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101.
《Expert opinion on therapeutic patents》2013,23(12):1919-1945
Angiogenesis refers to the formation of capillary blood vessels from existing blood vessels: a process that is believed to be a key driver in cancer growth and metastasis. Angiogenesis inhibition represents an active area of cancer drug discovery, with several agents and approaches now entering late clinical development. This review summarises the key aspects of recent patent applications referring to cancer chemotherapy and cancer drug discovery that involve inhibition or modulation of angiogenesis. The scope includes applications that have been published between April and August 2001. The review covers the main mechanism-based approaches such as MMPIs, inhibitors of the growth factor signalling pathways, integrin antagonists and urokinase inhibitors. 相似文献
102.
《Expert opinion on investigational drugs》2013,22(3):279-294
Diabetic nephropathy is a leading cause of end-stage renal disease, and accounts for significant morbidity and mortality in patients with diabetes. Diabetic nephropathy seems to occur as a result of an interaction between metabolic and haemodynamic factors, which activate common pathways that lead to renal damage. In the past, the treatment of diabetic nephro-pathy has focused on the control of hyperglycaemia. Newer targets, some of which are linked to glucose-dependent pathways, appear to be a major focus of new treatments directed against the development and progression of renal damage as a result of diabetes. It is anticipated that additional thera-peutic approaches that inhibit both metabolic and haemodynamic pathways will include strategies that target growth factors, cytokines and intracellular second messengers. Such an approach is expected to lead to improved therapies for the treatment of diabetic nephropathy. 相似文献
103.
Targeting platelet-derived growth factor with imatinib in idiopathic pulmonary arterial hypertension
《Expert opinion on therapeutic targets》2013,17(3):381-383
Background: In pulmonary arterial hypertension (PAH) vascular remodelling is a complex process which involves platelet-derived growth factor (PDGF), therefore its therapeutic targeting could be useful. Objective: To evaluate PDGF as a therapeutic target in idiopathic PAH (IPAH). Methods/results: Analysis of an study evaluating the pathogenic role of PDGF in IPAH and the effects of its blockade with imatinib. In IPAH the PDGF pathway was found to be overexpressed and imatinib showed antiproliferative effects on pulmonary artery smooth muscle cells. Conclusions: These results encourage clinical evaluation of imatinib as a potential antiremodelling therapy in IPAH. 相似文献
104.
Gabrielli A Svegliati S Moroncini G Pomponio G Santillo M Avvedimento EV 《Seminars in immunopathology》2008,30(3):329-337
Systemic sclerosis (SSc, scleroderma) is a devastating, immune-mediated, multisystem disorder characterized by microvasculature damage, circulating autoantibodies, and fibroblast activation, leading to massive fibrosis of skin, vessels, muscles, and visceral organs. Scleroderma causes disability and death as the result of end-stage organ failure. At present, no specific diagnostic nor therapeutic tools are available to handle the disease. In spite of significant effort, the etiology and pathogenesis of SSc remain obscure and, consequently, the disease outcome is unpredictable. Several years ago, Murrell suggested a unifying hypothesis linking the pathogenesis of scleroderma to the generation of a large excess of reactive oxygen species. This hypothesis has been substantiated by several reports indicating the presence of an abnormal redox state in patients with scleroderma. This review will summarize the available evidence supporting the link between free radicals and the main pathological features of scleroderma. 相似文献
105.
106.
目的:探究脾气虚证大鼠血管平滑肌细胞内PDGF、bcl-2、bax表达的变化及补脾益气方药对这种变化的调节作用。方法:将实验动物分成空白组、模型组、四君子汤组、六君子汤组、归脾汤组,用免疫组化法检测血管平滑肌细胞内PDGF、bcl-2、bax的表达。结果:与空白组比较,其他各组PDGF、bax的灰度值低,表达增强,bcl-2灰度值高,表达减弱(P<0.05)。与模型组比较,其他各组的PDGF、bax灰度值高,表达减弱,bcl-2灰度值低,表达增强,(P<0.05)。结论:脾气虚证大鼠血管平滑肌细胞内PDGF、bax表达增强,bcl-2表达减弱,而补脾益气中药能改善这种情况,从而为补脾益气中药防治心血管系统疾病提供实验室依据。 相似文献
107.
