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)

Primary hepatic tumours in children represent an heterogeneous group of neoplasms. Malignant tumours are more common (60% of primary liver tumours), but account for only 1.2-5% of all paediatric neoplasms. There are two main types of malignant tumour, those of epithelial origin, hepatoblastoma (HB) and hepatocellular carcinoma (HCC), and the rarer mesenchymal tumours, e.g. rhabdomyosarcoma and undifferentiated sarcoma, (Weinberg AG, Finegold, MJ. Primary hepatic tumours of childhood. Hum Pathol 1983, 14, 512-532). Vascular tumours e.g. haemangioendotheliomas are the most common of the benign tumours followed by mesenchymal hamartoma and the rare hepatic adenoma and focal nodular hyperplasia. This article will concentrate on the malignant epithelial tumours.
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PMID:Liver tumours. 1053 78

The forkhead rhabdomyosarcoma transcription factor (FKHR) is a promising candidate to be the transcription factor that binds to the insulin response element of the insulin-like growth factor-binding protein-1 (IGFBP-1) promoter and mediates insulin inhibition of IGFBP-1 promoter activity. Cotransfection of mouse FKHR increased IGFBP-1 promoter activity 2-3-fold in H4IIE rat hepatoma cells; insulin inhibited FKHR-stimulated promoter activity approximately 70%. A C-terminal fragment of mouse FKHR (residues 208-652) that contains the transcription activation domain fused to a Gal4 DNA binding domain potently stimulated Gal4 promoter activity. Insulin inhibited FKHR fragment-stimulated promoter activity by approximately 70%. Inhibition was abolished by coincubation with the phosphatidylinositol-3 kinase inhibitor, LY294002. The FKHR 208-652 fragment contains two consensus sites for phosphorylation by protein kinase B (PKB)/Akt, Ser-253 and Ser-316. Neither site is required for insulin inhibition of promoter activity stimulated by the FKHR fragment, and overexpression of Akt does not inhibit FKHR fragment-stimulated Gal4 promoter activity. These results suggest that insulin- and phosphatidylinositol-3 kinase-dependent phosphorylation of another site in the fragment by a kinase different from PKB/Akt inhibits transcription activation by the fragment. Phosphorylation of this site also may be involved in insulin inhibition of transcription activation by full-length FKHR, but only after phosphorylation of Ser-253 by PKB/Akt.
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PMID:Insulin inhibits the activation of transcription by a C-terminal fragment of the forkhead transcription factor FKHR. A mechanism for insulin inhibition of insulin-like growth factor-binding protein-1 transcription. 1070 99

Summary. Insulin is known to inhibit glucose-6-phosphatase gene expression through PI 3-kinase/PKB mediated phosphorylation and inactivation of the forkhead transcription factor FKHR, which is a potent transactivator of the glucose-6-phosphatase gene. To study the function and regulation of the transcription factor FKHR in hepatic cells, we constructed a hydroxytamoxifen-inducible version of FKHR by fusing a part of the hormone binding domain of the estrogen receptor (ER) to the C-terminus of FKHR (FKHR-ER). In HepG2-cells transiently transfected with plasmids encoding the FKHR-ER fusion protein and a glucose-6-phosphatase reporter construct, hydroxytamoxifen induced a marked induction of glucose-6-phosphatase promoter activity, whereas no effect was observed in control cells. We next generated a H4IIEC3 rat hepatoma cell line stably expressing both FKHR-ER and a glucose-6-phosphatase promoter-based reporter construct. After 2h stimulation with hydroxytamoxifen, the promoter activity was stimulated 3-5 fold, and continued to increase up to 100-fold after 15 h. The response was half maximal at 0.5 microM hydroxytamoxifen. Insulin (1 nM) decreased the hydroxytamoxifen induced promoter activity by about 70% of the maximal response. This cell system can be used for (1) the identification of FKHR dependent genes and for (2) high throughput screening (HTS) of agents affecting the activity of FKHR and its regulation by insulin. Abbreviations used: FKHR, forkhead in rhabdomyosarcoma; G6Pase, glucose-6-phosphatase; PKB, protein kinase B; PI 3-kinase, phosphatidyl-inositol 3-kinase; IRU, insulin-responsive unit; Tx, 4-hydroxytamoxifen, ER, estrogen receptor; HBD, hormone binding domain
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PMID:Construction and characterization of a conditionally active construct of the insulin-regulated forkhead transcription factor FKHR. 1237 35

