Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By restriction fragment length polymorphism (RFLP) analysis, it was found that loss of heterozygosity (LOH) at three different chromosomal loci, 3p, 13q, and 17p, occurs simultaneously in nearly 100% of small-cell lung carcinomas (SCLC). This was observed even in stage I tumors and an untreated tumor, and it occurred prior to NMYC amplification. The common region of LOH on chromosome 3p was 3p14-24.1, and this region was also frequently lost in carcinoma of the uterine cervix (100% at D3S2 on 3p14-21) as well as renal cell carcinoma (56% at ERBA beta on 3p22-24.1), suggesting the presence of tumor suppressor gene(s) for these cancers in this region. On chromosome 13, LOH was observed commonly in the region between 13q12 and 13q22, including the RB locus on 13q14, and normal RB protein was not detected in any of 9 SCLC cell lines by immunoprecipitation analysis. The common region of LOH on chromosome 17 was 17p13 and is the same as that in colon carcinoma and osteogenic sarcoma. Since LOH is supposed to unmask the recessive mutation of tumor suppressor gene in the remaining allele, these results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC. RFLP analysis was performed on several other types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, and stomach cancer to determine the chromosomal loci of putative tumor suppressor genes in each tumor. Chromosomal loci showing frequent LOH were different among these tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple genetic alterations in small-cell lung carcinoma. 257 37

The R16 strain, which carries the major histocompatibility complex-linked growth and reproduction complex (grc), and its normal counterpart, the ACP strain, were initiated at 8 wk of age with a single i.p. dose of diethylnitrosamine (DEN), and 2 wk later they were fed either a choline-deficient (CD) or a choline-supplemented (CS) diet. The rats were sacrificed 2, 4, 6, 10, and 12 mo later; complete autopsies were performed, and all of the tissues were examined histologically. Sections of the liver were also examined histochemically for gamma-glutamyl transpeptidase activity. Shortly after the administration of DEN, the R16 strain showed a significant increase in the number and size of gamma-glutamyl transpeptidase-positive foci and more severe histological changes (disruption of the lobular architecture, bile duct and oval cell proliferation, cellular atypia, and accumulation of fat) compared with the ACP strain. These changes occurred in animals fed either CD or CS diet, but they were much more extensive and severe in the animals on the CD diet. They did not occur in rats of either strain fed the diets alone. The first hepatocellular carcinoma appeared in the R16 rats on the CD diet at 4 mo after administration of the DEN and on the CS diet, at 10 mo. The only hepatocellular carcinoma that occurred in the ACP rats did so at 12 mo in one animal on the CD diet. Combining the data at 10 and 12 mo for the rats on the CD diet, 50% (20 of 40) of the R16 rats had hepatocellular carcinomas, whereas only 3% (one of 30) of ACP rats did. The R16 strain (22%, 9 of 40), but not the ACP strain (0 of 30), also had a variety of other malignancies: squamous cell carcinomas (8%); renal cell carcinomas (8%); lymphomas (5%); and pheochromocytoma (3%). A similar pattern of malignancies also occurred in the R16 rats on the CS diet, and there were no malignancies in the ACP rats. These observations indicate that the grc confers unusual susceptibility to the induction of cancer by the chemical carcinogen DEN and that this genetic susceptibility to cancer of the R16 strain extends beyond the primary target organ of the carcinogen used.
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PMID:Genetic control of susceptibility to diethylnitrosamine carcinogenesis in inbred ACP (grc+) and R16 (grc) rats. 281 21

This case report describes the localization and categorization of tumors using 99mTc(V)-dimercaptosuccinic acid and [131I]metaiodobenzylguanidine scans in a very uncommon case of medullary thyroid carcinoma associated with pheochromocytoma (Sipple's syndrome) and hepatocellular carcinoma. Technetium-99m(V)-dimercaptosuccinic acid showed accumulation only in medullary thyroid carcinoma, but [131I]metaiodobenzylguanidine scans were positive in both medullary thyroid carcinoma and pheochromocytoma. In advanced Sipple's syndrome, combined use of [99mTc(V)]dimercaptosuccinic acid and [131I]metaiodobenzylguanidine may be useful for the categorization of tumor mass lesions and planning appropriate therapy.
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PMID:Sipple's syndrome with liver tumors examined by iodine-131 MIBG and technetium-99m(V)-DMSA. 289 36