PDGF-A as an epicardial mitogen during heart development. 总被引:1,自引:0,他引:1
Jione Kang Ying Gu Peng Li Betsy L Johnson Henry M Sucov Penny S Thomas 《Developmental dynamics》2008,237(3):692-701
In the developing heart, reciprocal interactions between the epicardium and myocardium drive further sublineage specification and ventricular chamber morphogenesis. Several observations suggest that the epicardium is a source of secreted factors that influence cardiomyocyte proliferation, and these factors may have other roles as well. However, the identity of these epicardial factors remains mostly unknown. We have identified platelet-derived growth factor-A (PDGF-A) as one of several mitogens expressed by the rat EMC epicardial cell line (epicardial mesothelial cells), by embryonic epicardium and myocardium during mouse heart development, and by adult epicardium. Expression of the cognate receptor gene Pdgfra was detected in the epicardium, although a low level of expression in myocardium could not be ruled out. To address the potential role of PDGF signaling in heart development, we mutated both PDGF receptor genes in the myocardial and mesodermal compartments of the heart; however, this did not result in an observable cardiac phenotype. This finding suggests that mesodermal PDGF signaling is not essential in heart development, although its role may be redundant with other signaling pathways. Indeed, our results demonstrate the presence of additional mitogens that may have such an overlapping role. 相似文献
108.
目的研究雷珠单抗玻璃体腔注射辅助显微手术治疗对新生血管性青光眼(NVG)患者血管内皮生长因子(VEGF)和血小板衍生生长因子(PDGF)含量的影响。方法对我院32例(32眼)NVG患者资料进行回顾和分析,所有患者接受玻璃体腔注射雷珠单抗、小梁切除术和全视网膜光凝治疗。比较患者治疗前后眼压、视力、VEGF和PDGF,记录术后并发症和治疗成功率。结果 32例患者随访(8.57±1.69)个月,小梁切除术后1周、1个月、3个月、6个月眼压显著低于注药前,差异具有统计学意义(P0.05);术后末次随访视力较注药前显著提高(P0.05),视力提高率90.63%;患者注药后5 d和小梁切除术后1周、1个月、3个月、6个月房水、玻璃体液的VEGF和PDGF水平较注药前显著降低,差异具有统计学意义(P0.05);小梁切除术后前房出血率6.25%,包裹性滤过泡率6.25%,脉络膜脱落率3.13%;术后6个月手术成功率93.75%。结论雷珠单抗玻璃体腔注射辅助用于小梁切除术和全视网膜光凝治疗,可显著降低NVG患者VEGF和PDGF水平,降低眼压、提高视力,安全有效。 相似文献
109.
目的 探讨抗精神病药喹硫平对少突胶质细胞周期的影响及其作用机制。方法 采用血小板源性生长因子(PDGF)10 ng/ml、喹硫平10 μmol/L及两者混合物处理少突胶质前体细胞(OPCs)48 h,比较各组细胞周期、细胞周期退出指数及细胞分化情况。检测喹硫平干预后小鼠前额皮质8个细胞周期相关mRNA相对表达量。通过RNA干扰下调p21的表达,并分析其对细胞增殖和分化的影响。结果 PDGF可诱导G0/G1期细胞百分比下降(P <0.05),S期和G2期细胞百分比升高(P <0.05);喹硫平可抑制PDGF诱导的S期或G2期细胞百分比升高,并阻止G0/G1期细胞百分比降低(P <0.05)。PDGF抑制细胞周期退出(P <0.05);喹硫平促进细胞周期退出(P <0.05),并阻断PDGF对细胞周期退出的影响(P <0.05)。喹硫平可提高OPCs细胞的成熟率,降低低分化细胞数(P <0.05)。喹硫平干预后p21表达升高(P <0.05);下调p21可增加S期细胞百分比,降低G2期细胞百分比(P <0.05),增加溴脱氧尿苷阳性细胞数(P <0.05),减少髓鞘碱性蛋白阳性细胞(P <0.05)。结论 喹硫平可能通过调节少突胶质细胞的细胞周期来调节细胞分化。 相似文献
110.
Dolman ME Fretz MM Segers GJ Lacombe M Prakash J Storm G Hennink WE Kok RJ 《International journal of pharmaceutics》2008,364(2):249-257
Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tubular cells and reduced unwanted systemic effects. In our approach kinase inhibitors are linked to the renal carrier lysozyme using a platinum-based linker that binds drugs via a coordinative linkage. Many kinase inhibitors contain aromatic nitrogen atoms able to bind to this linker without the need of prior derivatization. The resulting drug-lysozyme conjugates are rapidly filtered in the glomerulus into the tubular lumen and subsequently reabsorbed via the endocytic pathway for clearance of low-molecular weight proteins. An important property of the formed conjugates is their in vivo stability and the sustained drug release profile within target cells. This review summarizes the state-of-the-art of drug targeting to the kidney. Furthermore, we will highlight recent results obtained with kinase inhibitor-lysozyme conjugates targeted to different kinases, i.e. the transforming growth factor (TGF)-beta-receptor kinase, p38 MAPkinase and Rho-associated kinase. Both in vitro and in vivo results demonstrated their efficient tubular uptake and beneficial therapeutic effects, superior to treatment with free kinase inhibitors. These proof-of-concept studies clearly indicate the feasibility of drug targeting for improving the renal specificity of kinase inhibitors. 相似文献