Papanastasiou M, Baxevanis C N, Papamichail M
Department of Immunology, Hellenic Anticancer Institute, Athens, Greece.
Cancer Immunol Immunother. 1992;35(2):145-50. doi: 10.1007/BF01741862.
The effect of prothymosin alpha (ProT alpha) on the survival of DBA/2 mice inoculated with syngeneic tumour cells was studied. DBA/2 mice inoculated intraperitoneally (i.p.) with 2 x 10(5) syngeneic leukaemic L1210 cells developed ascites within 8-12 days and died 10-14 days later. Treatment with ProT alpha consistently inhibited the development of ascites in 20% of the treated animals and prolonged the survival of 40%-60% of the animals up to 70 days. The most effective treatment schedule of ProT alpha was 300 ng/mouse given i.p. at 2-day intervals for 3 weeks followed by a rest period of 7 days, prior to tumour cell inoculation. Peritoneal exudate (PE) cells collected from mice treated with the optimal dose of ProT alpha produced, in the absence of exogenous stimulus, six- to eightfold higher levels of tumour necrosis factor alpha (TNF alpha) than PE cells from control mice. Furthermore these cells exhibited cytotoxic activity against several tumour cell lines including the syngeneic L1210, the TNF-insensitive P815 mastocytoma, the human MOLT-4 lymphoblastic leukaemia, as well as the murine TNF-sensitive L929 fibroblast cell line. Kinetic studies revealed that both production of TNF alpha and tumoricidal activity peaked 7 days after the last injection of ProT alpha and were maintained at high levels over a period of 1 month. Injections with 150 ng ProT alpha slightly improved the survival of mice whereas higher (500 ng and 1000 ng) doses of ProT alpha and a wide range of thymosin alpha 1 doses remained without any effect. PE cells collected from these mice produced extremely low levels of TNF alpha and exhibited negligible tumoricidal activity. Our data demonstrate that ProT alpha has a protective effect in vivo against the growth of adoptively transferred tumour cells and suggest that this effect is, at least in part, mediated by ProT alpha-activated PE cells. These cells were demonstrated to produce high levels of TNF alpha in vitro and to exhibit activity against both TNF-sensitive and TNF-resistant cell lines.
研究了前胸腺素α（ProTα）对接种同基因肿瘤细胞的DBA/2小鼠存活的影响。腹腔内（i.p.）接种2×10⁵个同基因白血病L1210细胞的DBA/2小鼠在8 - 12天内出现腹水，并在10 - 14天后死亡。用ProTα治疗持续抑制了20%受试动物腹水的形成，并使40% - 60%的动物存活期延长至70天。ProTα最有效的治疗方案是在肿瘤细胞接种前，以300 ng/小鼠的剂量，每隔2天腹腔注射1次，共3周，随后休息7天。从用最佳剂量ProTα治疗的小鼠收集的腹腔渗出液（PE）细胞，在无外源性刺激的情况下，产生的肿瘤坏死因子α（TNFα）水平比对照小鼠的PE细胞高6至8倍。此外，这些细胞对几种肿瘤细胞系表现出细胞毒性活性，包括同基因的L1210、TNF不敏感的P815肥大细胞瘤、人MOLT - 4淋巴细胞白血病以及小鼠TNF敏感的L929成纤维细胞系。动力学研究表明，TNFα的产生和杀肿瘤活性在最后一次注射ProTα后7天达到峰值，并在1个月内维持在高水平。注射150 ng ProTα可略微提高小鼠的存活率，而更高剂量（500 ng和1000 ng）的ProTα以及广泛范围的胸腺素α1剂量则没有任何效果。从这些小鼠收集的PE细胞产生极低水平的TNFα，并且表现出可忽略不计的杀肿瘤活性。我们的数据表明，ProTα在体内对过继转移肿瘤细胞的生长具有保护作用，并表明这种作用至少部分是由ProTα激活的PE细胞介导的。这些细胞在体外被证明可产生高水平的TNFα，并对TNF敏感和TNF抗性细胞系均表现出活性。
