘要 R01 CA213987“结直肠癌化学预防的更安全方法”行政补编 了解美洲印第安人与高加索人结直肠癌的基因组和代谢危险因素 俄克拉何马州。 此应用程序响应PA-18-842“支持癌症差异的行政补充” 合作研究“，重点是结直肠癌(CRC)。长期目标是改进 美国印第安人(AIS)和非裔美国人(AAS)的社区和临床结直肠癌相关实践 与俄克拉荷马州的高加索人(主要是非西班牙裔白人)相比。CRC是第二大 俄克拉荷马人和整个美国人口癌症相关死亡的共同原因。在……里面 一般说来，俄克拉荷马人的大多数癌症的发病率和死亡率都更高--尤其是对 死亡人数比美国平均CRC死亡率高21%的地区。尤其令人担忧的是 俄克拉荷马州的癌症发病率高出惊人的63%，而结直肠癌的死亡率高出51% 而不是主要来自高加索人口的全国通胀率。俄克拉荷马州AA也有更高的 发病率(~20%)和死亡率(54.9%)与美国总体死亡率相比。目前还没有深入的 已经进行了研究，以了解导致这些结直肠癌发病率和 与高加索人相比，俄克拉何马州的人工智能和人工智能的死亡率。因此，这个协作性 行政补充侧重于了解基因组和代谢风险因素 特别关注AI、AA和高加索血统的CRC患者的炎症。我们的协作 团队包括以实验室为基础的基础研究人员(C.V.Rao，Ph.D.；H.Yamada，Ph.D.，K.Morris，M.D.，C. 和来自斯蒂芬森癌症中心的癌症差异研究人员M.Doescher，M.D. Upender Manne博士(阿拉巴马大学伯明翰分校)，后者拥有AA癌症方面的专业知识 差距。我们在这份行政副刊中的具体目标是确定：i)增强 基因组突变负担；ii)基因表达改变；以及iii)更高的全身和结肠炎症 是俄克拉荷马州AIS和AAS发病率和死亡率较高的关键因素 俄克拉何马州的高加索人。研究结果将为开发新型抗病毒药物提供依据。 炎症(R01 213987特定目标)和免疫靶向方法作为佐剂来改善 AI和AA结直肠癌患者的无病生存。

项目成果

Targeting IL-23 for the interception of obesity-associated colorectal cancer.

• DOI: 10.1016/j.neo.2023.100939
• 发表时间: 2023-11
• 期刊: NEOPLASIA
• 影响因子: 4.8
• 作者: Madka, Venkateshwar;Chiliveru, Srikanth;Panneerselvam, Janani;Pathuri, Gopal;Zhang, Yuting;Stratton, Nicole;Kumar, Nandini;Sanghera, Dharambir K.;Rao, Chinthalapally V.
• 通讯作者: Rao, Chinthalapally V.

Inflammatory Mediators and Gut Microbial Toxins Drive Colon Tumorigenesis by IL-23 Dependent Mechanism.

• DOI: 10.3390/cancers13205159
• 发表时间: 2021-10-14
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Panneerselvam J;Madka V;Rai R;Morris KT;Houchen CW;Chandrakesan P;Rao CV
• 通讯作者: Rao CV

Targeting the paracrine hormone-dependent guanylate cyclase/cGMP/phosphodiesterases signaling pathway for colorectal cancer prevention.

• DOI: 10.1016/j.semcancer.2018.08.011
• 发表时间: 2019-06
• 期刊: Seminars in cancer biology
• 影响因子: 14.5
• 作者: N. Yarla;H. Gali;Gopal Pathuri;S. Smriti;M. Farooqui;J. Panneerselvam;G. Kumar;Venkateshwar Madka;C. Rao

Molecular Mechanisms of Cancer Prevention by Gooseberry (Phyllanthus emblica).

• DOI: 10.1080/01635581.2021.2008988
• 发表时间: 2022
• 期刊: Nutrition and cancer

Targeting Triglyceride Metabolism for Colorectal Cancer Prevention and Therapy.

针对结直肠癌预防和治疗的甘油三酯代谢。

• DOI: 10.2174/1389450122666210824150012
• 发表时间: 2022
• 期刊: Current drug targets
• 影响因子: 3.2
• 作者: Yarla,Nagendra;Madka,Venkateshwar;Rao,Chinthalapally
• 通讯作者: Rao,Chinthalapally