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)

To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients. Cumulative appearance rates of hepatocellular carcinoma were 19.4%, 44.3% and 58.2% at the end of the fifth, tenth and fifteenth years, respectively. When classified by the type of hepatitis virus infection, the appearance rates of hepatocellular carcinoma in 180 patients with only HBsAg and in 349 patients with only antibodies to hepatitis C virus were 14.2% and 21.5% at the fifth yr, 27.2% and 53.2% at the tenth yr and 27.2% and 75.2% at the fifteenth yr, respectively. Cox proportional hazard model identified that alpha-fetoprotein levels (p = 0.00001), age (p = 0.00067), positive hepatitis C virus antibodies (p = 0.00135), total alcohol intake (p = 0.00455) and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of hepatocellular carcinoma. Whereas age and indocyanine green retention rate were independent predictors for the appearance rate of liver tumor in the subgroup of HBsAg-positive patients, alpha-fetoprotein levels, age and past alcohol consumption were independent predictors in the group of hepatitis C virus antibody-positive patients. These epidemiological results suggest that some differences exist in the activity and modes of cancer promotion between hepatitis B virus infection and hepatitis C virus infection.
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PMID:A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. 768 79

In a 70 year old woman with a tumor in the head of the pancreas, the lesion was predominantly composed of papillary adenocarcinoma protruding into the main pancreatic duct, with periductal invasion. The major portion of the adenocarcinoma was intraductal and was composed of tall columnar epithelial cells with pseudostratified nuclei, had the appearance of primitive endodermal epithelium and was positive for carcino-embryonic antigen. In contrast, in the other portion of the adenocarcinoma which had the predominant component of periductal invasion, neoplastic cells had an irregular, eosinophilic cytoplasm, resembled ordinary pancreas adenocarcinoma of ductal origin and was positive for CA19-9. Neuro-endocrine and alpha-fetoprotein-positive cells with a primitive appearance were scattered among the neoplastic epithelial linings. In addition, a vimentin-positive sarcomatoid component intermingled with the adenocarcinoma. These findings suggest that the adenocarcinoma observed in this tumor with the primitive appearance also had a primitive phenotype. This was evidenced by immunohistochemistry and the divergent directions of differentiation. This particular case illustrates that pancreas adenocarcinoma of the ordinary histologic type can arise secondarily from the more primitive neoplastic cells during carcinogenesis within the pancreatic duct.
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PMID:A case of AFP-positive pancreas papillary carcinoma suggestive of a primitive endoderm phenotype. 769 May 15

We have demonstrated previously a pronounced increase in the expression of hepatocyte growth factor (HGF) (Z. Hu, R. P. Evarts, K. Fujio, E. R. Marsden, and S. S. Thorgeirsson, Am. J. Pathol., 142: 1823-1830, 1993), transforming growth factor alpha (TGF-alpha) (R. P. Evarts, H. Nakatsukasa, E. R. Marsden, Z. Hu, and S. S. Thorgeirsson, Mol. Carcinog., 5: 25-31, 1992), and acidic fibroblast growth factor (aFGF) (E. R. Marsden, Z. Hu, K. Fujio, H. Nakatsukasa, S. S. Thorgeirsson, and R. P. Evarts, Lab. Invest., 67: 427-433, 1992) that coincided with the proliferation and differentiation of putative hepatic stem cells and perisinusoidal stellate (Ito) cells. Here, we examine the earliest stages of stem cell activation in rat liver using an experimental model involving treatment with acetylaminofluorene and partial hepatectomy (R. P. Evarts, P. Nagy, E. Marsden, and S. S. Thorgeirsson, Carcinogenesis (Lond.), 8: 1737-1740, 1987). Histochemical identification of stem cell progeny and Ito cells was accomplished by OV6 and desmin antibodies, respectively. Expression of the 2.1-kilobase alpha-fetoprotein transcripts and the concomitant DNA synthesis ([3H]thymidine label) were used as indicators for the activation of the stem cell compartment. Expression of HGF, TGF-alpha, and aFGF was analyzed at the time of partial hepatectomy and 4, 12, 24, 48, 72, and 92 h after the operation. [3H]-Thymidine-labeled OV6- and desmin-positive cells were present in the portal space and in the Glisson capsule 4 h after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of hepatic stem cell compartment in the rat: role of transforming growth factor alpha, hepatocyte growth factor, and acidic fibroblast growth factor in early proliferation. 769 Nov 52

