Treshchalina E M, Sedakova L A, Vlasenkova N K, Zhukova O S, Firsova G A, Mikhaĭlova L M, Kolesnikova E Iu, Zimakova N I, Khabarov S V, Gerasimova G K
N.N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences, Moscow.
Vopr Onkol. 2001;47(3):321-7.
A synthesized analog of myelopeptide HP-2-->M[symbol: see text]-2 (Leu-Val-Val-Tyr-Pro-Trp) caused a significant (60-80%) and prolonged inhibition of s.c. grafted tumors P388, Ca-755, B-16 and sarcoma 180 in isogenic mice but did not affect the growth of tumor B-16 in nude mice. Nor did it influence proliferative activity or viability of cultured human tumor cells. The best results were obtained with s.c. injections of 0.5-2 mg/kg HP-2-->M[symbol: see text]-2, twice or trice a day, at 96 hr intervals. No symptoms of severe poisoning were registered at doses of HP-2-->M[symbol: see text]-2 100 times the therapeutic one. A pharmacokinetic study in mice revealed prolonged circulation of HP-2-->M[symbol: see text]-2 in blood and a high affinity for the bone marrow (t 1/2 (130.1 hr and 431.6 hr, respectively). HP-2-->M[symbol: see text]-2 restored in vitro the ascites P388-suppressed cytotoxicity of murine T-lymphocytes. HP-2-->M[symbol: see text]-2 is regarded as a candidate for clinical studies of its potential of immunocorrection in cancer patients suffering T-lymphocyte immunity disturbances.
髓肽HP - 2→M[符号：见正文] - 2（亮氨酸 - 缬氨酸 - 缬氨酸 - 酪氨酸 - 脯氨酸 - 色氨酸）的合成类似物，对同基因小鼠皮下移植的肿瘤P388、Ca - 755、B - 16和肉瘤180产生显著（60 - 80%）且持久的抑制作用，但不影响裸鼠体内肿瘤B - 16的生长。它也不影响培养的人肿瘤细胞的增殖活性或活力。皮下注射0.5 - 2 mg/kg的HP - 2→M[符号：见正文] - 2，每天两次或三次，间隔96小时，可获得最佳效果。在HP - 2→M[符号：见正文] - 2剂量为治疗剂量100倍时，未出现严重中毒症状。对小鼠的药代动力学研究表明，HP - 2→M[符号：见正文] - 2在血液中的循环时间延长，且对骨髓具有高亲和力（半衰期分别为130.1小时和431.6小时）。HP - 2→M[符号：见正文] - 2在体外恢复了腹水P388抑制的小鼠T淋巴细胞的细胞毒性。HP - 2→M[符号：见正文] - 2被视为对患有T淋巴细胞免疫紊乱的癌症患者进行免疫纠正潜力临床研究的候选药物。
