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

Insulin stimulates the growth and proliferation of a variety of somatic cells in culture, and evidence suggests that insulin is also an important regulator of growth in vivo. In cell culture, insulin interacts synergistically with other hormones and growth factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), tumor-promoting phorbol esters, and thrombin, to stimulate progression through the cell cycle of cells that have been arrested in G1 by deprivation for serum. In addition, insulin is required by most cells for optimal long term growth in hormone-supplemented serum-free media. In some cells, such as human skin fibroblasts, the growth-promoting effects of insulin appear to be mediated primarily by its low affinity interaction with receptors for insulin-like growth factor I (IGF-I). In other cells, such as hepatocytes, hepatoma cells, adrenocortical tumor cells, mammary carcinoma cells, and F9 embryonal carcinoma cells, insulin appears to stimulate growth by binding to high affinity insulin receptors. The insulin and IGF-I receptor proteins, like the receptor proteins for other growth-promoting hormones such as EGF and PDGF, are closely associated with tyrosine-specific protein kinase activities. The mechanism by which the binding of insulin to its receptor and activation of the receptor-associated tyrosine protein kinase activity control intracellular protein phosphorylation and dephosphorylation reactions, such as the phosphorylation of ribosomal protein S6, is a subject of considerable current interest. The phosphorylation of ribosomal protein S6 may be related mechanistically to the activation by insulin of protein synthesis, and hence the passage of cells through the G1 phase of the cell cycle. Malignant transformation does not generally result in a total loss of the growth requirement of cells for insulin or insulin-like growth factors, although transformation is accompanied in some cases by a qualitative reduction in the insulin/IGF requirement. Abnormalities in insulin production or sensitivity in vivo are accompanied by abnormalities in growth; thus, insulin appears to be an important regulator of growth in vivo. Some of the growth-promoting effects of insulin in vivo may be attributable to direct action of insulin, while other effects may be caused by the regulatory effect of insulin on somatomedin production, and possibly on somatomedin action.
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PMID:Growth-stimulatory actions of insulin in vitro and in vivo. 637 81

A total of 114 children with solid tumors refractory to conventional therapy were evaluated for response and/or toxic effects after receiving cisplatin at doses of 3.0-4.5 mg/kg with aggressive hydration and mannitol diuresis every 3 weeks; a minimum of two courses was required for evaluation of response (110 patients). Objective responses were noted in 18 patients: rhabdomyosarcoma (three), Wilm's tumor (three), osteogenic sarcoma (three). Ewing's sarcoma (two), neuroblastoma (one), undifferentiated sarcoma (one), hepatoblastoma (one), ovarian teratoma (one), hepatocellular carcinoma (one), embryonal carcinoma of the mediastinum (one), and thymoma (one). Twenty-six patients had some evidence of renal toxicity. Asymptomatic hearing loss was commonly found when audiometry was performed (eight of 18 patients tested). Eight additional patients had symptomatic hearing problems--tinnitus or hearing loss. Myelosuppression was mild. Hypomagnesemia and/or hypocalcemia were common but only one patient had symptoms. Cisplatin, administered at a dose of 3.0 mg/kg with aggressive hydration and mannitol diuresis, is reasonably well-tolerated. Its role in the therapy for those tumors against which it shows activity remains to be determined.
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PMID:Phase II trail cisplatin in refractory childhood cancer: Children's Cancer Study Group Report. 694 56

Murine extra-embryonic endodermal cells derived from either teratocarcinomas or cultured mouse blastocysts contain two protein species of Mr = 55,000 and Mr = 50,000 endodermal cytoskeletal proteins A and B, respectively) that are insoluble in nonionic detergent and 1 M NaCl and are not found in abundance in embryonal carcinoma cells, the stem cells of teratocarcinomas. Antiserum raised against the electrophoretically purified endo B protein immunoprecipitated endo B from [35S]methionine-labeled cell lysates of three parietal endodermal cell lines, a presumptive visceral endodermal cell line, and a mouse hepatoma line. Immunoprecipitable endo B was not found in murine embryonal carcinoma cells, fibroblasts, myoblasts, keratinocytes, erythroleukemic or neuroblastoma cells. These results are consistent with the view that endo B is not tubulin, vimentin, desmin, or keratin. Amino acid composition data, partial peptide analysis of immunoprecipitated endo B, and immunoprecipitation analysis with antikeratin serum support the suggestion that endo B is not a keratin. Indirect immunofluorescent staining of parietal endodermal cells with the endo B antiserum resulted in the fluorescence of a fibrillar cytoskeletal network. The synthesis of endo B was increased dramatically when embryonal carcinoma cells were induced to differentiate by treatment with retinoic acid. Endo B appears to be a cytoskeletal protein that is synthesized when malignant embryonal carcinoma cells differentiate to benign extra-embryonic endoderm.
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PMID:Identification and immunoprecipitation of cytoskeletal proteins from murine extra-embryonic endodermal cells. 726 44

