Biomedical subjects

B Sandler

Publications and source records attributed to B Sandler.

113 records · Page 7Linked to original sources

PubMedDate not supplied

Role of apoptosis, proliferating cell nuclear antigen and p53 protein in chemically induced colon cancer in rats fed corncob fiber treated with the fungus Pleurotus ostreatus.

The role of apoptosis, proliferative cell nuclear antigen (PCNA) and p53 protein in the preventive effects of dietary fiber treated with the fungus Pleurotus ostreatus on rat-colon tumorigenesis was studied. Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine (DMH), 20 mg/kg rat, once a week. Rats were fed a semi-synthetic fiberfree diet (control) or a high-fiber diet (15%) derived from corncob treated or non-treated with the fungus. The rats we sacrificed 24 weeks after the first carcinogenic injection. The fungus treated corn-cob significantly decreased tumor incidence (to 26%) as compared to 44% and 57% in the other dietary groups. The apoptotic index (AI) significantly decreased in malignant tissue as compared to non-tumorous tissue. PCNA and cytoplasmic content of p53 protein exhibited an increasing trend in malignant tissue as compared to benign tissue (at 15% and 18%, respectively). The fungus-treated corncob significantly increased the content of p53 in the cell cytoplasm (to 33%) and its serum levels in tumor-bearing rats (to 38%). The cellular concentration of PCNA decreased to 61% in tumors obtained from rats fed the fungus-treated corncob as compared to controls. A high positive correlation was found between tumor grade and p53 protein in the serum (r = 0.97) or in the cell cytoplasm (r = 0.77) and between tumor grade and PCNA (r = 0.81). An inverse relationship was found between tumor grade and AI (r = -0.63). We found that 15% of corncob fiber alone seems not to be enough to prevent chemically induced tumorigenesis. The corncob fiber (15%) treated with the fungus had a significant protective effect against DMH-induced rat colon cancer, even at 15% and this effect was accompanied by the activation of some cellular mechanisms such as apoptosis, PCNA and p53 protein activation. Incubation of corncob with the fungus Pleurotus os, increased the dietary fiber content up to 78%. Thus corncob inhibits colon cancer development, and, therefore, may considered of potential use to the public.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

Role of apoptosis, proliferating cell nuclear antigen and p53 protein in the immune response of rat colon cells to cancer and vaccination with anti-p53 polyclonal antibodies.

BACKGROUND: Previously it was shown that rabbit anti-p53 antibodies can exert tumor-suppressive effects on chemically induced rat colon cancer (Cancer J, 10:116-120, 1997). This work examines the role of some components of the immune system in the response of the rat colon cells to treatment with a carcinogen and anti-p53 antibodies. METHODS: The following groups of rats were studied: a) control non treated rats; b) tumor-free non vaccinated rats treated with a carcinogen; c) tumor-bearing non vaccinated rats; d) tumor-free vaccinated rats exposed to a carcinogen; e) tumor-bearing vaccinated rats. The manifestation of apoptosis, proliferating cell nuclear antigen (PCNA), mitotic index, T lymphocytes and p53 protein was compared between the different groups of rats. RESULTS: The apoptotic index and the number of p53-positive cells and T lymphocytes were significantly higher in colon adenocarcinomas obtained from vaccinated rats than in unvaccinated rats. PCNA was lower in tumors from the vaccinated rats, whereas the proliferating cell index was not different between the both groups of rats. An inverse relationship was seen between apoptosis and most other parameters studied. The inverse correlation found between apoptosis and p53 protein in this study demonstrated that apoptosis acts as a p53-independent parameter in chemically induced rat colon cancer. CONCLUSIONS: Our findings demonstrated that vaccination significantly activated apoptosis in both types of colon tissue, and induced synthesis of p53 protein in tumor tissue. Vaccination with anti-p53 polyclonal antibodies seemed to activate the immune system and to stimulate some of its cellular components responsible for tumor suppression.

Adenocarcinoma↗

PubMedDate not supplied

Immune response of rat spleen cells to a carcinogen and to vaccination with anti-p53 polyclonal antibodies.

BACKGROUND: The tumor-suppressive effects of rabbit anti-p53 antibodies on chemically induced rat colon cancer were demonstrated previously (Cancer J, 10:116-120, 1997). METHODS: In this communication, the spleen's role in the immune response of rats to cancer and vaccination was evaluated histologically and immunohistochemically. The following groups of rats were studied: a) control non treated rats; b) tumor-free non vaccinated rats treated with a carcinogen; c) tumor-bearing non vaccinated rats; d) tumor-free vaccinated rats exposed to a carcinogen; e) tumor-bearing vaccinated rats. RESULTS: Exposure to a carcinogen (group 2) caused the appearance of the proliferative and apoptotic changes associated with immune response. They included abundant blast transformation of CD20-positive B lymphocytes, expansion of germinal centers and of periarterial sheaths (CD3-positive T cells), an increase in the number of plasma cells, mitotic and apoptotic cells in the follicles, and in CD25 IL2-depending T cells. The presence of colon tumors (group 3) caused insufficiency of the splenic lymphoid system: blast transformation was weaker, the white pulp area decreased and its devastation was reflected in fewer lymphoid cells. There were less plasma cells in the red pulp, while the number of dendritic cells, CD25+ T cells, macrophages and neutrophils increased sharply, suggesting a compensatory reaction to the severe antigenic effects. Similar, but stronger changes, occurred in tumor-free vaccinated rats (group 4). In tumor-bearing vaccinated rats (group 5), the rate of proliferation change was higher than in group 3, probably as a result of a weaker splenic insufficiency. A strong correlation was found between the number of mitotic, apoptotic or dendritic cells, tumorigenesis and vaccination. CONCLUSIONS: A sharp increase in the number of dendritic cells in vaccinated tumor-bearing rats suggests that these cells participate in the host's reaction to tumorigenesis. We conclude that vaccination with anti-p53 polyclonal antibodies activates lymph components of the spleen.

