Antimitotic agents and tumor regression.

The selective action of nonantigenic tissue extracts on malignant cells was demonstrated using tissue culture techniques. The mitotic index of three strains of neoplastic cells was significantly reduced by the use of extracts which previously had proven effective in adversely affecting the development of spontaneous neoplasms. Under the same conditions the division rate of normal cells in tissue culture was not affected by the extracts. The malignant cells used were the Krebs 2, Sarcoma 180 and the L1210 leukemia. The normal cells were the L929 fibroblasts and epithelial-like cells from bone marrow and corneal tissue.

Prophylactic effects of gamma-aminobutyrylhistidine (homocarnosine) on experimental staphylococcal infections in mice.

Prophylactic administration of the dipeptide homocarnosine induced a high degree of resistance to staphylococcal infections in Swiss albino mice. It expressed its antistaphylococcal properties 1 hr after administration, and this protection lasted for at least 1 month. Although 5 mg per animal (approximately 200 to 250 mg/kg) was routinely used in our studies, experiments showed that comparable results could be obtained with 1.5 mg per animal. Rechallenge experiments indicated that an active infection by itself may confer immunity up to 4 weeks, but an infection after treatment with homocarnosine gave complete immunity to reinfection for at least 2 months. Studies in vitro showed that homocarnosine had no effect on the growth or certain other characteristics (ability to ferment mannitol, liquefy gelatin, and to produce coagulase, deoxyribonuclease, and pigment) of S. aureus. It appears that resistance induced by this peptide is an indirect effect mediated by some nonimmunological host reaction. The possible involvement of homocarnosine, among other compounds, in the protective action of deproteinized beef extract against staphylococcal infections is suggested.

A simplified medium for detecting the effect of lecithin on the growth of Propionibacterium acnes.

Thirty strains of Propionibacterium acnes were assayed to detect the effect of lecithin on their growth and to test the nutritional requirement of this bacterium for this phospholipid. The liquid lecithin medium (LLM) and solid lecithin medium (SLM), containing purified bovine lecithin (PBL) supported the growth of P. acnes strains assayed. Two percent PBL, which was an optimal concentration of lecithin (w/v in LLM and SLM) for the normal growth of P. acnes, was found to be inhibitory for the growth of a strain of Staphylococcus aureus tested. the growth of P. acnes in lecithin media was consistently comparable to the growth patterns of P. acnes in complex media. These results indicated that lecithin in lower concentrations than 2% stimulated the growth of P. acnes. There was an indication that this bacterium may produce enzymes capable of hydrolyzing this phosphoglyceride, incorporated in a defined basal medium, to use it as a source of carbon, energy and fatty acids.

In vitro effect of D-isoascorbic acid and betaine hydrate alone and in combination on normal and malignant cells.

D-Isoascorbic acid, an isomer of vitamin C, and betaine hydrate (quaternary amine) were found to inhibit mitoses of sarcoma 37, Ehrlich carcinoma, and L1210 leukemia cells in vitro. However, the combined effect of these compounds produced a greater inhibitory activity than when either was administered individually.

Effects of omega-amino acids and related compounds on staphylococcal infections in mice: a combined prophylactic-therapeutic procedure.

By a short-term combined prophylactic-therapeutic procedure, the following compounds were found to be active against staphylococcal infections in Swiss mice: gamma-aminobutyric acid, gamma-amino-beta-hydroxybutyric acid (GABOB), delta-amino-valeric acid (DAVA), epsilon-aminocaproic acid (EACA), trans-4-aminomethylcyclohexanecarboxylic acid (trans-AMCHA), taurine, and cysteic acid. Many of these compounds had displayed limited or no activity by a previously used prophylactic procedure. Although DAVA and GABOB were the most potent of the straight-chain omega-amino acids, trans-AMCHA displayed the greatest antistaphylococcic activity of the omega-amino acids thus far investigated. Homocarnosine (gamma-aminobutyrl histidine, which also was active by the prophylactic procedure) equalled trans-AMCHA in activity. Taurine was similar in potency to DAVA, and the activity of cysteic acid approximated that of EACA.

Activity of homocarnosine and other compounds against staphylococcal infections in mice.

Homocarnosine and carnosine have been identified in bovine brain extracts which are effective in protecting mice against infections by Staphylococcus aureus. These peptides, as well as l-1-methylhistidine, beta-alanine, gamma-aminobutyric acid, delta-aminovaleric acid, epsilon-aminocaproic acid, 1-aminomethylcyclohexane-4-carboxylic acid, and anserine, were tested as prophylactic agents against S. aureus infections in C3H and Swiss mice. Histidine and methylhistidine were ineffective in preventing mortality in both mouse strains. Carnosine, anserine, and epsilon-aminocaproic acid were effective in C3H but not in Swiss mice. beta-Alanine and gamma-aminobutyric acid were weakly effective (C3H) or ineffective (Swiss). delta-Aminovaleric and 1-aminomethylcyclohexane-4-carboxylic acid (tested only in Swiss) were somewhat effective in early stages of the infection. Homocarnosine was the best compound and was highly effective in protecting both mouse strains against S. aureus infections by the testing procedure employed.

Offsetting toxicity of antineoplastic agents.

PCO, a yeast extract, offsets at least in part the mitotic inhibitory effect of methotrexate and fluorouracil on bone marrow cells in vitro but increases the antimitotic activity of the drugs on ascites Krebs-2 carcinoma under similar conditions. In vivo, PCO enhances the action of methotrexate against the L-1210 lymphoid leukemia and does not interfere with the effectiveness of fluorouracil against the ascites Krebs-2 tumor.

Probiotics: nonantigenic tissue fractions in cancer control.

The effects of probiotics, nonantigenic fractions of normal and malignant cells on tumors, and of similar fractions of normal cells on bacteria and viruses are discussed. The effects are considered in relation to tumor growth and development. In a control group of mice given subcutaneous inoculations only of viable dbrB tumor cells in DBA/1 mice, 100% developed tumors. In a group receiving subcutaneous and intravenous injections of tumor cells and given the tumor fractions, 20% developed lung tumors and 53% developed subcutaneous tumors. In an experiment in which mice received only intravenous injections of viable tumor cells and the tumor fractions, 100% of the controls died with no deaths occurring in the treated group. It is concluded that nonantigenic cellular fractions (probiotics) effective in inducing resistance to some bacterial and viral diseases are effective in inducing resistance to tumors in an inbred strain of mice.