Two multifunctional receptors, low density lipoprotein receptor-related protein (LRP) and gp330, have been implicated in the cellular uptake and degradation of a wide spectrum of functionally diverse ligands including plasma lipoproteins, proteases, and proteinase-inhibitor complexes. The two receptors show distinct tissue-specific expression patterns, suggesting different physiological functions. We have examined the cellular degradation of two serine proteinase inhibitor (serpin)-protease complexes, alpha 1-antitrypsin-neutrophil elastase (alpha 1AT.NEL) and alpha 1-antichymotrypsin-cathepsin G (alpha 1ACT.CathG) by normal murine fibroblasts (MEF) expressing LRP, and by a mutant fibroblast cell line (PEA13) which is genetically deficient for LRP. alpha 1AT.NEL complexes bound to LRP on ligand blots and were degraded efficiently by the MEF cells, but not by PEA13 cells. Degradation of the complexes was also significantly reduced by antibodies directed against LRP, further suggesting that fibroblasts require LRP for the cellular uptake and degradation of alpha 1AT.NEL complexes. In contrast to alpha 1AT.NEL, MEF cells did not degrade alpha 1ACT.CathG complexes. However, these complexes were rapidly degraded by the rat embryonal carcinoma cell line L2p58 which abundantly expresses gp330, raising the possibility that the alpha 1ACT.CathG complex might be recognized by gp330. Both complexes were efficiently metabolized by the hepatoma cell line HepG2, presumably involving the serpin-enzyme complex receptor. The differential recognition of serpin-protease complexes by fibroblasts and hepatoma cells, however, indicates that LRP, gp330, and the serpin-enzyme complex receptor are distinct proteins.
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PMID:Differential recognition of alpha 1-antitrypsin-elastase and alpha 1-antichymotrypsin-cathepsin G complexes by the low density lipoprotein receptor-related protein. 785 58

The signaling functions of the membrane and soluble form of the mouse IL-11 receptor (mIL-11R) were compared in rat and human hepatoma cells, which have a low endogenous IL-11 response. The expression vectors encoding either the full length or a secretory form of the ligand binding subunit of mIL-11R together with IL-6-responsive reporter gene constructs were transiently transfected into the H-35 and HepG2 cells. An IL-11-specific stimulation of transcription was detected that was qualitatively similar to that mediated by the endogenous IL-6R. HepG2 cells were noted to synthesize constitutively IL-11, resulting in an autocrine stimulation of gene expression. Addition of COS cell-derived soluble mIL-11R to the hepatoma cell cultures prominently enhanced IL-11 regulation of transfected reporter gene constructs and expression of endogenous acute phase plasma protein genes. Similarly, the complex of soluble mIL-11R and IL-11 was capable of mediating an IL-6-type signaling in cells that are naturally deficient in IL-11 response as shown by the activation of STAT1 and STAT3 in mouse embryonal carcinoma cells and human T cells. The results indicate that the IL-11R can serve as a substitute to IL-6R in activating gene expression in target cells that are devoid of the appropriate ligand-binding receptor subunits.
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PMID:Complex of the soluble IL-11 receptor and IL-11 acts as IL-6-type cytokine in hepatic and nonhepatic cells. 868 27

A case of a 62 year old Japanese woman with an endometrial adenocarcinoma producing alpha-fetoprotein (AFP) is described. Microscopically, the tumour was composed of a major medullary portion and a minor tubular adenocarcinoma which had invaded the myometrium, the myometrial lymphatics and blood vessels. Neoplastic cells in the medullary portion were polygonal with glycogen-rich cytoplasm. Vascular permeation by neoplastic cells was prominent. Extensive hepatoma-like features were observed. The tumour cells lacked features suggestive of a diagnosis of embryonal carcinoma or endodermal sinus tumour. The production of AFP by the tumour cells was demonstrated immunohistochemically using the PAP technique. Only two cases of AFP producing endometrial adenocarcinomas have been reported previously.
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PMID:Alpha-fetoprotein production by a hepatoid adenocarcinoma of the uterus. 870 61

