BASE TITLE: PREVENT PRECLINICAL DRUG DEVELOPMENT PROGRAM: PRECLINICAL EFFICACY AND INTERMEDIATE BIOMARKERSTASK ORDER TITLE: PREVENTING FAP-CRC USING
基本标题:预防临床前药物开发计划:临床前疗效和中间生物标志物订单标题:预防 FAP-CRC 使用
基本信息
- 批准号:10652736
- 负责人:
- 金额:$ 14.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-28 至 2022-12-27
- 项目状态:已结题
- 来源:
- 关键词:AdenocarcinomaAffectApcMin/+ miceBiological MarkersCellsColorectal CancerDevelopmentDoseFamilial Adenomatous Polyposis SyndromeGenesHumanIndividualIntestinal PolypsIntestinesLeadMYC geneMetabolicMetabolismModelingMusMutationPatientsPlayPolypsPreclinical Drug DevelopmentProgram DevelopmentRattusRecombinantsRoleTissue SampleTissuesToxic effectadenomabasebeta cateninc-myc Genescancer typecarcinogenesiscell growthcolorectal cancer preventionendopeptidase Laknock-downoverexpressionpreclinical efficacypreventtreatment duration
项目摘要
The Myc oncogene is thought to play a role in many different types of cancer, including colorectal cancer (CRC). In individuals with familial adenomatous polyposis (FAP), Apc or β-catenin mutations lead to the overexpression of Myc, which in turn drives the metabolic alterations that occur at the adenoma stage of CRC carcinogenesis. The knockdown of Myc has been shown to reset this altered metabolism and in turn suppress cell growth, making Myc an attractive target for CRC prevention, especially in FAP patients.
Bacterial Lon protease can reduce c-MYC levels in human cells and murine tissues. In addition, recombinant Lon (rLon) can reduce the number of intestinal polyps and increase the survival of Apcmin/+ mice when administered for 14 days. No gross signs of toxicity were detected during a 14-day treatment period in either wildtype or Apcmin/+ mice. Notably, in healthy rLon protease-treated mice, Myc expression was not strongly affected in intestinal tissue samples. In contrast to Apcmin/+ mice, expression of Myc-related genes in rLon protease-treated healthy mice were not altered, suggesting that the effects of Lon protease may be more potent when Myc is overexpressed. The purpose of this Task Order is to validate and expand upon these findings in the PIRC rat model of CRC.
Myc癌基因被认为在许多不同类型的癌症中发挥作用,包括结直肠癌(CRC)。在患有家族性腺瘤性息肉病(FAP)的个体中,Apc或β-连环蛋白突变导致Myc的过表达,这反过来驱动了在CRC癌变的腺瘤阶段发生的代谢改变。Myc的敲除已被证明可以重置这种改变的代谢,从而抑制细胞生长,使Myc成为CRC预防的有吸引力的靶点,特别是在FAP患者中。
细菌Lon蛋白酶可以降低人细胞和鼠组织中的c-MYC水平。此外,重组Lon(rLon)在给药14天后可减少肠息肉的数量并增加Apcmin/+小鼠的存活率。在野生型或Apcmin/+小鼠的14天给药期间,未检测到毒性的大体体征。值得注意的是,在健康的rLon蛋白酶处理的小鼠中,Myc表达在肠组织样品中没有受到强烈影响。与Apcmin/+小鼠相反,Myc相关基因在rLon蛋白酶处理的健康小鼠中的表达没有改变,这表明当Myc过表达时,Lon蛋白酶的作用可能更有效。本任务指令的目的是验证并扩展PIRC大鼠CRC模型中的这些发现。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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CHINTHALAPALLY RAO其他文献
