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91.
Chen J Röcken C Nitsche B Hosius C Gschaidmeier H Kahl S Malfertheiner P Ebert MP 《Cancer letters》2006,233(2):328-337
Imatinib targets KIT and platelet-derived growth factor receptors (PDGFR) and is highly effective in the treatment of CML and GIST patients. Pancreatic cancers express KIT and PDGFRs. Therefore, 26 patients with unresectable pancreatic cancer were randomized to either gemcitabine (1000 mg/m2 weekly) or imatinib (2x400 mg po) treatment daily. Pancreatic adenocarcinoma was confirmed histologically and expression of KIT and PDGFRbeta was determined immunohistochemically in the biopsy specimens. Quality of life was assessed with two standard questionnaires. No objective responses were seen in either group. Median time to progression was 77 and 29 days (P=0.411) and median survival time was 140 and 60 days (P=0.517) for gemcitabine and imatinib, respectively. Survival and treatment responses were independent of KIT and PDGFRbeta expression in patients treated with imatinib. Grade 3/4 toxicities of imatinib treatment were anemia, elevated liver enzymes, vomiting, and dyspnea. Patients treated with imatinib reported diarrhoea and/or altered bowel function more frequently, which were treatable symptomatically. Quality of life was similar in both groups. In this small series of pancreatic cancer patients, treatment with imatinib was not associated with a significant control of cancer progression. 相似文献
92.
Gosain A Matthies AM Dovi JV Barbul A Gamelli RL DiPietro LA 《The Journal of surgical research》2006,135(2):218-225
BACKGROUND: In healing wounds, rising levels of vascular endothelial growth factor (VEGF) induce a period of robust angiogenesis. The levels of pro-angiogenic factors in the wound begin to decline just before a period of vascular regression, suggesting that these mediators are necessary to sustain vessel density. The purpose of this study was to determine if the maintenance of pro-angiogenic stimuli in the wound would prevent physiological vessel regression. MATERIALS AND METHODS: A standard subcutaneous sponge wound model was modified by the addition of a mini-osmotic pump, allowing manipulation of the wound milieu by the addition of exogenous growth factors. After initial characterization of this model, exogenous VEGF (10 microg/mL), FGF (10 microg/mL), PDGF (10 microg/mL), or VEGF (10 microg/mL) plus FGF (10 microg/mL) were delivered to wounds and blood vessel density analyzed by immunohistochemistry. RESULTS: VEGF administration resulted in a transient increase in wound vessel density (P < 0.05). None of the pro-angiogenic growth factors (VEGF, FGF, PDGF, VEGF/FGF) were able to prevent vascular regression (P = NS). CONCLUSIONS: These findings suggest that the anti-angiogenic signals that mediate physiological vascular regression in wounds are strongly dominant over pro-angiogenic stimuli during the later phases of wound healing. Clinical manipulation of anti-angiogenic signals in addition to the currently used pro-angiogenic targets may be needed to achieve therapeutic modulation of blood vessel density. 相似文献
93.
94.
Double blockade of cell cycle progression by coptisine in vascular smooth muscle cells 总被引:3,自引:0,他引:3
Coptisine, an isoquinoline alkaloid isolated from rhizome of Coptis japonica, inhibits proliferation of vascular smooth muscle cells (VSMCs). The aim of this study was to evaluate the action of coptisine, along with berberine (a structurally similar isoquinoline alkaloid), on progression of the cell cycle in VSMCs. Coptisine displayed antiproliferative action against VSMCs by blocking the cell cycle at G(1) and G(2)/M phases. The G(1) block was shown by inhibition of [(3)H]thymidine incorporation into VSMCs at coptisine concentrations higher than 15 microM. The mechanism underlying the G(1) arrest involved a decrease in cyclin D1 protein, although cyclin E, A, and B were not affected by coptisine treatment. The selective reduction in cyclin D1 protein was mainly attributable to accelerated proteolysis via proteasome-dependent pathway, since it was inhibited by a proteasome inhibitor, N-carbobenzoxy-L-leucinyl-L-leucinyl-L-norleucinal (MG132) and further the mRNA level of cyclin D1, protein synthesis, and mitogen-activated protein kinase (MAPK) activity remained unaltered. The mechanism underlying the G(2)/M arrest involved partial inhibition of tubulin polymerization, which was apparent at coptisine concentration of 3 microM. Berberine arrested the cell cycle at G(1) phase via a mechanism identical with coptisine, but did not cause block at G(2)/M phase. The results demonstrate that a small difference in the structure between isoquinoline alkaloids produces a big difference in activity, and that coptisine has a unique double action in arresting the cell cycle of VSMCs. 相似文献
95.
