Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of three levels of piroxicam and three levels of D,L-alpha-difluoromethylornithine (DFMO) fed individually and in combination during the postinitiation phase of carcinogenesis was studied in male F344 rats to generate a data base on the efficacy and synergistic and additive effects of these compounds as inhibitors of colon carcinogenesis. The maximum tolerated dose of DFMO was determined in male F344 rats and found to be 5000 ppm in the AIN-76A diet. Piroxicam at levels of 25, 75, and 150 ppm and DFMO at concentrations of 400, 1000, and 4000 ppm (20, 50, and 80% maximum tolerated dose) in AIN-76 diet were tested individually and in combinations. At 7 weeks of age, while the rats were consuming the control diet (AIN-76A), all animals except the vehicle (saline)-treated controls were given a single s.c. injection of azoxymethane (CAS: 25843-45-2) at a dose level of 29.6 mg/kg body weight to induce intestinal tumors. One week after azoxymethane injection, animals were transferred to their respective experimental diets containing piroxicam and DFMO. Fifty-six weeks after azoxymethane injection, all animals were necropsied and colon and small intestinal tumor incidences and multiplicity were compared among the various dietary groups. Feeding of diets containing 75 and 150 ppm piroxicam or 1000 and 4000 ppm DFMO significantly inhibited the incidence (percentage of animals with tumors) of colon adenocarcinomas compared to that of control diet. The multiplicity (number of tumors/rat) of adenocarcinomas was significantly inhibited in animals fed the 25, 75, and 150 ppm piroxicam or 400, 1000, and 4000 ppm DFMO diets. Results analyzed by the linear regression method suggested a dose-dependent inhibition in colon adenocarcinoma incidence with increasing levels of piroxicam or DFMO. The incidence and multiplicity of colon adenocarcinomas were significantly inhibited in animals fed the diets containing combinations of 25, 75, and 150 ppm piroxicam and 400, 1000, and 4000 ppm DFMO. Piroxicam and DFMO administered together had a stronger inhibitory effect than did those given individually. Piroxicam and DFMO when administered individually had no significant inhibitory effect on colon adenoma incidence and multiplicity; in contrast, combinations of these compounds significantly inhibited colon adenomas. No consistent differences were found in the incidence and multiplicity of small intestinal tumors among the dietary groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet. 210 53

An Eco-RI restriction fragment length polymorphism occurring in a DNA fragment containing the first exon of the murine KRAS2 gene was shown to correlate with the inherited susceptibility of inbred strains of mice to urethan (CAS: 51-79-6)-induced pulmonary adenomas. Eco-RI digestion of murine DNA yielded four KRAS2-specific fragments. Polymorphic variation occurred in the smallest molecular-weight fragment with alleles of either 0.70 or 0.55 kb in size. Genotyping of 14 inbred strains of mice revealed a correlation between KRAS2 Eco-RI polymorphic variation and the differential susceptibility among inbred strains to development of pulmonary adenomas. Strains with a high incidence of pulmonary adenomas, either spontaneously occurring or in response to carcinogen induction, had the 0.55-kb KRAS2 allele whereas adenoma-resistant strains had the 0.70-kb allele. Analysis of a series of recombinant inbred strains (AXB, BXA) that developed from reciprocal crosses between a highly susceptible strain (A/J) and a highly resistant strain (C57BL/6J) revealed a statistically significant threefold difference in lung tumor susceptibility on the basis of KRAS2 genotype. Further analysis of individual F2 mice of a C57BL/6 female X A/J male cross also demonstrated a threefold difference in tumor susceptibility on the basis of KRAS2 allelic variation.
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PMID:KRAS2 as a genetic marker for lung tumor susceptibility in inbred mice. 289 65

