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)

Clinical findings and cytological data of 100 non-pregnant in-patients with squamous metaplastic cells in their cervical canal aspiration smears were compared to 100 randomly selected women without metaplastic cells, both groups having been diagnosed as ovarian disturbances. In women with squamous metaplastic cells more frequent cervical canal erosions, abnormal results of water-salt test and diagnosis of hypothalamic postpregnancy syndrome were stated. The findings together with the drift to the right of the Maturation Index, higher the Maturation Value and Eosinophilic Index and lower the Cytolytic Index, may suggest that the disturbances of the neurohormonal background are important in pathogenesis of the endocervical squamous metaplasia and that the latter may play a role in carcinogenesis.
 ...
PMID:Squamous metaplastic cells in cervical canal aspiration smears in women with ovarian function disorders. 7 65

Effects of dietary bile acids and their sodium salts on the development of pepsinogen-altered pyloric glands (PAPG) were examined in male WKY/N Crj rats initially given a single dose of 160 mg/kg body weight of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gastric intubation. From week 3 the animals were administered basal diet containing 0.5% supplements of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA) or their sodium salts (Na-C, Na-DC and Na-CDC), or 5% ascorbic acid (ASA) or its salt (Na-AS) for 18 weeks. The concentration of DCA and Na-DC was reduced to 0.3% from week 12. At week 20, animals were killed and the numbers of immunohistochemically-demonstrated PAPG were determined. Values were significantly higher with Na-C and Na-CDC than with the corresponding parent acids, and in the Na-C case PAPG development was greater than with MNNG alone. In addition, Na-CDC itself induced the numbers of PAPG significantly. These results suggest that bile salts are possible intrinsic promoters of gastric carcinogenesis. They were without effect, however, on forestomach lesions.
 ...
PMID:Effects of various bile acids and their sodium salts on development of pepsinogen-altered pyloric glands in rats. 136 59

The expression of alpha 6 beta 4 integrin has been analyzed in several keratinocyte cell lines representative of various stages of mouse epidermal carcinogenesis. The immunological analyses carried out show that alpha 6 beta 4 is expressed at the cell surface of the cell lines which exhibit an epithelial or epithelioid morphology. The relative levels of alpha 6 beta 4 expressed at the cell surface increase noticeably from premalignant to malignant cells, as detected by fluorescence flow cytometry. This increase also correlates with the abundance of soluble beta 4 subunit detected by Western immunoblotting in the different cell lines. However, complete absence of alpha 6 beta 4 has been found in spindle carcinoma cells showing a fibroblast-like phenotype in culture. The integrin remains associated to detergent- and high salt-insoluble cytoskeletal components, organized in stable anchoring contacts, as in human keratinocytes (Carter et al., J. Cell Biol., 111, 3141, 1990). In addition, a significant fraction of the beta 4 subunit is detected associated to highly purified cytokeratin fractions. These results, together with those regarding the organization of both cellular components in drug-treated cells, support the existence of a close association between alpha 6 beta 4 and the intermediate filaments of the cytoskeleton.
 ...
PMID:Expression of alpha 6 beta 4 integrin increases during malignant conversion of mouse epidermal keratinocytes: association of beta 4 subunit to the cytokeratin fraction. 137 91

Evidence from pathology and epidemiology studies has been provided for a human model of gastric carcinogenesis with the following sequential stages: chronic gastritis; atrophy; intestinal metaplasia; and dysplasia. The initial stages of gastritis and atrophy have been linked to excessive salt intake and infection with Helicobacter pylori. The intermediate stages have been associated with the ingestion of ascorbic acid and nitrate, determinants of intragastric nitrosation. The final stages have been linked with the supply of beta-carotene and with excessive salt intake. Nitrosating agents are candidate carcinogens and could originate in the gastric cavity or in the inflammatory infiltrate.
 ...
PMID:Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. 2129 57

