Natural history of aberrant crypt foci. A surgical approach.
Journal - Diseases of the colon and rectum (UNITED STATES )
BACKGROUND. The aberrant crypt focus (ACF) appears to be an important early step in colorectal carcinogenesis. Our objectives were to determine the natural history of ACF in a surgical model. METHODS. The natural history of ACF was followed by marking the lesions in vivo with tattoos. Rats were given four weekly injections of azoxymethand (AOM; 20 mg/kg). One hundred days after the first injection of AOM, rats were anesthetized, and individual aberrant crypt focus was identified by staining with methylene blue. A 3 x 3 mm area, identifying one large (4-8 crypts) ACF was marked with a tattoo dye in each colon. Control animals received saline or AOM injections and were tattooed in areas without ACF. At 200 days, colons were examined for the presence of macroscopic lesions. RESULTS. A total of 54 tumors were found in the study group of 38 animals, and 21 of these were in the transverse and proximal descending colon. The marked areas (all in transverse and proximal descending colon) yielded 6 tumors and 2 ACF, but in 30 instances no abnormality was noted. Probability of observing a tumor in the 3 x 3 mm area of the colon that was identified as containing ACFs was 17 times greater than expected from the observed tumor rate in approximately the same zone (16 vs. 1.7 percent; 95 confidence interval, 10 to 22 and 0.5 to 1.3 percent). Twenty control animals receiving saline had no tumors of epithelial origin. Nine control animals that were carcinogen-treated and tattooed in areas without ACF had no tumors in the marked areas. CONCLUSION. Results thus show regression of many ACF identified early in the carcinogenesis process. Results also support the hypothesis that some ACF are precursor lesions for adenomas and cancers.
|ISSN : ||0012-3706|
|Mesh Heading : ||Adenoma Animals Carcinoma Carcinoma in Situ Colon Colonic Neoplasms Female Precancerous Conditions Rats Rats, Inbred F344|
|Mesh Heading Relevant : ||pathology pathology pathology pathology pathology pathology|
Cytotoxicity of B72.3XOKT3 bispecific antibody recognizing human colon cancer.
Journal - The Journal of surgical research (UNITED STATES )
Bispecific monoclonal antibodies can be used to redirect peripheral blood lymphocytes against tumor cells. In the present study, a murine bispecific monoclonal antibody was developed using somatic hybrydization. The antibody has two different binding arms: one arm directed against human CD3 receptor expressed on T-lymphocytes and the other against tumor associated glycoprotein TAG-72, expressed on human carcinomas, such as colon, breast, and pancreas. Partially purified antibody was capable of inducing human T-cell proliferation and preventing growth of colon cancer cell line in nu/nu mice in a tumor neutralization assay.
|ISSN : ||0022-4804|
|Mesh Heading : ||Animals Antibodies, Bispecific Antibodies, Monoclonal Cell Separation Colonic Neoplasms Flow Cytometry Humans Immunoglobulin Isotypes Lymphocyte Activation Lymphocytes Mice Mice, Inbred BALB C Mice, Nude T-Lymphocytes isolation & purification classification immunology physiology|
|Mesh Heading Relevant : ||Antibody Specificity Cytotoxicity, Immunologic toxicity immunology immunology|
Improved engraftment of human tumours in SCID mice pretreated with radiation and anti-asialo GM1.
Journal - Anticancer research (GREECE )
The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.
|ISSN : ||0250-7005|
|Mesh Heading : ||Animals Antibodies Cell Division Cytotoxicity Tests, Immunologic Female G(M1) Ganglioside Humans Immunity Male Mice Mice, SCID Neoplasm Transplantation Neoplasms Transplantation, Heterologous Tumor Cells, Cultured physiology radiation effects pathology radiation effects|
|Mesh Heading Relevant : ||pharmacology immunology immunology immunology methods|