In studies designed to determine the influence of dietary Se on pancreatic carcinogenesis, Syrian golden hamsters were fed unsupplemented torula yeast diet or diet supplemented with 0.1 or 5.0 ppm Se, from sodium selenite, starting at 4 weeks of age until the termination of the study. In separate groups, hamsters were given the diet supplemented with 0.1 ppm Se until 5 days after carcinogen treatment. Then they were fed either the unsupplemented diet or the diet supplemented with 5.0 ppm Se until the end of the experiment. N-Nitrosobis(2-oxopropyl)amine (BOP; CAS; 60599-38-4) treatment was given as a single sc injection of 20 mg/kg (body wt) at 8 weeks of age, and surviving hamsters were killed 50 weeks later. As a measure of Se status, glutathione peroxidase (GSHPX) activities were determined in plasma, erythrocytes, and liver. Values were elevated in animals fed higher levels of dietary Se. BOP treatment depressed plasma GSHPX at 24 hours and elevated erythrocyte and liver values at 4 weeks. Pancreatic ductular adenoma yields were inhibited with each elevation of dietary Se in female hamsters fed the diets, both before and after BOP administration, and were further inhibited in females that were fed diets containing 0.1 ppm Se before BOP administration and that were changed to the unsupplemented or 5.0-ppm-supplemented diets after BOP was given. Pancreatic ductular adenoma yields were highest in all male groups given diets of 0.1 ppm Se before BOP administration, irrespective of the Se level after BOP was fed. Adenoma yields in males were lowest in hamsters fed unsupplemented diet, both before and after BOP treatment. Pancreatic carcinoma yields were low and not influenced by dietary Se. The incidence of hepatic necrosis was elevated in BOP-treated hamsters fed the unsupplemented diet, and that of biliary cystic adenomas was highest in the group fed 0.1 ppm Se before and after BOP treatment.
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PMID:Effects of dietary selenium on bis(2-oxopropyl)nitrosamine-induced carcinogenesis in Syrian golden hamsters. 346 17

Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following a single brief exposure to methylazoxymethanol acetate [(MAM-Ac) CAS: 592-62-1]. Fish 6-10 days old were exposed to concentrations of MAM-Ac up to 100 mg/liter for 2 hours. Exposed specimens were transferred to carcinogen-free water and sampled periodically for tumor development. Pancreatic neoplasms occurred in approximately 9% of histologically examined individuals exposed to 10 mg MAM-Ac/liter or less. Neoplastic lesions were not found in 122 control specimens. The neoplasms included 6 cases diagnosed as adenoma, 7 cases diagnosed as acinar cell carcinoma, and 2 cases diagnosed as adenocarcinoma. Adenomas consisted mainly of well-differentiated acinar cells that were filled with zymogen granules. Two adenomas also contained foci of atypical, less-differentiated acinar cells possessing basophilic, fibrillar cytoplasm. Acinar cell carcinomas occurred in several cellular patterns that ranged from well-differentiated to more anaplastic lesions; however, none exhibited areas of ductular proliferation. Adenocarcinomas, on the other hand, exhibited a glandular growth pattern and contained numerous ductlike structures. Both types of carcinomas appear to arise from primary acinar cells. Thus lesions probably progress from adenomas to acinar cell carcinomas and adenocarcinomas. The findings of carcinogen-induced pancreatic neoplasms in guppies further strengthen the usefulness of small fish species in carcinogen testing and provide an additional model for pancreatic tumors.
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PMID:Exocrine pancreatic neoplasms induced by methylazoxymethanol acetate in the guppy Poecilia reticulata. 347 May 47

The influence of dietary selenium and cabbage on the formation of colon tumors in female Swiss mice treated with 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8] was reported. Mice received a control diet (laboratory chow), the control diet plus selenium in the drinking water (1 mg/liter), or the control diet with added cabbage (12.8 g/100 g diet). They also received 8 weekly sc injections of DMH. The experiment was divided into two time periods: a) from 5 weeks before the first injection until 3 days after the last one (initiation period), and b) the subsequent 19.5 weeks until sacrifice of the mice (promotion period). Selenium had a strong protective effect when given during the initiation period; adenomas were reduced to a much greater extent than adenocarcinomas. The only effect of selenium supplementation in the promotion period was a small decrease in adenomas. Cabbage apparently had two opposing actions. It increased tumor incidence, particularly adenocarcinomas, if given in the initiation period, but it reduced adenoma formation considerably when given in the promotion period.
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PMID:Selenium and cabbage and colon carcinogenesis in mice. 347 39

