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)

Using the differential display method to analyze mRNA expression in hepatocellular carcinoma (HCC) and nontumor livers, we cloned a full-length cDNA of 2263 bp, which was designated GTR2-2 and was identical with MXR7. The MXR7 mRNA was detected in 143 of 191 (74.8%) primary and recurrent HCCs taken from 154 patients but only in 5 (3.2%) nontumor livers. MXR7 mRNA was detected in one of two hepatoblastomas but not in hepatocellular adenoma, cholangiocarcinoma, or metastatic carcinomas to the liver. In human cancer of other anatomical sites, MXR7 mRNA was detected in low levels in one Wilms' tumor and in 4 of 40 gastric adenocarcinomas but not in several other types of cancer and 21 nonhepatocellular human tumor cell lines examined. MXR7 mRNA was expressed in high levels in the placenta, fetal liver, lung, and kidney, but it was undetectable in adult liver and was expressed in very low levels in adult lung and kidney. Our observations suggest that the MXR7 gene is regulated developmentally and expressed preferentially in HCC. To study its potential biological significance, we selected 113 patients who had unicentric primary HCC and had been followed for more than 4 years for further analysis. The MXR7 mRNA expression correlated closely with elevated serum alpha-fetoprotein (AFP) levels (88 versus 55%; P = 0.0001) and with expression of AFP mRNA (87 versus 55%; P = 0.005) and CD24 mRNA in HCC (80 versus 50%; P < 0.04), high tumor grade (76 versus 56%; P = 0.05), and tumor invasion (76 versus 55%; P < 0.05), but not with patient outcome. In HCC < or =3 cm, the frequency (77%) of MXR7 mRNA expression was significantly higher than that of elevated serum AFP (43%; P < 0.007) and AFP mRNA expression in HCC (41%; P < 0.004). Thus, MXR7 may serve as a sensitive early tumor marker for HCC and warrants more study to better understand its biological function.
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PMID:Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution. 937 21

AIM:To clone and identify the whole cDNA of MXR7 gene and to find out its expression in human HCC, and normal tissues.METHODS:The DNA primers were designed and synthesized according to the whole cDNA sequence of MXR7 gene. The cDNA of human HCC was taken as the template while the cDNA of MXR7 gene was synthesized by polymerase chain reaction (PCR). Recombinant DNA conforming to reading frame was constructed by connecting purified PCR product of the cDNA of MXR7 gene with expression vector pGEX-5X-1 of fusion protein. The plasmid MXR7/pGEX-5X-1 was identified by sequencing. Using (32)P labeled MXR7 cDNA as probe, MXR7 mRNA expression was detected by Northern blot analysis in 12 different human normal tissues, 7 preoperatively untreated non-liver tumor tissues, 30 preoperatively untreated HCC, the paracancerous liver tissues and 12 normal liver tissues samples.RESULTS:Restriction enzyme and sequence analysis confirmed that the insertion sequence in vector pGEX-5X-1 was the same as the cDNA sequence of MXR7 gene. Northern blot analysis showed no expression of MXR7 mRNA in 12 kinds of normal human tissues including liver, 7 tumor tissues in other sites and 12 normal liver tissues, the frequencies of MXR7 mRNA expression in HCC and paracancerous liver tissues were 76.6% and 13.3%, respectively. The frequency of MXR7 mRNA expression in HCC without elevation of serum AFP and in HCC <5cm was 90% (9/10) and 83.3% (5/6), respectively.CONCLUSION:MXR7 mRNA is highly expressed in human HCC, which is specific and occurs at an early stage of HCC, suggesting MXR7 mRNA can be a tumor biomarker for HCC. The detection of MXR7 mRNA expression in the biopsied liver tissue is helpful in discovering early subclinical liver cancer in those with negative serum AFP.
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PMID:Cloning and expression of MXR7 gene in human HCC tissue. 1181 23

Glypican-3 (GPC3) encodes a cell-surface heparan-sulfate proteoglycan mutated in type 1 Simpson-Golabi-Behmel syndrome (SGBS1), an X-linked overgrowth syndrome. The phenotype of SGBS1 patients and of GPC3 knockout mice suggests that GPC3 plays a negative role in cell proliferation, and an apoptosis-inducing role in specific tissues. Ectopic expression of GPC3 in some cell lines has supported the idea that GPC3 inhibits cell growth. Here we report that blocking endogenous GPC3 expression with an antisense transcript promotes the growth of Hep G2 and Hep 3B hepatoma cell lines. Moreover, antisense inhibition releases Hep 3B cells from cell cycle arrest. Hence, our data further support the notion that GPC3 is an inhibitor of cell proliferation and demonstrate that it modulates cell cycle progression.
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PMID:Blocking endogenous glypican-3 expression releases Hep 3B cells from G1 arrest. 1287 92

