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Structural patterns and histological behaviour of experimental sarcomas. I. General considerations, histology and histochemistry.

Methylcholanthrene-induced rat sarcomas were used as a model for the examination of morphological and cytological differentiations in tumours of the connective tissue. Particular attention was paid to the question how far these sarcomas are comparable to human connective tissue tumours. The histological examination yields a broad spectrum of mesenchymal differentiations ranging from undifferentiated anaplastic sarcomas over less differentiated fibrosarcomas and malignant fibrous histocytomas to well-differentiated fibrosarcomas, myosarcomas and haemangiopericytomas. It is worth mentioning that different histological structures can be encountered with one and the same tumour.

Animals

Effect of prophylactic and therapeutic administration of BCG vaccine on growth of experimental sarcoma.

The effect of prophylactic and therapeutic administration of BCG vaccine on growth of transplantable sarcomas induced by MSV-Harvey (MSVT1) and 3-methylcholanthrene (MC 11 and MC 12) in C57BL/10Sn mice was studied. Growth of MSVT1 sarcomas was not inhibited by oral or intratumoral BCG therapy. Nor was prophylactic oral administration of BCG followed by therapeutic oral BCG treatment effective. On the other hand, intradermal administration of an adequate dose of BCG vaccine preceding the tumour transplantation inhibited tumour growth. The low (0.05-0.2 mg.) doses of BCG induced resistance comparable to the effect of subcutaneous immunization with tumour cells, whereas the higher (0.5-1.0 mg) doses had no effect. Growth of MC 11 and MC 12 tumours was not affected by prophylactic intradermal BCG administration.

Administration, Oral

Antitumor activity of prumycin.

The antifungal antibiotic, prumycin, was studied for antitumor activity against several tumor systems. It was found to possess potential antitumor activity against a well-established mouse mammary adenocarcinoma in C3H/He mice. It was also active in prolongation of the lifespan of mice bearing P-388 lymphocytic leukemia. Moreover, prumycin did not depress the white blood cell counts in the mouse peripheral blood. However, severe alopecia was observed in mice treated with this agent at dosage level near the LD50.

Aminoglycosides

Reproducibility and relation to specific and non-specific anti-tumor resistance of the tumor "sneaking through" phenomenon.

The reproducibility and immunological specificity of the tumor "sneaking through" phenomenon and enhancement of tumor growth were studied in syngeneic and random-bred Syrian hamsters by means of a quantitative modification of the transplantation test. After primary challenge the phenomenon was neither observed in normal animals nor in animals effectively immunized against tumor. However, it was regularly observed in some "immune" animals after secondary challenge. In primary challenge of animals "sneaking through" phenomenon was most often observed in animals pretreated with large doses of heat-inactivated tumor cells. This characteristic could not be transferred with serum of pretreated animals. In contrast to specific tumor immunity, the "sneaking through" pbenomenon appeared to be immunologically non-specific. This was observed in cross-transplantation tests with tumor cells bearing different TSTAs. Thus, TSTA is not an inducer and apparently not a target for a response leading to enhancement of tumor growth in pretreated hamsters. Experiments demonstrating enhanced tumor growth in pretreated animals at the same time demonstrate two other possibly more essential findings: (1) normal animals are naturally resistant to transplantation of 1 to about 1 x 10(3) (or more) tumor cells; and (2) this resistance can be totally abrogated by the pretreatment of normal animals with tumor cell preparations. The preliminary data demonstrate that abrogation of natural anti-tumor resistance in adult hamsters subsequently inoculated with SV40 leads to rapid development of primary tumors in such animals. The development of specific anti-tumor immune response in animals treated with inactivated tumor cell preparations was also studied. Significant non-specific inhibition of sponse in Syrian hamsters treated with inactivated syngeneic tumor cells was observed. The data obtained are considered to demonstrate two anti-tumor defense systems in the animal, i.e., non-specific natural resistance and specific anti-tumor immunity. The first seems to be responsible for elimination of low numbers of tumor cells in the normal organism and also to be esseitial for effective induction and functioning of the specific anti-tumor immunity.

Animals

Antitumor activity of 1-alkylcarbamoyl derivatives of 5-fluorouracil in a variety of mouse tumors.