The endoplasmatic glucose-6-phosphate transporter is involved in the control of hepatic glucose production and blood glucose homeostasis. In this study, the expression of a luciferase reporter gene under the control of the glucose-6-phosphate transporter gene promoter was examined in transiently transfected hepatoma cells. The promoter activity was stimulated approximately 2.5-fold by dexamethasone. Mutational analyses demonstrated that the regions nucleotide (nt) -215/-209 and nt -197/-183 relative to the translation start site were critical for this regulation. In gel electrophoretic mobility shift assays the transcription factor Fox O1, also called forkhead in rhabdomyosarcoma (FKHR), overexpressed in 293 cells, bound to a probe with the sequence nt -215/-209. The overexpression of Fox O1 stimulated the induction of glucose-6-phosphate transporter promoter activity by dexamethasone via nt -215/-209 in hepatoma cells. Recombinant glucocorticoid receptor DNA binding domain protein bound to a probe with the sequence of nt -197/-183 in gel electrophoretic mobility shift assays and an oligonucleotide with this sequence transferred glucocorticoid responsiveness to a heterologous promoter. The data indicate that the glucose-6-phosphate transporter promoter contains a glucocorticoid response unit consisting of binding sites for Fox O1 and the glucocorticoid receptor.
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PMID:Characterization of cis-elements mediating the stimulation of glucose-6-phosphate transporter promoter activity by glucocorticoids. 1459 89

Cardiac tumors in infants and children are extremely rare. Their clinical manifestations vary widely from asymptomatic presentations to life-threatening cardiac events. Improvements in diagnostic techniques, such as those offered by echocardiography, have made early detection of cardiac masses possible, with or without the presence of clinical symptoms. Fifteen pediatric cases of cardiac tumor were diagnosed at our institution between July 1989 and July 2002 (male-female ratio, 10:5; age range, one day to nine years). Eleven of the cases involved primary cardiac tumors [rhabdomyoma (n = 10) and fibroma (n = 1)]. Ninety percent of the rhabdomyomas (9/10) were associated with tuberous sclerosis. Four of the fifteen cases were secondary metastatic tumors [hepatoblastoma (n = 2), hepatoma (n = 1) and rhabdomyosarcoma (n = 1)]. Clinical manifestations of the cardiac tumors included shortness of breath (n = 5), seizure (n = 4), cardiac murmur (n = 6), and cyanosis (n = 3). Surgery was performed for three of 11 patients with primary cardiac tumor (27%) due to severe obstruction of flow (n = 2) and other cardiac defects (n = 1). The primary cardiac tumor spontaneously regressed in five of the tuberous sclerosis patients. All four of the patients with secondary cardiac tumors continued to receive chemotherapy, and only one of them subsequently experienced regression. Based on our experiences, we conclude that: 1) rhabdomyoma is the most common primary cardiac tumor in children; 2) most pediatric tumors are associated with tuberous sclerosis; 3) clinical presentation is determined by the tumor size and number of tumors, and whether expansion of the malignancy has resulted in cardiac blood-flow obstruction; 4) there is a strong possibility of regression of the primary cardiac tumor, with surgery recommended only when cardiac symptoms are severe; and, 5) unless there is a significant obstruction of blood flow, chemotherapy is still the treatment of choice for secondary cardiac tumors.
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PMID:Cardiac tumors in infants and children. 1467 25

A mixed epithelial and mesenchymal tumor of the liver arising in an adult is rare and is mostly classified as sarcomatoid hepatocellular carcinoma (HCC). In this study, a case of sarcomatoid HCC in an adult with hepatoblastoma (HB)-like features, which produced difficulty in the differential diagnosis between sarcomatoid HCC and mixed HB, is presented. The epithelial component of the tumor composed of poorly differentiated HCC, Edmondson's grade III, and more primitive components, which were embryonal and small cell undifferentiated components of HB-like areas. The small undifferentiated cells surrounded HCC and the embryonal component of HB-like area, and revealed transition partly to areas of rhabdomyosarcoma. A small portion of chondrosarcoma was also noted. Immunohistochemical analysis showed that HCC and the embryonal component of HB-like areas expressed alpha-fetoprotein (AFP) and cytokeratin 8. The small undifferentiated cells were negative for AFP but stained with cytokeratin 8 as well as CD56, which is a marker of primitive cells in many sarcoma and HB. It is not certain whether small undifferentiated cells belong to hepatic progenitor cells or primitive mesenchymal cells. Polymerase chain reaction-single-strand conformation polymorphism analysis for beta-catenin mutation using microdissection revealed no mutation of any components. A review was undertaken of the cases previously reported as adult hepatoblastoma without detailed immunohistochemical study and consider many of them may be sarcomatoid HCC. These primitive and sarcomatoid components would be arising from the dedifferentiation process of HCC.
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PMID:Sarcomatoid hepatocellular carcinoma with hepatoblastoma-like features in an adult. 1514 5

