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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Increased tumor uptake of chemotherapeutics and improved chemoresponse by novel non-anticoagulant low molecular weight heparin.
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Increased tumor uptake of chemotherapeutics and improved chemoresponse by novel non-anticoagulant low molecular weight heparin.

机译：新型非抗凝低分子量肝素可增加化疗药物对肿瘤的吸收，并改善化学反应。

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BACKGROUND: Recent prospective clinical trials of low molecular weight heparins (LMWHs) have demonstrated that these agents may provide significant advantages in terms of progression-free and overall survival in certain subgroups of cancer patients. The mechanisms of improved survival associated with LMWHs are not known, and may involve direct and/or indirect effects on tumor growth. The purpose of this study was to investigate the effects of LMWH and a sulfated non-anticoagulant LMWH (S-NACH) on tumor chemotherapeutic uptake and chemoresponse. MATERIALS AND METHODS: LMWH and S-NACH were tested for their ability to reduce tumor growth and tumor-associated angiogenesis using three different in vivo models. Biodistribution studies were undertaken to determine the effect of these agents on uptake of paclitaxel (PACL) and doxorubicin (Dox) by breast cancer tumor xenografts. RESULTS: LMWH and S-NACH (10 mg/kg s.c. daily) effectively limited tumor growth of human A549 lung adenocarcinoma xenografts in the nude mouse. In an MDA453/LCC6 breast tumor xenograft model, PACL plus S-NACH showed significant (p < 0.01) tumor growth suppression and improved survival when compared to PACL alone. LMWH increased [(124-)I]-PACL uptake into MDA453/LCC6 tumors, with tumor:muscle ratios several fold greater than that of [(124-)I]-PACL alone 24 h post-injection. Similarly, LMWH and S-NACH significantly (p < 0.01) increased the uptake of Dox by 1.5-2 fold in MCF7 Dox-resistant tumor xenografts. CONCLUSION: Protocols utilizing adjuvant or neo-adjuvant therapy with LMWH or S-NACH could lead to increased tumor chemo responsiveness, potentially overcoming tumor chemoresistance.
机译：背景：最近的低分子量肝素（LMWHs）的前瞻性临床试验表明，这些药物在某些癌症亚组的无进展生存期和总体生存率方面可能具有显着优势。与LMWH相关的改善生存的机制尚不清楚，可能涉及对肿瘤生长的直接和/或间接影响。这项研究的目的是调查LMWH和硫酸化的非抗凝LMWH（S-NACH）对肿瘤化疗药物吸收和化学反应的影响。材料与方法：使用三种不同的体内模型测试了LMWH和S-NACH减少肿瘤生长和与肿瘤相关的血管生成的能力。进行了生物分布研究，以确定这些药物对乳腺癌肿瘤异种移植对紫杉醇（PACL）和阿霉素（Dox）摄取的影响。结果：LMWH和S-NACH（每天10 mg / kg皮下注射）有效地限制了裸鼠中人A549肺腺癌异种移植物的肿瘤生长。在MDA453 / LCC6乳腺肿瘤异种移植模型中，与单独的PACL相比，PACL加S-NACH表现出显着（p <0.01）的肿瘤生长抑制作用，并提高了生存率。注射后24小时，LMWH增加了[（124-）I] -PACL对MDA453 / LCC6肿瘤的摄取，其肿瘤：肌肉比率比单独的[（124-）I] -PACL高几倍。同样，在耐MCF7 Dox的肿瘤异种移植物中，LMWH和S-NACH显着（p <0.01）使Dox的摄取增加了1.5-2倍。结论：使用LMWH或S-NACH的辅助或新辅助疗法的方案可能导致肿瘤化学反应性增强，可能克服肿瘤化学耐药性。

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