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.

项目总结/摘要 本提案将促进候选人的研究和职业发展培训，以实现其目标， 成为一名具有口腔癌免疫学专业知识的知名独立研究者， 化学预防仅在美国，预计将有48，330例新病例和9，570例 2016年死亡人数。值得注意的是，非洲人口腔癌的死亡率高得不成比例， 美国男性因此，新的和有效的口腔癌预防和治疗策略是拼命 needed.最近的临床和临床前研究表明，黑树莓（BRB）的显着能力， 以抑制口腔中的肿瘤形成。然而，关于哪些生物活性化合物仍然是有限的知识， 在抑制口腔癌方面，BRB中的作用最为重要，以及它们如何影响不同的细胞和分子， 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作用。此K 01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，重点是两个 已知促进癌发生的口腔肿瘤微环境的基本组分：（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）。我们推测BRB中的植物化学物质通过阻止MDSC来抑制口腔癌的发生 募集/活性以及抑制MIF信号传导途径，可以在口服给药中利用的性质 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在口腔癌中的作用具体目标2中建议的研究将确定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中拟议的研究将 确定与BRB植物化学物质的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，并促进他向独立研究的过渡，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;（ii）生物统计学;和（iii）癌症临床试验。这将是 通过与经验丰富和忠诚的导师团队互动，正式的教学和 实践培训、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过渡到一个既定的和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)