Importance of timing in cyclophosphamide therapy of MOPC-315 tumor-bearing mice.
Importance of timing in cyclophosphamide therapy of MOPC-315 tumor-bearing mice.
复制标题
MOPC-315 荷瘤小鼠环磷酰胺治疗时机的重要性。
作者：
J. Hengst;M. Mokyr;S. Dray
发现肿瘤接种后环磷酰胺（CY）给药的时机对于成功治疗MOPC-315荷瘤小鼠至关重要。接种3.5 × 106个活肿瘤细胞后，对携带10- 25 mm肿瘤的小鼠（第8 - 14天）单次腹腔注射CY（15 mg/kg）治愈了大多数小鼠，而对携带不可触及肿瘤的小鼠（第4天）注射CY仅治愈了少数小鼠。肿瘤接种和CY给药之间的时间间隔而不是肿瘤大小对成功治疗至关重要，因为接种105个活肿瘤细胞后12至13天携带不可触及肿瘤的小鼠通过CY治疗治愈。此外，CY治疗小鼠携带大（19毫米）肿瘤是没有治愈的小鼠，以前已经治疗时，他们的肿瘤是不可触及的。治愈注射CY到小鼠携带大肿瘤导致增强的能力，他们的脾细胞安装细胞毒性抗肿瘤反应后，在体外免疫与丝裂霉素C处理的刺激肿瘤细胞。这并没有通过消耗玻璃粘附细胞而进一步增强，并且伴随着脾脏中携带表面MOPC-315骨髓瘤蛋白的细胞百分比的降低。来自CY处理的小鼠的体外免疫的脾细胞表现出的抗肿瘤细胞毒性水平与来自未处理的荷瘤小鼠的体外免疫的脾细胞表现出的抗肿瘤细胞毒性水平相当，所述未处理的荷瘤小鼠在体外免疫之前耗尽了玻璃粘附细胞。由于在体外免疫之前从肿瘤携带者脾细胞中去除玻璃粘附细胞显示出比通过去除肿瘤细胞获得的抗肿瘤细胞毒性更大的增强（25），因此目前的数据表明，除了药物的杀肿瘤活性外，它还消除了脾中的其他抑制因子。CY治疗后治愈肿瘤的小鼠表现出高度的抗肿瘤免疫力，这在体内通过它们拒绝大肿瘤攻击的能力来判断，在体外通过它们的脾细胞在体外免疫后产生“次级型”抗肿瘤应答的能力来判断。
The timing of cyclophosphamide (CY) administration after tumor inoculation was found to be critical for successful therapy of MOPC-315 tumor-bearing mice. Following inoculation with 3.5 × 106 viable tumor cells, a single i.p. injection of CY (15 mg/kg) into mice bearing 10- to 25-mm (Days 8 to 14) tumors cured most mice, whereas injection into mice bearing nonpalpable (Day 4) tumors cured only a few of the mice. The time interval between tumor inoculation and CY administration rather than the tumor size was critical for successful therapy since mice bearing nonpalpable tumors 12 to 13 days postinoculation with 105 viable tumor cells were cured by CY therapy. Furthermore, CY therapy of mice bearing large (19-mm) tumors was not curative for mice that had been treated previously when their tumors were nonpalpable. A curative injection of CY into mice bearing large tumors resulted in an augmented ability of their spleen cells to mount a cytotoxic antitumor response upon in vitro immunization with mitomycin C-treated stimulator tumor cells. This was not further augmented by depletion of glass-adherent cells and was accompanied by a decrease in the percentage of cells bearing surface MOPC-315 myeloma protein in the spleen. The level of antitumor cytotoxicity exhibited by in vitro -immunized spleen cells from CY-treated mice was equivalent to that exhibited by in vitro -immunized spleen cells from untreated tumor-bearing mice that prior to in vitro immunization were depleted of glass-adherent cells. Since depletion of glass-adherent cells from tumor bearer spleen cells prior to in vitro immunization was shown to result in greater augmentation of antitumor cytotoxicity than that obtained by depletion of tumor cells (25), the present data suggest that in addition to the drug's tumoricidal activity, it also eliminates other suppressor elements in the spleen. Mice cured of tumors following CY therapy exhibited a high degree of antitumor immunity as judged in vivo by their ability to reject a large tumor challenge and in vitro by the ability of their spleen cells to mount a “secondary type” antitumor response upon in vitro immunization.