结合liposome-entrapped, ends-modified raf反义寡核苷酸(LErafAON)提高了顺铂的抗癌功效,表阿霉素、米托蒽醌、多烯紫杉醇、吉西他滨。

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裴J,张C, Gokhale PC,拉赫曼,Dritschilo,艾哈迈德,Kasid联合国

结合liposome-entrapped, ends-modified raf反义寡核苷酸(LErafAON)提高了顺铂的抗癌功效,表阿霉素、米托蒽醌、多烯紫杉醇、吉西他滨。

抗癌药物。2004年3月,15 (3):243 - 53。

PubMed ID

15014358 (在PubMed

]

文摘

Raf-1蛋白质的丝氨酸/苏氨酸激酶在细胞增殖和细胞生存方面起着重要的作用。我们曾描述了一种新型阳离子liposome-entrapped制定raf反义oligodeoxyribonucleotide (LErafAON)及其辐射敏化剂使用。本研究的目的是检查的影响结合LErafAON和人类前列腺癌的化学治疗剂在增长(曲泽)和胰腺肿瘤异种移植在无胸腺的老鼠(Aspc-1和科罗拉多州357)。曲泽肿瘤小鼠,管理的结合LErafAON(注射。、25毫克/公斤/剂量x10/16)、顺铂(注射。,11.0毫克/公斤/剂量,x3),盐酸表柔比星(EPI)(注射。,9.0毫克/公斤/剂量,x3)或米托蒽醌(MTO)(注射。,2.5毫克/公斤/剂量,x3)导致增强的肿瘤生长抑制与单一代理(LErafAON +顺铂与顺铂,p < 0.0002, n = 8;LErafAON + EPI和EPI, p < 0.0001, n = 6;LErafAON + MTO和MTO, p < 0.05, n = 5)。在前列腺癌或小鼠胰腺肿瘤,结合LErafAON(注射。、25毫克/公斤/剂量x10/13)与多烯紫杉醇(泰素帝)(注射。, 5, 7.5 or 10 mg/kg/dose, x2/4) led to tumor regression or enhanced growth inhibition as compared with single agents (PC-3: LErafAON+Taxotere versus Taxotere, p<0.02, n=7; Aspc-1: LErafAON+Taxotere versus Taxotere, p<0.03, n=5; Colo 357: LErafAON+Taxotere versus Taxotere, p<0.04, n=7). Combination of LErafAON (i.v., 25 mg/kg/dose, x10/13) with gemcitabine (i.v., 75 mg/kg/dose, x4/6) also caused a significant tumor growth inhibition in the two pancreatic carcinoma models studied (Aspc-1: LErafAON+gemcitabine versus gemcitabine, p<0.0001, n=7; Colo 357: LErafAON+gemcitabine versus gemcitabine, p<0.002, n =5). LErafAON treatment (i.v., 25 mg/kg/dose, x10) caused inhibition of Raf-1 protein expression in these tumor tissues (around 25-60%, n=4-7). Interestingly, Taxotere treatment per se also led to decreased steady state level of Raf-1 protein in PC-3 and Aspc-1 tumor tissues (i.v., 10 mg/kg/dose, x1 or 7.5 mg/kg/dose, x2; around 25-80%, n=2/6). Present studies demonstrate enhanced tumor growth inhibition or regression in response to a combination of a chemotherapeutic drug and LErafAON. These data provide a proof-of-principle for the clinical use of LErafAON in combination with chemotherapy for cancer treatment.

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药物

LErafAON