Luteolin prevents PDGF-BB-induced proliferation of vascular smooth muscle cells by inhibition of PDGF beta-receptor phosphorylation 总被引:1,自引:0,他引:1
Kim JH Jin YR Park BS Kim TJ Kim SY Lim Y Hong JT Yoo HS Yun YP 《Biochemical pharmacology》2005,69(12):1715-1721
Luteolin occurs as glycosylated forms in celery, green pepper, perilla leaf and camomile tea, and has been shown to possess antimutagenic, antitumorigenic, antioxidant and antiinflammatory properties. In this study, we have investigated the antiproliferable effect and its mechanism of luteolin on platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic vascular smooth muscle cells (VSMCs). Luteolin significantly inhibited PDGF-BB-induced proliferation and DNA synthesis of rat aortic VSMCs in a concentration-dependent manner. In addition, flow cytometry analysis of DNA content revealed blocking of the PDGF-BB-inducible cell cycle progression by luteolin. Pre-incubation of rat aortic VSMCs with luteolin significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and phospholipase C (PLC)-gamma1 activation as well as c-fos gene expression. Consisted with these findings, luteolin inhibited PDGF-Rbeta phosphorylation induced by PDGF-BB in a concentration-dependent manner. These results suggest that the inhibitory effect of luteolin on the PDGF-BB-induced proliferation of rat aortic VSMCs may be mediated by blocking phosphorylation of PDGF-Rbeta. 相似文献
96.
系膜细胞的增生是多种原发性和继发性肾小球疾病的主要病理特点,系膜细胞增殖和细胞外基质沉积是导致肾小球硬化的重要因素。系膜增生性肾炎(MsPGN)是我国原发性肾小球疾病中常见的病理类型,约占我国肾穿刺病人的20%~25%。因此,抑制系膜细胞增生及细胞外基质的沉积成为治疗此类疾病的关键。本篇就系膜增生性肾病与TGF-β的表达、基质金属蛋白酶类(ma-trix metalloproteinases,MMPs)的活化、NF-KB的活化和PDGF的旁分泌或自分泌之间的关系加以论述。 相似文献
97.
98.
Hayashi T Morishita E Ontachi Y Yamazaki M Asakura H Yoshida T Nakao S 《American journal of hematology》2006,81(2):121-123
Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogenic bone marrow transplantation. Even with aggressive treatment, cGVHD is associated with a significant degree of morbidity and mortality. cGVHD resembles autoimmune disorder, particularly systemic sclerosis (SSc). Sarpogrelate hydrochloride (SH) is an antagonist of the 5-hydroxytryptamine2A (5HT2A) receptor and has been reported to be effective in the treatment of systemic sclerosis (SSc) patients with Raynaud phenomenon. We used SH to treat a cGVHD patient, and we measured plasma PDGF and total TGF-beta levels. After SH treatment, his plasma PDGF and total TGF-beta levels decreased, and he noticed improvement in his skin pigmentation. In the present case, SH may have improved the skin lesion by inhibiting the synthesis of PDGF and TGF-beta. 相似文献
99.
乙肝后肝硬化患者血清CTGF、PDGF、TGF-β_1测定的意义 总被引:2,自引:0,他引:2
目的:探讨乙型肝炎后肝硬化患者血清CTGF、PDGF、TGF-β1水平的变化及临床意义。方法:将50例乙肝后肝硬化患者按不同的病情分为轻度、中度及重度三组;设体检健康人45名作为对照组。血清TGF-β1水平采用放射免疫分析;CTGF及PDGF则采用ELISA测定。并将测定结果进行统计分析。结果:结果显示,血清CTGF水平轻度组与对照组比较略有升高,但无统计学意义(P〉0.05);中度组患者该指标水平则显著高于对照组(P〈0.05);重度组水平更为显著(P〈0.01)。且发现其递增规律与肝硬化病情的严重程度呈明显的平行关系。PDGF测定值显示,轻度组水平显著高于对照组(P〈0.05),中度和重度两组水平则较对照组升高更为显著(P均〈0.01)。其水平的递增关系也与病情的严重程度相一致。TGF-β1水平的变化趋势同PDGF。结论:本文患者三项血清指标水平的变化与乙肝后肝硬化的发病及病情进展有关;其测定有助于了解本病的发生机制和预后评估。 相似文献
100.
HiB5 is a multipotent hippocampal stem cell line whose differentiation into cells of a neuronal phenotype is promoted by neurotrophic factors such as PDGF and brain-derived neurotrophic factor (BDNF). We examined the potential role of Src homology 2 (SH2)-containing protein tyrosine phosphatase (Shp2) in this differentiation process. We found that Shp2 became tyrosine phosphorylated following PDGF treatment. Wild-type Shp2 enhanced the expression of neurofilament, synapsin I and PSD95 by PDGF and BDNF, whereas their expression was attenuated by the catalytically inactive mutants Shp2C/S and Shp2DeltaP. Formation of dendritic spine-like structures increased with wild-type Shp2, but diminished with Shp2C/S and Shp2DeltaP. PSD95, localized in the post-synaptic density region of dendritic spines, PDGFRbeta and TrkB were co-immunoprecipitated with Shp2 antibodies. These results suggest that Shp2 plays a positive role in mediating PDGF- and BDNF-activated signaling which promotes the formation of dendritic spines. 相似文献