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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-Methyl-N-nitrosourea (MNU) induces thymic lymphosarcoma in numerous mouse strains. We determined the neoplastic phenotype induced by MNU in 20 C57B1/6J mice. Eleven neoplasms were composed of cells that were CD4-CD8+, four neoplasms were composed of cells that were CD4+CD8+, two neoplasms were mixtures of CD4+CD8+ and CD4-CD8+ cells, and three neoplasms were made up of cells that expressed neither CD4 nor CD8. Expanded populations of CD4+CD8- cells were observed within individual neoplasms. Of 10 neoplasms that were further classified, all were composed of cells that were J11d+, indicating immaturity. CD3 expression was generally negative, while IL2R expression was variable in these neoplasms. These data from C57B1/6J mice, a strain with a low incidence of spontaneous (viral-associated) thymic lymphosarcoma, indicate that a continuous spectrum of immature phenotypes are produced by MNU. The finding that each immature cell population can be expanded in this model system differs from previous reports. Our data do confirm the general finding in AKR mice, a strain with a high incidence of spontaneous thymic lymphosarcoma, that cells with immature phenotypes, particularly CD4-CD8+J11d+, make up MNU-induced thymic lymphosarcomas.
Carcinogenesis 1992 Mar
PMID:Flow cytometric analysis of thymic lymphosarcoma induced by N-methyl-N-nitrosourea in C57B1/6J mice. 154 44

There has been much speculation as to the role of Langerhans cells (LC) in the induction of anti-tumor immunity. Whereas there is considerable circumstantial evidence that disruptions in the density and function of these cells during the early stages of ultraviolet (UV) light- and chemical carcinogen-induced carcinogenesis may be important for enabling developing neoplasms to escape immune destruction, the role of the large number of these cells found infiltrating developed skin tumors is less clear. To investigate this we have compared the LC density infiltrating transplanted non-immunogenic and immunogenic UV-induced murine tumors as well as LC in the epidermis overlying the tumors. Whereas two non-immunogenic tumor lines attracted large numbers of Ia+ dendritic cells, an immunogenic tumor line did not. Similar results were obtained whether the tumors were transplanted into syngeneic immunocompetent or athymic immunodeficient mice. Hence, there was no relationship between tumor immunogenicity or host immunocompetence and Ia+ dendritic cell density. Furthermore, there was no correlation with the pattern of T-cell infiltration of the tumors or CD4/CD8 cell ratio. Our results also indicate that whereas UV light decreased Ia+ cell density, both in the epidermis and the tumors, it did not inhibit the tumors from attracting Ia+ dendritic cells. Thus, the Ia+ dendritic cells infiltrating skin tumors are unlikely to indicate a host immune response to the tumor, but are more likely to be attracted by tumor-derived cytokines.
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PMID:Langerhans cell migration into ultraviolet light-induced squamous skin tumors is unrelated to anti-tumor immunity. 168 Sep 31

Several studies have found pattern and model makers to be at increased risk for colorectal polyps and colorectal cancers. One study found an increased prevalence of lymphocytopenia. The association of total lymphocyte, CD4 (T-helper cell), CD8 (T-suppressor cell), CD2 (total T-cell), and CD16 (natural killer cell) counts with biopsy-proved colorectal polyp status was investigated in 70 patternmakers participating in one or more of four sequential screenings. In logistic regression analyses after adjusting for age or trade years, pack-years smoked, and material worked with most, a history of any type of polyp was significantly associated with total lymphocyte count (odds ratio of 2.01 for a 500 cell/cc decrease, P = 0.03), and somewhat associated with decreased CD4 and CD2 counts (P values of 0.06 and 0.07, respectively). In linear regression models adjusted for age, pattern and model makers had (regardless of polyp status) significantly lower CD4, CD8, CD2, and CD16 counts than did laboratory reference controls (P value less than 0.01 for each comparison). These findings appear consistent with a sequence of carcinogenesis initiated by pattern and model makers' work-place exposures that depress immune surveillance thus promoting the development of colorectal polyps as a precursor of carcinoma.
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PMID:Lymphocytopenia, T-lymphocyte subsets, and colorectal polyps in automotive pattern and model makers. 203 6

