Roles of inflammation-driven chemokines in the pathogenesis of ovarian cancer

炎症驱动的趋化因子在卵巢癌发病机制中的作用

基本信息

批准号：
8515310
负责人：
DEOK-SOO SON
金额：
$ 33.74万
依托单位：
MEHARRY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8515310
关键词：
1-Phosphatidylinositol 3-Kinase Anti-Inflammatory Agents Anti-inflammatory Ascites Aspirin Attenuated Automobile Driving Basic Science Binding Bioinformatics Biological Markers Biomedical Research CXCL1 gene Cancer Etiology Cell Proliferation Cessation of life Chronic Clinical Collaborations Core Facility Data Development Diagnosis Disease EGF gene Endocrine Environment Epidermal Growth Factor Receptor Epithelial Epithelial Cells Equipment Etiology Event Exposure to Flow Cytometry Foundations Funding Funding Mechanisms Future Genes Genetic Goals Growth Growth and Development function Gynecologic Oncology IL8RB gene In Vitro Infiltration Inflammation Inflammatory Interleukin-8B Receptor Intraperitoneal Injections Knockout Mice Laboratories Lead Letters Leukocytes Link Mainstreaming Malignant - descriptor Malignant Neoplasms Malignant neoplasm of ovary Manuscripts Measures Methods Minority Mitogen-Activated Protein Kinases Modification Molecular Molecular Biology Molecular Target Morbidity - disease rate Mus Mutation Nuclear Oncogenes Ovarian Ovary Paper Pathogenesis Pathway interactions Patient Care Patients Peer Review Peritoneal Pharmaceutical Preparations Plasma Postdoctoral Fellow Prevention Probability Process Proto-Oncogene Proteins c-akt Publications Publishing Receptor Activation Receptor Signaling Research Research Personnel Resources Role Scientist Serine Signal Transduction Son Staging Stimulus Students System Techniques Therapeutic Threonine Time Training Transfection Tumor Burden Tumor Cell Invasion Tumor Necrosis Factor-alpha Tumor Suppressor Genes Universities Vascular Endothelial Growth Factors Veterinarians Western Blotting Woman Women&apos s Health Work Yang abstracting angiogenesis animal care cancer cell cancer risk carcinogenesis cell growth chemokine chemokine receptor cytokine female reproductive system improved in vitro Assay in vivo inhibitor/antagonist medical schools member migration mortality novel novel therapeutics overexpression planetary Atmosphere prevent programs research study response restoration square foot tissue culture tumor tumor growth tumor microenvironment tumor progression tumorigenic

项目摘要

Project Summary/Abstract Ovarian cancer is the fifth leading cause of cancer deaths among women because this deadly insidious disease is typically asymptomatic until the malignancy has reached beyond the ovaries. Although the precise etiology remains unknown, the increasing evidence indicates ovarian cancer is one of inflammation-associated cancers derived from inflammatory diseases. Compared with normal ovarian epithelial cells, ovarian cancer cells expressed highly tumor necrosis factor-¿ (TNF) as a main proinflammatory cytokine that controls directly or indirectly chemokine networks. Growth-regulated oncogene (CXCL1) was significantly increased in ovarian cancer cells, and in the plasma and ascites of patients with ovarian cancer. Our recent studies have resulted that CXCL1, 2 and 8 are main inflammation-driven chemokines produced primarily and abundantly from ovarian cancer cells in response to inflammation. In other system, CXCL1 binds its specific receptor (CXCR2) and exert several functional roles such as cell proliferation, invasion, tumor formation and angiogenesis, which may be critical in the pathogenesis of ovarian cancer. These facts support that inflammation-driven chemokines promote ovarian cancer through inflammatory tumor microenvironments, which lead to massive ascites and widespread peritoneal dissemination as described in advanced ovarian cancer followed by the high mortality rate. In particular, genetic modifications such as p53 inactivity and EGFR/Akt overexpression are frequent in high- grade malignant ovarian cancer. The genetic modifications potentiate inflammation- driven chemokines, probably exacerbating the pathogenesis of ovarian cancer. However, the mechanisms inflammation-driven chemokines contribute to the pathogenesis of ovarian cancer are still poorly understood. The long-range goal of this research is to determine the specific contribution of chemokine networks to ovarian carcinogenesis. Targeting inflammation-driven chemokines will lead to a better understanding of the pathogenesis of ovarian cancer and provide important future applications for the potential use of chemokines as a biomarker and for use of specific chemokine receptor inhibitors and anti-inflammatory agents in the prevention and treatment of ovarian cancer. Preventing peritoneal dissemination and ameliorating ascites through blockage of inflammation-driven chemokines improve patient care and overall survival of women with ovarian cancer and other tumors related to inflammation.

项目摘要/摘要卵巢癌是女性癌症死亡的第五个主要原因，因为这致命的阴险疾病通常是不对称的，直到恶性肿瘤达到超越卵巢。尽管精确的病因仍然未知，但增加有证据表明卵巢癌是与炎症相关的癌症之一来自炎症性疾病。与正常的卵巢上皮细胞相比癌细胞表达高度肿瘤坏死因子 - （TNF）作为主要促炎性直接或间接控制趋化因子网络的细胞因子。生长调节卵巢癌细胞中的癌基因（CXCL1）显着增加卵巢癌患者的血浆和腹水。我们最近的研究导致了 CXCL1，2和8是主要炎症趋化趋化因子产生的原发性趋化因子，并且绝对来自卵巢癌细胞响应炎症。在其他系统中， CXCL1结合其特定受体（CXCR2），并发挥几种功能作用，例如细胞增殖，侵袭，肿瘤形成和血管生成，这可能至关重要卵巢癌的发病机理。这些事实支持炎症驱动的趋化因子通过炎症性肿瘤微环境促进卵巢癌，这会导致大规模的腹水和广泛的腹膜传播晚期卵巢癌，然后是高死亡率。特别是遗传诸如p53不活动和egfr/akt之类的修改经常在高中等级恶性卵巢癌。遗传修饰潜在注射 - 驱动的趋化因子可能加剧了卵巢癌的发病机理。然而，炎症趋化趋化因子的机理有助于卵巢癌仍然很了解。这项研究的远程目标是确定趋化因子网络对卵巢癌发生的特定贡献。靶向炎症驱动的趋化因子将使人们更好地理解卵巢癌的发病机理，为未来的重要应用趋化因子作为生物标志物的潜在用途和用于特定趋化因子接收器的使用预防和治疗卵巢的抑制剂和抗炎药癌症。防止腹膜传播和通过阻塞改善腹水以炎症为导向的趋化因子改善了患者护理和女性的整体生存卵巢癌和与炎症有关的其他肿瘤。