Mechanistic Insights of BME mediated inhibition of head and neck cancer growth

BME 介导抑制头颈癌生长的机制见解

• 批准号: 9414026
• 负责人: Ratna B. Ray
• 金额: $ 37.88万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-15 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9414026
• 关键词: Address; Alternative Medicine; American Cancer Society; Animal Model; Biological; Cell Death; Cell Line; Clinical Research; Clinical Trials; Cytotoxic Chemotherapy; Data; Development; Diabetes Mellitus; Diet; Disease; Distant; Epidermal Growth Factor Receptor; Epithelium; Far East; Folk Medicine; Food; Future; Genes; Goals; Growth; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; In Vitro; Larynx; Lip structure; Malignant Epithelial Cell; Malignant Neoplasms; Mediating; Melons; Modality; Molecular; Momordica charantia; Mucous Membrane; Nasal cavity; Natural Killer Cells; Natural Products; Nose; Operative Surgical Procedures; Oral cavity; Outcome; Patients; Pharyngeal structure; Plants; Pre-Clinical Model; Prevention; Preventive; Quality of life; Radiation; Radiation therapy; Recurrence; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Sinus; Supportive care; Survival Rate; Techniques; Testing; Therapeutic; Therapeutic Agents; Therapeutic Effect; Tongue; Translating; Treatment Efficacy; United States; base; c-myc Genes; cancer cell; chemotherapy; effective therapy; immunoregulation; improved; innovation; insight; mouse model; novel; pre-clinical; prevent; public health relevance; stem-like cell; targeted treatment; therapy resistant; treatment strategy; tumor microenvironment; tumor progression

 DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) refers to a group of biologically similar cancers that start in the lip, tongue, oral cavity (mouth, nasal cavity (inside the nose), paranasal sinuses, pharynx, and larynx. HNSCC is the sixth most common cancer worldwide, and accounts for about 3-5% of all cancers in the United States. American Cancer society estimates 55,070 people will develop head and neck cancers in 2014. The 5- year survival rate of HNSCC patients is ~60% and has improved only marginally during the past few decades. Although improvements in surgical techniques, chemotherapy and radiation delivery, and supportive care have improved quality of life for patients with HNSCC, the regional and distant recurrence remain common and is almost always fatal. The impact of current cytotoxic therapies for HNSCC is limited by disease recurrence and resistance to therapy. Thus, there is a tremendous need for development of targeted and effective therapies. We have recently identified a plant-derived natural product, bitter melon extract (BME), which can induce HNSCC cell death. We have observed that BME treatment on HNSCC cells inhibits c-Met/EGFR and downstream signaling molecules (Stat3, c-myc and Mcl-1), and enhances natural killer (NK) cell activity, implicating its potential role in inhibition of head and neck cacer. The long-term objective of our project is to evaluate preventive and therapeutic efficacy of BME against HNSCC and understanding the underlying mechanisms. We hypothesize that BME and its active component(s) will prevent and inhibit HNSCC by multiple mechanisms including: modulation of genes critical to cancer progression, effect on cancer stem-like cells and tumor microenvironment in preclinical animal models. Results from this study will extend and translate our findings to future clinical studies. Innovation: Our application will examine for the first tim the mechanistic, preventive, and therapeutic effect of BME in highly relevant HNSCC animal models.

 描述（申请人提供）：头颈鳞状细胞癌（HNSCC）是指一组生物学上相似的癌症，起始于唇、舌、口腔（嘴、鼻腔（鼻子内）、鼻窦、咽和喉）。HNSCC 是全球第六大常见癌症，约占美国所有癌症的 3-5%。 癌症协会估计 2014 年将有 55,070 人患上头颈癌。头颈癌患者的 5 年生存率约为 60%，并且在过去几十年中仅略有改善。尽管手术技术、化疗和放疗以及支持治疗的改进改善了 HNSCC 患者的生活质量，但区域和远处复发仍然很常见，并且几乎总是致命的。电流的影响 HNSCC 的细胞毒疗法受到疾病复发和治疗耐药性的限制。因此，非常需要开发靶向且有效的疗法。我们最近发现了一种植物源性天然产物苦瓜提取物（BME），它可以诱导 HNSCC 细胞死亡。我们观察到 BME 治疗 HNSCC 细胞会抑制 c-Met/EGFR 和下游信号分子 （Stat3、c-myc 和 Mcl-1），并增强自然杀伤 (NK) 细胞活性，暗示其在抑制头颈癌方面的潜在作用。我们项目的长期目标是评估 BME 对 HNSCC 的预防和治疗功效并了解其潜在机制。我们假设 BME 及其活性成分将通过多种机制预防和抑制 HNSCC，包括： 在临床前动物模型中调节对癌症进展至关重要的基因、对癌症干细胞样细胞和肿瘤微环境的影响。这项研究的结果将扩展我们的发现并将其转化为未来的临床研究。创新：我们的应用将首次检查 BME 在高度相关的 HNSCC 动物模型中的机制、预防和治疗效果。