PC 12h pheochromocytoma cells were subcutaneously transplanted into rat. We found the transplanted tumors accumulated some fucogangliosides associated with PC 12 cells. These gangliosides were isolated and purified by DEAE-Sephadex A-25 and Iatrobeads column chromatographies. Their structures were determined by fast atom bombardment mass spectrometry, proton nuclear magnetic resonance spectrometry, permethylation study, and sequential degradation using various exoglycosidases and mild acid hydrolysis. Two tumor-associated fucogangliosides were found to possess the blood group B determinant as follows: G6: IV2Fuc alpha, IV3Gal alpha, II3NeuAc, GgOse4Cer; G11: IV2Fuc alpha, IV3Gal alpha, II3 (NeuAc)2, GgOse4Cer. A ganglioside with the similar structure as ganglioside G6 was isolated from rat hepatoma cells (Holmes, E.H., and Hakomori, S-I. (1982) J. Biol. Chem. 257, 7698-7703). However, ganglioside G11 has not previously been reported in the literature. These fucogangliosides reacted with the monoclonal antibody prepared by immunizing mice with PC 12h cells. Other fucogangliosides were also found to accumulate in the transplanted tumor tissues. They were identified as fucosyl-GM1 and fucosyl-GDlb. These fucogangliosides did not react with the monoclonal antibody against PC 12h cells.
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PMID:Characterization of tumor-associated fucogangliosides from PC 12 pheochromocytoma cells. 365 55

The polypeptide growth factors, nerve growth factor, epidermal growth factor, and platelet-derived growth factor, as well as insulin do not induce ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) unless a minimal concentration of an ornithine decarboxylase-inducing amino acid, such as asparagine, is present in the medium. The effects of the growth factors were studied in appropriately responsive cell lines: pheochromocytoma (PC12) cells for nerve and epidermal growth factors, fibroblasts (NIH 3T3) for platelet-derived growth factor, and fibroblasts and hepatoma (KRC-7) cells for insulin. The nonmetabolizable amino acid analog alpha-aminoisobutyric acid can replace asparagine, indicating that the covalent modification of the inducing amino acid is not necessary for the induction of ornithine decarboxylase by these growth factors. For the same intracellular concentration of the inducing amino acid, the presence of the growth factors induces higher levels of ornithine decarboxylase. The evidence indicates that these growth factors do not induce ornithine decarboxylase by raising the intracellular concentration of amino acids but rather act synergistically with the inducing amino acid. Evidence is provided that the induction of polyamine-dependent growth by these growth factors is mediated by amino acids. The relationship of these results to the A and N amino acid transport systems and to the Na+ influxes in relation to growth is discussed.
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PMID:Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids. 389 32

While magnetic resonance imaging (MRI) is not a screening examination in the search for metastatic disease, it has already demonstrated its value when performed as a carefully directed study to detect focal hepatic lesions. In the past 18 months we have encountered nine patients (six men, three women--ages 14-66) with a variety of primary tumors (renal cell carcinoma, two; colon carcinoma, two; hepatocellular carcinoma, two; pancreatic carcinoma, one; pheochromocytoma, one; rhabdomyosarcoma, one) whose MR scans revealed hepatic metastases after normal or nondiagnostic computed tomographic (CT) scans. The lesions were most clearly demonstrated using spin echo (SE) technique with recovery times (TR) of 2.0 seconds and delay times (TE) of 56 msec; metastases usually imaged with greater signal intensity than surrounding liver parenchyma. Lesions were solitary in three patients, multiple in six, and were found in all hepatic lobes without any specific location predominating. Pathologic confirmations of MR diagnoses were available in six of nine patients. In two patients, CT scans were of poor technical quality because streak artifacts from surgical clips obscured portions of the liver. In one patient iodinated contrast medium could not be given. In the remaining six patients CT scan quality was acceptable. This report is not a comparison study of the two modalities. We simply present nine patients in whom metastases were not detected by CT for various reasons but were found by MRI using SE technique.
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PMID:Magnetic resonance imaging diagnosis of hepatic metastases in the presence of negative CT studies. 408 52

1. All available evidence for and against the concept of ectopic hyperparathyroidism, including 307 case reports of tumor hypercalcemia, was collated. 2. Of 104 combined cases of tumors of the kidney, lung, liver, head, neck and esophagus, 91 (88%) were in men. 3. The parathyroid glands were examined in 170 of 307 cases and parathyroid hyperplasia or adenoma were described in 34 cases. This high frequency may reflect higher likelihood of reporting such association. 4. Analysis of the histological pattern of tumors associated with humoral hypercalcemia revealed a marked association with certain histological types in different organs, such as clear-cell carcinoma of the kidney and ovary, hepatocarcinoma and cholangiocarcinoma, pheochromocytoma, and squamous-cell carcinoma of the lung, head, neck, esophagus, and urogenital tract. This histological correlation is not compatible with the "random derepression" hypothesis. 5. The existence of tumor humoral hypercalcemia is well documented, as 61 of 74 operated patients sustained remission of hypercalcemia following tumor removal. 6. The evidence for ectopic PTH being produced by tumor is not well documented and is based on conflicting radioimmunoassay results. We have found no case in the literature which fulfilled unequivocally criteria of ectopic production of biologically active PTH. There has been a lack of studies of tumors for the presence of biologically active hypercalcemic factors because only relatively insensitive bioassays are available at present. More information is also required on microscopic bone changes in tumor hypercalcemia as x-ray studies alone are inadequate. 7. On the basis of the present evidence, causes and mechanisms of tumor hypercalcemia are likely to be multiple.
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PMID:Tumor hypercalcemia and "ectopic hyperparathyroidism". 699 43

