Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low levels of anti-viral activity, mainly interferon alpha/beta (IFN-alpha/beta), are regularly found in lymphoid tissues of BALB/c mice infected with the C3H strain of mammary tumor virus. At the time of tumor development, significant amounts of anti-viral activity were detected in homogenates of spleen and mammary tumors, but not in blood and normal mammary glands. This activity is pH2-resistant and neutralized by antibody to IFN/alpha-beta. The pathogenetic role of IFN in mammary carcinogenesis was investigated in 2 ways: (a) by treating virus-infected newborn mice with antibody to IFN-alpha/beta, and (b) by giving either the latter antibody or IFN-alpha/beta to virus-free animals transplanted with pre-neoplastic lesions. Mice were treated only for 2 months, starting either 1 week after birth or immediately after tumor transplant. In case (a), treatment with antibody to IFN-alpha/beta shortened the incubation period of mammary carcinomas and decreased the mean survival time. In case (b), anti-IFN antibody did not significantly affect the development of mammary tumors. However, exogenous IFN-alpha/beta markedly reduced both tumor incidence and mortality rate. These results indicate that endogenous IFN-alpha/beta plays a crucial role in the in vivo restriction of the early infectious phase of spontaneous carcinogenesis and that relatively high doses of IFN-alpha/beta may inhibit the progression of pre-neoplastic lesions.
 ...
PMID:Interferon-alpha/beta in virus-induced mouse mammary carcinogenesis: effects on the spontaneous process and on the progression of transplanted pre-neoplastic lesions. 132 80

Bladder tumors were induced in rats by the oral administration of 0.025% N-butyl-N-(hydroxybutyl) nitrosamine (BBN). In order to study the suppressive effects of rat interferon-alpha (IFN-alpha) on induction of carcinogenesis in vivo, rats were treated with IFN-alpha i.m. twice a week. The treatment began at 5th week of BBN administration. The bladder mucosa was observed macroscopically and microscopically, and NK activity was examined. The results were as follows. 1) There was no significant difference in the bladder to body weight ratio between the BBN + IFN-alpha and BBN groups in during stage A (10th-14th week when changes in the mucous membrane such as hypertrophy in the bladder wall or vascular formation are observed). This ratio in the BBN + IFN-alpha group was less than that in the BBN group in during stages B and C (15th-19th week and 20th-30th week respectively when tumors are visually recognizable). 2) The rate of carcinogenesis in the BBN + IFN-alpha group was less than that in the BBN group in stages A and C. 3) The pathological grade and stage of the bladder cancer in the BBN + IFN-alpha group were lower than those in the BBN group in stages B and C. 4) There was no significant difference in NK activity between the two groups in stage A, but NK activity of the BBN + IFN-alpha group was higher than that of the BBN group in stage B. 5) These findings substantiated the hypothesis that IFN-alpha can suppress tumor-growth in BBN induced bladder carcinoma.
 ...
PMID:[Inhibitory effects of IFN on N-butyl-N-(hydroxybutyl) nitrosamine induced rats bladder tumors]. 156 22

The inhibitory effect of murine interferon alpha/beta (Mu-IFN) on the induction of adenocarcinoma of the duodenum in C57BL/6 mice given N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was examined. ENNG was given continuously in drinking water for 4 weeks and Mu-IFN was given intraperitoneally for 12 weeks. Then, the duodenal tumors of mice were examined stereomicroscopically and histologically. The level of IFN activity and natural killer (NK) activity were evaluated after an intraperitoneal single injection of Mu-IFN, and the level of NK activity was evaluated 2, 5 and 8 weeks after giving ENNG and Mu-IFN. In the mice given Mu-IFN, the incidence of duodenal tumors was significantly decreased (P less than 0.01), compared with that in mice given ENNG alone. Further, anti-asialo GM1 was given intraperitoneally every 5 days for 8 weeks to depress NK function and the incidence and size of duodenal tumors were examined. The results indicated that NK cells also have an important effect on the process of carcinogenesis. These data suggest that chemoprevention with IFN may be feasible.
 ...
PMID:The effect of interferon on carcinogenesis by N-ethyl-N'-nitro-N-nitrosoguanidine in the duodenum of mice. 190 27

A cell-mediated mutagenesis assay employing cultured primary SENCAR keratinocytes for the metabolism of promutagens, and V-79 fibroblasts as target cells for the resulting genotoxic metabolites, was used to survey the effects of murine beta-interferon (IFN-beta) on 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP)-dependent mutagenesis and cytotoxicity. Pre-incubation of the keratinocyte cultures with greater than 100 units/ml IFN-beta, but not mock IFN, partially inhibited DMBA (25-60%) and BP (25-63%) dependent mutagenesis, but had little effect on the cytotoxicities of these agents. The level of inhibition was influenced by the length of keratinocyte pre-incubation with IFN-beta, and the concentration of IFN-beta, and the number of keratinocytes per nmol of promutagen. IFN-beta dependent inhibition of DMBA mutagenesis correlated with alterations in DMBA metabolism, including a decrease in the intra- and extracellular concentrations of the proximal promutagen (+/-) trans-DMBA-3,4-dihydrodiol.
Carcinogenesis 1985 Dec
PMID:Interferon-beta inhibits 7,12-dimethylbenz[a]anthracene-dependent mutagenesis in a keratinocyte cell-mediated mutation assay. 241 68