CHINTHALAPALLY RAO的其他文献
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{{ truncateString('CHINTHALAPALLY RAO', 18)}}的其他基金
Base Title: PREVENT Preclinical Drug Development Program: Preclinical Efficacy and Intermediate Endpoint BiomarkersTask Order Title: Colorectal Cancer (CRC) Prevention by TPST-1495 in PIRC rat mod
基本标题:预防临床前药物开发计划:临床前功效和中间终点生物标志物任务顺序标题:TPST-1495 在 PIRC 大鼠模型中预防结直肠癌 (CRC)
- 批准号:
10927554 - 财政年份:2023
- 资助金额:
$ 14.33万 - 项目类别:
TITLE: BLADDER CANCER CHEMOPREVENTION USING THE ANDROGEN RECEPTOR INHIBITOR APALUTAMIDE
标题:使用雄激素受体抑制剂阿帕鲁胺进行膀胱癌化学预防
- 批准号:
10677989 - 财政年份:2022
- 资助金额:
$ 14.33万 - 项目类别:
TASK ORDER TITLE: PREVENTING LUNG ADENOCARCINOMA (LUAD) USING TRAIL INDUCING AGENT, ONC201BASE CONTRACT TITLE: PREVENT PRECLINICAL DRUG DEVELOPMENT
任务单标题:使用踪迹诱导剂预防肺腺癌 (LUAD),ONC201BASE 合同标题:预防临床前药物开发
- 批准号:
10705393 - 财政年份:2022
- 资助金额:
$ 14.33万 - 项目类别:
PREVENT CANCER PRECLINICAL DRUG DEVELOPMENT PROGRAM - A NOVEL MULTI-ANTIGEN VACCINE (TNBCVAX) TO PREVENT TRIPLE NEGATIVE BREAST CANCER
预防癌症临床前药物开发计划 - 预防三阴性乳腺癌的新型多抗原疫苗 (TNBCVAX)
- 批准号:
10503245 - 财政年份:2021
- 资助金额:
$ 14.33万 - 项目类别:
PREVENT CANCER PRECLINICAL DRUG DEVELOPMENT PROGRAM - A NOVEL MULTI-ANTIGEN VACCINE (TNBCVAX) TO PREVENT TRIPLE NEGATIVE BREAST CANCER
预防癌症临床前药物开发计划 - 预防三阴性乳腺癌的新型多抗原疫苗 (TNBCVAX)
- 批准号:
10678625 - 财政年份:2021
- 资助金额:
$ 14.33万 - 项目类别:
PREVENT EFFICACY POOL: PREVENT CANCER PRECLINICAL DRUG DEVELOPMENT PROGRAM
预防功效池:预防癌症临床前药物开发计划
- 批准号:
10411703 - 财政年份:2021
- 资助金额:
$ 14.33万 - 项目类别:
TASK ORDER TITLE: PREVENTING COLORECTAL CANCER USING TRAIL-INDUCING ONC201 ALONE OR IN COMBINATION WITH NSAID
任务单标题:单独使用 TRAIL 诱导 ONC201 或与 NSAID 联合使用预防结直肠癌
- 批准号:
10269144 - 财政年份:2020
- 资助金额:
$ 14.33万 - 项目类别:
CHEMOPREVENTION WITH AEROSOLIZED LET-7 MICRORNA IN MOUSE MODELS OF NON-SMALL CELL LUNG CANCER (ADENOCARCINOMA AND SQUAMOUS CELL CARCINOMA)
在非小细胞肺癌(腺癌和鳞状细胞癌)小鼠模型中使用雾化的 Let-7 微小RNA进行化学预防
- 批准号:
10020543 - 财政年份:2019
- 资助金额:
$ 14.33万 - 项目类别:
IGF::OT::IGF PROSTATE CANCER PREVENTION BY ASPIRIN AND/OR OTHER NSAIDS TORFP 2016-E03HHSN2612015000381PERIOD OF PERFORMANCE: 07/07/2016 - 03/06/2019
通过阿司匹林和/或其他非甾体抗炎药预防 IGF::OT::IGF 前列腺癌 TORFP 2016-E03HHSN2612015000381执行周期:07/07/2016 - 03/06/2019
- 批准号:
9360885 - 财政年份:2016
- 资助金额:
$ 14.33万 - 项目类别:
IGF::OT::IGF PREVENT EFFICACY: OPTIMIZATION OF GEM MODELS FOR HIGH-RISK COHORTS OF HUMAN PANCREATIC CYSTADENOMAS, IPMNS, AND PANINS PROGRESSION TO PDAC.
IGF::OT::IGF 预防功效:针对人类胰腺囊腺瘤、IPMNS 和 Panins 进展至 PDAC 高风险群体的 GEM 模型的优化。
- 批准号:
9152469 - 财政年份:2015
- 资助金额:
$ 14.33万 - 项目类别:
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