Adrenal 4 binding protein (Ad4BP) is a transcription factor that regulates the expression of the steroidogenic enzymes and is expressed primarily in steroidogenic cells. We immunolocalized Ad4BP in adrenocortical carcinoma (eight cases) and various malignancies that histologically simulate an adrenocortical carcinoma to evaluate the value of Ad4BP as an immunohistochemical marker of adrenocortical carcinoma. These malignancies examined were renal cell carcinoma (20 cases), hepatocellular carcinoma (10 cases), malignant melanoma (eight cases), ovarian (six cases) and uterine (three cases) clear cell carcinoma, large cell carcinoma of the lung (five cases), and pheochromocytoma (three cases). Nuclear Ad4BP immunoreactivity was observed only in adrenocortical carcinoma cases but not in other tumors examined. Almost all of the adrenocortical carcinoma cells were immunohistochemically positive for Ad4BP including cells associated with bizarre nuclei. These results show that application of Ad4BP immunostain can contribute greatly to the differential diagnosis of adrenocortical carcinoma.
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PMID:Transcription factor adrenal 4 binding protein as a marker of adrenocortical malignancy. 755 51

The oligonucleosomal pattern of DNA fragmentation is the best-characterized biochemical marker of apoptosis and believed to be generated by a, as yet unidentified, Ca2+, Mg(2+)-dependent endonuclease. All apoptotic cells fragment their genome. However, not every cell type undergoing apoptosis is capable of internucleosomal DNA cleavage. We have analyzed the endonuclease activities and patterns of DNA fragmentation in four established cell lines undergoing apoptosis following serum deprivation, i.e., rat 5123tc hepatoma and PC12 pheochromocytoma, as well as human MCF7 breast and DU145 prostatic carcinoma cells. Whereas apoptotic 5123tc and PC12 cells degraded their DNA into oligonucleosomes, the MCF7 and DU145 cells generated only > 50 kilobase pairs (kbp) DNA fragments. However, when isolated nuclei from all four cell lines were incubated with both Ca2+ and Mg2+ ions, their DNA was cleaved into internucleosomal fragments. Following washing with a low ionic strength buffer, the nuclei could only degrade DNA to > 50-kbp fragments. DNA ladders were produced again in these washed nuclei after reconstitution with the nuclear wash, which contained an endonucleolytic activity of approximately 97 kilodaltons. These experiments showed that cells maintain separate pools of endonucleolytic activities responsible for the high and low molecular mass DNA fragmentation, and depending on the cell type, one or both enzymatic pools become activated during apoptosis.
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PMID:Separate pools of endonuclease activity are responsible for internucleosomal and high molecular mass DNA fragmentation during apoptosis. 765 36

GADD153, a ubiquitously expressed member of the CCAAT/enhancer-binding protein (C/EBP) family is induced by a wide variety of growth-arresting and DNA-damaging agents. Functionally, GADD153 has been postulated to act as a dominant-negative regulator of C/EBPs. Therefore we sought to gain evidence for interactions between GADD153 and other C/EBPs during cellular responses to stress. In this report we have demonstrated that treatment of rat pheochromocytoma PC12 cells with sodium arsenite leads to enhanced expression of C/EBP-beta and GADD153 (growth arrest and DNA damage inducible gene 153) but not other C/EBPs. Coimmunoprecipitation experiments provided evidence for the formation of endogenous GADD153-C/EBP-beta complexes in arsenite-treated cells. Additional experiments were performed to determine the role of such complexes in regulating GADD153 expression. Previous studies in our laboratory demonstrated that the GADD153 promoter contains a C/EBP binding site through which other C/EBPs interact to transactivate GADD153 expression in liver hepatoma cells. Here, we demonstrate that extracts prepared from arsenite-treated PC12 cells likewise show increased amounts of factors capable of binding to the GADD153-C/EBP site and that these complexes are comprised at least in part of C/EBP-beta. Forced expression of C/EBP-beta was found to be capable of transactivating the GADD153 promoter in PC12 cells cotransfected with plasmids expressing a GADD153 reporter gene and C/EBP-beta protein. However, overexpression of GADD153 inhibited the transactivation of the GADD153 promoter by C/EBP-beta. These findings provide evidence for an autoregulatory loop in which stress-induced GADD153 feeds back to attenuate GADD153 expression during the cellular response to stress.
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PMID:Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress. 866 54


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