Ruggiero R A, Di Gianni P D, Franco M, Bustuoabad O D
Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Medicina (B Aires). 1996;56 Suppl 1:57-64.
Concomitant resistance of tumor-bearing mice against a second tumor challenge was evaluated in euthymic and athymic mice using 17 tumors with different degrees of immunogenicity. Two temporarily separated peaks of concomitant resistance were detected during tumor development: the first peak was only observed associated with small immunogenic tumors (< 500 m3., it was tumor-specific and mediated by T cell-dependent immunological mechanisms. The second peak was exhibited by large tumors (> 2000 mm3) independently of their immunogenicity; it was non-tumor specific, thymus-independent and correlated with a serum-activity (neither antibodies nor complement) which inhibited the in vitro proliferation of tumor cells. Out of 17 tumors studied, 15 tumors exhibited a moderate or strong concomitant resistance. The remaining two, which exhibited a weak or undetectable concomitant resistance and correlatively, a low or absent serum-inhibitory activity were the only tumors which included lung metastases. This fact suggested a correlation between concomitant resistance, absence of metastases and the existence of an inhibitory factor(s) in the serum. This inhibitory factor was partially characterized: it was resistant to boiling (5-10' at 100 degrees C) and to variations of pH; its molecular weight was estimated between 850 and 1200 D; it was recovered in only one fraction from HPLC (high power liquid chromatography) columns presenting maximum absorption at 215 and 266 nm; amino acid analysis and magnetic nuclear resonance studies suggested the presence of a molecule of thyrosine and one or two molecules of carbohydrates in its structure.
利用17种具有不同免疫原性程度的肿瘤,在正常胸腺小鼠和无胸腺小鼠中评估荷瘤小鼠对第二次肿瘤攻击的伴随抗性。在肿瘤发展过程中检测到两个暂时分开的伴随抗性峰值:第一个峰值仅在与小的免疫原性肿瘤(<500立方毫米)相关时观察到,它是肿瘤特异性的,由T细胞依赖性免疫机制介导。第二个峰值由大肿瘤(>2000立方毫米)表现出来,与它们的免疫原性无关;它是非肿瘤特异性的,不依赖胸腺,并且与一种抑制肿瘤细胞体外增殖的血清活性(既不是抗体也不是补体)相关。在所研究的17种肿瘤中,15种肿瘤表现出中度或强烈的伴随抗性。其余两种肿瘤表现出弱的或不可检测的伴随抗性,相应地,血清抑制活性低或不存在,这是仅有的包含肺转移的肿瘤。这一事实表明伴随抗性、无转移与血清中存在抑制因子之间存在相关性。这种抑制因子得到了部分表征:它对煮沸(100℃下5 - 10分钟)和pH变化具有抗性;其分子量估计在850至1200道尔顿之间;它仅在高效液相色谱(HPLC)柱的一个馏分中回收,该馏分在215和266纳米处呈现最大吸收;氨基酸分析和核磁共振研究表明其结构中存在一个酪氨酸分子和一两个碳水化合物分子。