Syrian golden hamsters were fed four diets in experiments designed to evaluate the effects of the interaction of dietary fat and protein on carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4]. The diets consisted of two levels of dietary fat [4.5 g (low fat, LF) or 18 g (high fat, HF) of corn oil/385 kilocalories (kcal)]. These levels were fed with each of two levels of dietary protein [9 g low-protein (LP) and 36 g high-protein (HP) casein/385 kcal]. The four diets were fed to two separate groups of hamsters at two different periods in their life-span. For testing of the effects of diet on tumor initiation, one group received the diets from 3 to 7 weeks of age. At 8 weeks, they were given injections sc of 10 mg BOP/kg body weight and placed on a control diet [9 g corn oil (medium fat) and 18 g casein (medium protein)/385 kcal]. The other group received control diet until 8 weeks of age, at which time they were given injections of BOP and placed on the four diets. This group was designed to test the effects of the diets on tumor development. BOP-induced lesions in the lungs, liver, common bile duct, gallbladder, and kidneys are described; results in the pancreas were reported separately. In hamsters fed the four diets after BOP treatment, the LF-LP groups had the fewest tumors, the LF-HP-fed and HF-LP-fed groups had intermediate yields of tumors, and the hamsters given HF-HP diet exhibited the largest numbers of neoplasms. Several specific tumor types showed a similar pattern. For example, the pulmonary adenoma incidence, which was low in the non-BOP-treated hamsters, was higher in the HF-HP group than in those fed LF-HP diet after BOP, but it was not influenced by fat at the LP level. In addition, renal adenomas were observed at a low incidence in non-BOP-treated hamsters and in hamsters fed LF-LP levels before or after BOP treatment (0.5% incidence) but were present at an 8% incidence in all other BOP-treated groups. The incidence of biliary cystic adenomas was highest in male hamsters that received HF diets, irrespective of BOP treatment, and BOP treatment resulted in increased yields of this lesion in females only in groups given HF-LP diet.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of the interaction of dietary fat and protein on N-nitrosobis(2-oxopropyl)amine-induced carcinogenesis and spontaneous lesions in Syrian golden hamsters. 385 80

Effects of phenobarbital [(PB) CAS: 50-06-6], a systemic tumor promoter, on carcinogenesis initiated by the broad-spectrum carcinogen N-nitroso-N-methylurea [(NMU) CAS: 684-93-5] were investigated in F344/NCr rats. Single and divided doses of NMU were evaluated for this purpose in 4-week-old rats of both sexes. Rats received iv injections of either 0.2 mmol NMU/kg (body wt) once or 0.05 mmol NMU/kg (body wt) for 4 weeks (1 injection/wk), followed by or concurrently with PB (0.05% in drinking water) that was continued until the termination of the experiment. Half the rats were killed at 52 weeks and survivors at 80 weeks. At 52 weeks, PB given subsequent to NMU or concurrently with divided doses of NMU significantly enhanced the incidence of thyroid follicular tumors only in male rats. This sex difference in thyroid tumorigenesis was somewhat less pronounced in animals killed at 80 weeks. Only 1 liver cell adenoma occurred in males and none in females given NMU alone. PB given concurrently with divided doses of NMU enhanced the yield of hepatocellular foci/cm2 but had no significant effect on hepatic tumor development. Subsequent exposure to PB, however, significantly promoted hepatocarcinogenesis in rats of both sexes given NMU in divided doses; 50% of males and 40% of females given NMU (0.05 mmol/kg, administered four times) followed by PB had hepatocellular adenomas and carcinomas by 80 weeks. PB did not affect the incidence of any other kind of neoplasms seen in NMU-initiated or control rats. These lesions included squamous cell neoplasms of the skin, oropharynx, and forestomach; nonsquamous epithelial tumors of mammary gland, pituitary body, intestinal mucosa, and urinary bladder; tumors of the central and peripheral nervous system; and mesenchymal tumors of the kidney. A sequence of multiple low doses of NMU appeared to be a convenient and useful systemic, multitissue, tumor-initiation regimen for systematic investigation of organ-specific tumor promotion in rats.
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PMID:N-Nitroso-N-methylurea initiation in multiple tissues for organ-specific tumor promotion in rats by phenobarbital. 386 12

The present study was designed to test the possibility that spontaneous regression of hepatocellular tumors might be observed in mice. This problem was studied by sequential liver biopsies in C3H male mice that had been treated with dieldrin (CAS: 60-57-1) as well as in animals treated with N-diethylnitrosamine (CAS: 55-18-5) and in untreated control mice. Adenomas were seen in some animals at the second laparotomy when there had been no tumor at the first laparotomy. In a few mice there was histologic progression from adenoma to carcinoma. A change in predominant cell type in adenomas from clear to basophilic or eosinophilic was also observed in some cases. Additional hepatocellular carcinomas were observed in some animals necropsied at 2 years of age. These observations suggest that spontaneous hepatic tumors and tumors in mice treated with either complete carcinogens or nongenotoxic compounds have a strong tendency to progress. Tumor regression in mice appears to be unusual. No consistent relationship of histologic grade of hepatocarcinoma to the type of chemical employed was observed.
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PMID:Irreversibility of liver tumors in C3H mice. 658 41

