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Carcinogenicity testing for control of environmental tumor development in man.

After briefly reviewing the present status of carcinogenicity testing as an aid to the control of environmental carcinogenesis in man, and discussing in somewhat more detail the relative advantages and limitations of animal testing and the two most widely used short-term assays--the Ames test and in vitro carcinogenesis--special attention is given to two points: 1) the difficulties inherent in extrapolating from the results of experimental tests an index of potential carcinogenic hazards in man; 2) the urgent need for additional testing procedures for the detection of associated factors (such as, cocarcinogenic factors and promoting agents) operating in human carcinogenesis.

Animals

[Changes in the resistance of different strains of mice to tumor development in the presence of immunologic responses].

The experiments on adult mice of varions breed lines have shown that direction of change of the resistance to cancer under conditions of the same immunological influence can be determined by genetic properties of an organism. The author believes that it is worthy of attention that anticancer resistance decreases only in that lines of mice in which was observed some predisposition to appearing of condition of allergy to tuberculine, as it was shown in experiments using the full adjuvant of Freund.

Animals

[Evaluation of the protective effect of Prussian blue, sodium alginate and calcium phosphate according to tumor development after single and chronic exposure to strontium 90 and cesium 137 mixture].

The mixture of radionuclides was employed in the concentrations of 100.0, 400.0 and 0.8, 2.0 mc/rat for strontium-90 and cesium-137 in single and chronic administration correspondingly. Prussian blue, sodium alginate and calcium were employed in amounts of 50 mg, 800 mg and 258 mg per rat a day. The data obtained are correlated with the results of the same experiments without using the protection. In compared doses of the irradiation the protective action of the substances under study was noted only in chronic experiments. In this case, the appearance of malignant neoplasms was nearly twice less, and the survival was 120 days longer. The absorbed doses were decreased by 17 times for cesium-137 in the whole body and nearly by 4 times for strontium-90 in the skeleton.

Alginates

Cell origin of human adenovirus type 12-induced subcutaneous tumor in Syrian hamsters.

Single subcutaneous inoculation of human adenovirus type 12 (Ad.12), 0.05-0.1 ml of 10(8.0) TCID50 HEK cells/0.1 ml, was made on the back of 0-day-old hamsters. In 21 of 25 hamsters (84.0%), multiple solid tumors developed close to the inoculation site within 3 months. No control hamsters developed tumors. Tumor histopathology revealed the characteristic Homer Wright rosettes of neuroblastoma. Ad. 12-specific tumor antigens were demonstrable in both the primary and the cultured tumor cells by the immunofluorescein technique. Histochemical demonstration of cholinesterase and NADH oxidoreductase gave rise to a predominantly positive intracytoplasmic granule within the tumor cells. Electron microscopy showed remarkably uniform cell morphology: small, undifferentiated neuroblastic cells with poorly developed intracytoplasmic organelles; many possessed characteristic solitary cilia in a 9 + 0 tubules pattern. Intercellular junctions were poorly developed. Search for an incipient tumor cell aggregate by means of immunofluorescein T-antigen detection was carried out through a 240-h period following Ad. 12 inoculation. A sequential study in parallel with electron microscopic examination of the normal subcutaneous tissue proved that neuroblastic cells closely associated with the muscle spindle anlage could preferentially become the most sensitive target for Ad. 12 tumorigenesis.

Adenoviruses, Human

Antibody stimulation of benzo(a)pyrene carcinogenesis.

Benzo(a)pyrene (BP) was conjugated to horse serum albumin (HSA) and then attached to aldehyde fixed human erythrocytes. These cells were used in a passive hemagglutination test to measure BP antibody. BP antibodies were found to be induced in Swiss mice injected with tumorigenic doses of BP. Of the mice treated with BP, those which developed tumors soonest had the highest levels of BP antibody. This observation suggested that the antibody to BP may stimulate tumor development. When rabbit antibody to BP was injected with BP a significantly increased tumor formation occurred. Active immunization using BP conjugated to a foreign protein also significantly increased tumor formation when the mice were treated with BP. Our findings suggest that the immune response to carcinogens is an important component of the carcinogenic process.

