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

Intracytoplasmic hyaline globules (IHG) were found in 16 out of 105 hepatocellular carcinomas (15.2%). In all cases, there was a male preponderance, most of the patients were Black, and the mean age was in the fifth decade. IHG were mostly noted in the better-differentiated tumors. Bile production was present in 12% of all tumors. Over 80% of tumors with globules showed necrosis as compared with 40% of the tumors without globules. Cirrhosis was present in almost half the cases, with liver cell dysplasia in 15%. These globules are possibly alpha-fetoprotein. Some of them may be giant lysosomes. Their role in carcinogenesis and prognosis is uncertain.
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PMID:Intracytoplasmic hyaline globules in hepatocellular carconomas. 5 81

Functional markers and growth behavior of abnormal hepatocytes at several stages of liver carcinogenesis were studied. Early lesions, i.e., hyperplastic foci and areas, did not accumulate iron in siderotic livers, had persistent glycogen stores, were not more agglutinable by concanavalin A, and were associated with alpha-fetoprotein secretion, but were not independent secretors of high amounts. The cells in the early lesions had an increased mitotic index, but cells from livers with early lesions did not have an increased survival in cell culture or the ability to grow in soft agar. The more developed lesions, hyperplastic nodules, also did not store iron, had persistent glycogen, did not display increased concanavalin A agglutinability, and were not independent secretors of high levels of alpha-fetoprotein. Similarly, nodule cells were proliferative but did not display an increase in survival in cell culture. In addition, both iso- and autotransplantation of nodules into mammary fat pads resulted in persistence but not growth of nodule cells. On the other hand, hepatocellular carcinomas regularly grew upon transplantation. Thus, early lesions and hyperplastic nodules were proliferative lesions did not possess autonomous growth capability comparable to that of hepatocellular carcinomas.
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PMID:Functional markers and growth behavior of preneoplastic hepatocytes. 5 21

Localization of alpha-fetoprotein (alpha-FP) has been followed in hepatal tissue and tumors during induction of primary hepatomas with the aid of 0.12% 3'-Me-DAB (3'-methyl-4-dimethylammoazobenzene) in Wistar rats. The indirect immunofluorescence method was used for the localization of alpha-FP positive cells. During the course of carcinogenesis, alpha-FP in serum was detected by means of the crossing over immunoelectrophoresis. This study has yielded the following results: Alpha FP positive cells resembling small hepatocytes occurred dispersed and in groups beginning with the 5th week of a carcinogenic diet until the appearance of tumors. No alpha-FP positive oval cells have been found. Alpha-FP positive cells were always found in rats with alpha-FP positive serum, but they were rarely present in rats with alpha-FP negative serum. From the 10th week, tumors of the cholangiohepatoma type began to be formed in which variously scattered alpha-FP positive cells of the type of small hepatocytes were present, with the serum being negative. Between week 14 and 21 hepatoma nodules began to be formed. At week 21 frequent alpha-FP positive cells close to normal hepatocytes were observed both singly and in groups. These are considered to be the sites of developing tumor nodules. In all the hepatoma nodules, the number of positive tumorous cells and the intensity of fluorescence proved to be directly proportional to alpha-FP concentration in serum.
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PMID:Localization of alpha-fetoprotein by immunofluorescent method during induction of rat liver tumors by 3'-methyl-4-dimethylaminoazobenzene. 7 94

The concentration of serum alpha-fetoprotein (AFP) was followed in C3H mice having a high incidence of spontaneous liver-cell cancer. No general elevation of serum AFP level with age was seen in mice without tumor. With a single exception, mice bearing hepatocellular carcinomas had increased serum AFP levels. In some mice this increase followed a biphasic course. Mice killed within 1 month of the time when an elevation of serum AFP was first observed had small tumors or no detectable tumor. Premalignant lesions were present in the livers of 11 out of 16 mice that had elevated AFP but no cancer, while only one out of 14 mice with normal AFP had such alterations. Our results strongly suggest that spontaneous hepatocarcinogenesis proceeds through almost the same premalignant lesions as chemically induced carcinogenesis, and that an increase in AFP production occurs early during this process, often preceding macroscopic lesions. Autologous antibodies to AFP were produced in a group of C3H mice by immunization with rat AFP. These anti-AFP antibodies reduced the amount of serum AFP but had no effect on the incidence of spontaneous hepatomas.
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PMID:Early increase of serum alpha-fetoprotein in spontaneous hepatocarcinogenesis in mice. 7 9