Paired samples of hepatocellular carcinoma and non-tumorous hepatic tissue from 12 southern African blacks were examined for loss of heterozygosity at two loci (D4S409 and D4S392) in chromosome 4q12-q13 (mapping to the same region as the locus for the gene for alpha-fetoprotein). Deoxyribonucleic acid was extracted from carcinoma and non-tumorous tissues and amplified using the polymerase chain reaction. The primers used were based on flanking regions of minisatellite DNA specific for the loci. Products of PCR amplification were separated by denaturing polyacrylamide gel electrophoresis and analysed for allelic losses. At the D4S409 locus one of seven informative samples showed loss of heterozygosity, whereas none of eight informative samples showed loss of heterozygosity at the D4S392 locus. If these findings are considered together with those previously reported in hepatocellular carcinomas from black Africans, the prevalence of loss heterozygosity in chromosome 4q12-q13 in hepatocellular carcinoma in southern African blacks (33 per cent) is the same as that in tumours from Japanese patients. Loss of heterozygosity at chromosome 4q12-q13 is infrequent during hepatocellular carcinogenesis in southern African blacks.
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PMID:Loss of heterozygosity in chromosome 4q12-q13 in hepatocellular carcinoma in southern African blacks. 861 34

Among various kinds of tumor markers, alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) are very important and widely used in the clinical medicine. AFP is a specific marker for diagnosis of hepatocellular carcinoma (HCC). AFP is a glycoprotein composed of 590 amino acid residues and has one asparagine-linked sugar chain at the 232nd position from N-terminal of the AFP molecule. A difference exists between the sugar chain of HCC AFP and the chain from a cirrhotic patient. This difference is easily detected by a lectin-binding analysis using LCA or PHA-E4. This technique enabled us to predict a risk of tumor occurrence in patients with a high probability of HCC development. Exciting progress in molecular biology has been made in the field of AFP and CEA research. The gene structures and the regulatory mechanism of synthesis of AFP and CEA has been elucidated successively. These results may provide a clue to the solution of the mechanism of carcinogenesis and may provide more sensitive tools for detection of tumors as well as practical therapies.
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PMID:[Carcino-fetal antigens]. 869

The reason why only some hepatocellular carcinomas synthesize alpha-fetoprotein is not known. Both the frequency with which this foetal globulin is produced and the major aetiological associations of hepatocellular carcinoma vary between populations with high and low incidences of the tumour, raising the possibility that re-expression of the gene for alpha-fetoprotein is determined, or influenced by, the molecular genetic events that occur during hepatocellular carcinogenesis. This hypothesis could be tested by comparing serum alpha-fetoprotein concentrations in populations in which the major risk factors for hepatocellular carcinoma differ. Two such populations are urban and rural southern African blacks. We measured serum alpha-fetoprotein concentrations by radioimmunoassay in 234 southern African blacks with hepatocellular carcinoma: 78 of the patients were urban and they were age-matched with 156 patients born in rural areas, one-half of whom had remained in a rural environment (rural), whereas the others had migrated to the cities in adulthood (rural-urban). Urban patients were more likely than rural-born patients to have a normal serum alpha-fetoprotein value [23.1% (18/78) compared with 10.2% (16/156); p = 0.02]. There was no significant difference between the concentrations in rural and rural-urban patients. The absolute values of the raised serum alpha-fetoprotein values did not differ between urban (69,558 +/- 176,737 ng/ml; and rural-born patients (53,998 +/- 125,681 ng/ml), or between rural (69,207 +/- 159,975 ng/ml) and urban-rural patients (40,434 +/- 83,028 ng/ml). These findings are compatible with the hypothesis that re-expression of the alpha-fetoprotein gene in hepatocellular carcinoma is related to the aetiology or pathogenesis of the tumour.
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PMID:Serum alpha-fetoprotein concentrations in urban and rural Southern African blacks with hepatocellular carcinoma. 885 49

The association between multiple births and subsequent maternal breast cancer risk was explored in a nested case-control study in Sweden encompassing 19,368 parous women with breast cancer diagnosed up to age 65 years, and 100,459 parous controls. Among cases and controls, there were 329 and 2,031 women, respectively, with a history of at least one live multiple birth. Compared with singleton mothers, breast cancer risk was 12 percent lower (odds ratio = 0.88, 95 percent confidence interval = 0.78-0.99) in women who had had a multiple birth. After stratification for age at diagnosis, evidence of a significant inverse association was found only in women aged 54 years or younger. Birth order of the multiple pregnancy had no apparent risk-modifying effect. Age at earliest multiple birth was unrelated to breast cancer risk. The inverse association between twinning and breast cancer risk may reflect protective physiological features of twin pregnancies. Further research is needed to investigate the role, if any, of increased levels of steroid hormone-binding globulins in mothers of twins and the proposed inhibitory effects of human chorionic gonadotropin and alpha-fetoprotein, both of which are increased during multiple gestations, on breast carcinogenesis. Breast feeding patterns in mothers of twins also may modify their risk of developing breast cancer.
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PMID:Maternal risk of breast cancer following multiple births: a nationwide study in Sweden. 887 51

