Therapeutic ratio of mono or combination bacterial lipopolysaccharide therapy in methylnitrosourea ? induced rat mammary carcinoma

Abstract

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.

Treatment of chemically induced autochthonous rat mammary and colorectal carcinomas with interleukin-2

“…This study on the role of IL-2 in established autochthonous mammary and colorectal cancers was intended to investigate its efficacy in models more relevant to the human situation [10,12,19]. Both models have been characterized by a number of chemotherapeutic studies and have been considered useful for the preclinical evaluation of new cytostatic agents [3][4][5]27] as well as biological response modifier [6,19]. Differences between the clinical and the experimental situation described, however, should be noted: patients usually undergo surgical intervention, and subsequent therapy is given to treat metastatic disease, whereas the IL-2 treatment in this study was given to treat primary tumours.…”

Lipid A-Mediated Tolerance and Cancer Therapy

“…The authors reported, however, that they were unable to produce sufficient anticancer therapy with acceptable toxicity using this approach. 49 …”