The role of platelets in tumor growth, wound healing and other angiogenesis disea

血小板在肿瘤生长、伤口愈合和其他血管生成疾病中的作用

• 批准号: 8825177
• 负责人: Giannoula Lakka Klement
• 金额: $ 16.38万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8825177
• 关键词: role; platelets; tumor; growth; wound

DESCRIPTION (provided by applicant): The role of platelets in tumor growth, wound healing and other angiogenesis disease states The role of platelets in angiogenesis has been appreciated in the past both clinically and pre- clinically. We have recently published evidence that platelets actively sequester angiogenesis stimulators as well as inhibitors, and that there may be a higher organization of these opposing roles within platelet. This higher organization may facilitate the ability of platelets to modify angiogenesis in many angiogenesis-dependent disorders such as wound healing, atherosclerosis, tumor growth, macular degeneration and many others. Since the ability of platelets to enhance wound healing is restricted to intact platelets and does not extend to previously frozen platelets, the process most likely involves a reciprocal interaction between live, fully functional platelet and the wound microenvironment. Unlike other cells, platelets are destroyed by freezing. This proposal will a) characterize the molecular and cellular mechanisms by which platelets sequester and store angiogenesis regulators (Specific Aim 1); b) evaluate the mechanisms of release of these angiogenesis regulators from platelets (Specific Aim 2); c) test the potential therapeutic relevance of strategies designed to selectively release stimulators or inhibitors of angiogenesis from platelets in wound and tumor models (Specific Aim 3). The goal of these studies will be to provide a framework for development of novel targeted therapies for improvement of wound care, as well as for inhibition of tumor growth. It is expected that many agents that modify platelet function, secretion of proteins from platelets, and/or platelet adhesion will be applicable for management pathologic angiogenesis.

描述（由申请人提供）：血小板在肿瘤生长、伤口愈合和其他血管生成疾病状态中的作用血小板在血管生成中的作用在过去在临床和临床前均已得到认识。我们最近发表的证据表明，血小板主动隔离血管生成刺激剂和抑制剂，并且血小板内可能存在更高的这些相反作用的组织。这种高级组织可能会促进血小板在许多血管生成依赖性疾病中改变血管生成的能力，例如伤口愈合、动脉粥样硬化、肿瘤生长、黄斑变性等。由于血小板促进伤口愈合的能力仅限于完整的血小板，并且不能扩展到先前冷冻的血小板，因此该过程很可能涉及活的、功能齐全的血小板与伤口微环境之间的相互作用。与其他细胞不同，血小板会被冷冻破坏。该提案将 a) 描述血小板隔离和储存血管生成调节剂的分子和细胞机制（具体目标 1）； b) 评估血小板释放这些血管生成调节剂的机制（具体目标 2）； c) 测试旨在从伤口和肿瘤模型中的血小板选择性释放血管生成刺激剂或抑制剂的策略的潜在治疗相关性（具体目标 3）。这些研究的目标是为开发新型靶向疗法提供框架，以改善伤口护理以及抑制肿瘤生长。预期改变血小板功能、血小板蛋白质分泌和/或血小板粘附的许多药剂将适用于控制病理性血管生成。

项目成果

Escape from tumor dormancy and time to angiogenic switch as mitigated by tumor-induced stimulation of stroma.

• DOI: 10.1016/j.jtbi.2016.01.024
• 发表时间: 2016-04
• 期刊: Journal of theoretical biology
• 影响因子: 2
• 作者: I. Kareva

Role of platelet chemokines, PF-4 and CTAP-III, in cancer biology.

• DOI: 10.1186/1756-8722-6-42
• 发表时间: 2013-06-24
• 期刊: Journal of hematology & oncology
• 影响因子: 28.5
• 作者: Pilatova K;Greplova K;Demlova R;Bencsikova B;Klement GL;Zdrazilova-Dubska L
• 通讯作者: Zdrazilova-Dubska L

Isolation and proteomic analysis of platelets by SELDI-TOF MS.

通过 SELDI-TOF MS 对血小板进行分离和蛋白质组分析。

• DOI: 10.1007/978-1-61779-418-6_12
• 发表时间: 2012
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Downing,SeanR;Klement,GiannoulaL
• 通讯作者: Klement,GiannoulaL

[Platelets in the pathogenesis of solid tumors].

血小板在实体瘤发病机制中的作用。

• 发表时间: 2014
• 期刊: Casopis lekaru ceskych
• 作者: Bencsiková,Beatrix;Greplová,Kristína;Pilátová,Kateřina;Volejníková,Zuzana;Valík,Dalibor;Klement,GiannoulaLakka;Zdražilová-Dubská,Lenka
• 通讯作者: Zdražilová-Dubská,Lenka

Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics.

• DOI: 10.1007/s10549-012-2256-5
• 发表时间: 2012-11
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Mayer EL;Isakoff SJ;Klement G;Downing SR;Chen WY;Hannagan K;Gelman R;Winer EP;Burstein HJ
• 通讯作者: Burstein HJ