Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: B0001 .4
 471,332 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using in vitro double labeling with two different doses of [3H]thymidine, we measured the S-phase duration and the labeling index in biopsy samples taken from human rectal and colonic adenocarcinomas. Samples from the adjacent healthy mucosa, taken at the same time as the tumor samples, were simultaneously subjected to the same measurements. The mean labeling index in tumors was higher than in the normal mucosa (32.5 and 17.0%, respectively). The mean S-phase value was also longer than in the normal tissue (19.4 versus 11.2 hr). These observations are discussed with reference to similar observations made in tumors of the human epidermis, especially considering the possible relationship of an increased S-phase duration with carcinogenesis. While no definitive conclusions may be reached, it seems prudent to consider an S-phase duration that is longer than normal to be a justification for attentive follow-up of the patient.
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PMID:In vitro autoradiographic determination of cell kinetic parameters in adenocarcinomas and adjacent healthy mucosa of the human colon and rectum. 126 Jul 40

Microcystin-LR (MC-LR), an inhibitor of protein phosphatases 1 and 2A, is a potent tumor promoter in rat liver initiated with diethylnitrosamine. To understand its biochemical process in hepatocytes, primary cultured rat hepatocytes were treated with MC-LR. MC-LR (1 microM) induced phosphorylation of various proteins. Two 55 and 49 kDa proteins were phosphorylated at a 3-fold higher rate than other proteins, and these proteins were identified to be cytokeratins 8 and 18 respectively, by immunoprecipitation and Western blot analysis using monoclonal anti-cytokeratin 8 and 18 antibodies. The basic cytokeratins 8 and 18 showed pI 6.4 and 5.4 respectively, in two-dimensional gel electrophoresis. MC-LR dose dependently increased phosphorylation of cytokeratins 8 and 18 in a cell-free system by incubation with a cytosolic fraction of rat liver containing both protein kinases and protein phosphatases 1 and 2A, and with [gamma-32P]ATP. Cytokeratins 8 and 18 were target proteins for phosphorylation induced by inhibition of protein phosphatases 1 and 2A, in vitro and in rat hepatocytes. Thus, the treatment of rat hepatocytes with MC-LR induced hyperphosphorylation of cytokeratins 8 and 18 associated with morphological changes, indicating that intermediate filament networks were rearranged in the cytoplasm. The hyperphosphorylation of cytokeratins is a significant biochemical process associated with liver tumor promotion.
Carcinogenesis 1992 Dec
PMID:Hyperphosphorylation of cytokeratins 8 and 18 by microcystin-LR, a new liver tumor promoter, in primary cultured rat hepatocytes. 128 96

The effect of natural carotenoids on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitroguanidine (MNNG) was studied in 4 groups containing 105 rats. Highly carotenoid complex from wild rose fruits was added to drinking water of Group 1 (30 rats) at a dose of 15 mg/kg (as calculated per beta-carotene) 3 times weekly; as well as MNNG was present in water (0.01%). The carotenoid complex was supplemented to the ration 2 months before MNNG treatment and was continued within 15 months; MNNG treatment occurred within 6 months. Group 2 (30 rats) and Group 3 (30 rats) were treated with MNNG and the carotinoid complex, respectively; the 4 group (15 rats) was used as an intact control. Tumors were detected in 16 rats of 28 animals studied in Group 1 (57.1%) and in 11 rats of 25 animals in Group 2 (44%) (P < 0.05); malignization was found in the stomach and small intestine. The rate of involvement with gastric tumor in Group 1 was 3-fold higher as compared with those in the only MNNG treated animals--50% and 16%, respectively (P < 0.01). Tumors of the small intestine were detected in 5 rats of Group 1 (17.8%) and in 9 rats of Group 2 (36.6%); differences were statistically insignificant. However, carcinogenesis tended to accelerate. The mean time of stomach and small intestine tumor detection in Group 1 was equal to 286 and 276 +/- 46 days, respectively, and in Group 2--339.7 +/- 25.4 and 350.7 +/- 25.4 days, respectively (differences are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of carotenoids on rat stomach carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine]. 129 19

Thirty-two cases (20.13%) of primary lung cancer from 159 coal miner autopsies of Beijing coal mining area are reported in this study. The ratio of peripheral type to central type of lung cancer is 1.9:1; among them the adenocarcinoma is the most frequent (56.25%). Pathological examination shows that the diffuse interstitial type is the most common lung cancer. The occurrence of adenocarcinoma and the degree of lung fibrosis is related. The average number of ferruginous bodies is 190.2 +/- 8.06 in adenocarcinoma, 165.4 +/- 2.60 in squamous carcinoma, the difference is statistically significant (P < 0.05). The amount of trace elements-Fe, Al, Al/Si and Zn/Cu in lung with cancer is less than that without cancer. This article also discusses the relationship between coal mine pneumoconiosis with lung cancer of the formation of ferruginous bodies in the lung tissue of coal miner autopsies, which resembles the lung cancer combined with asbestosis. We also discussed the carcinogenesis of trace element in lung.
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PMID:[Study on the incidence of coal mine pneumoconiosis and lung cancer in Beijing coal mining district]. 129 8

