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.

项目概要/摘要 该提案将促进候选人的研究和职业发展培训，以实现他的目标 成为一名具有口腔癌免疫学专业知识的独立研究者， 化学预防。仅在美国，预计新增病例将达到 48,330 例，新增病例将达到 9,570 例。 2016 年死亡人数。值得注意的是，非洲人口腔癌死亡率异常高。 美国男性。因此，迫切需要新的、有效的口腔癌预防和治疗策略。 需要。最近的临床和临床前研究证明了黑树莓 (BRB) 的卓越能力 抑制口腔肿瘤的形成。然而，对于哪些生物活性化合物的了解仍然有限 BRB 在抑制口腔癌方面最重要，以及它们如何影响口腔癌的不同细胞和分子 构成口腔肿瘤微环境。这些知识对于促进发展至关重要 BRB 植物化学物质在口腔癌预防和治疗中的应用。此 K01 应用程序的目标是确定 生物活性 BRB 植物化学物质抑制口腔癌的机制，重点关注两个 已知促进癌变的口腔肿瘤微环境的重要组成部分：（i）骨髓 衍生抑制细胞 (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预防 MDSC 来抑制口腔癌的发生 募集/活性以及抑制 MIF 信号通路，这些特性可在口服中利用 癌症干预。具体目标 1 中提出的研究将确定 BRB 植物化学物质对 MDSC 在口腔癌期间的功能。具体目标 2 中提出的研究将确定 BRB 的效果 植物化学物质对口腔癌期间 MIF 相关信号传导的影响。最后，具体目标 3 中提出的研究将 确定 BRB 植物化学物质组合方法预防口腔癌的功效， 治疗。这些研究将扩大我们对 BRB 植物化学物质抑制口腔癌的理解， 推进 BRB 植物化学物质作为口腔癌补充治疗策略的应用。 为了实现这些研究目标并促进他向研究独立的过渡，候选人将 丰富他在以下方面的培训和专业知识：(i) 代谢组学； ㈡ 生物统计学； (iii) 癌症临床试验。这将是 通过与经验丰富、忠诚的导师团队、正式的教学和 实践培训以及研究教育和培训计划。拟议的培训和研究 活动将协助候选人过渡为一名成熟且富有成效的独立调查员 一项研究计划，重点是利用生物活性植物化学物质的免疫调节特性 改善癌症预防和治疗结果。

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

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

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

Berries vs. Disease: Revenge of the Phytochemicals.

• DOI: 10.3390/ph17010084
• 发表时间: 2024-01-09
• 期刊: Pharmaceuticals (Basel, Switzerland)
• 作者: Lamenza FF;Upadhaya P;Roth P;Shrestha S;Jagadeesha S;Horn N;Pracha H;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)