Major histocompatibility complex (MHC) antigen expression has been postulated to have an important role in host defences against tumour development. In this study the expression of MHC class I and class II antigens in vitro, both constitutive and in response to interferon gamma (IFN gamma), was examined in a series of cell lines established from a rat model of oral carcinogenesis. Constitutive expression of MHC class I and class II antigens was not related to the degree of malignancy of the cell lines, as reflected by their anchorage independence in agarose gels and their capacity to form tumours in athymic mice. MHC class I response to IFN gamma stimulation did not correlate with tumorigenicity, but the MHC class II response was significantly decreased in one of the four tumorigenic cell lines. The results show that the expression of MHC antigens in response to IFN gamma varied between different keratinocyte cell lines but did not consistently reflect the tumorigenic phenotype.
 ...
PMID:The expression of MHC antigens on cultured oral keratinocytes and relationship to malignancy. 246 29

Human brain tumor cell strains were previously found by others to be sensitive to growth inhibition by human interferon-beta (HuIFN-beta). We noticed that the sensitive strains were some that we had found deficient in the repair of O6-methylguanine (O6MeG), a characteristic of 20% of the human tumor cell strains we have studied. We confirmed this sensitivity to HuIFN-beta, and have further shown that human brain tumor cells which repair O6MeG are resistant to the growth inhibitory effects of HuIFN-beta. In addition, treatment with HuIFN-alpha or HuIFN-beta resulted in more killing (reproductive inactivation) of six human tumor cell strains deficient in repairing O6-methylguanine in DNA than did such treatment of six strains of cells proficient in such repair. Further, we found two human lines, altered to become O6MeG repair deficient after establishment of the primary tumor cell culture, that were resistant to interferon. IFN treatment produced no DNA damage detectable by either chemical or biological assays. It is suggested that the genes responsible for resistance to IFN treatment and to agents that produce O6MeG are often coordinately shut down.
Carcinogenesis 1985 Jun
PMID:Human tumor cell strains both unable to repair O6-methylguanine and hypersensitive to killing by human alpha and beta interferons. 400 75

The endogenous production of nitric oxide (NO) and its role in the neoplastic transformation of C3H 10T1/2 mouse fibroblasts were investigated. NO production, as indicated by NO2- in the culture medium, was increased in cells initiated with 3-methylcholanthrene or stimulated with the combination of interferon-gamma (IFN gamma, 10 ng/ml) plus bacterial lipopolysaccharide (LPS, 1 micrograms/ml). NO2- was detectable within 24-48 h of IFN gamma/LPS treatment and accumulated to micromolar concentrations within 4 days. NO production was inhibited in a dose-dependent manner by analogs of L-arginine in which the terminal guanidino nitrogen is blocked, consistent with NO production by the oxidative deamination of L-arginine by nitric oxide synthase (NOS). IFN gamma/LPS-stimulated cells expressed a 4.4 kb mRNA which hybridized to a probe for the mouse macrophage-inducible NOS. Expression of the rat cerebellar constitutive NOS was not detected in these cells. Arginine analogs added to the culture medium during the post-confluence promotional stages of the C3H 10T1/2 transformation assay blocked the formation of transformed foci in a dose-dependent manner comparable to their inhibition of NO production. These data demonstrate that C3H 10T1/2 mouse fibroblasts are a useful model for the study of the effects of endogenous NO production in carcinogenesis and suggest that NO plays a significant role in the promotional phase of neoplastic transformation of these cells.
Carcinogenesis 1993 Aug
PMID:Inhibitors of endogenous nitrogen oxide formation block the promotion of neoplastic transformation in C3H 10T1/2 fibroblasts. 768 37