The antitumor properties of 1-alkylcarbamoyl derivatives of 5-fluorouracil were examined in various mouse tumor systems to select promising compounds for clinical use. Almost all alkylcarbamoyl derivatives were active against various tumors when given by oral administration. Among them, 1-methyl, 1-ethyl, 1-isopropyl, 1-hexyl and 1-octyl carbamoyl derivatives of 5-fluorouracil were moderately or markedly active in six mouse tumor systems tested. However, 1-methyl, 1-ethyl, and 1-isopropyl carbamoyl derivatives were toxic to mice, though not lethal. As a result, 1-hexyl and 1-octyl carbamoyl derivatives were selected as the best candidates for antitumor agents in further study.

Adenocarcinoma

The spread of cancer in the organism. Facts and problems.

In this review, cancer is conceived as an alteration of the suface-monitored social behavior of cells. Apart from impaired growth controls, loss of residency (tissue affiliation) is the most important consequence of this homeostatic disorder. It results in local spread (penetration) which is initiated by locomotive and/or desctructive activities of the neoplastic cells. Access of cancer elements to the circulation possibly leads to distant spread (metastasis). Penetration and metastasis largely depend upon reactions of the organism, which are of an ill-understood, ambiguous nature favoring both the tumor and the host.

Animals

Effect of ascorbic acid on tumour growth.

The growth of tumours in guinea-pigs was observed for 20 weeks after placing them on various doses of vitamin C. Complete tumour regression occurred in 55% of those animals receiving 0-3 mg/kg/day ascorbic acid, whereas animals given 10 mg/kg/day showed tumour inhibition but no regression. In contrast, tumours in animals maintained on 1 g/kg/day ascorbic acid grew without sign of retardation. When increased amounts of ascorbic acid were restored to the diet of scorbutic tumour-bearing animals, tumours which had not regressed responded with enhanced growth. Likewise, animals previously maintained on 10 mg/kg ascorbic acid responded in turn to the additional vitamin with enhanced tumour growth. In contrast, all tumour-bearing animals maintained on 1 g/kh ascorbic acid died within 3 weeks when this dose was replaced with 0-3 mg/kg.

Animals

The immunological basis of endotoxin-induced tumor regression. Requirement for a pre-existing state of concomitant anti-tumor immunity.

It was shown that of four syngeneic, murine tumors investigated, only those that evoked the generation of a state of concomitant anti-tumor immunity were susceptible to endotoxin-induced regression. Moreover, the temporal relationship between the generation of concomitant immunity and the onset of susceptibility to endotoxin-induced regression points to the likely possibility that tumor regression depends on the preceding acquisition of the specifically-sensitized, effector T cells that express concomitant immunity. It is suggested that endotoxin-induced hemorrhagic necrosis which invariably precedes tumor regression serves to create conditions inside the tumor that are conducive to the entry and the functioning of effector T cells. It is also suggested that tumor necrosis factor causes hemorrhagic necrosis rather than tumor regression.

Animals

Induction of tumors by a guinea pig herpesvirus-transformed hamster cell line.

Syrian hamster embryo cells that had been transformed in vitro by guinea pig herpes-like virus (GPHLV) were found to be oncogenic when inoculated into hamster sc or ip. Of 71 animals inoculated, 30 showed tumors at the site of inoculation. Tumors appeared 4-23 weeks after inoculation of the transformed cells at passage 37 or higher. Inbred and randombred hamsters of all ages were susceptible. Upon microscopic examination the tumors were characterized as fibrosarcomas. The cultured hamster tumor cells were easily transplanted into hamsters, but produced no evidence of tumors when inoculated into guinea pigs. Infectious GPHLV was not isolated from the tumor cells, but GPHLV-specific surface antigens were detected in tumor cells by immunofluorescence of GPHLV antiserum produced in rabbits. Sera from tumor-bearing hamsters did not contain GPHLV-neutralizing antibodies, but sera from 4 of 23 hamsters bearing primary tumors and 12 of 41 bearing transplanted tumors produced nuclear fluorescence in cells infected with GPHLV, thus establishing the relationship between the guinea pig herpesvirus and the hamster tumors.

Animals