The expression of two markers of fetal liver, alpha-fetoprotein (AFP) and gamma-glutamyltranspeptidase (GGT), was studied in chemical and spontaneous hepatocarcinogenesis in mice. Serum AFP concentration increased within 3 weeks 3 weeks from the commencement of feeding of o-aminoazotuluene. This early elevation subsided about 3 months after the beginning of the administration of the carcinogen. A new, sustained elevation of the serum AFP level followed at 5 to 6 months accompanied by the appearance of liver tumors. In immunofluorescence, some small oval cells and scattered adult-type hepatocytes contained AFP during the early stage of chemical carcinogenesis. During the later phase, AFP was detected in a few of the nodular areas, in solitary hepatocytes, and in groups of carcinoma cells. GGT activity in the liver increased within 1 week after the carcinogen regimen was started, preceding the early increase of AFP production. At the final stage, the chemically induced hepatomas contained about 80 times more GGT than did normal liver. In histochemical staining, proliferating oval cells and small areas of hepatocytes stained for GGT during the early weeks, and later most nodules, small areas of nonnodular parenchyma, and carcinomas contained GGT. During spontaneous carcinogenesis in male C3HeB/FeJ mice, premalignant lesions, accompanied by a slight increase of serum AFP, precede the appearance of liver tumors. No cells staining for AFP were detected during this early stage. Once overt liver cancers had developed, AFP was readily detectable in the tumors and was localized to some but not all carcinoma cells. The corresponding serum AFP levels were highly elevated. In contrast to the high levels of GGT found during chemical carcinogenesis, no elevation of GGT was found in livers at various stages of spontaneous carcinogenesis, including cancers in eight individual mice. These results indicate that the production of AFP and GGT is not turned on as a single "genetic package," and that these two markers differ in their behaviour in liver carcinogenesis.
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PMID:Differential expression of alpha-fetoprotein and gamma-glutamyltranspeptidase in chemical and spontaneous hepatocarcinogenesis. 8 98

Localization of characteristic precancerous lesions was compared with that of alpha-fetoprotein (alpha-FP) positive cells during hepatocarcinogenesis in Wistar rats fed 0.06% 3'-methyl-4-dimethylaminoazobenzene in basal diet. Proliferative activity of liver cells was simultaneously followed by deoxycytidylate deaminase. The first alpha-FP positive hepatocytes were found after 3 weeks of carcinogenesis in certain parts of the capsule 0.1--0.2 mm thick. In the seventh week of carcinogenesis their number increased and they were present in groups also subcapsularly. At this stage, hyperplastic islets began to be formed in the liver parenchyma. After 14 weeks of carcinogenesis, alpha-FP positive cell clusters and islets were also found in the deeper layers of liver parenchyma in regions with proliferation of transitory cells. Hyperplastic basophilic foci and islets occurred regularly, however, these were not identical with alpha-FP positive sites and their incidence was more frequent.
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PMID:Relationship between alpha-fetoprotein positive cells and precancerous lesions in rat liver during 3'-methyl-4-dimethylaminoazobenzene carcinogenesis. 9 42

