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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An antioxidative fraction was extracted from green tea and the major compounds in the fraction identified as epicatechins. Experimental results showed that green tea epicatechin compounds (GTEC) inhibited the mutagenicity and/or chromosomal damage caused by different carcinogens in both bacterial and mammalian cells. In vitro, GTEC inhibited transformation of BALB/3T3 cells induced by BP, X-rays, or MCA/TPA. In vivo, green tea extract decreased the incidence of carcinoma in the forestomach and esophagus of mice induced by sarcosine and NaNO2. GTEC inhibited the development of gamma-glutamyl transpeptidase-positive foci in the livers of rats treated with diethyl nitrosamine (DEN) or DEN/phenobarbital. Our investigations indicate that the antimutagenic and anticarcinogenic mechanisms of GTBC are related to the following: increased glutathione-S-transferase activity; inhibition of edema, hyperplasia, and ODC activity induced by TPA; free radical scavenging; blocked tumor promoter-induced inhibition of intercellular communication; and enhanced cell-mediated immunity. GTEC might be useful in the prevention of some kinds of cancer and a variety of oxidation-related diseases.
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PMID:Progress in studies on the antimutagenicity and anticarcinogenicity of green tea epicatechins. 181 62

Expression of TGF-alpha mRNA, which correlates well with the ability of cells to condition medium with an EGF-like activity, clonally segregates best with tumorigenicity among the several single phenotypes considered in this study. The results of unreported studies in which we have analyzed the quantitative relationships between the expression of selected phenotypes and tumorigenicity, suggest that the elevated expression of myc and TGF-alpha mRNAs interact in their associations with tumor yield. These results suggest that elevated myc expression sensitizes hepatic epithelial cells to the possible tumorigenic action of TGF-alpha. This observation may explain why the correlation between the qualitative expression of TGF-alpha and tumorigenicity, described here, is not perfect. Conventionally applied markers of transformation in hepatocytes in vivo and in cultured liver epithelial cells in vitro that we studied -histochemical expression of GGT, ability to grow in medium containing low levels of calcium, and ability to grow in soft agar- clonally segregated with tumorigenicity poorly in liver epithelial cells transformed in vitro. We conclude that these phenotypes are not adequate markers for determining the lineage of hepatic epithelial neoplasms (including, probably hepatocellular cancers arising in vivo). This study appears to be the first to attempt to analyze clonally the association of these markers with tumorigenicity, and to quantify the sensitivity, specificity, and predictive value of the associations. Our study suggests that the relatively weak associations of these phenotypes with tumorigenicity may be related only to their stronger associations with expression of TGF-alpha, or to some other property that is strongly associated with tumorigenicity. Expression of TGF-alpha is more strongly associated with expression of GLC, for example, than is the GLC phenotype with tumorigenicity. At least for GLC, autocrine stimulation by TGF-alpha is likely, since EGF increases growth of WB cells in low calcium medium. This observation may explain the perfect correlation between expression of TGF-alpha and GLC. EGF also stimulates lactate dehydrogenase, pyruvate kinase, and glucose 6-phosphate dehydrogenase in WB cells. However, quantitative correlation between GGT activity and TGF-alpha is less strong. Thus, our data from these studies suggest that the tumorigenic phenotype of cultured hepatic epithelial cells is intimately dependent on the expression of the TGF-alpha gene, possibly producing autocrine stimulation of growth via the cells' EGF receptors. This is the most simple view of the potential relationship between TGF-alpha expression and tumorigenicity in liver epithelial cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clonal analysis of neoplastic transformation in cultured diploid rat liver epithelial cells. 181 88