The fasting-induced adipose factor (FIAF, ANGPTL4, PGAR, HFARP) was previously identified as a novel adipocytokine that was up-regulated by fasting, by peroxisome proliferator-activated receptor agonists, and by hypoxia. To further characterize FIAF, we studied regulation of FIAF mRNA and protein in liver and adipose cell lines as well as in human and mouse plasma. Expression of FIAF mRNA was up-regulated by peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARbeta/delta agonists in rat and human hepatoma cell lines and by PPARgamma and PPARbeta/delta agonists in mouse and human adipocytes. Transactivation, chromatin immunoprecipitation, and gel shift experiments identified a functional PPAR response element within intron 3 of the FIAF gene. At the protein level, in human and mouse blood plasma, FIAF was found to be present both as the native protein and in a truncated form. Differentiation of mouse 3T3-L1 adipocytes was associated with the production of truncated FIAF, whereas in human white adipose tissue and SGBS adipocytes, only native FIAF could be detected. Interestingly, truncated FIAF was produced by human liver. Treatment with fenofibrate, a potent PPARalpha agonist, markedly increased plasma levels of truncated FIAF, but not native FIAF, in humans. Levels of both truncated and native FIAF showed marked interindividual variation but were not associated with body mass index and were not influenced by prolonged semistarvation. Together, these data suggest that FIAF, similar to other adipocytokines such as adiponectin, may partially exert its function via a truncated form.
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PMID:The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment. 1519 76

Expression profiling of hepatocellular carcinoma has demonstrated that glypican 3 (GPC3), a heparan sulfate proteoglycan anchored to the membrane, is expressed at a markedly elevated level in hepatocellular carcinoma. In this paper, two monoclonal antibodies against GPC3, GPC3-C02 and A1836A, were confirmed to specifically recognize GPC3 molecule in cells from hepatocellular carcinoma and hepatoblastoma cell lines by immunoblotting, and both were confirmed to recognize different epitopes of the GPC3 molecule by epitope mapping. Then, we evaluated the feasibility of GPC3-immunohistochemistry in the pathological diagnosis of benign and malignant hepatocellular lesions by applying these monoclonal antibodies to formalin-fixed and paraffin-embedded specimens. The immunoreactivity turned out to be identical in the two monoclonal antibodies and was thus confirmed to represent the actual expression of the GPC3 molecule. The expression was observed in the fetal liver, but not in normal adult liver, liver cirrhosis or hepatitis except for a tiny focus of a regenerative nodule of fulminant hepatitis. Diffusely positive staining of GPC3 was observed in malignant hepatocytes in hepatoblastomas and in hepatocellular carcinomas (47/56, 84%). GPC3 expression was independent of the differentiation and size of the hepatocellular carcinoma. On the other hand, there was only weak and focal staining in low-grade (2/8) and high-grade dysplastic nodules (6/8). GPC3 immunoreactivity was detected in only one of 23 metastatic lesions of colorectal carcinoma, and its expression was entirely absent in the liver cell adenoma (0/7), carcinoid tumor (0/1), and cholangiocellular carcinoma (0/16). When compared with immunohistochemistry of hepatocyte antigen and alpha-fetoprotein, GPC3-immunohistochemistry was significantly much more specific and sensitive for hepatocellular carcinomas. Thus, GPC3 was confirmed to be one of the oncofetal proteins now attracting attention for their promise both as markers of hepatocellular carcinoma in routine histological examination and as targets in monoclonal antibody-based hepatocellular carcinoma therapy.
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PMID:The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. 1592 May 46

The patients with hepatitis B or C based liver cirrhosis are at high risk for developing Hepatocellular carcinoma (HCC), and HCC patients treated surgically or by other therapies are also at high risk for recurrence. As a result, the prognosis of HCC remains poor, and new therapies for the prevention of cancer development and recurrence are urgently needed. We previously reported that glypican 3 (GPC3) was over expressed specifically in HCC. In this report, we found the HLA-A2 or HLA-A24 restricted GPC3 epitope peptide, and investigated whether these peptides could induce GPC3 reactive CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A2+ or HLA-A24+ HCC patients. We used HLA-A2.1 (HHD) transgenic mice (Tgm) to identify the HLA-A2-restricted GPC3 epitopes. We found that these epitope peptides could induce peptide-reactive CTLs in about 50% of HLA A2+ or HLA-A24+, and GPC3+ HCC patients. Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for prevention of cancer development and recurrence of HCC.
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PMID:[Possibilities of glypican-3-specific immunotherapy for hepatocellular carcinoma]. 1721 93