Nickel(II) acetate (NiAcet), a soluble nickel salt known to be an effective initiator of renal epithelial tumors in adult rats, was studied for possible transplacental carcinogenicity. Pregnant F344/NCr rats were given NiAcet i.p. either once a day on day 17 (90 mumol/kg body wt; group 1) or twice on days 16 and 18 of gestation (45 mumol/kg body wt/day; group 2). Offspring of these rats were further subdivided into groups 1A and B and 2A and B, respectively. Groups 1A and 2A received ordinary tap water while groups 1B and 2B received drinking water containing 500 p.p.m. sodium barbital (NaBB) during weeks 4-85 of age. Renal cortical epithelial and renal pelvic transitional epithelial tumors occurred in male offspring given NiAcet prenatally followed by NaBB postnatally (group 1B, 15 tumors in 8/15 rats; group 2B, 10 tumors in 7/15), but not in male offspring given NiAcet only (0/32) or in controls given prenatal sodium acetate (NaAcet) only (0/15) and rarely in males given NaAcet followed by the promoter NaBB (1/15). No renal tumors occurred in females. Pituitary tumor incidence was significantly higher in offspring of both sexes given NiAcet prenatally (NaAcet controls, 4/31, both sexes combined; group 1A, 14/33, P = 0.012; group 2A, 14/31, P = 0.008). Pituitary tumors appeared much earlier in rats given NiAcet prenatally, with or without postnatal NaBB, and often were malignant by cytologic and histologic criteria including pleomorphism and invasion of adjacent structures, unlike the well-differentiated adenomas that occurred less frequently in untreated rats. These results are the first evidence that Ni(II) is a potent transplacental initiator of epithelial tumors in fetal rat kidney and a complete transplacental carcinogen for rat pituitary.
Carcinogenesis 1992 Aug
PMID:Transplacental carcinogenic effects of nickel(II) acetate in the renal cortex, renal pelvis and adenohypophysis in F344/NCr rats. 149 87

Glucocorticoid hormones are thought to play a role in carcinogenesis as they regulate cell differentiation and proliferation. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon glucocorticoid treatment, PROb cells were found to secrete an additional Mr approximately 40,000 protein. The synthesis and the release in the culture medium of this protein is stimulated specifically by glucocorticoid agonists, and not by other steroid hormones. The anti-glucocorticoid RU 38486 is inefficient and suppresses the induction of this protein by dexamethasone. Induction is sensitive to actinomycin D, suggesting that regulation may be related to an alteration of the rate of mRNA synthesis. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The PROb cells contained more specific glucocorticoid-binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody, was found to be more degraded in the PROb cell line.
 ...
PMID:Biological effects of glucocorticoid hormones on two rat colon adenocarcinoma cell lines. 156 48

Chlorophyllin (CHL), the water soluble sodium/copper salt of chlorophyll, was investigated for its effect on colorectal cancer risk in the rat-dimethyldrazine colon carcinogenesis model. Ninety weanling Fisher 344 male rats were treated with five weekly injections of 1,2 dimethylhydrazine (DMH), 20 mg base/kg body weight. Rats had been previously divided into three groups, consuming either rat chow and water (Group I), rat chow and CHL 1.5 mM in water throughout the experiment (Group II), or water and rat chow during DMH injection, adding CHL 1.5 mM to the drinking water after completion of the DMH treatments. At sarcifice, the incidence and yield of colorectal tumors were as follows: Group I 10% and 0.1; Group II, 23% and 0.27; and Group III, 47% and 0.53 (p less than 0.005 for incidence and = 0.003 for yield). These data demonstrate that, though it is well established that CHL is an antimutagen, CHL in this colorectal carcinogenesis model acted as a tumor promoter.
 ...
PMID:Chlorophyllin, an antimutagen, acts as a tumor promoter in the rat-dimethylhydrazine colon carcinogenesis model. 162 32