Animals↗

PubMedDate not supplied

Effects of dietary fiber on the rat intestinal mucosa exposed to low doses of a carcinogen.

BACKGROUND: Changes in morphological and immunohistochemical parameters were studied in the rat intestinal mucosa exposed to low doses of a carcinogen and administered with dietary fibers. METHODS: Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine, 10 mg/kg rat, once a week. Rats were fed a semi-synthetic fiber-free diet (control) or a high-fiber diets (15%) derived from cellulose, tomato peels or white grape. The rats were sacrificed 24 weeks after the first carcinogen's injection. The ileum, colon and tumors were removed for the study. Areas of the mucosal stroma and of lymph infiltrations, and mitotic index were studied along with morphological parameters. Immunohistochemical parameters included determination of Ki-67 proliferating protein and apoptotic index. RESULTS: Areas of the stroma in colon tumors increased in rats fed tomato peels. Changes in areas of lymphoid infiltrates were related to the type of diet and tumor presence. Lymphoid infiltrations were found to be highly developed in the colon area close to tumors, especially in rats fed the white-grape diet. Mitotic index and Ki-67 protein increased significantly in the colon area close to a tumor and in tumors themselves without any relation to the fiber varieties consumed. Changes in the rate of apoptosis were not related to the preventive effect of diets: apoptotic index was high in tumors obtained from rats fed the high-cellulose diet with high tumor-preventive effects and also from rats fed the high-tomato-peel diet with low tumor-preventive effects. CONCLUSIONS: No morphological changes were found in the ileum of rats exposed to a carcinogen and fed different dietary fibers. In the colon, a carcinogen even in low concentrations inhibited the lymphoid system in the mucosa located far from the tumor or close to the tumor. An increase in the proliferation rate in the colon close to the tumor may reflect the development of precanceromatous processes or may be related to the effect of growth factors expressed by tumor cells. Finding adenoma-like dysplasia near tumors may be possible in early stages of the development of new tumors. In addition, activation of the lymphoid system of the colon following consumption to specific dietary fiber may be a mechanism by which fiber protect against cancer.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

Tumor-preventive effects of the soluble p53 antigen on chemically-induced skin cancer in mice.

BACKGROUND: The tumor-suppressive effects of the rat soluble p53 antigen on chemically induced skin cancer in mice and the role of the spleen in the immune response to a carcinogen and vaccination were studied. METHODS: Skin cancer was induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). Vaccination was initiated by injection of liposomes with the soluble p53 antigen (10-12 micrograms/mouse) while boosters were with the p53 mixed with Freund's incomplete adjuvant (two injections). Four months later, the spleen and tumors were removed and examined morphometrically (determination of areas of different spleen's zones) and immunohistochemically (determination of number of B lymphocytes and macrophages, apoptotic index). The following groups of mice were studied: A) control non treated mice; Bl) tumor-free mice treated with a carcinogen; B2) tumor-bearing mice; Cl) tumor-free vaccinated mice exposed to a carcinogen; C2) tumor-bearing vaccinated mice. RESULTS: Mice exposed to a carcinogen, which were tumor-free, displayed high proliferative activity of the spleenic lymphoid constitutes such as B lymphocytes and macrophages. This was reflected in the remarkable transformation of B lymphocytes in lymphoblasts (blast transformation) and an increase in the area of germinal centers, compared to untreated controls. In tumor-bearing non vaccinated mice, significantly more spleenic apoptotic cells were found than in their tumor-free counterparts. Shrinkage of the mantle layer and a decrease in cellular density of follicles were seen in all carcinogen-treated mice, reflecting the reduced total production of lymphoid cells, and thus the insufficiency of the immune reaction of animals to a carcinogen. A sharp decrease in the apoptotic index in the spleen of tumor-free mice may reflect an inhibition of apoptotic activity of the spleen by a carcinogen. Vaccination with the soluble p53 protein decreased the incidence of tumors and their size, significantly increased the apoptotic index within tumors, and reversed the splenic parameters of immune insufficiency. CONCLUSIONS: The immune system is active during tumorigenesis. Vaccination with the soluble p53 antigen had positive tumor-suppressive effects. The findings may facilitate the development of vaccines for the prevention of recurrent cancers in humans.

9,10-Dimethyl-1,2-benzanthracene↗