p16Ink4 and p15Ink4B are cyclin-dependent kinase 4 inhibitors and link to the regulation of cell cycle in mammalian cells. The genes encoding these inhibitors are located at 9p21, which is a frequent site of allelic loss in various types of tumors. Twenty-five primary biliary tract cancers were examined for somatic mutations in p16Ink4/CDKN2, p15Ink4B/MTS2, p53, and K-ras genes and allelic loss of 9p21 by microsatellite analysis. Four biliary tract cancer cell lines were analyzed for homozygous deletions and point mutations. We found frequent homozygous deletions in p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in the biliary tract cancer cell lines. Each cancer cell line had alteration of either p16Ink4/CDKN2, p15Ink4B/MTS2, or p53 genes. In primary tumors, 16 of 25 (64%) biliary tract cancers had point mutations in the p16Ink4/CDKN2 gene. These include 14 missense and 2 silent mutations. The frequency of mutations in gall bladder cancer and hilar bile duct cancer were 80% (8 of 10) and 63% (5 of 8), respectively. Each of codons 1, 80, and 111 was changed in two cases of these cancers. One of three intrahepatic bile duct cancers, one of two common bile duct cancers, and one of two ampullary cancers had mutations in the p16Ink4/CDKN2 gene. In contrast, no mutation in the p15Ink4B/MTS2 gene, one base change in the K-ras gene, and one loss of heterozygosity at the IFN alpha locus in 25 cancers and one base change in the p53 gene in 19 cancers were observed. These results suggest that p16Ink4/CDKN2, rather than p15Ink4B/MTS2 or p53 genes, and its inactivation may be important in biliary tract carcinogenesis.
 ...
PMID:Mutations of p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in biliary tract cancers. 779

SENCAR mice develop more papillomas in two-stage skin carcinogenesis protocols if gamma interferon (IFN-gamma) is co-administered with 12-O-tetradecanoylphorbol-13-acetate (TPA) during the promotion phase. In the current study preparations of murine alpha, beta and gamma IFNs were surveyed for their abilities to modulate TPA-dependent promotion and induction of epidermal hyperplasia, inflammation and ornithine decarboxylase activity (ODC). Single or multiple i.p. administrations of IFN-alpha, -beta or -gamma (< or = 2500 units) did not induce epidermal hyperplasia, inflammation or ODC activity. Single or multiple i.p. administrations of IFN-alpha, -beta or -gamma (2500 units) to mice being topically promoted with 0.1 or 1 microgram of TPA did not alter the epidermal hyperplasia induced by the phorbol ester. The vascular permeability of the skin, as evaluated by the extravasation of Evans blue dye, was increased in a dose-dependent fashion by TPA over the range of 0.1-1 microgram. Treatment of mice promoted with 0.1 microgram of TPA with IFN-gamma (> or = 2500 units) significantly increased the skin's vascular permeability. Comparable effects were not obtained with IFN-beta (IFN-alpha not tested). Treatment of TPA-promoted mice with IFN-gamma, and to a lesser extent IFN-beta, weakly potentiated the TPA-dependent induction of epidermal ODC activity. Under conditions in which IFN-gamma had co-promoting activities in an initiation-promotion protocol, co-treatment of initiated mice with 1 microgram of TPA and IFN-alpha or -beta (100-5000 units) did not reproducibly alter tumor latency., or papilloma and carcinoma multiplicities. These findings suggest that the co-promoting activities of IFNs are restricted to the gamma class, and are not uniformly reflected by parameters commonly employed as short-term markers of tumor promotion.
Carcinogenesis 1993 Mar
PMID:Differential co-promoting activities of alpha, beta and gamma interferons in the murine skin two-stage carcinogenesis model. 845 12

Recent allelotyping of chemical-induced lung tumors in hybrid mice has detected loss of heterozygosity on chromosome 4 in a region involving the interferon-alpha (IFN-alpha gene cluster that is syntenic to human chromosome 9p21-22, the location of the p16INK4a (p16) and p15INK4b (p15) tumor suppressor genes. The purpose of the current investigation was to characterize the expression of p16 and p15 in lung tumors and tumor-derived cell lines induced in A/J mice by exposure to the tobacco-specific nitrosamine, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK). Expression of p16 and p15 was detected in all primary lung tumors; however, levels of expression of p16 differed by up to 15-fold between tumors. This is the first study to note a marked difference in the expression of the p16 gene in primary lung tumors. The apparent low levels of expression seen in approximately half of the tumors was not attributed to deletion, mutation or methylation of the p16 gene. Conversely, the high levels of p16 expression were not the result of effects on the retinoblastoma gene (Rb) or cyclin D1 proteins but most likely in response to a dysfunction elsewhere within this pathway. In contrast to the detection of p16 expression in primary tumors, this gene was deleted in all four cell lines. Three of four cell lines also showed loss of the p15 gene. Mapping of these homozygous deletions on chromosome 4 revealed that the p16 gene resides near the D4MIT77 marker, which is located approximately 12 cM proximal to the IFN-alpha gene cluster, thereby implicating the p16 gene as one of the targets within the allelic deletions detected previously in primary lung tumors from hybrid mice.
Carcinogenesis 1997 Jan
PMID:Deletion and differential expression of p16INK4a in mouse lung tumors. 905 97


1 2 3 4 5 6 7 8 9 10 Next >>