The differential diagnosis between hepatocellular carcinoma (HCC) and regenerative liver nodules and other primary liver tumors may be very difficult, particularly when performed on liver biopsies. Difficulties in histological typing may be often minimized by immunohistochemistry. Among the numerous markers proposed, CK18, Hep Par1 and glypican 3 (GPC3) are considered the most useful in HCC diagnosis. Here we report a case of HCC in a 72-year-old male with HBV-related chronic liver disease, characterized by a marked morphological and immunohistochemical intratumoral variability. In this case, tumor grading ranged from areas extremely well differentiated, similar to regenerative nodule, to undifferentiated regions, with large atypical multinucleated cells. While almost all sub nodules were immunostained by Hep Par 1, immunoreactivity for glypican 3 and for Ck18 was patchy, with negative tumor region adjacent to the highly immunoreactive areas. Our case stresses the relevance of sampling variability in the diagnosis of HCC, and indicates that caution should be taken in grading an HCC and in the interpretation of immunohistochemical stains when only small core biopsies from liver nodules are available.
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PMID:Intratumoral sampling variability in hepatocellular carcinoma: a case report. 1766 22

Glypican 3 is an oncofetal antigen that shows great promise as an adjunct to the diagnosis of hepatocellular carcinoma. To investigate whether glypican 3 might also appear in nonneoplastic liver cells, we performed immunostains on 60 biopsies of chronic hepatitis C, 30 with low-grade activity and 30 with high-grade activity. Glypican 3 immunoreactivity was detected in 25 (83.6%) of 30 in the high-grade but in none in the low-grade group. In 20% of the positive cases, glypican 3 produced strong cytoplasmic staining of more than 25% of hepatocytes and could potentially lead to a misdiagnosis of hepatocellular carcinoma. Pathologists should be aware of this phenomenon and exercise caution in interpreting biopsies or other specimens of suspected hepatocellular carcinoma when active necroinflammatory disease is present.
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PMID:Glypican-3 expression in benign liver tissue with active hepatitis C: implications for the diagnosis of hepatocellular carcinoma. 1794 78

Several studies have shown that glypican 3 (GPC3) could be a useful diagnostic marker for hepatocellular carcinoma (HCC) and for differentiating HCC from nonneoplastic and preneoplastic liver disease. To systematically investigate the epidemiology of GPC3 expression in the liver and in other organs and tissues, we used tissue microarray technology comprising 4,387 tissue samples from 139 tumor categories and 36 nonneoplastic and preneoplastic tissue types. The immunohistochemical expression of GPC3 was assessed semiquantitatively using a 10% cutoff score and was detected in 9.2% of nonneoplastic liver samples (11/119), 16% of preneoplastic nodular liver lesions (6/38), and 63.6% of HCCs (140/220), underlining the role of GPC3 in hepatocarcinogenesis. Furthermore, several other tumors revealed consistent expression of GPC3, including squamous cell carcinoma of the lung (27/50 [54%]), testicular nonseminomatous germ cell tumors (32/62 [52%]), and liposarcoma (15/29 [52%]).
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PMID:Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples. 1848 6

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. HCC occurs mainly in chronically diseased livers, e.g. following hepatitis B and C infection. These high-risk patients are closely followed up, and increasing numbers of small equivocal lesions are detected by imaging diagnosis. They are now widely recognized as precursor or early-stage HCCs and are classified as dysplastic nodule or early HCC. These lesions lack typical imaging and histology of ordinary HCC and do not show elevated serum markers of alpha-fetoprotein and PIVKA-II, for example. Molecular analysis of these lesions would help to develop molecular markers for objective histological diagnosis of early HCC and possibly new serum markers for early detection of HCC. It has been reported that HSP70, CAP2, glypican 3 and glutamine synthetase could serve as molecular markers for early HCC. Further analysis is expected to evaluate their usefulness in routine pathological diagnosis including biopsy diagnosis and also as serum markers for early detection of HCC.
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PMID:Candidate molecular markers for histological diagnosis of early hepatocellular carcinoma. 1854 47


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