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Biomedical subjects

C A Brailovsky

Publications and source records attributed to C A Brailovsky.

32 records · Page 2Linked to original sources

A comparative study of the intravesical MTP and BCG treatment of transplantable bladder cancer.

We induced transitional cell cancer of the urinary bladder in Fischer rats by feeding them N-[4(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT). Tumors were subsequently transplanted orthotopically in the bladder submucosa of Fischer rats. This animal model was used to compare the therapeutic effects of maltose tetrapalmitate (MTP), and bacillus Calmette Guérin (BCG). The routes of administration compared were intravesical alone or intravesical and oral for MTP, and intravesical alone or intravesical and subcutaneous for BCG. The intravesical and oral MTP treatment was more effective than the intravesical and subcutaneous BCG as regards the tumor size, incidence of tumor metastasis and the immunologic status of the tumor bearing host.

Adjuvants, Immunologic↗

Orthotopic implantation of primary N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide-induced bladder cancer in bladder submucosa: an animal model for bladder cancer study.

Primary bladder tumors induced in Fischer 344 inbred rats by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide were transplanted in syngeneic rats by the intravesical, s.c., i.v., and orthotopic routes. Attempts were made to establish bladder cancer cell lines in vitro. No success was achieved in transplantation by either the s.c., i.v., or intravesical routes when primary tumor cells were transplanted as cell suspensions. Cell suspensions of primary tumors also failed to grow in culture. However, orthotopic implantation into the bladder submucosa gave 45% success. Tumor fragments obtained from either the primary tumor or its lung metastases resulted in 10.6 and 36% tumor takes, respectively, when implanted s.c. However, after one orthotopic passage in the bladder submucosa, the tumor cells injected as cell suspension grew s.c. in 14% and orthotopically in 79% of the animals. Tumor fragments obtained from orthotopic tumors and implanted s.c. resulted in 15% tumor takes. After the second orthotopic passage, tumor cells could be grown in cultures and orthotopically in 100% of animals. The technique of orthotopic implantation as well as the usefulness of this tumor model for bladder cancer studies are described.

Animals↗

Effects of structural variations in synthetic glycolipids upon mitogenicity for spleen lymphocytes, adjuvancy for humoral immune response and on anti-tumour potential.

Synthetic glycolipids prepared by esterification of various sugars and sorbitol, and containing various numbers of saturated or unsaturated fatty acid residues as well as bacterial lipid A and lipopolysaccharide, were tested for mitogenicity of splenic cells of Fischer rats and Swiss mice and for the augmentation of humoral immune response against sheep red blood cells in these species. Subsequently a few of the humoral immune-response-enhancing glycolipids were compared with non-enhancers in their anti-tumour activity against 13762 rat mammary carcinoma in inbred Fischer 344 rats and Ehrlich tumour in Swiss mice. They were given systemically after tumour inoculation and intratumourally in squalene and Tween emulsion after intradermal MAC tumour development. It was observed that certain structural characteristics in glycolipids with respect to the type of sugar, the type and number of fatty-acid residues were needed for their adjuvant action of the humoral arm of the immune response. Although humoral immune-response enhancers were somewhat superior to non-enhancers in their anti-tumour activity, the correlation coefficient demonstrated a lack of significant concordance. It is concluded that glycolipids selected for their ability to augment humoral immune responses against standard antigens need not be suspect as tumour-enhancers on the grounds that they would elicit blocking antibodies in vivo against tumour-associated antigens.

Adenocarcinoma↗

The antitumour activity of maltose tetrapalmitate compared with other immunoadjuvants, and its effectiveness after tumour surgery.

The effectivenss of maltose tetrapalmitate (MTP) as an antitumour immune adjuvant was verified by its comparison with other known immunopotentiators, namely BCG, Corynebacterium parvum, levamisole and pyran copolymer. Copenhagen x Fisher 344/CRBL F1 hybrid male rats inoculated s.c. with the Dunning R3327A prostatic adenocarcinoma were used as the test system. All animals treated with immunoadjuvants showed a delay in tumour appearance and inhibition of early tumour growth. MTP was found to be the most effective, followed by levamisole, BCG, pyran copolymer and C. parvum in order of decreasing efficacy. Intratumoral treatment of small or large s.c. tumours with BCG, MTP and C. parvum was ineffective in our cases. However, this treatment was effective with MTP and BCG if they were used against a differentiated form of R3327 tumour. MTP and levamisole were found to be equally effective when given orally in drinking water. Experiments involving surgical excision of tumours followed by MTP therapy in two s.c. implanted animal tumour models (viz. a poorly immunogenic ascites mammary carcinoma 13762 in Fisher 344/CRBL rats, and an SV40 virus-induced sarcoma of low immunogenicity in Syrian hamster) showed beneficial effects of MTP on local tumour recurrence and tumour growth. Pre- and postoperative MTP treatment was at least as effective as postoperative MTP treatment alone.

