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Biomedical subjects

M J Groves

Publications and source records attributed to M J Groves.

83 records · Page 5Linked to original sources
PubMedDate not supplied

Isolation and biological activities of an antineoplastic protein-polysaccharide complex (PS4A) obtained from Mycobacterium vaccae.

A mixture of water-soluble protein-polysaccharides (PS4A) was isolated by boiling intact cells of Mycobacterium vaccae, a fast growing mycobacterium. Sephadex G-75 column chromatography of the crude extract separated the biologically active high molecular weight (> 50 kDa) fraction (in the void volume) from the low molecular weight degradation products. Compositional analysis demonstrated that PS4A contained protein and polysaccharide in a ratio of approximately 1.5 to 1, but no lipids were detected. The antineoplastic activity was tested in vivo by a S-180 murine sarcoma model using female CFW mice. The immunostimulating activity was tested in vitro using murine peritoneal macrophages isolated from BALB/C mice. The results demonstrated that PS4A significantly decreased tumor incidence in vivo and produced activation of murine peritoneal macrophages. However, the antineoplastic activity was only attributable to the high molecular weight fraction of the protein-polysaccharide complex. The low molecular weight fraction had no antineoplastic activity in vivo despite stimulation of TNF-alpha production in vitro. In vitro experiments also demonstrated that although all PS4A components significantly increased TNF-alpha production by macrophages, the high molecular weight fraction stimulated more IL-1 production, indicating a better immunostimulating activity.

Animals↗
PubMedDate not supplied

The activity of unloaded gelatin nanoparticles on murine melanoma B16-F0 growth in vivo.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccine is a non-specific immunostimulant which has been used clinically in the treatment of melanoma. In this communication, the antimelanoma activity of BCG was related to its fibronectin-binding properties and mimicked using gelatin nanoparticles. MATERIALS AND METHODS: The fibronectin-binding properties of aqueous gelatin solutions, gelatin nanoparticles, BCG vaccine, and PS1 (a glucan extracted from Tice BCG) were compared by an enzyme-linked immunosorbent assay and their ability to suppress murine B16-F0 melanoma in vivo investigated. RESULTS: Aqueous gelatin solutions, gelatin nanoparticles and BCG all bound to fibronectin in vitro. The immunostimulant PS1 did not. In vivo, BCG and gelatin nanoparticles suppressed melanoma growth while PS1 and aqueous gelatin solutions had no effect. CONCLUSIONS: The antimelanoma activity of BCG is not due to the associated immunostimulatory glucan but can be correlated to its fibronectin-binding properties. Since solutions of gelatin have no effect whereas nanoparticles produce total suppression, this suggests a relationship between the volume of the fibronectin-binding entities and their antitumour activity. Thus, gelatin nanoparticles may represent an attractive alternative to the use of BCG vaccine in melanoma treatment.

Animals↗
PubMedDate not supplied

Relative tumor inhibitory and stimulatory activities of BCG vaccine preparations, lots and substrains in a quantitative mouse sarcoma bioassay.

A quantitative in vivo assay for BCG anticancer efficacy was developed to maximize detection of tumor-antagonistic mechanisms. Cultured S180 sarcoma cells admixed with various quantities of Mycobacterium bovis-BCG organisms were injected subcutaneously into CFW Swiss-Webster mice and response was measured as tumor incidence 14 days after injection. Assay of various BCG substrains, lots and killed preparations revealed characteristic patterns of BCG dose-dependent tumor inhibition and enhancement that suggest the existence in the vaccine of multiple active components, the relative concentrations of which vary among cultures. Inhibition of tumor growth by high doses of BCG (greater than 10 micrograms dry weight) was found to be a function of total cell mass and not of the bacterial viability, suggesting that this activity is dependent upon one or more heat-stable components.

Animals↗
PubMedDate not supplied

Initial characterization of an antineoplastic, polysaccharide-rich extract of Mycobacterium bovis BCG, Tice substrain.

A purified hot-water extract from Mycobacterium bovis (BCG vaccine) has been found to have significant antitumor activity against a murine sarcoma in vivo, but not in vitro, suggesting that the active compound is behaving as an immunostimulant. The material, termed PS1, has an average molecular weight of 22.4 kDa, is freely soluble in water, but has low solubility in acetone or ethanol, and is remarkably heat-stable, as is the parent BCG vaccine in terms of high-dose antitumor activity. PS1 contains at least 50% carbohydrate, consisting mainly of glucose, galactose and mannose, and about 10% lipid that may correspond to phosphatidylinositol. It shares chemical and biological properties with an arabinomannan isolated from M. tuberculosis, but it contains only trace quantities of lipoarabinomannan (LAM). Crossed immunoelectrophoresis indicated that PS1 contains the mycobacterial antigen 89, but only a single, non-migrating precipitin arc appeared on immunoelectrophoresis against a standard anti-BCG serum. PS1 appears to be non-toxic in mice up to a dose of 5 mg/kg, while as little as 70 micrograms/kg is sufficient to inhibit tumor formation significantly.

Animals↗
PubMedDate not supplied

USP perspectives on particle contamination of injectable products.

It is widely recognized that the level of particulate matter in an injectable product is one measure of quality, directly reflecting the success with which the manufacturer applies good quality control. The current USP XXII 1990 limits for particulate matter derived from knowledge that goes back to the 1970s but does not reflect the quality of the product available today. This presentation will discuss the purpose and background of proposed new limits intended to be adopted in the USP 23 revision cycle. The limits tests are structured in two stages for both Large-Volume and Small-Volume Injections, effectively employing an improved light obscuration method as a screening procedure. Product which fails this stage is then evaluated by a second stage, filtration and microscopic examination using a considerably improved procedure in which all of the container contents are sampled (or pooled to 25 mL) and the filter examined episcopically.

Drug Contamination↗
PubMedDate not supplied

Activity of a mycobacterial antineoplastic glycan against human breast cancer.

BACKGROUND: Attenuated Mycobacterium bovis, Bacillus Calmette Guerin, BCG vaccine, is a general immune stimulant and is now an approved clinical treatment for superficial bladder cancer. Isolation and characterization of a series of complex polysaccharides (glycans) from BCG and other mycobacteria has shown that these materials are remarkably heat stable and have considerable in vivo activity against a number of animal cancer models. This present communication describes the testing of a glycan, PS1, obtained from the Tice substrain of BCG against the hormonal dependent human breast cancer cell line MCF-7 and the hormonally independent BT-20 line, using 5-fluorouracil (5-FU) as a positive control. MATERIALS AND METHODS: The PS1 was obtained by methods previously described. Cells were obtained from the American Type Culture Collection (Rockville, MD) and athymic nu/nu mice from Frederick (MD). The cells were implanted into the flanks of 20g female nude mice (n = 10). After two weeks, volumes of phosphate buffered saline (control), 5-FU (positive control) or PS1 solutions were injected and the tumor growth rates followed for up to six weeks. RESULTS: The 5-FU was effective in slowing tumor growth of both tumors. The MCF-7 cell line was markedly affected by the PS1, especially in the presence of estradiol. The BT-20 cell line was only marginally affected by PS1, with or without estradiol. CONCLUSIONS: Since PS1 is known to have macrophage stimulating activity and nude mice are deficient in both T-cells and natural killer cells, the mechanism of activity is postulated to involve MHC-1 antigen secretion by the hormonal-dependent tumor cells, enhanced in the presence of hormone. These cells are then actively identified and destroyed by local macrophages.

Adjuvants, Immunologic↗