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81.
《Expert opinion on pharmacotherapy》2013,14(4):849-863
The thalidomide product is a racemic mixture of the L- and D-enantiomeric forms of a synthetic glutamic acid derivative that contains a phthalimide ring and a glutarimide ring. Initially marketed as a sedative, it was withdrawn from the world market after it was found to be associated with severe birth defects. Recently, the compound has generated renewed interest because of its immunomodulatory and anti-angiogenic properties. The nature of its immunologic effects is under active investigation. It is orally bioavailable and can be administered in once daily dosing. Its primary route of metabolism is spontaneous hydrolysis. In controlled clinical trials, thalidomide has proven effective in the treatment of erythema nodosum leprosum, oral and oesophageal aphthous ulceration associated with advanced HIV infection and oral ulceration associated with Behcet’s syndrome. Promising results have been obtained in preliminary studies of other immunologic and neoplastic disorders, but controlled clinical studies are still lacking for these entities. Adverse effects include teratogenicity peripheral neuropathy and sedation. In the US, thalidomide can be prescribed only through a restricted drug distribution program. 相似文献
82.
Andrew C. Prince Neel G. Patel Lindsay S. Moore Andrew S. McGee John C. Ahn Christopher D. Willey 《Journal of drug targeting》2013,21(2):193-200
AbstractIntratumoural metabolic demands result in excessive angiogenic cytokine release leading to unorganised vasculature. Resultant fluid dynamics oppose blood flow and drug penetration due to a marked increase in interstitial fluid hydrostatic pressure. It is hypothesised that anti-angiogenic therapy may function to ‘prune’ vasculature and lead to improved chemotherapeutic penetration. Subcutaneous, OSC19 tumour bearing mice (n?=?5/dose/agent) were administered varying doses of an anti-mouse VEGFR2 (DC101) or an anti-mouse VEGFR3 (31C1) –3 d, –1 d, 0 d, +1 d and +3 d prior to 200?µg of cetuximab fluorescently labelled with IRDye800CW. Fluorescence imaging of tumours was performed 10 d post cetuximab-IRDye800CW dose to monitor therapeutic uptake. Co-administration of dual anti-angiogenic agents at 50–50%, 75–25% and 25–75% using optimal dose and time (–1 d 10?mg/kg anti-VEGFR2 and –1 d 40?mg/kg anti-VEGFR3) was also evaluated. In order to establish vessel normalisation, NG2 (pericyte marker) and CD31 (endothelial cells) ratios were assessed during immunohistochemical staining of tumour sections. Twenty-mg/kg anti-VEGFR3?+?5?mg/kg anti-VEGFR2 significantly (p?<?.0005) reduced tumour size (–73%) compared to control (59%). The 20?mg/kg anti-VEGFR3?+?5?mg/kg anti-VEGFR2 and 30?mg/kg anti-VEGFR3?+?2.5?mg/kg anti-VEGFR2 significantly (p?<?.0004) improved percent-injected cetuximab-IRDye800CW dose/gram tumour tissue compared to other groups. Adjuvant, dual anti-angiogenic therapy targeting VEGFR2 and VEGFR3 significantly enhances tumour chemotherapeutic uptake compared to control. 相似文献
84.
Anti-Cancer,Anti-Diabetic and Other Pharmacologic and Biological Activities of Penta-Galloyl-Glucose 总被引:1,自引:0,他引:1
Jinhui Zhang Li Li Sung-Hoon Kim Ann E. Hagerman Junxuan Lü 《Pharmaceutical research》2009,26(9):2066-2080
1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose (PGG) is a polyphenolic compound highly enriched in a number of medicinal herbals. Several in vitro and a handful of in vivo studies have shown that PGG exhibits multiple biological activities which implicate a great potential for PGG in the therapy
and prevention of several major diseases including cancer and diabetes. Chemically and functionally, PGG appears to be distinct
from its constituent gallic acid or tea polyphenols. For anti-cancer activity, three published in vivo preclinical cancer model studies with PGG support promising efficacy to selectively inhibit malignancy without host toxicity.
Potential mechanisms include anti-angiogenesis; anti-proliferative actions through inhibition of DNA replicative synthesis,
S-phase arrest, and G1 arrest; induction of apoptosis; anti-inflammation; and anti-oxidation. Putative molecular targets include p53, Stat3, Cox-2,
VEGFR1, AP-1, SP-1, Nrf-2, and MMP-9. For anti-diabetic activity, PGG and analogues appear to improve glucose uptake. However,
very little is known about the absorption, pharmacokinetics, and metabolism of PGG, or its toxicity profile. The lack of a
large quantity of highly pure PGG has been a bottleneck limiting in vivo validation of cancer preventive and therapeutic efficacies in clinically relevant models. 相似文献
85.
