glucosaminylmuramyl-2-alanine-d-isoglutamine and Neoplasms

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Drug Evaluation; Humans; Immune System Diseases; Immunity; Immunity, Cellular; Infections; Neoplasms; Treatment Outcome

The current study was designed to investigate direct inhibitory effects of N-acetyl-glucosaminyl-muramyldipeptide (GMDP) over the cytotoxic nature of TNF-alpha. A lactate dehydrogenase (LDH) assay of the inhibition of TNF-alpha cytotoxicity was done in vitro on the following cell lines: A549 (human lung carcinoma cells), A431 (human breast cancer cells) and L929 (mouse breast cancer cells). In a double-blind placebo-controlled trial, cancer patients with an elevated activity of all five LDH isoensymes were randomized to receive either a GMDP solution or a placebo; 63 patients were evaluated every third day for the mean daily number of episodes of nausea or vomiting, changes in clinical status, cell blood count and blood chemistry. A 95% inhibition of LDH release was noticed on A549 cells. Other cell lines were less sensitive to GMDP, with an observed 72% dose-dependent reduction in LDH activity. In vivo, LDH activity was decreased by 41% (+/-4%) (mean+/-SD) in all 21 subjects who were given 0.5-1.0 mg of GMDP daily. A lowering of LDH activity by 73.4% (+/-4%) was observed in 23 patients who received GMDP at a dosage of 1.5mg/kg daily. Correspondingly, a 10% (+/-2%) increase in LDH activity was noticed in 19 patients who were given a placebo (P < 0.01). During the follow-up period, the overall clinical condition of all patients treated with GMDP was improved. No side effects were observed. In nine patients who experienced nausea from tumor toxicity before treatment, the symptom subsided. In parallel, an extremely beneficial effect on lipids metabolism was noticed in all patients with elevated cholesterol and trigliceride levels. A dietary supplementation of GMDP has been shown to reduce systemic TNF-alpha cytotoxicity during tumor shock.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Adolescent; Adult; Animals; Breast Neoplasms; Double-Blind Method; Female; Humans; In Vitro Techniques; L-Lactate Dehydrogenase; Lung Neoplasms; Male; Mammary Neoplasms, Animal; Mice; Middle Aged; Neoplasms; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

We have demonstrated that biologically active muramyl peptides, in particular, glucosaminylmuramyl dipeptide (GMDP), augmented in vitro cytotoxic activity of tumor necrosis factor-alpha (TNF-alpha) against murine fibrosarcoma L929 cells. The introduction of GMDP resulted in cytotoxic effect characteristic for substantially higher dose of cytokine. Even more potent was the combination of GMDP, TNF-alpha and Actinomycin D (ActD). According to clonogenic and MTT assays 100% L929 cells could be killed in culture with low doses of TNF-alpha and ActD if GMDP was present. When cisplatin was substituted for ActD similar results were obtained. GMDP also enhanced cytotoxicity of TNF-alpha and cisplatin against human breast carcinoma MCF7 and histiocytic lymphoma U937 cells. Normal cells, namely human peripheral blood leucocytes and murine peritoneal macrophages, were resistant to selected doses of TNF-alpha/cisplatin/GMDP.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Antineoplastic Agents; Cell Death; Cells, Cultured; Cisplatin; Cytotoxicity, Immunologic; Dactinomycin; Drug Therapy, Combination; Humans; L Cells; Mice; Neoplasms; Tumor Necrosis Factor-alpha; U937 Cells