Berger M R, Petru E, Schmähl D
J Cancer Res Clin Oncol. 1987;113(5):437-45. doi: 10.1007/BF00390037.
Four experiments investigating the antitumor activity of bacterial lipopolysaccharide (LPS) against the autochthonous methylnitrosourea-induced mammary carcinoma are summarized. Administration of LPS alone i.v. caused distinct regression of small tumors following its first injection. This therapeutic effect, however, was short-lived and could not be maintained by administering a second dose. The observed antineoplastic activity of LPS was dose-related, whereas no dose-response relationship was observed with respect to its toxicity. A series of experiments in which LPS was combined with other compounds to possibly exploit its activity while reducing the toxicity were performed. Neither the combination with cytotoxic drugs such as 4'-(9-acridinylamino)-methansulfone-m-aniside or cyclophosphamide nor that with 1-octadecyl-2-methoxy-rac-glycero-3-phosphocholine or hexadecylphosphocholine showed sufficient anticancer activity at acceptable toxicity. In all experiments promising efficacy was observed at high dosages but also high toxicity. When the dosages were reduced, diminished antineoplastic activity was found together with overproportionally high mortality. It might therefore be concluded that the active dose range of LPS cannot be reached clinically because of its inherent toxicity.
总结了四项关于细菌脂多糖（LPS）对甲基亚硝基脲诱导的自发性乳腺癌抗肿瘤活性的实验。单独静脉注射LPS，首次注射后可使小肿瘤明显消退。然而，这种治疗效果是短暂的，第二次给药无法维持。观察到LPS的抗肿瘤活性与剂量相关，而其毒性方面未观察到剂量反应关系。进行了一系列实验，将LPS与其他化合物联合使用，以在降低毒性的同时发挥其活性。LPS与细胞毒性药物如4'-（9-吖啶基氨基）-甲砜基间茴香胺或环磷酰胺联合使用，以及与1-十八烷基-2-甲氧基-rac-甘油-3-磷酸胆碱或十六烷基磷胆碱联合使用，在可接受的毒性水平下均未显示出足够的抗癌活性。在所有实验中，高剂量时观察到有前景的疗效，但毒性也很高。当剂量降低时，抗肿瘤活性降低，同时死亡率过高。因此可以得出结论，由于其固有的毒性，临床上无法达到LPS的有效剂量范围。