Phenobarbital (PB) is an effective growth stimulator of hepatic hyperplastic nodules developed with diethylnitrosamine and 2-acetylaminofluorene plus partial hepatectomy (the Solt-Farber model), but it does not apparently stimulate the growth of preneoplastic lesions produced with aflatoxin B1 (AFB). Some studies have suggested a correlation between the induction of specific cytochrome P450 enzymes and the tumor promoting effects produced by repeated treatment with PB. To examine this hypothesis further, hepatic hyperplastic nodules were produced with AFB (10 ip doses of AFB, 150 micrograms/kg/day, followed by partial hepatectomy) or by a modified Solt-Farber protocol (DEN/AAF), and the effects of PB on nodule growth and expression of cytochrome(s) P450 2B1 and/or P450 2B2 (P450 2B1/2) were determined. Both treatment protocols (without PB) produced multiple, large nodules within 10-17 weeks of carcinogen administration. These nodules stained intensely for glutathione S-transferase p (GST-p; GST7-7) and gamma-glutamyl transpeptidase (GGT) and weakly for P450 2B1/2. Pentoxyphenoxazone dealkylation activity was decreased to less than 50% of the surrounding tissue levels in both types of nodules. PB treatment of animals with DEN/AAF-induced nodules greatly increased P450 2B1/2 expression in surrounding tissues, whereas most, but not all, nodules were not inducible. Pentoxyphenoxazone dealkylation was increased 31- to 35-fold in surrounding tissue, but it was increased only 2-fold in pooled nodular tissue, relative to untreated control liver. In contrast to the DEN/AAF group, immunohistochemical staining and pentoxyphenoxazone dealkylation in the AFB group demonstrated that P450 2B1/2 was equally inducible in nodular and surrounding tissues. Short-term treatment (5 days) with PB produced a 2-fold increase in the number and total area of GGT-positive nodules in the DEN/AAF group, but it had no significant effect on the number, size distribution, or total area of GGT-positive nodules in the AFB group. All large GGT-positive nodules in the DEN/AAF group were nonresponsive to induction of P450 2B1/2, whereas all of the GGT-positive nodules which were responsive to P450 2B1/2 induction by PB in this group were relatively small. The size and area of AFB-induced GGT-positive nodules was not affected by PB treatment, and P450 2B1/2 in all of these nodules was inducible by PB. Although a causal, inverse relationship between the responsiveness of nodules to PB induction of P450 2B1/2 and their reaction to PB growth stimulation cannot be firmly established, these data are consistent with such a hypothesis.
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PMID:Differential regulation of cytochrome(s) P450 2B1/2 by phenobarbital in hepatic hyperplastic nodules induced by aflatoxin B1 or diethylnitrosamine plus 2-acetylaminofluorene in male F344 rats. 194 30

Ductectatic-type mucinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K-ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT----GAT (Gly----Asp) with the remaining one, found in a cancer, being GGT----GTT (Gly----Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K-ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma-carcinoma sequence in the evolution of this type of neoplasm and we suggest that K-ras activation may be an important event in the phase of adenoma development.
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PMID:c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas. 195 73

One of the critical issues in risk assessment for chemical carcinogens is the evaluation of dose-response relationships for tumor promoters. In the studies reported here we have systematically investigated dose-response relationships for the liver tumor-promoting actions of 17 alpha-Ethinylestradiol (EE2) following a single injection of diethylnitrosamine (200 mg/kg) to ovariectomized female rats. Parameters measured included tumor incidence, gamma-glutamyltranspeptidase (GGT) positive foci, serum prolactin and serum EE2. The length of tumor promotion ranged from 30 to 60 wk. Results showed a linear increase in GGT-positive foci between doses of 16 and 90 micrograms EE2 kg/d for 30 wk. This was associated with corresponding increases in liver tumor incidence at 60 wk. Seventy-five percent of the animals had either hepatocellular adenoma or hepatocellular carcinoma in the group promoted with 90 micrograms EE2/kg for 60 wk. No liver tumors were evident in either controls or animals receiving estrogen only. Serum prolactin concentrations were elevated in all estrogen-treated groups. In summary, our studies have evaluated dose-response relationships for GGT-positive foci and tumor incidence in a two-stage model for hepatocarcinogenesis using EE2 as the promoting agent.
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PMID:Dose-response relationships in promotion of rat hepatocarcinogenesis by 17 alpha-ethinylestradiol. 196 81