Tobacco (smoking and smokeless) use and excessive consumption of alcohol are considered the main risk factors for oral cancer (ICD9 140-149). Conspicuous national and international variations in oral cancer incidence and mortality rates, as well as observations in migrant populations, raise the possibility that diet and nutritional status could be an important etiologic factor in oral carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious nutritional implications for the host, and generates increased production of reactive free radicals as well as eliciting immunosuppression. Maintenance of optimal competence of the immune system is critical for cancer surveillance. Active oxygen species and other reactive free radicals mediate phenotypic and genotypic alterations that lead from mutation to neoplasia. Consequently, the most widely used chemopreventive agents against oral cancer (e.g., vitamins A, E, C, and beta-carotene) are anti-oxidants/free radical scavengers. These anti-oxidants, both natural and synthetic, neutralize metabolic products (including reactive oxygen species), interfere with activation of procarcinogens, prevent binding of carcinogens to DNA, inhibit chromosome aberrations, restrain replication of the transformed cell, suppress actions of cancer promoters, and may even induce regression of precancerous oral lesions such as leukoplakia and erythroplakia. Malnutrition is characterized by marked tissue depletion of anti-oxidant nutrients, including GSH (gamma-glutamyl-cysteinyl-glycine), a key cellular anti-oxidant as well as a modulator of T-cell activation. GSH or its precursor cysteine inhibits activation of the nuclear transcription factor kB(NFkB), and has been shown to be protective against chemically induced oral cancer and leukoplakia. Alcohol-, tobacco-, and/or malnutrition-induced immunosuppression promotes impaired salivary gland function and oral mucosal immunity, a prominent reduction in the number of helper CD4 cells with less marked changes in number of suppressor T-cells, and depressed NK cell activity, among others. These suggest a breakdown in capacity or the malnourished to mount effective tumor surveillance. This review article underscores the compounding but important roles of nutritional/dietary factors in the long-established causal link between abuse of alcohol and tobacco (smoking and smokeless) and oral cancer.
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PMID:Bionutrition and oral cancer in humans. 763 67

N-methylnitrosourea (MNU) induces thymic lymphoma in a high proportion of susceptible C57BL/6xSJL (C57/SJL) mice. Expression of the human DNA repair gene, MGMT cDNA, which encodes O6-methylguanine-DNA-methyltransferase, in transgenic mice effectively prevents MNU-induced thymic lymphomas. In this study, we determined the phenotype of thymocytes expressing the transgene and defined whether the target cell population for MNU induced lymphomas were actually those that expressed the transgene. Transgene expression was characterized by in situ hybridization for MGMT mRNA and immunohistochemistry for the human alkyltransferase protein and was compared to the phenotype of the MNU induced lymphomas. The MGMT transgene was expressed uniformly in immature cortical thymocytes that were CD4+CD8+J11d+ and to a lesser extent in the medullary thymocyte. Lymphomas were induced by single [50 or 80 mg/kg] or multiple doses [30 mg/kg x 5] of MNU to evaluate the dose response of tumor induction and protection by the MGMT-CD2 transgene. Forty-seven of the 108 treated mice developed lymphomas: 38 of 58 nontransgenic and 9 of 50 MGMT+ mice. The T-cell phenotype of thymic lymphomas was established by immunohistochemistry and FACS analysis. Most of the lymphomas were J11d+ (98%), 70% of the tumors were CD4+CD8+, 21% were CD4-CD8+, 9% were CD4-CD8-, and none were CD4-CD8-. All lymphomas in MGMT+ transgenic mice were CD4+CD8+. Since the main phenotype of MNU induced lymphomas in these mice, CD4+CD8+J11d+, is also the cell phenotype which expresses the MGMT-CD2 transgene at high levels, it appears that MGMT-induced protection has occurred in the cell target for MNU induced transformation.
Carcinogenesis 1995 May
PMID:The immature thymocyte is protected from N-methylnitrosourea-induced lymphoma by the human MGMT-CD2 transgene. 776 63

