Mechanisms of Oral Cancer Inhibition by Bioactive Phytochemicals in Black Raspberries

黑树莓中生物活性植物化学物质抑制口腔癌的机制

• 批准号: 10240472
• 负责人: Steve Onyeka Oghumu
• 金额: $ 14.3万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240472
• 关键词: Advanced Development; Affect; African American; Aftercare; Anthocyanins; Antineoplastic Agents; Biological Markers; Biometry; CXCL1 gene; Cancer Intervention; Career Choice; Cell physiology; Cells; Cessation of life; Chemotactic Factors; Clinical Research; Clinical Trials; Clinical Trials Design; Complementary therapies; Data; Ellagi-Tannins; Erlotinib; Family; Funding; Goals; Hour; Immune; Immunologics; In Vitro; Inflammatory; Intervention; Knowledge; Mediating; Mentors; Migration Inhibitory Factor; Molecular; Mouth Neoplasms; Mus; Myeloid-derived suppressor cells; Oral; Oral cavity; Pathway interactions; Persons; Phytochemical; Positioning Attribute; Prevention strategy; Production; Property; Public Health; Raspberries; Rattus; Recruitment Activity; Reporter; Research; Research Activity; Research Personnel; Signal Pathway; Signal Transduction; Signaling Molecule; Survival Rate; Technology; Therapeutic; Training; Training Activity; Training Programs; Transgenic Mice; Treatment outcome; United States; United States National Institutes of Health; anticancer activity; base; cancer cell; cancer chemoprevention; cancer clinical trial; cancer prevention; cancer therapy; carcinogenesis; career; career development; combinatorial; cytokine; design; education research; efficacy evaluation; experience; immunoregulation; improved; in vivo; male; malignant mouth neoplasm; metabolomics; mortality; mouse model; multidisciplinary; novel; oral cancer prevention; oral carcinogenesis; preclinical study; prevent; programs; receptor expression; recruit; research and development; treatment strategy; tumor; tumor immunology; tumor microenvironment

PROJECT SUMMARY/ABSTRACT This proposal will facilitate the research and career development training of the candidate in his goal to become an established independent investigator with expertise in oral cancer immunology and chemoprevention. In the United States alone, it is expected that there will be 48,330 new cases and 9,570 deaths in 2016. Significantly, there is a disproportionately high mortality rate of oral cancer among African- American males. Therefore, new and effective oral cancer prevention and treatment strategies are desperately needed. Recent clinical and preclinical studies demonstrate the remarkable ability of black raspberries (BRBs) to inhibit tumor formation in the oral cavity. Yet, there is still limited knowledge on which bioactive compounds in BRBs are most important in inhibiting oral cancer, and how they affect the different cells and molecules that make up the oral tumor microenvironment. This knowledge is essential in order to advance the development of BRB phytochemicals in oral cancer prevention and treatment. The goal of this K01 application is to determine the mechanisms underlying oral cancer inhibition by bioactive BRB phytochemicals, with a focus on two essential components of the oral tumor microenvironment known to promote carcinogenesis: (i) myeloid derived suppressor cells (MDSC) and (ii) the pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF). We hypothesize that phytochemicals in BRBs inhibit oral carcinogenesis by preventing MDSC recruitment/activity as well as suppressing MIF signaling pathways, properties which can be exploited in oral cancer intervention. Studies proposed in Specific Aim 1 will determine the impact of BRB phytochemicals on MDSC function during oral cancer. Studies proposed in Specific Aim 2 will determine the effects of BRB phytochemicals on MIF-associated signaling during oral cancer. Finally, proposed studies in Specific Aim 3 will determine the efficacy of combinatorial approaches with BRB phytochemicals for oral cancer prevention and treatment. These studies will expand our understanding of oral cancer inhibition by BRB phytochemicals and advance the application of BRB phytochemicals as complementary therapeutic strategies against oral cancer. To accomplish these research goals and facilitate his transition to research independence, the candidate will enrich his training and expertise in: (i) metabolomics; (ii) biostatistics; and (iii) cancer clinical trials. This will be accomplished through interaction with an experienced and committed team of mentors, formal didactic and hands-on training, and research education and training programs. The proposed training and research activities will assist in the candidate’s transition to an established and productive independent investigator with a research program focused on exploiting the immunomodulatory properties of bioactive phytochemicals to improve cancer prevention and treatment outcomes.

