cord-factors and Neoplasms

Topics: Bacterial Infections; Carcinogens; Chronic Disease; Cord Factors; Cytokines; DNA Damage; Humans; Inflammation Mediators; Lung Neoplasms; Mycobacterium tuberculosis; Neoplasms; Oxidative Stress; Risk; Time Factors; Tuberculosis, Pulmonary

Trehalose dimycolate (TDM), a well-defined component of Mycobacterium tuberculosis cell wall has been tested in vivo and in vitro for its effect on the tumoricidal activity of Rat peritoneal macrophages. Macrophages could be rendered cytolytic against syngeneic tumor cells by an intraperitoneal injection of an aqueous suspension of TDM. However, as we failed to render them tumoricidal in vitro, we consider that the activation process is not due to a direct effect on macrophages.

Topics: Animals; Antineoplastic Agents; Cell Survival; Cord Factors; Glycolipids; Injections, Intraperitoneal; Macrophage Activation; Macrophages; Neoplasms; Rats

We have purified the cell-wall skeletons (CWS) of Mycobacterium bovis BCG, Nocardia rubra, Propionibacterium acnes and Listeria monocytogenes as the adjuvant-active principles of these bacterial cells. These cell-wall skeleton preparations were shown to have antitumor activities in experimental tumor systems. Especially BCG-CWS and N. rubra-CWS were applied for the treatment of human cancer. The synthetic immunoadjuvants such as cord factor, mycoloyl and quinonyl derivatives of N-acetylmuramyldipeptides were prepared and their immunological properties were investigated. The effectiveness of synthetic adjuvants on the stimulation of nonspecific host resistance against bacterial and viral infections was also discussed.

Topics: Adjuvants, Immunologic; Antineoplastic Agents; BCG Vaccine; Cell Wall; Cord Factors; Humans; Influenza, Human; Listeria; Neoplasms; Nocardia; Stomach Neoplasms

The toxic, clinical, and immunological effects of suspensions of mycobacterial cell wall skeleton (CWS) and trehalose dimycolate (TDM) attached to oil droplets and given intravenously in doses of 100-2,000 micrograms/m2 (CWS) every 1 or 2 weeks was investigated in this Phase I study. The major limiting side effects were fever and chills at a dose of 2 mg/m2 body surface area. There was no significant hematopoietic, renal, hepatic, or pulmonary toxicity. Evaluation of changes in the white cell count and lymphocyte and monocyte populations and function showed an increase in the white blood count, an increase in the number of T cells, and a decrease in blood monocytes. Measurements of lymphocyte blastogenesis, monocyte suppressor activity, and monocyte cytostasis showed no consistent changes. Intravenous therapy with oil/CWS/TDM was associated with complete regression of a bronchial squamous cell carcinoma in one of three patients receiving 2 mg/m2 weekly. Subsequent Phase II studies can be conducted at a weekly dose of 1-2 mg/m2.

Topics: Adjuvants, Immunologic; Cell Wall; Combined Modality Therapy; Cord Factors; Drug Evaluation; Glycolipids; Humans; Immunotherapy; Mycobacterium; Neoplasms; Oils

We described elsewhere that the synergistic antitumor activity of endotoxic extracts from Re mutants of gram-negative bacteria and trehalose mycolate against guinea pig syngeneic line 10 tumor was abrogated after peptide substances accompanying these extracts had been removed. This activity could be restored by combining peptide-free endotoxin either with cell wall skeleton from Bacillus Calmette-Guérin, a polymeric mycolic acid-arabinogalactan-mucopeptide complex, or with a combination of two separate components, trehalose dimycolate and N-acetylmuramyl-L-alanyl-(L-seryl)-D-isoglutamine (MDP). We report here that when a combination of endotoxin (150 microgram) and a mixture of MDP (150 microgram) and trehalose dimycolate (150 microgram) was inoculated into established dermal tumors, a significant number of the animals died, presumably of endotoxic shock. All surviving animals suffered severe but temporary lethargy. When administered alone intradermally in the dose levels tested, none of the components caused severe lethargy or lethality. The lethal effects of 159 microgram of MDP also occurred in combination with relatively weak endotoxic products, such as Pseudomonas vaccine (Pseudogen), and these effects did not depend upon the presence of malignant tissue. Guinea pigs inoculated i.v. were even more susceptible inasmuch as the addition of as little as 6 microgram of MDP to 150 microgram of Pseudogen, itself not lethal, caused the death of 80% of the animals.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Cord Factors; Endotoxins; Glycopeptides; Guinea Pigs; Immunotherapy; Mycobacterium bovis; Neoplasms; Pseudomonas aeruginosa; Salmonella typhimurium; Shock, Septic