The fragility of the evidence for SV40 association with human cancer is seen in studies of NHL. A publication in 1999 stated that SV40 is rarely present in NHL. In 2002, two laboratories reported SV40 sequences in 42% to 43% of cases of NHL . One of these laboratories also detected SV40 sequences in small proportions of pediatric tumors (e.g., Wilm's tumor, hepatoblastoma, rhabdomyosarcoma, medulloblastoma, osteosarcoma, and retinoblastoma) and adult carcinomas (e.g., lung, colon, breast, and prostate) These positive results were not confirmed in subsequent studies published in 2003. Capello et al and Mackenzie et al failed to detect SV40 sequences in NHL tissues. Sanjose et al examined sera from patients with NHL and from controls for antibodies reactive to SV40 VLPs, and they detected no significant differences between the two groups. The association of SV40 with NHL is in doubt. An etiologic link between a virus and a cancer becomes plausible when evidence from different lines of enquiry (e.g., epidemiology, pathogenesis, and molecular mechanisms) is mutually reinforcing and together provides a coherent picture that can connect the biology the virus to the characteristics of the disease. The associations of human papillomaviruses with cervical cancer and hepatitis B and C viruses with hepatocellular carcinoma are examples in which the etiologic link is clear. With SV40 and mesothelioma, the data on viral sequences in tumors is inconsistent and disputed, and serologic evidence does not support any association. The epidemiologic data do not show that documented exposures tt SV40 increase the risk of mesothelioma. It seems improbable that a single virus (which cannot be conclusively demonstrated to be present in the community) contributes to the development of such a wide variety of tumors, spanning all age groups and histologic types. The weaknesses in the evidence linking SV40 with mesothelioma are summarized in Box 11 It seems unlikely that infection with SV40 contributes to the development of human mesothelioma or any other human cancer.
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PMID:Causality of mesothelioma: SV40 question. 1555 56

No more than 11 cases of carcinosarcoma of the liver have been reported in the past 40 years that fulfill the definition of hepatocellular carcinoma combined with differentiated sarcomatous elements. Most cases consist of hepatocellular carcinoma with 1 to 2 heterologous elements. We report a case of a 51-year-old woman with liver carcinosarcoma consisting of 3 carcinomatous components and 4 sarcomatous components. Hepatocellular carcinoma, fibrolamellar type, was accompanied by neuroendocrine carcinoma (neuron-specific enolase and synaptophysin positive) and adenocarcinoma (cytokeratin 7 and 20 positive). The sarcomatous elements consisted of poorly differentiated spindle cell neoplasm (vimentin positive), leiomyosarcoma (smooth muscle actin positive), rhabdomyosarcoma (desmin positive), and osteosarcoma. To our knowledge, this is the first case of liver carcinosarcoma with this many differentiated heterologous features. There are differing views on the pathogenesis of this tumor. Findings in this case support the view that metaplasia of carcinomatous cells gives rise to the sarcomatous elements.
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PMID:Carcinosarcoma of the liver: a case report and review of the literature. 1591 31

Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors.
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PMID:Toward the definition of immunosuppressive regimens with antitumor activity. 1596 62

Two new benzopyrans 6-[1'-oxo-3'(R)-hydroxy-butyl]-5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran (1) and 6-[1'-oxo-3'(R)-methoxy-butyl]-5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran (2) were isolated from the leaves of Mallotus apelta Muell.-Arg., (Euphorbiaceae). Their chemical structures were elucidated by spectroscopic analyses, especially by 1 D-, 2D-NMR and MS spectra. Compound 1 was found to have strong cytotoxic effect against two human cancer cell lines as human hepatocellular carcinoma (Hep-2, IC50: 0.49 microg/mL) and rhabdosarcoma (RD, IC50: 0.54 microg/mL), while compound 2 showed moderate activity against Hep-2 cell line (IC50, 4.22 microg/mL) by in vitro assay.
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PMID:New cytotoxic benzopyrans from the leaves of Mallotus apelta. 1627 67


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