Animals

Immunologic manipulation of DMBA tumorigenesis in hamster cheek pouch by DNCB contact hypersensitivity.

Hamster cheek pouches were sensitized with the potent allergen DNCB either before the initiation of DMBA tumorigenesis or by direct application to already developed tumors. Among animals treated prior to tumorigenesis induction there was an apparent delay in onset of tumors and decreased rate of tumor growth. Direct application of DNCB to already established tumors seemed to temporarily arrest tumor growth; later, however, tumor growth rate resumed to approximately that in untreated control animals. It is concluded that DNCB contact hypersensitivity may exert some influence on the DMBA tumorigenesis process as manifested by delay in tumor onset or by temporarily retarding growth of established tumors. It appears that DNCB sensitization prior to tumorigenesis is generally more effective than DNCB applied after tumor development.

9,10-Dimethyl-1,2-benzanthracene

Reduced incidence of spontaneous mammary tumors in C3H/He mice after treatment with polyadenylate-polyuridylate.

The effect of treatment with the double-stranded polynucleotide complex polydenylate with polyuridylate [poly(A) with poly(U)] on tumor development in C3H/He mice was evaluated. Poly(A) with poly(U) was injected in newborn females, and mice were observed for 380 days. During this experimental period 42 percent of treated mice developed tumors, while the incidence in the control group was 63 percent. This difference was statistically significant.

Animals

Suppressed murine mammary tumor virus (MuMTV) expression in RIII female mice treated neonatally with goat antiserum to MuMTV.

Passive immunization of newborn inbred RIII (R3) mice with the globulin fraction of goat antiserum to murine mammary tumor virus (MuMTV) successfully suppressed MuMTV expression in the milk of some of the treated mice throughout nine successive lactations. No mammary tumors developed in the MuMTV-suppressed mice during the first 9 months, whereas all untreated R3 female breeders expressed MuMTV in the milk of the third lactation, and all developed tumors before 9 months of age (mode and median: 189 days).

Animals

[Humoral reactions in BALC/c mice with sarcomatous Moloney-induced tumor].

In a progressive course of the blastomatous process induced by MSV-Moloney the antitumor antibodies level in the whole blood serum was practically unchanged, while the level of antibody-forming cells (AFC) in the spleen of these mice was considerably decreased as compared with that in the spleen of intact mice of the same age. If the tumor development was followed by its subsequent resorption, a biphase character of enhancement of the cytotoxic activity both of the whole serum and its fractions was noted. In the utmost developed tumor a reduced AFC level was observed, while in its resorption -- a gradual restoration of the AFC values up to the level characteristic of intact animals of the same age group.

Animals

Tumor-specific transplantation antigen(s) of bovine adenoviruses.

Protection against bovine adenovirus type 3-induced primary or transplantable tumors was studied in hamsters immunized with bovine adenoviruses, human adenovirus type 12 (A-12), simian adenovirus type 7 (SA7), or chicken-embryo-lethal-orphan (CELO) virus. Newborn hamsters inoculated with 2.3 times 10-5 plaqueforming units of bovine adenovirus type 3 were given injections of bovine serotypes 1, 2, or 3 during the latent period of tumor development. No hamsters immunized with type 3 and only 47% of those inoculated with types 1 or 2 developed tumors as compared to a control incidence of 90%. Primary tumors were not prevented when hamsters inoculated at birth with bovine adenovirus type 3 were immunized during the latent period with A-12, SA7, or CELO, even though 10-100 times more infectious virus was used. When adult hamsters were given injections of the bovine adenoviruses on 3 successive weeks and then challenged with graded doses of tumor cells, the three serotypes produced a 20-fold to 200-fold increase in the 50% tumor-producing dose of tumor cells. These studies indicate that bovine adenoviruses types 1, 2, and 3 induce cross-reactive transplantation antigens which, however, do not cross-react with those induced by oncogenic adenoviruses of either avian, simian, or human origin.

Adenoviridae