In order to investigate the role of local immune response in uterine cervical carcinogenesis, lymphocyte phenotypes infiltrating the cervical region were studied by indirect immunoperoxidase staining for natural killer (NK) cells, macrophages. Langerhans cells (LC), memory T cells, CD4-positive cells and CD8-positive cells. The specimens used in this study were 9 normal ectocervical epithelium samples, 28 with mild dysplasia, 28 with moderate dysplasia, 31 with severe dysplasia and 9 with carcinoma in situ (CIS). A quantitative study was conducted in 23 patients with persistent cervical dysplasia and a comparable control group of 17 patients with regressive dysplasia. Human papillomavirus (HPV) types 16 and 18 DNA was analyzed by using polymerase chain reaction techniques, and differences in local immune responses between cases with and others without HPV types 16 and 18 were studied. The results are as follows. 1) The numbers, of NK cells and macrophages increased as the grade of cervical dysplasia increased and the numbers of these cells in cases of cervical dysplasia were greater than in normal ectocervical epithelium and CIS. 2) The numbers of LC, memory T cells and CD4-positive cells also increased with the grade of cervical dysplasia. The number of memory T cells was significantly greater in severe cervical dysplasia than in normal ectocervical epithelium or mild dysplasia (p < 0.05). 3) There were statistically significant correlations between the number of white blood cells and those of stroma-infiltrating memory T cells (r = 0.98) and CD4-positive cells (r = 0.88). A positive correlation was found between the numbers of lymphocytes in epithelium and in subepithelium. 4) A significant reduction in CD4-positive cells was founded in persistent dysplasia compared with regressive dysplasia (p < 0.05). 5) Cases with and without HPV types 16 and 18 did not differ significantly with respect to local immune responses. It is therefore considered that the increased number of lymphocytes in cervical dysplasia and the decreased number in CIS might reflect active local immunosurveillance in the process of carcinogenesis. Lymphocytes, especially CD4-positive cells, may play an important role in surveillance against the development and progression of cervical cancer.
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PMID:[Local immune responses in uterine cervical carcinogenesis]. 894 Jun 95

Foreign-body (FB) carcinogenesis is a classic model of multistage tumour development in rodents. Previous studies have demonstrated that the physical characteristics of the implant, and not the chemical composition, are the critical determinants of tumour development. The recent controversy over silicone breast implants has raised questions regarding the potential carcinogenicity of lifetime tissue exposure to silicone products. The present study was designed to determine whether the inflammatory and fibrotic reactions associated with silicone implants are due to a non-specific foreign-body reaction or whether these responses reflect the unique chemical composition of silicone. F344 rats were implanted subcutaneously with one of three biomaterials: silicone elastomer (Group 1); impermeable cellulose acetate filters (Group 2, positive control); or porous cellulose acetate filters (Group 3, negative control). The silicone and cellulose implants of Groups 1 and 2 have been previously shown to induce fibrosarcomas in rodents, whereas the porous cellulose acetate implants of Group 3 have been shown to be non-carcinogenic. One week and two months after implantation, the pericapsular tissues were evaluated using histopathological and in situ immunohistochemical analyses. Endpoints included expression of leucocyte antigens CD4 (T helper/inducer), CD8 (T suppressor/cytotoxic) and CD11 b/c (macrophage), proliferating cell nuclear antigen (PCNA) as an indicator of proliferation, and in situ end-labelling (ISEL) of 3'OH DNA strand breaks as an indicator of DNA damage and apoptosis. The results indicated that the acute and chronic cellular responses to silicone (Group 1) were not different from impermeable cellulose filters (Group 2) of identical size and shape, suggesting that these responses were not unique to silicone. The inflammatory response to the carcinogenic cellulose and silicone implants (Groups 1 and 2) was attenuated and associated with the formation of a thick fibrotic capsule. In contrast, the porous cellulose filters (Group 3) induced a markedly different cellular response in which the inflammatory reaction was more extensive, prolonged and associated with minimal fibrosis. Within the fibrotic capsule surrounding the tumorigenic implants, but not the non-tumorigenic implants, cell proliferation and apoptotic cell death were increased and associated with persistent DNA strand breaks. Taken together, the results suggest that the micrometre-scale surface morphology of the implant determines the nature of the subsequent cellular response which may predispose to tumour development. Further, these studies serve to emphasize the critical importance of appropriate physical controls in studies designed to evaluate carcinogenic or autoimmune manifestations associated with silicone implants in order to rule out the contribution of the chronic foreign-body reaction.
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PMID:Characterization of cellular response to silicone implants in rats: implications for foreign-body carcinogenesis. 915 98