The involvement of tumor promotion in the hepatocarcinogenic action of peroxisome proliferators has not been generally accepted. We studied the effect of nafenopin (NAF) as a model compound in a two-stage initiation-promotion protocol. Carcinogenesis was initiated by a single dose of aflatoxin B1 (AFB1) in female (AFB1, 5 mg/kg) and male (AFB1, 2 mg/kg) Wistar rats. After recovery NAF was fed via the diet, providing a daily dose of 100 mg/kg body weight. Phenobarbital (PB) (50 mg/kg body weight) was fed to female rats as a positive control. The following results were obtained. (a) At weeks 40, 55, 59, and 70, significantly more and larger liver tumors were present in AFB1-NAF-treated rats than in rats receiving either compound alone, and the effect of the combined treatment was clearly more than additive, in three independent experiments including both sexes. This suggests tumor promotion by NAF. Male rats responded more strongly than females. Similarly, PB enhanced the yield of liver tumors. Histologically, tumors were hepatocellular adenoma or carcinoma. In group AFB1-PB the majority consisted of eosinophilic and glycogenstoring cells. However, adenoma and carcinoma of groups AFB1-NAF and O-NAF consisted of weakly basophilic cells. (b) Phenotypically altered foci were evaluated in hematoxylin- and eosin-stained liver sections from the female rats. NAF treatment after AFB1 had little effect on number and size of eosinophilic-clear cell foci and decreased the number of trigroid foci. However, it led to a dramatic increase (20-fold after 70 weeks of NAF treatment) in number and size of foci of a special phenotype that was extremely rare after AFB1 alone and virtually absent in group AFB1-PB. Hepatocytes in these foci are characterized by weak diffuse basophilia and some eosinophilia, similar to the phenotype in adenoma and carcinoma, and by absence of gamma-glutamyltranspeptidase (GGT) expression. Based on these findings, we propose the hypothesis that NAF promotes the development of liver tumors via a mechanism involving amplification of a specific subtype of altered hepatic foci.
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PMID:Tumor promotion by the peroxisome proliferator nafenopin involving a specific subtype of altered foci in rat liver. 197 Nov 96

To assess the effects of the combination of persistent hepadnavirus infection and chemical carcinogen exposure, aflatoxin B1 (AFB) was administered p.o. for 60 days to congenitally duck hepatitis B virus (DHBV)-infected and virus-free Pekin ducks, starting at 3 days of age, during a 28-month study. Hepatic neoplasia occurred only in AFB-dosed ducks. Hepatocellular carcinomas or biliary carcinomas occurred in 4 of 8 DHBV-infected and 3 of 4 DHBV-free ducks, and hepatocellular adenomas developed in 2 DHBV-infected AFB-dosed ducks that survived 20 months or longer. Altered foci of hepatocytes similar to those observed in chemical carcinogen-dosed rodents, characterized by enlarged eosinophilic hepatocytes or vacuolated cytoplasm, occurred in AFB-dosed ducks. Cells in foci or hepatic neoplasms did not contain histochemically detectable gamma-glutamyltranspeptidase but were distinguished from uninvolved parenchyma by altered glycogen content. Immunohistochemical staining indicated that DHBV core antigen persisted in liver, spleen, pancreas, and, to a lesser extent, kidney of most congenitally infected ducks up to 28 months of age. Hepatic neoplasms contained only patches of hepatocytes were detectable viral antigen. Southern blot analysis of restriction endonuclease-digested neoplastic and normal liver DNA revealed high molecular weight forms of DHBV DNA consistent with integration of viral DNA into the genome of hepatic neoplasms from 3 of 4 DHBV-infected ducks but not nontumorous liver. These findings indicate that AFB is a potent hepatic carcinogen in ducks and that persistent congenital DHBV infection did not contribute significantly to the emergence of hepatic neoplasia in ducks under these conditions.
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PMID:Hepatic neoplasms in aflatoxin B1-treated, congenital duck hepatitis B virus-infected, and virus-free pekin ducks. 197 46