Chlorophyllin (CHL), a copper/sodium salt of chlorophyll used in the treatment of geriatric patients, is an anti-mutagen that has been demonstrated to inhibit carcinogen--DNA binding in vivo. To study the mechanism of inhibition, the microsomal metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and the kinetics of IQ--DNA binding were investigated in the presence and absence of CHL. In time-course studies, CHL produced greater than 80% inhibition of IQ--DNA binding and blocked the metabolism of IQ, such that 80% of the initial dose of carcinogen was recovered unmetabolized from the incubations after 1 h. Kinetic constants were determined for the in vitro DNA binding reaction, with the reaction rate measured as 'pmol IQ bound/mg DNA/min/mg microsomal protein'. Without altering V(max), the Km of the IQ--DNA binding reaction was increased by CHL, and the replot of Km/V(max) versus CHL concentration yielded a straight line with an inhibitor constant of 58.3 microM CHL. Spectrophotometric studies provided evidence in vitro for the formation of a non-covalent complex between CHL and IQ. The CHL--IQ complex had a stoichiometric ratio of 2:1 (mole ratio method) and an apparent dissociation constant from the Benesi-Hilderbrand plot of 1.41 x 10(-4)M at pH 7.4. These results are discussed in the context of a CHL inhibitory mechanism involving enzyme inhibition and molecular complex formation.
Carcinogenesis 1992 Jul
PMID:Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding by chlorophyllin: studies of enzyme inhibition and molecular complex formation. 163 77

In northeast Thailand, the traditional habit of eating ground, raw freshwater and salt-fermented fish on a daily basis results in a local population repeatedly exposed to both liver fluke (Opisthorchis viverrini) infection and consuming nitrosamine-contaminated food from early in life. Epidemiological studies have revealed a coincident high prevalence of cholangiocarcinoma in this region and we have demonstrated in animal models that dietary contamination with nitrosamines and Opisthorchiasis are strong predisposing factors for cholangiocarcinogenesis. Thus all Syrian golden hamsters receiving a combination of subcarcinogenic doses of dimethylnitrosamine (DMN) and infection with flukes developed cholangiocarcinomas, while chemical administration or fluke infection alone did not cause cancer. Synergistic induction by chemical carcinogens and liver fluke infection was found to be related to levels of exposure to both. In this two-stage carcinogenesis model, nitrosamines are considered to act as genotoxicants exerting carcinogenic effects, while the liver flukes are assumed to play epigenetic roles. In our studies of biliary pathology related to worm burden in humans we found that while most of the subjects had worms, only a minority (25%) demonstrated a pathology of adenomatous hyperplasia, which is believed to predispose bile ducts to subsequent development of carcinomas, indicating the possible role of flukes as promoters. Biliary changes in nontumorous areas of hepatectomy specimens, including fibrosis (with or without adenomatous hyperplasia) which is found in most cases, and dysplasia in the fibrotic ducts indicate a conversion event in carcinogenesis: other factors may be required to aggravate the simple proliferation lesion so that they subsequently change to carcinomas. Furthermore, commonality in tumor phenotypes and expressions of ras p21 in both fluke related and non-fluke-related cholangiocarcinomas suggest that some similar mechanisms might be operating, at least in the relatively late stages of this multistage carcinogenesis involving the bile ducts.
 ...
PMID:Multistage carcinogenesis of liver-fluke-associated cholangiocarcinoma in Thailand. 166 94

Calcium valproate is an anticonvulsant agent with pharmacokinetic properties similar to sodium valproate and valproic acid. Potential carcinogenesis of calcium valproate was evaluated in B6C3F1 mice and Wistar rats given 125, 250 and 500 mg/kg in the diet for 104 weeks. Survival in treated rats increased in a dose-related pattern despite a tumorigenic response in females. Adenocarcinomas of the uterus and cervix were increased in treated rats when compared to controls. The incidence of uterine neoplasia was 8, 20, 14 and 32% in the control, 125, 250 and 500 mg/kg groups, respectively. Neoplasia in treated rats were detected against a higher than expected background of adenocarcinomas in concurrent controls, since 8% incidence in controls was substantially above the laboratory historical database value of 0.6%. Tumors varied from epithelial masses confined to the endometrium, to transmural, highly desmoplastic neoplasms that invaded the serosa lining and the peritoneal cavity. These tumors metastasized in treated rats but not in controls. The statistically significant (P less than 0.01) increase in uterine adenocarcinomas found in females given 500 mg/kg of calcium valproate contrasts the absence of this tumor type in a previous rat carcinogenicity bioassay with valproic acid. Subcutaneous fibrosarcomas were significantly increased in valproic acid-treated males, but no uterine tumors were reported in females. It is puzzling that a true carcinogenic potential would be expressed by markedly different target organs as obtained with the acid and calcium salt of this moiety.
 ...
PMID:Calcium valproate-induced uterine adenocarcinomas in Wistar rats. 172 66


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