The dioxin-binding Ah receptor (AHR) is a ligand-activated transcription factor that regulates the expression of several drug-metabolizing enzymes and has been implicated in immunosuppression, teratogenesis, cell-specific hyperplasia, and certain types of malignancies and toxicities. In order to examine tissue-specific regulation of the mouse Ah receptor gene (Ahr), we studied chimeric deletion constructs, containing the Ahr 5' flanking region and the firefly luciferase reporter gene (Luc). Transient transfection assays were performed in five established mouse cell lines: Hepa-1c1c7 (derived from hepatoma), JB6-C1 41-5a (epidermis), MLE-12 (lung epithelium), F9 (embryonal carcinoma), and NIH/3T3 (fibroblasts). Treatment of the cell lines included: dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), retinoic acid (RA), cyclic adenosine 3':5'-monophosphate (cAMP), or 12-O-tetradecanoylphorbol 13-acetate (TPA). Expression levels of Luc varied widely from one untreated cell line to another, this finding was also confirmed by measurements of AHR mRNA steady-state levels. In all cell lines except F9 cells, maximal constitutive expression was observed with constructs containing 78 bp of Ahr promoter sequences, which include several putative binding sites for the transcription factor Sp1. In contrast, in F9 cells, inclusion of sequences between -174 and -78 resulted in a fourfold stimulation of constitutive expression, suggesting that other transcription factors are important in Ahr gene expression in these cells. In MLE-12 and 41-5a cells, expression was significantly decreased by treatment with dioxin, RA, cAMP, or TPA. A similar inhibitory effect was observed in cAMP-treated MLE-12 and F9 cells; this result was confirmed by RT-PCR measurements of AHR mRNA steady-state levels. These results indicate that both up- and down-regulation of the Ahr gene occur and exhibit tissue-and cell-type specificity.
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PMID:Differential regulation of mouse Ah receptor gene expression in cell lines of different tissue origins. 880 68

The BI-PCT method showed the profile of BI-associated fragments of LNA in the cell line of the mouse hepatoma MH-22a to differ from that of the liver cells of C3HA mice, hepatoma cells incorporating the DNA fragments with 450 bp and those with 600bp disappearing. Application of the same method failed to reveal any differences in the profiles of BI-associated DNA fragments in the differentiated and non-differentiated cells of the embryonal carcinoma F9 induced by retinoic acid and cAMP dibutyryl treatment. It is suggested that the spectra of BI-associated DNA fragments might correlate with genetic stability in tumor cells.
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PMID:[The use of B1-PCR method for studying the genomic polymorphism involved in malignant growth]. 912 2

In a retrospective study, the prognostic value of monitoring the decay of alpha-fetoprotein (AFP) was assessed. Serum AFP was determined serially in 18 children with malignant germ-cell or hepatic tumors: 7 endodermal sinus tumor, 3 embryonal carcinoma, 5 malignant teratoma, 2 hepatoblastomas, and 1 hepatocellular carcinoma. The actual half-life (AHL) of AFP was computed after surgical resection of the tumor. In group 1, which had complete resection and no recurrence during follow-up (n = 13), the AHL of AFP was 4.0 +/- 0.9 days. In group 2, which had incomplete resection or recurrence during follow-up (n = 5), the AHL of AFP was 24.8 +/- 20 days, significantly longer than that of group 1 (P = 0.0026). The increased AHL of AFP indicated residual active tumor after surgical resection. The AHL of AFP may be more sensitive than serial monitoring of AFP in detecting preclinical recurrence after surgical resection of AFP-secreting tumors. Treatment strategies can be based on AFP clearance, and prospective clinical trials are warranted.
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PMID:Actual half-life of alpha-fetoprotein as a prognostic tool in pediatric malignant tumors. 935 34

The aromatic hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of several drug-metabolizing enzymes and has been implicated in immunosuppression, teratogenesis, cell-specific hyperplasia, and certain types of malignancies and toxicities. The mouse Ahr gene 5' proximal promoter region, which contains four potential Sp1 motifs, is required for efficient basal expression. Using a fragment spanning the region from nt -174 to +70 of the Ahr promoter, we found that four regions corresponding to four Sp1 sites were protected from DNase I digestion using nuclear extracts from MLE-12 (lung), F9 (embryonal carcinoma), Hepa-1 (hepatoma), and 41-5a (epidermal) cells. The Hepa-1 and F9 cell lines were shown by reverse transcriptase-polymerase chain reaction and Western blot to contain mRNA and protein for Sp1 and Sp3, but not Sp2 and Sp4. In electrophoretic mobility shift assays using oligonucleotide probes corresponding to the four Ahr Sp1 sites, nuclear extracts from Hepa-1 and F9 cells formed complexes that were determined immunologically to contain both Sp1 and Sp3 protein. The two Ahr proximal Sp1 sites (A and B) were shown to bind both Sp1 and Sp3 proteins, whereas the more distal sites (C and D) bound only Sp1. Competition gel shift experiments showed that sites A and B had 10-fold higher affinity for Sp factors than did sites C and D. To determine the transactivation potential of each of the four Ahr Sp1 sites, we fused the Ahr promoter to a luciferase (LUC) reporter gene and transfected the construct into the Drosophila cell line Schneider-2, which contains no Sp1 or Sp1-like factors. Cotransfection of this construct with expression plasmids for each of the Sp factors revealed that Sp3 was approximately 1.6-fold more efficient than Sp1 in Ahr transactivation. Mutation of the four Sp1 sites individually and in combination demonstrated that each site contributes to the overall level of expression of the reporter gene and that interactions between these sites play a minor role in regulation of the Ahr-LUC construct. These results suggest that basal Ahr expression may be regulated by the expression and distribution of Sp1-like factors.
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PMID:Regulation of mouse Ah receptor (Ahr) gene basal expression by members of the Sp family of transcription factors. 977 40


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