44 patients with large bowel cancer were randomly divided into two groups, therapeutic and control group. The level of serum selenium, T lymphocyte subsets consisted of CD3, CD4, CD8, CD4/ CD8, NK and LAK cell activity were measured preoperation and postoperation. Simultaneously se content in tumor and normal tissue of the large bowel were measured in 35 cases. Serum se level (0.81 +/- 0.14 umol/L) was lowered in patients with large bowel cancer and increased significantly after se supplementation in the therapeutic group (P < 0.01). It was significantly different from that of the control group (P < 0.01), CD3, CD4, CD4/CD8, NK and LAK cell activity were obviously increased postoperatively in the therapeutic group and significantly different from those of the control group. The results suggest that supplement of Se can promote cell-mediated immunity in humans. In addition, Se can promote cell-mediated immunity in humans. The Se level of 22. 13 +/- 1.76 umol/g in tumor was significantly lower than that of 24.30 +/- 1.96 umol/g in normalmucosa in case of large bowel cancer (P < 0.01). This indicates that there may be a close relationship between low se level and the carcinogenesis of the colon and rectum.
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PMID:[The relationship between selenium and immunity in large bowel cancer]. 927 90

The association between genetic instability in repetitive DNA domains and cancer has been reported in different types of malignancies. In this work we perform a comparative study of 29 gastric tumors with paired normal tissue using seven tetra-(FES/FPS, VWA31/A, HTPO, TH01, MBPB) and pentanucleotide (CD4, TP53) STR polymorphic markers regarding loss of heterozygosity and replication error status. Furthermore, we compare the gene frequencies obtained in normal tissue from patients with those of a normal control population from the same area, looking for allele associations between any of these polymorphic loci and gastric cancer risk. The results have shown that FES/FPS and TP53 present the higher rates of somatic instability. The observed results for TP53 are in accordance with those previously reported in gastric carcinogenesis, while instability of FES/FPS is for the first time reported in this tumor type. Our data suggest that different loci show different rates of instability and/or loss of heterozygosity and do not seem to consist of a result of an RER+ phenotype affecting several genomic repetitive domains. Furthermore, the instability in markers TH01, MBPB, TP53, and FES was generally detected in genotypes involving alleles with a high number of repeats. Comparing gene frequencies in patients and normal controls, no significant differences were found, although longer alleles are consistently more frequent in patients for the markers MBPB, TH01, and CD4.
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PMID:Tetra- and pentanucleotide short tandem repeat instability in gastric cancer. 937 35

Extracts from mistletoe (Viscum album L.) are assumed to exert an antineoplastic activity through their toxicity at high doses or by immunomodulation by nanogram quantities of a lectin. They are used as an unconventional therapy modality in the management of a wide range of cancer diseases, although no anticancer potential has yet been demonstrated. This prompted us to study the effect of galactoside-specific lectin (VAA)--a major protein constituent of mistletoe with immunomodulatory properties--on chemically induced tumor development in the urinary bladder of rats and on the local cellular immune response after long-term administration. To induce urothelial neoplasms N-methyl-N-nitrosourea (MNU) was administered in a single intravesical dose (7.5 mg/kg body weight). Highly purified VAA was given subcutaneously at its immunomodulatory dose (1 ng/kg body weight) twice a week over the total experimental period of 15 months. The incidences of epithelial bladder tumors were 25.0% following administration of MNU alone and 22.9% in the rats additionally receiving VAA, which proved not to be significantly different (P = 0.81). Quantitative immunohistochemistry analyzing a panel of immune cell types, including T lymphocytes, T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8), T cells positive for interleukin-2 receptor (CD25), B lymphocytes and plasma cells, macrophages, natural killer cells, granulocytes and all leukocytes expressing the leukocyte common antigen (CD45), yielded no evidence for the ability of VAA to stimulate a substantial cellular immunological reaction in the wall of the normal urinary bladder or during urothelial carcinogenesis. In conclusion, the current experimental findings provide no support at all that the galactoside-specific mistletoe lectin is capable of inhibiting chemically induced bladder carcinogenesis and triggering a local cellular immune response after prolonged application. It thus seems highly improbable that commercial mistletoe preparations or VAA will be effective in the management of human bladder cancer by a cell-mediated immunological mechanism.
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PMID:Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosourea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration. 965 90


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