Adenocarcinoma↗

Binding of Salmonella minnesota R-form glycolipid mR595 to rat fibroblasts and its effect on cell metabolism and cell behaviour.

Trypsinized normal rat embryo fibroblasts and untrypsinized and trypsinized transformed rat fibroblasts have two orders of binding sites for bacterial glycolipid mR595. The high order sites fix 1--3 micrograms glycolipid mR595/10(5) cells and those of the low order fix about 6 microgram glycolipids mR595/10(6) cells. Ca++ is required for the low order glycolipid mR595 binding to be trypsinized but not to the untrypsinized transformed rat fibroblasts. The low order binding is temperature dependent with the transition temperature lying between 25 and 37 degrees C. Exogenously added ganglioside and glycoproteins contained in the fetal calf serum do not inhibit fixation of glycolipid mR595. Only beta-lipoprotein at high concentrations is slightly inhibitory. Glycolipid mR595 fixation to transformed fibroblast does not alter their morphology and appears to slightly improve cell attachment to substratum. Glycolipid mR595 fixation results in a lengthening of the S-phase of the cell cycle and a reduction in 2-deoxyglucose uptake. Uptake of inorganic phosphate is not affected. Inhibition of phospholipid synthesis is observed in mR595 fixed fibroblasts whereas synthesis of cell surface glycoproteins and the content of cellular gangliosides is not affected.

Binding Sites↗

A study of cell surface constituents restricting Salmonella minnesota R form glycopid mR595 fixation to normal rat embryo fibroblasts.

The nature of the cell surface constituent(s) containing sialic acid that block fixation of bacterial glycolipid mR595 to normal rat fibroblasts was explored. Indirect evidence suggests that a trypsin-sensitive, high molecular weight glycoprotein, present in larger amounts on the surface of normal cells (as compared with transformed rat fibroblasts), may be involved as a blocking agent.

Animals↗

Plasma membrane associated proteins and glycoproteins of a temperature-sensitive hamster cell line (ts 3).

Hamster ts 3 cells grown at 32 and at 39 degrees C were compared for (a) cell phenotype and growth rates, (b) sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) patterns of plasma membrane polypeptides, and (c) distribution of radioactivity in SDS-PAGE of plasma membrane glycopeptides metabolically labeled with [3H]glucosamine and [3H]fucose. It was observed that ts 3 cells growing at 39 degrees C and having a normal phenotype contained increased amounts of a glycopeptide of about 250000 daltons and a polypeptide of about 200000 daltons, as compared with ts 3 cells grown at 32 degrees C and having a transformed phenotype. No other alterations of major significance were observed.

Carbohydrates↗

Maltose tetrapalmitate, a nontoxic immunopotentiator with antitumor activity.

The attempt to synthesize a lipid A-like component (the active portion of lipopolysaccharides, but lacking its endotoxic activity) resulted in the production of fatty acyl sugars of which maltose tetrapalmitate was seen to yield the most promising results. It shows no endotoxic activity and elicits an antitumor response in tumor-transplanted animals as shown by (a) an enhancement of the host's capacity to reject a large number of tumor cells, (b) retardation of growth in tumor size, and (c) induction of hemorrhagic necrosis in certain tumors. Experiments with mammary ascites carcinoma show maltose tetrapalmitate to be as effective as is bacterial glycolipid mR595 in its antitumor activity. The degree of sensitivity to maltose tetrapalmitate varies with the tumor-host system: mammary ascites carcinoma less than NH = Cl2TSV5S = B16 less than L26. The mode of action of maltose tetrapalmitate appears to be via its modulation of the immune system. It is itself noncytotoxic to tumor cells in vitro. It is seen to stimulate the spleen cells of certain animals mitogenically, although it causes tumor rejection in all the types of animals tested. Also, it activates peritoneal exudate macrophages in tumor-bearing animals; whether specifically or nonspecifically has not yet been established.

Animals↗

Adjuvant immunotherapy of N-[4(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced bladder tumors.

The prophylactic effect of maltose tetrapalmitate (MTP), a newly developed non specific immunoadjuvant in preventing or delaying bladder cancer induction by N-[4(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) or in reducing the growth rate of the induced tumor was compared to other well-known immunoadjuvants (BCG, C. parvum, levamisole and pyran copolymer). The evaluation of the prophylactic role of immunoadjuvants demonstrated that MTP, levamisole and C. parvum were the most effective in prolonging animal survival. MTP was found superior to either of them in reducing the tumor size. The development of lung metastasis was lower in the group receiving MTP or C. parvum. Next, MTP was studied for its therapeutic effect against primary FANFT induced tumor. The subcutaneous (s.c.) and oral routes of MTP administration and their combination with intravesical route were tried. Combinations of intravesical with s.c. or oral MTP were most effective in reducing tumor size, obtaining lower metastases along with greater mononuclear lymphocyte infiltration in the primary tumor.

Adjuvants, Immunologic↗