Bezault J, Walsh C, Tarcsay L, Frost H, Liebes L, Furmanski P
New York University, Department of Biology, New York 10003.
In Vivo. 1993 Nov-Dec;7(6A):487-91.
The synthetic molecule muramyl tripeptide (CGP 19835A) encapsulated in liposomes is effective in increasing the survival of mice with spontaneous experimental lung metastases induced by the RENCA renal adenocarcinoma and B16 melanoma tumor models. The present study was aimed at extending the effects of CGP 19835A to another highly metastatic carcinoma model and at evaluating the efficacy of combination therapy with standard cytotoxic agents and other immunomodulators. C57BL/6 mice received whole tumor implants of PancO2, a spontaneously metastasizing pancreatic adenocarcinoma, subcutaneously in the hind leg. Therapeutic effects were measured by increased survival which is a direct function of the growth of spontaneous lung metastases in this system. No therapeutic efficacy was observed with CGP 19835A alone or in combination with any of a series of cytotoxic or biological agents, including cis-platinurn (cis-Pt), mitomycin C (MMC), adriamycin (ADR), cyclophosphamide (CP), interferon gamma (IFN gamma), and interleukin 2 (IL-2). In accord with previous studies, when the B16-F10 melanoma was used as an experimental metastatic tumor model, CGP 19835A, alone and in combination with CP, significantly reduced the number of pulmonary metastases. Cis-Pt, however, partially negated the effects of CGP 19835A when a combination of the two agents was used. The results indicate that CGP 19835A is an effective therapeutic agent in some models of spontaneous or experimental lung metastases, but not others, and that the effects of CGP 19835A are not enhanced by the accompanying cytotoxic drugs tested here.
包裹在脂质体中的合成分子胞壁酰三肽（CGP 19835A）可有效提高由RENCA肾腺癌和B16黑色素瘤肿瘤模型诱导的自发性实验性肺转移小鼠的存活率。本研究旨在将CGP 19835A的作用扩展到另一种高转移性癌模型，并评估与标准细胞毒性药物和其他免疫调节剂联合治疗的疗效。C57BL/6小鼠在其后腿皮下接受了PancO2（一种自发性转移的胰腺腺癌）的全肿瘤植入物。通过提高存活率来衡量治疗效果，存活率是该系统中自发性肺转移生长的直接函数。单独使用CGP 19835A或与一系列细胞毒性或生物制剂（包括顺铂（cis-Pt）、丝裂霉素C（MMC）、阿霉素（ADR）、环磷酰胺（CP）、干扰素γ（IFNγ）和白细胞介素2（IL-2））联合使用时，均未观察到治疗效果。与先前的研究一致，当将B16-F10黑色素瘤用作实验性转移肿瘤模型时，CGP 19835A单独使用或与CP联合使用均能显著减少肺转移灶的数量。然而，当两种药物联合使用时，顺铂部分抵消了CGP 19835A的作用。结果表明，CGP 19835A在某些自发性或实验性肺转移模型中是一种有效的治疗剂，但在其他模型中并非如此，并且此处测试的伴随细胞毒性药物并未增强CGP 19835A的作用。