Although oval cell proliferation is observed prior to the appearance of hepatic nodules and hepatocellular carcinomas during ethionine-induced liver carcinogenesis in the rat, the role of these presumptive hepatic stem cells during the neoplastic process remains controversial. In order to investigate this question, we have used a panel of monoclonal antibodies against antigens associated with normal hepatocytes, oval cells and transplantable hepatocellular carcinomas (THC) to trace antigenic pathways leading to liver cancer. Male ACI rats were fed a choline-deficient diet containing 0.1% DL-ethionine for 4, 16 or 30 weeks. Immunocytochemical analysis of frozen liver sections revealed a subpopulation of hepatic nodules (7/52), carcinomas (8/15) and lung metastases (3/5) containing populations of cells expressing both oval cell, hepatocyte and neoplastic markers. Carcinomas expressing oval cell markers often appeared as a mosaic of well-defined patches composed of phenotypically distinct cells. Many of the phenotypes expressed closely mimicked patterns of expression observed in fetal and neonatal liver. THC derived from primary tumors positive for oval cell antigens (4/5) continued to express these markers. Northern blot analysis and immunocytochemical analysis revealed that 4/5 primary hepatocellular carcinomas (PHC) and THC expressed alpha-fetoprotein (AFP) and albumin transcripts and contained subpopulations expressing AFP together with hepatocyte and oval antigens. In contrast, a well-differentiated PHC and its corresponding THC lacked AFP mRNA and oval cell antigens but showed strong expression of both hepatocyte and neoplastic markers. These results demonstrate that a subpopulation of malignant and metastatic hepatocellular carcinomas are comprised of cells expressing multiple oval cell markers in this model system.
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PMID:Delineation of antigenic pathways of ethionine-induced liver cancer in the rat. 888 73

In the present study the establishment and characterization of a nontumorigenic liver epithelial cell line (HACL-1) derived from a human hepatocellular adenoma is described. The HACL-1 cells have a finite life span (i.e., they proliferate for a period of 2 months and then senesce), show cell-cell contact inhibition, do not grow in soft agar, are not tumorigenic when injected in nude mice, and possess a normal diploid karyotype. The cultured cells resemble hepatocytes, but exhibit some features of dedifferentiation. At the ultrastructural level the cells are endowed with round or oval nuclei, abundant cytoplasmic organelles, and varying amounts of glycogen. The rough endoplasmic reticulum is disorganized, while peroxisomes and matrix granules within mitochondria are lacking. HACL-1 cells are cytokeratin 18-positive as well as (transiently) albumin- and alpha-fetoprotein-positive, but do not express cytokeratin 19. Furthermore, no mutations were observed in exons 5-8 of the tumor suppressor gene p53. Taken together these results show that HACL-1 cells are nontumorigenic proliferating liver epithelial cells, which might prove to be of great value in future studies on diverse aspects of human liver cell biology and carcinogenesis.
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PMID:Establishment and characterization of a nontumorigenic cell line derived from a human hepatocellular adenoma expressing hepatocyte-specific markers. 936 26

GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha1-6 fucosyltransferase (alpha1-6FucT) catalyzes the transfer of a fucosyl residue from GDP-fucose to the asparagine-linked GlcNAc residue of complex N-glycans via alpha1-6 linkage. These oligosaccharide structures are essential for the attachment of polysialic acid to the neural-cell-adhesion molecule, and its levels are useful for the differential diagnosis of hepatocellular carcinomas with respect to the microheterogeneity of alpha-fetoprotein. We have been successful in the purification and cDNA cloning of alpha1-6FucT from porcine brain and from a human gastric-cancer cell line. In the present study, mRNA expression of alpha1-6FucT in various rat tissues and human cancer cell lines was examined, along with the expression of alpha1-6FucT mRNA and the induction by treatment with several cytokines. Northern-blot analysis indicated high expression levels of alpha1-6FucT in brain and gastrointestinal-tract tissues of normal rats, as well as for a number of lung-cancer, gastric-cancer and colon-cancer cell lines. Although various cytokines did not induce alpha1-6FucT mRNA, differentiation of a tumor cell enhanced the mRNA by 2- to 3-fold. These results may provide new insight into studies on alpha1-6FucT in terms of carcinogenesis or differentiation.
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PMID:Expression of alpha1-6 fucosyltransferase in rat tissues and human cancer cell lines. 937 48


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