Safer Approaches to CRC Chemoprevention

更安全的 CRC 化学预防方法

基本信息

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
项目类别：
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

项目摘要

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/摘要行政补充TOR01 CA213987“更安全的CRC化学预防方法” 了解美国印第安人与高加索人的CRC的基因组和代谢组危险因素俄克拉荷马州。该应用程序对PA-18-842响应“支持癌症差异的行政补充合作研究”，专注于结直肠癌（CRC）。长期目标是改善美国印第安人（AIS）和非洲裔美国人（AAS）的社区和临床CRC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是第二个俄克拉荷马人和整个美国人口中与癌症相关的死亡的常见原因。在将军，俄克拉荷马人对大多数癌症的事件和死亡率更高 - 尤其如此 CRC死亡比美国平均CRC死亡率高21％。特别关心俄克拉荷马州的AIS的出现率惊人的63％> CRC的死亡率高51％比全国性利率主要来自白人人口。俄克拉荷马州AAS也有更高与美国总死亡率相比，事件（约20％）和死亡率（54.9％）。目前没有深入的已经进行了研究，以了解导致这些CRC事件的危险因素和与高加索人相比，俄克拉荷马州的AIS和AAS的死亡率。那，这个合作行政补充侧重于了解具有基因组和代谢危险因素 AI，AA和高加索血统的CRC患者的炎症特别关注。我们的合作团队包括基于实验室的基础研究人员（C.V. Rao，博士； H。Yamada，Ph.D，K。Morris，M.D，C。 Xu，Ph.D.）和癌症差异研究人员M. Docher，M.D。，来自斯蒂芬森癌症中心和Upender Manne，博士（阿拉巴马大学，伯明翰），后者具有AA癌的专业知识差异。我们在这种行政补充中的具体目标是确定以下方面是否：i）增强基因组突变伯恩； ii）基因表达改变； iii）更高的全身和结肠注射是俄克拉荷马州AI和AAS的更高事件和死亡率的关键因素和AAS的死亡率俄克拉荷马州高加索人口。结果将为发展新颖的反 - 炎症（R01 213987特定目标）和免疫靶向方法作为调节器，以改善 AI和AA CRC患者的无疾病生存。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
通讯作者：
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).