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Impaired induction of type II interferon in tumor-bearing mice.

The response of mice to type II interferon inducers such as purified protein derivative of tuberculin or OK-432 was significantly impaired after either the implantation of tumor cells or the injection of cell-free tumor ascitic fluids. Complete inhibition of type II interferon induction occurred in 3 to 5 days. This inhibitory effect persisted until the death of mice implanted with tumors or for 7 days after i.p. injection of 0.2 ml of tumor ascitic fluid. The inhibitory activity was seen even with 0.2 ml of the 10,000-fold dilution of the fluid and with its filtrate passed through a Diaflo UM-10 membrane (greater than 10,000-dalton exclusion), However, such tumor ascitic fluids did not affect the induction of type I interferon in mice by polyriboinosinic-polyribocytidylic acid or tilorone-HCl. Moreover, adjuvant-induced nontumorous ascitic fluid had no inhibitory activity. These results indicate that the in vivo induction of type II interferon is specifically impaired by tumor-mediated factor(s) with molecular weights of less than 10,000.

Animals↗

Effects of multiple putative anticarcinogens on the carcinogenicity of trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole.

In an attempt to dissociate the chemotherapeutic from the carcinogenic properties of the antischistosomal and antitrypanosomal nitrovinylfuran trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]1,2,4-oxadiazole [(SQ18506) CAS: 28754-68-9; (E)-5-amino-3-(2-(5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole], potential inhibitors of carcinogenesis were administered to female outbred CD-1 mice before and during exposure to SQ18506. The compounds tested were ascorbic acid, etretinate, butylated hydroxyanisole (BHA), cysteamine hydrochloride, cysteine hydrochloride, dimercaprol, disulfiram, 1,4-dithiothreitol, reduced glutathione, and spermidine phosphate. The primary types of tumors observed were squamous cell carcinomas of the stomach and thymic and nonthymic lymphomas. BHA reduced the incidence of malignant tumors to control levels, whereas cysteine hydrochloride, spermidine phosphate, and disulfiram reduced the incidence of chemically induced tumors by 42, 34, and 32%, respectively. Although cysteamine hydrochloride and disulfiram had no or only a modest effect on the overall incidence of tumors, the data suggested possible tissue-specific anticarcinogenic properties for these agents. Of the 8 antioxidants tested, only 1 had marked anticarcinogenic properties against SQ18506. These data indicate that antioxidant properties alone cannot account for the anticarcinogenic activity of the compounds tested. Coadministration of the anticarcinogen BHA with SQ18506 also blocked the chemotherapeutic effects of this agent on female CD-1 mice infected with Schistosoma mansoni.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗

Hepatic artery occlusion for liver cancer.

The survival of patients with tumour growth in the liver is very restricted. Interruption of the arterial blood supply to the liver is one method used to control tumour growth. This method is based on the findings that liver tumours are mainly nourished by the hepatic artery. Different methods are used in order to interrupt the arterial blood supply to the liver. Hepatic artery ligation (HAL) has been found in animal experiments to be the most reproducible method to temporary retard tumour growth. Survival has been shown to be prolonged in animals with liver tumours subjected to HAL compared with untreated controls. In humans no effect on the survival time has been observed, but the quality of life of these patients has been claimed to be improved especially those with the carcinoid syndrome. Although interruption of the hepatic arterial blood supply has been used clinically for more than 15 years the method is still an experimental procedure. Further clinical research in this field requires properly designed randomized studies.

Adenocarcinoma↗

Quantitative studies of natural immunity to solid tumours in rats. Persistence of natural immunity throughout reproductive life, and absence of suppressor cells in infant rats.

Consideration of cell-mediated cytotoxicity as an enzyme-substrate reaction provided a theoretical and practical basis for the quantification of natural immunity to solid tumours. The natural cytotoxic activity of spleen cells from normal rats towards cultured target cells from solid tumours, measured in a 6 h chromium release assay, developed between 2 and 5 weeks after birth and, in contrast to previous reports of natural cytotoxicity against lymphoid tumour cells, showed no sign of decline up till at least 22 months of age. Both virgin and breeder (multiparous) females showed equally good maintenance of natural immunity, and the apparent specificity of this natural immunity on a panel of four target cells did not change between 8 weeks and 18 months of age. The low level of natural immunity in infant spleen, and also in adult lymph nodes and thymus, was not caused by suppressor cells but rather by an absence of appropriate effector cells.

Aging↗

[Experimental use of antitumor preparations in low doses].

The susceptibility of tumor tissue to therapeutic and smaller doses of chemotherapeutic drugs was assessed on the basis of SH-group inhibition in vitro. As therapeutic dose was decreased, rhythmic changes of tumor susceptibility were observed. In the experiments on tumor-bearing rats, the small dose of chemotherapeutic agent, which in preliminary in vitro experiments proved to be as effective as therapeutic one (1/5 therapeutic dose), was found to cause the same suppression of tumor growth. However, it did not induce leukopenia, lymphopenia, thymus involution or any other manifestations of stress which followed multiple injections of therapeutic doses. The white blood cell and thymus indices in rats, which received the small dose, suggest the development of reactions of training and activation which increase the nonspecific resistance of organism.

Adaptation, Physiological↗

IgA containing immune complexes in dogs bearing a spontaneous mammary adenocarcinoma.

Sera from dogs with mammary adenocarcinoma were assessed for the presence of immune complexes (IC) and the physicochemical composition of these complexes was investigated. Employing 125I-anti-canine IgG as indicator, elevated levels of C1q binding IgG were detected in sera of dogs with mammary adenocarcinoma. Polyacrylamide gel electrophoresis (PAGE) analysis of IC isolated by G-200 fractionation and protein A affinity chromatography revealed the presence of a dense polypeptide band corresponding to the alpha chain of IgA which was present in the mammary adenocarcinoma sera but not in normal dog sera or sera from dogs with other tumours. Employing monospecific radiolabelled anti-canine IgA as indicator in solid phase C1q binding radioimmunoassays, significantly elevated levels of C1q binding IgA were detected in five of eight mammary adenocarcinoma sera but not in sera of normal dogs or other tumour bearing dogs (P less than 0.05). Sera from mammary adenocarcinoma bearing dogs treated with 5% polyethylene glycol (PEG) and subjected to sucrose density gradient ultracentrifugation revealed IgA containing IC in fractions greater than 7S to greater than 19S. Findings suggest that IC are present in sera of dogs with mammary adenocarcinoma and that that IgA is a major and unique component of these complexes and, hence, may play a significant role in the development and evolution of the canine immune response to mammary adenocarcinoma.

Animals↗

Behavior of different nuclear probes for detection of cancer by nuclear magnetic resonance.

A physical explanation is given for the finding that the spin-lattice relaxation time T1, obtained by nuclear magnetic resonance from equivalent malignant and non-malignant samples, is greater for the phosphorus isotype 31P than for the proton 1H. The nuclear relaxation of the phosphorus proceeds by way of its interaction with associated cell water. Within limits determined by other variables, T1 is expected to vary inversely as the square of the gyromagnetic ratio.

Animals↗