项目摘要/摘要 该建议将促进候选人的研究和职业发展培训，以实现其目标 成为具有口腔癌免疫学专业知识的既定独立研究者， 化学预防。仅在美国，预计将会有48,330例新案件和9,570例 2016年的死亡。重要的是，非洲的口腔癌死亡率较高 美国男性。因此，新的有效的口腔癌预防和治疗策略拼命 需要。最近的临床和临床前研究表明了黑色覆盆子（BRB）的显着能力 抑制口腔中的肿瘤形成。但是，关于哪种生物活性化合物仍然有限 在BRB中，对于抑制口腔癌以及它们如何影响不同细胞和分子的最重要 组成口腔肿瘤微环境。这些知识对于促进发展至关重要 口腔癌预防和治疗中的BRB生理化学物质。该K01应用程序的目的是确定 生物活性BRB植物化学物质抑制口腔癌的基础机制，重点是 口腔肿瘤微环境的基本成分已知可以促进致癌作用：（i）髓样 衍生的抑制细胞（MDSC）和（ii）促炎细胞因子，巨噬细胞迁移抑制因子 （MIF）。我们假设BRB中的植物化学物质通过防止MDSC抑制口服癌变 招聘/活动以及抑制MIF信号通路，可以在口服中探索的特性 癌症干预。特定目标1中提出的研究将确定BRB理化学对BRB的影响 口腔癌期间的MDSC功能。在特定目标2中提出的研究将确定BRB的影响 口腔癌期间与MIF相关信号传导的植物化学物质。最后，在特定目标3中提出的研究将 确定与BRB理化学对口腔癌预防和的组合方法的效率 治疗。这些研究将扩大我们对BRB生理学抑制口腔癌的理解和 推动将BRB理化学物作为针对口腔癌的完整治疗策略的应用。 为了实现这些研究目标并促进他向研究独立性的过渡，候选人将 丰富了他的培训和专业知识：（i）代谢组学； （ii）生物统计学； （iii）癌症临床试验。这将是 通过与经验丰富且坚定的导师团队的互动，正式的教学和 动手培训以及研究教育和培训计划。拟议的培训和研究 活动将有助于候选人向既定且产品独立调查员的过渡 一项研究计划，旨在利用生物活性物理的免疫调节特性 改善预防癌症和治疗结果。

项目成果

STAT1 gene deficient mice develop accelerated breast cancer growth and metastasis which is reduced by IL-17 blockade.

• DOI: 10.1080/2162402x.2017.1361088
• 发表时间: 2017
• 期刊: Oncoimmunology
• 影响因子: 7.2
• 作者: Varikuti S;Oghumu S;Elbaz M;Volpedo G;Ahirwar DK;Alarcon PC;Sperling RH;Moretti E;Pioso MS;Kimble J;Nasser MW;Ganju RK;Terrazas C;Satoskar AR
• 通讯作者: Satoskar AR

Ly6Chi inflammatory monocytes promote susceptibility to Leishmania donovani infection.

Ly6Chi 炎症单核细胞促进杜氏利什曼原虫感染的易感性。

• DOI: 10.1038/s41598-017-14935-3
• 发表时间: 2017
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Terrazas,Cesar;Varikuti,Sanjay;Oghumu,Steve;Steinkamp,HeidiM;Ardic,Nurittin;Kimble,Jennifer;Nakhasi,Hira;Satoskar,AbhayR
• 通讯作者: Satoskar,AbhayR

Inhibition of PI3K Isoform p110γ Increases Both Anti-Tumor and Immunosuppressive Responses to Aggressive Murine Head and Neck Squamous Cell Carcinoma with Low Immunogenicity.

• DOI: 10.3390/cancers13050953
• 发表时间: 2021-02-25
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Anderson K;Ryan N;Alkhimovitch A;Siddiqui A;Oghumu S
• 通讯作者: Oghumu S

Berry Extracts and Their Bioactive Compounds Mitigate LPS and DNFB-Mediated Dendritic Cell Activation and Induction of Antigen Specific T-Cell Effector Responses.

• DOI: 10.3390/antiox12091667
• 发表时间: 2023-08-24
• 期刊: Antioxidants (Basel, Switzerland)

Effect of Short-Term Tacrolimus Exposure on Rat Liver: An Insight into Serum Antioxidant Status, Liver Lipid Peroxidation, and Inflammation.

• DOI: 10.1155/2021/6613786
• 发表时间: 2021
• 期刊: Mediators of inflammation
• 影响因子: 4.6
• 作者: Fatima N;Sheikh N;Satoskar AR;Akhtar T;Tayyeb A;Ashfaq I;Ryan N;Ambreen S;Jha BK;Oghumu S
• 通讯作者: Oghumu S