The Neurotransmitter dopamine and angiogenesis

神经递质多巴胺和血管生成

• 批准号: 7148077
• 负责人: DEBABRATA MUKHOPADHYAY
• 金额: $ 27.69万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-05 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148077
• 关键词: Address; Adenovirus Vector; Affect; Agonist; Amino Acids; Angiogenesis Inhibition; Angiogenesis Inhibitors; Animal Model; Ascites; Biochemical; Biology; Blood Vessels; Cell Proliferation; Clinical; Condition; Data; Development; Dopamine; Dopamine D2 Receptor; Endothelial Cells; Engineering; Experimental Designs; G-Protein-Coupled Receptors; Genetic; Growth Factor; Heart failure; Implant; Investigation; Knockout Mice; Link; Malignant Neoplasms; Mediating; Modeling; Mus; Nerve Endings; Nervous system structure; Neurotransmitters; Newborn Infant; Ovarian; Paclitaxel; Parkinson Disease; Pathologic Neovascularization; Pathway interactions; Peripheral; Pharmaceutical Preparations; Physiologic Neovascularization; Play; Pre-Clinical Model; Protein Overexpression; Purpose; Rattus; Receptor Signaling; Resistance; Retina; Role; Signal Pathway; Signal Transduction; Solid Neoplasm; Testing; Tetanus Helper Peptide; Therapeutic; Time; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; Vascular Endothelium; Vascular Permeabilities; angiogenesis; antiangiogenesis therapy; chemotherapeutic agent; cytokine; design; in vivo; migration; novel; ovarian neoplasm; pre-clinical; preclinical study; receptor; research study; response; size; therapeutic angiogenesis; tumor; tumor growth

Angiogenesis is essential for tumor growth beyond minimal size and is important in many other pathophysiological situations. It is widely anticipated that modulation of angiogenesis (inhibition in tumors, stimulation in vascular insufficiency) will provide important therapeutic benefit. Many different cytokines and growth factors express angiogenic activity, of these VPFNEGF stands out because of its potency, selectivity for vascular endothelium, and its consistent overexpression in malignant tumors and in other clinical conditions in which angiogenesis plays an important role. Very recently, we have described for the first time that the neurotransmitter dopamine (DA), which has long been used in the treatment of Parkinson's disease (as well as the treatment of cardiac failure), and DA D2 receptor agonists, potently and selectively blocks VPFNEGF-induced angiogenesis in vivo, whether induced by tumors or by an adenoviral construct engineered to express VPF/VEGF. The experiments proposed here are designed to investigate the mechanistic details by which DA or its related compounds inhibit VPFNEGF-induced angiogenesis. In Aim 1, we will examine how DA D2 receptor, a G-protein coupled receptor (GPCR), can influence VEGFR-2 signaling pathways. By utilizing genetic and pharmacological approaches, Aim 2 will focus to reveal how peripheral DA might affect normal and pathological angiogenesis mediated by VPFNEGF. In Aim 3, investigation will be carried out to define the role of DA and its related molecules as anti-angiogenic agents in both tumor ascites as well as solid tumor models. Moreover, we will examine whether DA or related compounds can be employed with other conventional drugs (such as Taxol) in preclinical settings. Furthermore, the role of DA in angiogenesis mediated by other angiogenic molecules will also be investigated in animal models. Developmental angiogenesis in the retinas of newborn rats will be utilized to test the effect of DA in normal physiological angiogenesis. Taken together, the proposed studies will draw an important conceptual link between angiogenesis and the nervous system and suggest that DA, already in clinical use for other purposes, may have value in anti-angiogenesis therapy.

血管生成对于肿瘤生长超过最小尺寸是必不可少的，并且在许多其他肿瘤中是重要的。 病理生理状况。广泛预期调节血管生成（抑制肿瘤， 血管功能不全中的刺激）将提供重要的治疗益处。许多不同的细胞因子和 生长因子表达血管生成活性，其中VPFNEGF因其效力、选择性 在恶性肿瘤和其他临床肿瘤中， 血管生成在其中起重要作用的条件。最近，我们首次描述了 神经递质多巴胺（DA）长期以来一直用于治疗帕金森病， (as以及心力衰竭的治疗）和DA D2受体激动剂，有效地和选择性地阻断 VPFNEGF诱导的体内血管生成，无论是由肿瘤还是腺病毒构建体诱导 工程化以表达VPF/VEGF。这里提出的实验旨在研究 DA或其相关化合物抑制VPFNEGF诱导的血管生成的机制细节。在Aim中 1，我们将研究DA D2受体，一种G蛋白偶联受体（GPCR），如何影响VEGFR-2 信号通路通过利用遗传和药理学方法，目标2将重点揭示如何 外周DA可影响VPFNEGF介导的正常和病理性血管生成。在目标3中， 将进行调查，以确定DA及其相关分子作为抗血管生成剂在 肿瘤腹水以及实体瘤模型。此外，我们将研究是否DA或相关 在临床前环境中，化合物可以与其他常规药物（如紫杉醇）一起使用。 此外，DA在其他血管生成分子介导的血管生成中的作用也将被研究 在动物模型中。将利用新生大鼠视网膜中的发育性血管生成来测试效果 DA在正常生理血管生成中的作用总的来说，拟议的研究将得出一个重要的结论， 血管生成和神经系统之间的概念联系，并建议DA，已经在临床上用于 其他目的，可能在抗血管生成治疗中具有价值。

项目成果

Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis.

金纳米颗粒在B-气淋巴细胞性白血病（BCLL）中的潜在治疗应用：增强细胞凋亡。

• DOI: 10.1186/1477-3155-5-4
• 发表时间: 2007-05-08
• 期刊: JOURNAL OF NANOBIOTECHNOLOGY
• 影响因子: 10.2
• 作者: Mukherjee, Priyabrata;Bhattacharya, Resham;Bone, Nancy;Lee, Yean K.;Patra, Chitta Ranjan;Wang, Shanfeng;Lu, Lichun;Secreto, Charla;Banerjee, Pataki C.;Yaszemski, Michael J.;Kay, Neil E.;Mukhopadhyay, Debabrata
• 通讯作者: Mukhopadhyay, Debabrata