POTENTIATION OF CYTOTOXIC THERAPIES BY TNP-470 AND MINOCYCLINE IN MICE BEARING EMT-6 MAMMARY-CARCINOMA
POTENTIATION OF CYTOTOXIC THERAPIES BY TNP-470 AND MINOCYCLINE IN MICE BEARING EMT-6 MAMMARY-CARCINOMA
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DOI：
10.1007/bf00666043
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发表时间：
1995-01-01
影响因子：
3.8
通讯作者：
GOFF, D
中科院分区：
文献类型：
--
作者：
TEICHER, BA;HOLDEN, SA;GOFF, D
研究了抗血管生成药物TNP-470和米诺环素单独或联合应用于小鼠EMT-6乳腺癌及其耐药亚系EMT-6/CTX和EMT-6/CDDP中增强多种细胞毒疗法的抗肿瘤作用的能力。然而，它们与环磷酰胺、顺铂或硫代替巴一起使用，显著增加了这些细胞毒疗法对药物反应的肿瘤生长延迟--TNP-470和米诺环素一起增加了大约2倍。在耐药肿瘤中，抗血管生成药物的治疗没有逆转耐药性，但确实增加了细胞毒药物的效果。TNP-470/米诺环素治疗也增加了这三种肿瘤的氧合。因此，TNP-470/米诺环素的应用提高了分次放射治疗的疗效，特别是在与全氟化钠乳剂氧气递送剂/碳素一起使用时。这些结果表明，包括针对肿瘤内增殖的正常细胞的治疗方案以及针对恶性细胞的治疗方案可以产生更好的结果。
The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP.The antiangiogenic agents alone or in combination did not alter the growth of the tumors. However, their administration along with cyclophosphamide, CDDP, or thiotepa substantially increased the tumor growth delay produced by these cytotoxic therapies in tumors responsive to the drugs - the increase was about 2-fold for TNP-470 and minocycline together. In drug resistant tumors, treatment with the antiangiogenic agents did not reverse drug resistance but did increase the effect of the cytotoxic drugs.Treatment with TNP-470/minocycline also increased the oxygenation of each of the three tumors. Thus, TNP-470/minocycline administration increased the efficacy of fractionated radiation therapy, especially when used along with a perflubron emulsion oxygen delivery agent/carbogen.These results indicate that treatment regimens including therapies directed toward the proliferating normal cells within a tumor mass as well as therapies directed toward the malignant cells can produce improved outcomes.