目的:研究白头翁醇提物对昆明小鼠H22肝癌细胞皮下移植瘤的抗血管生成作用。方法:建立鼠H22肝癌细胞小鼠皮下移植瘤模型,给予不同剂量白头翁醇提物灌胃治疗,连续用药10天后,观察用药后肿瘤的大小,计算瘤重抑制率并测定肿瘤微血管密度(MVD)。结果:20g/kg白头翁醇提物对小鼠H22细胞皮E移植瘤作用后瘤重显著低于对照组(P=0.01)。10g/kg、20g/kg白头翁醇提物对小鼠H22细胞皮下移植瘤治疗后的微血管计数均显著低于对照组(P值分别为0.037、0.01)。结论:白头翁醇提物对荷瘤鼠H22肝癌移植瘤具有抗肿瘤作用,其作用机理可能与抗肿瘤血管生成作用有关。 相似文献
86.
87.
Anti-angiogenic effects of the thienopyridine SR 25989 in vitro and in vivo in a murine pulmonary metastasis model 总被引:2,自引:0,他引:2
Mah-Becherel MC Céraline J Deplanque G Chenard MP Bergerat JP Cazenave JP Klein-Soyer C 《British journal of cancer》2002,86(5):803-810
Neovascularisation is a key step in tumour growth and establishment of distant metastases. We have recently demonstrated that the thienopyridine SR 25989 an enantiomer of the anti-aggregant clopidogrel (Plavix) lacking anti-aggregant activity, inhibits endothelial cell proliferation in vitro by increasing the expression of endogenous thrombospondin-1, a natural potent inhibitor of angiogenesis. The anti-angiogenic effect of SR 25989 was further assessed in vitro in a quantitative assay of angiogenesis comprising a fragment of rat aorta embedded in a fibrin gel and in vivo in a pulmonary metastatic model using C57BL/6 mice inoculated in the foot pad with the highly metastatic melanoma cell line B16 F10. SR 25989 induced a dose dependent inhibition of spontaneous microvessel development in vitro reaching half maximal inhibition at around less than 50 microM and caused platelet derived growth factor induced angiogenesis to regress as a function of thienopyridine concentration. In vivo, SR 25989 did not alter significantly the growth rate of the primary tumour in the foot pad and did not inhibit development of inguinal nodes which appeared after amputation. However, the number and size of lung metastases were reduced in treated animals when examined at the time of sacrifice. In addition, the few metastases over 1 mm3 did not show any neovascularisation, as confirmed by negative von Willebrand immunostaining and in contrast to intense vascularisation seen in metastases developed by control mice. These results confirm that SR 25989 possesses potent anti-angiogenic properties and is able to inhibit metastatic dissemination and growth. The lack of effect on the primary tumour and inguinal nodes illustrates the complexity of the mechanisms involved in tumoural neo-angiogenesis and points out the possibility for distinct processes leading to neovascularisation in primary tumour as opposed to metastases. 相似文献
88.
Role of the Tumor Microenvironment in Mediating Response to Anti-angiogenic Therapy 总被引:10,自引:0,他引:10
Jung YD Ahmad SA Akagi Y Takahashi Y Liu W Reinmuth N Shaheen RM Fan F Ellis LM 《Cancer metastasis reviews》2000,19(1-2):147-157
Despite the development of innovative anti-angiogenic strategies, early clinical trials have not replicated the results observed from preclinical models. One reason for this apparent discrepancy is the fact that tumor endothelium is phenotypically distinct from normal tissue endothelium. Moreover, it has recently become apparent that each individual tumor may display a different angiogenic phenotype. The expression of angiogenic factors in tumors is controlled by both intrinsic factors in the tumor cell and the influence of the host microenvironment. The diversity of angiogenic factor expression in tumors growing at different sites, combined with the fact that endothelial cells in different organs and tumors are phenotypically distinct, constitutes a formidable challenge for the development of effective anti-angiogenic regimens. This review provides an overview of how the microenvironment regulates tumor angiogenesis and affects the efficacy of anti-angiogenic therapy. 相似文献
89.
90.
硫酸软骨素对鸡胚绒毛尿囊膜的血管生成抑制作用 总被引:7,自引:1,他引:7
目的观察硫酸软骨素的血管生成效应。方法将 15g/L硫酸软骨素溶液 4 μl加到孵化 4d的鸡胚绒毛尿囊膜血管网上 ,2 4h后观察对血管生长的影响。同时设有同浓度的氢化可的松组和肝素组及三蒸水组作为对照组。结果硫酸软骨素使鸡胚绒毛尿囊膜血管发生大面积褪色 ,血管密度减低 ;氢化可的松组血管结构模糊 ,分枝发生断裂 ,颜色变浅 ,血管密度减少 ;肝素组血管生长旺盛 ,血管密度增加 ;正常对照组血管网清晰 ,呈叶脉状 ,放射状生长。结论硫酸软骨素有显著的抗血管生成活性。 相似文献