We studied the development of liver tumors in male transforming growth factor alpha (TGF-alpha) transgenic mice of the CD1 strain and examined the expression of the transgene by immunohistochemistry and in situ hybridization. Livers of 4-5-week-old transgenic mice contained areas of centribobular hypertrophy with low glucose-6-phosphatase activity. These areas progressively expanded, and hypertrophy and dysplasia became generalized in livers of mice at 10-12 months of age. The expression of the transgene, determined by either immunohistochemistry or in situ hybridization, was uneven in animals that were 10 weeks old or older. The positive hepatocytes formed patches with a predominant centrilobular distribution. We studied a total of 23 liver tumors (7 hepatocellular carcinomas and 16 adenomas) obtained from 11 mice at 13-15 months of age and from one 7-month-old animal which received zinc sulfate to induce the transgene. The carcinomas were well differentiated tumors, without glucose-6-phosphatase or gamma-glutamyltranspeptidase activity, that developed from the dysplastic parenchyma and occasionally within an adenoma. In all carcinomas and in 56% of the adenomas there was overexpression of the transgene in relationship to the surrounding tissue. The majority of the tumors that overexpressed TGF-alpha were alpha-fetoprotein positive, while alpha-fetoprotein staining was not detected in tumors (all adenomas) that did not show excessive transgene expression. We conclude that TGF-alpha functions as a promoter of liver carcinogenesis through its effect as an autocrine inducer of hepatocyte proliferation. Further, the data indicate that TGF-alpha overexpression may favor tumor progression.
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PMID:Development of liver tumors in transforming growth factor alpha transgenic mice. 132 2

New hepatocyte-like cell lines (mhAT) were derived from the liver of a transgenic mouse expressing SV40 early genes under the direction of the liver-specific antithrombin III gene promoter (ATIII-TSV40). Their differentiated phenotypes were improved and stabilized by the use of liver-specific growth media (arginine-free, glucose-free, or low-fructose/glucose-free medium). The best differentiated lines display a very high level of albumin, transferrin, and L-type pyruvate kinase (L-PK) gene expression that is comparable to that observed in the mouse liver. Abundance of the aldolase B and phosphoenolpyruvate carboxykinase (PEPCK) transcripts varied from 5 to 35% of the in vivo concentrations while abundance of the alpha-fetoprotein and phenylalanine hydroxylase transcripts remained very low. Hormonal (cAMP and insulin) and nutritional (glucose) gene controls of PEPCK and L-PK were, at least partially, conserved. mhAT cells are readily transfectable by the calcium phosphate coprecipitation technique and exhibit a liver-specific pattern of expression of exogenous genes. Thus, mhAT cells seem suitable for the analysis of the regulatory regions involved in the tissue-specific transcription of genes. This work demonstrates, therefore, the great efficiency of targeted carcinogenesis in transgenic mice to create new differentiated cell lines. The availability of various lines of liver-specific cells with different phenotypes will constitute useful tools to establish correlations between expression of trans-acting factors and control of the phenotype.
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PMID:Gene expression in hepatocyte-like lines established by targeted carcinogenesis in transgenic mice. 137 87

In this second section of generalizations, methylation, differentiation and carcinogenesis are reviewed. Special consideration is given to the alpha-fetoprotein gene which is used extensively as a model embryonic gene. Specific correlations are made between the glucocorticoid response element and the alpha-fetoprotein gene. A further correlation was made between retinoic acid and alpha-fetoprotein synthesis.
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PMID:Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XXVII. Intermediate generalizations (Part B). 137 94

To clarify the physiologic response of splenic lymphocytes to liver damage and the role of this response in regeneration versus malignant transformation, we cultured rat spleen lymphocytes with portal sera from rats subjected either to partial (70%) hepatectomy or to long-term oral administration of the hepatic carcinogen 3'-methyl-4-dimethylaminoazobenzene. Sera taken within 24h after partial hepatectomy contained a previously described signal protein which serves as a marker of liver damage. The MW 5,000-10,000 serum fraction also contained a factor that promoted cell growth, DNA synthesis, glucose utilization, and the production of anti-sheep erythrocyte plaque-forming cells in cultures of rat splenic lymphocytes. In contrast, the sera of rats subjected to liver damage by the carcinogen had no more effect on the cultured lymphocytes than sera from sham-operated or untreated controls. The signal protein was present initially in portal sera from carcinogen-treated rats, but decreased as hepatitis gave way to cirrhosis. Subsequent malignant transformation was marked by the appearance of serum alpha-fetoprotein. Our results suggest that activation of splenic lymphocytes by serum factor(s) is involved in hepatic regeneration and that this process is deranged in carcinogenesis.
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PMID:In-vitro immune response of splenic lymphocytes to portal serum agents from rats undergoing hepatic regeneration or hepatic carcinogenesis. 139 18


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