The hepatoma-specific band of serum gamma-glutamyl transferase II (GGT II) and other three markers were evaluated in 77 patients with primary hepatocellular carcinoma (PHC). The positive rate of GGT II (87%) was much higher than that of the increased alpha-fetoprotein (AFP greater than or equal to 400 ng/ml, 54.5%), the increased alpha-1-antitrypsin (AAT greater than or equal to 400 mg/dl, 64.9%) and alkaline phosphatase isoenzyme I (ALP I, 13.0%). In patients with AFP less than 400 ng/ml, the positive rate of GGT II was 95.2%, higher than that of ALP I (22.8%) and AAT (60.0%). The positive rate of GGT II was positively correlated to the volume of PHC (r = 0.324, P less than 0.05), but even in patients with small PHC (less than or equal to 65 cm3), the positive rate of GGT II (78.6%) was higher than that of AFP (50.0%) and AAT (28.6%). The ALP I positivity was only seen in patients with larger PHC. Follow-up study showed that GGT II, like AFP, might occur before liver tumor could be detected by B-mode ultrasonography and computerized tomography. Therefore, GGT II is a valuable marker of PHC, especially in patients whose AFP was negative or slightly increased; GGT II may be useful for relatively early diagnosis of PHC.
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PMID:Reappraisal of diagnostic significance of a hepatoma-specific band of serum gamma-glutamyl transferase. 197 81

The livers of rats given either the peroxisome proliferating hepatocarcinogen di(2-ethylhexyl)phthalate (DEHP) following initiation by 2-acetylaminofluorene (AAF) or the neoplasm promoter phenobarbital (PB) were studied for changes in 8 histochemical properties. Male F344 rats were fed 200 ppm AAF for 7 weeks to induce hepatocellular altered foci, and were then fed diets containing either no chemical, 12,000 ppm DEHP or 500 ppm PB for 24 weeks. In hepatocytes, DEHP increased alkaline phosphatase activity throughout the lobule, but reduced gamma-glutamyltransferase (GGT) activity in periportal hepatocytes. PB, in contrast, increased GGT activity in periportal hepatocytes. In foci that were induced by AAF, DEHP reduced the histochemical activity of GGT and did not increase the number, mean volume or volume % of foci detected by deficiencies in iron storage, glucose-6-phosphatase, adenosine triphosphatase or fibronectin. PB enhanced the expression of all 8 phenotypic abnormalities in foci such that either more profiles were detected or the area of foci was increased.
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PMID:Effects of the peroxisome proliferator di(2-ethylhexyl)phthalate on enzymes in rat liver and on carcinogen-induced liver altered foci in comparison to the promoter phenobarbital. 197 53

Colorectal cancer is a potentially curable tumour when diagnosed in the early stages. In order to improve the results obtained up to now, we propose application of a diagnostic program among patients who undergo curative resection for colorectal adenocarcinoma, which would consist of using a panel of tumor markers, in combination with endoscopic, histologic and ultrasonographic diagnostic methods. For this study we studied 105 patients, divided into two groups: A) Group 1: 30 control patients. B) Group 2: 75 patients diagnosed as having colorectal cancer. We performed the preoperative determination of a series of tumor markers (CEA, CA 19.9, GGT and PHI), endoscopy/biopsy and hepatic ultrasonography on these patients. Our results suggest that the design of the preoperative diagnostic program makes early detection of hepatic metastases possible. The tumor marker panel combination provided a visible increase in sensitivity for detecting hepatic metastases.
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PMID:[Tumor markers in liver metastases of colorectal carcinoma]. 198 May 90


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