Food additive butylated hydroxytoluene (BHT) (CAS: 128-37-0; 2,6-di-tert-butyl-p-cresol) can modulate the formation of lung adenomas in mice treated with the carcinogen urethan (CAS: 51-79-6; ethyl ester carbamic acid). An ip injection of BHT administered 6 hours before a single urethan injection decreased the number of tumors formed, whereas six weekly BHT injections following a single urethan dose increased tumor multiplicity. Biotransformation of BHT was apparently required for both prophylaxis and enhancement. Pretreatment of mice with cedrene, which perturbs drug metabolism, prevented both of these BHT activities. Analogues of BHT with different substitutions at position 6 of the phenol ring also affected tumor formation. 2-tert-Butyl-4-methylphenol inhibited, not enhanced, adenoma formation. 2-tert-Butyl-4,6-dimethylphenol (BDMP) (CAS: 1879-09-0; 6-tert-butyl-2,4-xylenol); increased tumor number in A/J but not in the BALB/cByJ mouse strain; its prophylactic activity could not be measured since urethan injection following BDMP treatment was lethal. Thus the presence of an alkyl group at this site on the phenol ring was not required for prophylaxis but was necessary for tumor enhancement. These results were consistent with the possibility that different BHT metabolites were responsible for each effect. Adenoma formation was enhanced by BHT in four strains of mice with a U+ phenotype (susceptible to urethan-induced lung adenomas); these strains were A, BALB/cBy, SWR/J, and RIIIS/J. BHT had no such effect, however, in the U+ strain 129/J. A U+ B- phenotype (urethan inducible but unresponsive to BHT enhancement) also was found among the recombinant inbred lines originally derived from a cross between U+B+ BALB/-cByJ and U-/B- C57BL/6ByJ progenitor strains. This finding showed that the genes determining sensitivity to urethan and to BHT had recombined independently of each other. An inability to metabolize BHT was probably not involved in the B- phenotype, since BHT caused reversible lung damage in the 2 U+B- recombinant inbred lines and strain 129, and biotransformation was required for this effect. These U+B- mice thus can be used to characterize the lung toxic effects of BHT in the absence of its tumor-enhancing activity and will serve as valuable controls in studies on mechanisms of tumor enhancement.
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PMID:Pharmacologic and genetic studies on the modulatory effects of butylated hydroxytoluene on mouse lung adenoma formation. 659 88

It has long been postulated that angiogenesis plays important roles in tumor cell proliferation and hormonal secretion of endocrine tumors, including adrenocortical neoplasms. Detailed examination of vascularity, however, has not been reported in adrenocortical tumors. In this study, we quantitatively examined vascularity in normal adrenal, adrenocortical adenoma, and carcinoma using an image analysis system to evaluate vascularity or angiogenesis in these lesions. Vascular density (VD: vessel number/mm2), endothelial area of each vessel (EA: microm2/vessel) and vascular area (VA: the percentage of EA per field) were examined using immunohistochemical analysis of CD34 and the CAS 200 image analysis system. EA and VA of adrenocortical carcinomas (EA, 113.4 +/- 33.1; VA, 6.34 +/- 2.03) were significantly higher than those of adenoma (EA, 66.1 +/- 43.0; VA, 3.11 +/- 1.56) and normal adrenal tissue (EA, 65.4 +/- 26.0; VA, 4.26 +/- 1.19). There were no significant differences in VD among normal cases (702.2 +/- 173.2), adenomas (488.9 +/- 153.2), and carcinomas (573.2 +/- 185.2). These results suggest that adrenocortical carcinoma might be associated with increased endothelial cell proliferation but not with an increased number of intratumoral microvessels. There were no significant differences in these parameters of vascularity examined in the zona glomerulosa, zona fasciculata, and zona reticularis of aldosteronomas, Cushing's adenomas, and nonfunctioning hormonally inactive adenomas nor between specimens from patients who died of the disease and those from patients who did not.
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PMID:Vascularity in human adrenal cortex. 957 82


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