In children and adolescents from two areas of Costa Rica with contrasting gastric cancer risks, two factors suspected to be linked to the natural history of the disease were tested: serum antibodies to Helicobacter pylori and serum pepsinogen levels. One hundred fifty-five subjects from the high-risk area of Turrubares were compared to 127 from the low-risk area of Hojancha. No significant differences were found in the prevalence of IgG or IgA antibodies to Helicobacter pylori between the two regions. The prevalence of IgG was 65.8% in the high-risk area and 72.4 in the low-risk area, and that of IgA was 43% in both areas. The levels of pepsinogen, especially pepsinogen C, were significantly elevated in subjects with H. pylori antibodies in their serum. The mean levels of pepsinogen C in those negative, positive, and strong positive for H. pylori antibodies were 8.7, 14.3, and 21.1 ng/ml. These findings suggest that H. pylori-associated gastritis, predominantly of antral localization, is very prevalent in Costa Rican children and adolescents. Such gastritis might be associated with a high prevalence of intestinal metaplasia and a high gastric cancer risk in the inland, but not the coastal rural populations. H. pylori may therefore be an insufficient cause whose role in gastric carcinogenesis is contingent upon the presence of other factors.
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PMID:Antibodies to Helicobacter pylori and pepsinogen levels in children from Costa Rica: comparison of two areas with different risks for stomach cancer. 130 56

The effects of the radiosensitizer misonidazole (MISO) and the radioprotector WR-2721 on radiation-induced carcinogenesis in C3Hf/Kam mice were investigated. The right hind legs were exposed to graded single doses of gamma-rays. MISO and WR-2721 were given i.p. 30 min before irradiation at a dose of 1 mg/g and 0.4 mg/g, respectively. The RCD50, or radiation dose inducing tumors in 50% of the irradiated legs, was determined 650 days after treatment. The same animals were also checked for the effect of these drugs on hair loss and radiation-induced leg contractures. MISO enhanced radiation carcinogenesis by a factor of 1.43, whereas WR-2721 reduced it by a factor of 1.75. These effects on carcinogenesis correlated well with the modifying effects of the two agents on radiation-induced hair loss (early damage) and leg contractures (late damage).
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PMID:Modification of radiation-induced carcinogenesis in mice by misonidazole and WR-2721. 131 77

Retinoic acid is known to inhibit mammary carcinogenesis in rodents and to inhibit proliferation and steroid hormone receptor gene expression in human breast cancer cells. Since these effects are likely to be mediated by nuclear retinoic acid receptors (RARs) the present study was initiated to determine the expression and regulation of RARs in human breast cancer cell lines. Differential cellular gene expression of the RARs was determined by Northern blot analysis of total RNA prepared from 5 ER+ and 6 ER- cell lines. RAR alpha was detected as mRNA species of 2.7 and 3.4 kilobases in all cell lines and the level of gene expression was greater in ER+ cell lines (P less than 0.001). RAR beta mRNA (3.7 kilobases) was detected in seven of the eleven lines tested and was expressed most commonly in ER- cell lines. RAR gamma mRNA was expressed in all cell lines as a transcript of 3.4 kilobases at levels that were similar in both ER+ and ER- cell lines. Retinoic acid failed to regulate the expression of the RAR alpha and RAR gamma genes. The effect of steroid hormones on RAR alpha and RAR gamma mRNA levels was also examined. In four PR+ cell lines (T-47D, BT 474, MCF-7M, and MDA-MB-361), progestins markedly decreased RAR alpha mRNA levels. The progestin effect on RAR alpha levels in T-47D cells was detectable at concentrations of 0.05 nM and was maximal at 1 nM 16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione ORG 2058, whereas dihydrotestosterone and dexamethasone were without effect. RAR alpha and RAR gamma mRNA levels were rapidly decreased by progestin, and the effect was maximal 3-6 h after ORG 2058 treatment. However, the mRNA loss was transient, and recovery of RAR alpha and RAR gamma mRNA levels was noted 12-24 h after retinoic acid treatment. Although RAR gamma mRNA returned to control levels by 24 h, the decrease in RAR alpha mRNA was maintained at around 50% control until at least 48 h. In summary, RAR alpha and RAR gamma were expressed in all human breast cancer cell lines and were regulated by progestins in the PR+ T-47D cell line. The previously reported ability of retinoic acid to down-regulate PR mRNA and the present demonstration that progestins down-regulate RAR alpha and RAR gamma mRNA suggest that mutual regulation may be a mechanism through which PR and the RARs interact in human breast cancer cells.
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PMID:Expression and regulation of retinoic acid receptors in human breast cancer cells. 131 39

To challenge the theory of tissue specificity of tumor promoters, the biochemical and tumor promoting effects of okadaic acid (OA), a potent tumor promoter on mouse skin, were studied in the mucosa of rat glandular stomach. OA strongly inhibited protein phosphatases 1 and 2A, and increased 4-fold the phosphorylation of elongation factor 2 in vitro in the mucosa. Intubation of 10 micrograms (12.4 nmol) OA induced ornithine decarboxylase in the mucosa. Tumor promotion of OA was studied in the glandular stomach initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in a two-stage carcinogenesis experiment. OA in drinking water, 10 micrograms (12.4 nmol) per rat per day from weeks 9-55 of the experiment, and 20 micrograms (24.8 nmol) from weeks 56-72, significantly enhanced development of the neoplastic changes in the glandular stomach (P < 0.05). The neoplastic changes included adenomatous hyperplasias and adenocarcinomas, both of which correspond to papillomas and carcinomas in a two-stage mouse skin carcinogenesis experiment. The percentages of neoplastic change-bearing rats of the groups treated with MNNG plus OA, MNNG alone or OA alone were 75.0, 46.4 and 0% respectively. OA enhanced tumorigenesis in the MNNG-initiated glandular stomach of rats through the same mechanisms of action as in mouse skin. The OA pathway mediated through inhibition of protein phosphatases 1 and 2A is applicable to various organs as a general mechanism of tumor promotion.
Carcinogenesis 1992 Oct
PMID:An alternative theory of tissue specificity by tumor promotion of okadaic acid in glandular stomach of SD rats. 133 Mar 44

Highly purified cytochrome P-450 reductase (also called cytochrome c reductase; EC 1.6.2.4.) and NADPH were used to generate superoxide radical (O2.-) from 11 different heterocyclic amines (HCAs) as identified by electron spin resonance spectroscopy using the spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The signal intensity of DMPO-OOH(-O2-) (i.e., the DMPO spin adduct of O2.-) was strongest for 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). The O2.- generation with HCAs decreased in the following order: 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) = 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) > 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (diMeIQx) > or = other HCAs; O2.- generation was lowest with 2-amino-3-methyl-9H-pyrido[2,3-b]indole .CH3COOH (MeA alpha C). By using Lineweaver-Burk plots, Km values of cytochrome P-450 reductase for mitomycin C, IQ, and MeIQ were determined to be 1.60 x 10(-6) M, 1.97 x 10(-5) M, and 2.83 x 10(-6) M, respectively. The present findings have important implications for carcinogenesis because of the known effect of oxygen radicals on cell proliferation.
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PMID:Evidence of direct generation of oxygen free radicals from heterocyclic amines by NADPH/cytochrome P-450 reductase in vitro. 133 93

We evaluated cell proliferative activity and expression of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and DU-PAN-2 in various bile duct lesions in livers with hepatoliths, using histochemical and immunohistochemical methods. Histologically, the bile duct lesions were divisible into hyperplasia, dysplasia, adenocarcinoma in situ and invasive adenocarcinoma. All cases showed mucosal hyperplasia in stone-bearing bile ducts. Livers with invasive adenocarcinoma frequently contained adenocarcinoma in situ and dysplasia, and livers with adenocarcinoma in situ occasionally harboured dysplasia. Proliferating cell nuclear antigen (PCNA) labelling index was low in hyperplasia (mean +/- SD = 20.5 +/- 8.7%), intermediate in dysplasia (35.4 +/- 15.9%), and high in adenocarcinoma in situ (46.4 +/- 9.3%). The mean number of argyrophilic nucleolar organizer regions (AgNORs) was low in hyperplasia (1.52), intermediate in dysplasia (2.26) and high in adenocarcinoma in situ (2.69). There was a significant positive correlation between PCNA labelling index and AgNORs count. CEA was expressed on invasive adenocarcinoma cells and adenocarcinoma in situ cells in most cases and on dysplastic cells in about a half, while CEA was never present in hyperplastic epithelia. Expression of CA 19-9 was low in adenocarcinoma, intermediate in dysplasia and rather high in hyperplasia. There was no significant difference in DU-PAN-2 expression among these bile duct lesions. These data suggest that cell replicative activity is low in hyperplasia, intermediate in dysplasia and high in adenocarcinoma in situ, and that CEA appears in the following order: dysplasia, adenocarcinoma in situ, invasive adenocarcinoma. We suggest that carcinogenesis in biliary epithelial in livers with stones is a multi-step process through hyperplasia, dysplasia and adenocarcinoma in situ to invasive adenocarcinoma.
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PMID:Cell kinetic analyses and expression of carcinoembryonic antigen, carbohydrate antigen 19-9 and DU-PAN-2 in hyperplastic, pre-neoplastic and neoplastic lesions of intrahepatic bile ducts in livers with hepatoliths. 134 89


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