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)

The MAGE-1 gene, originally isolated from a human melanoma cell line, directs the expression of a potential tumor-rejection antigen, MZ2-E. This antigen is recognized by autologous cytotoxic T lymphocytes in association with a major histocompatibility complex class I molecule (HLA-A1), and has provided a basis for specific immunotherapy for melanoma patients. Here we show a high frequency of expression of the MAGE-1 gene in hepatocellular carcinoma (HCC). We examined the expression of the MAGE-1 gene in cell lines originated from hepatoma cells and in tumor and nontumor tissues of livers with HCC by reverse-transcription polymerase chain reaction (RT-PCR) and subsequent Southern blotting. MAGE-1 messenger RNA (mRNA) was expressed in three of four HCC cell lines (75%) and in 16 of 20 (80%) resected HCCs though none was detected in nontumor tissues. The high frequency expression of MAGE-1 gene in HCCs suggests the possibility as a target for tumor-specific immunotherapy for HCC patients.
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PMID:High frequency of the MAGE-1 gene expression in hepatocellular carcinoma. 893 77

Serological analysis of recombinant cDNA expression libraries (SEREX) using tumor mRNA and autologous patient serum provides a powerful approach to identify immunogenic tumor antigens. We have applied this methodology to a case of esophageal squamous cell carcinoma and identified several candidate tumor targets. One of these, NY-ESO-1, showed restricted mRNA expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma. NY-ESO-1 encodes a putative protein of Mr 17,995 having no homology with any known protein. The pattern of NY-ESO-1 expression indicates that it belongs to an expanding family of immunogenic testicular antigens that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. These antigens, initially detected by either cytotoxic T cells (MAGE, BAGE, GAGE-1) or antibodies [HOM-MEL-40(SSX2), NY-ESO-1], represent a pool of antigenic targets for cancer vaccination.
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PMID:A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. 905 Aug 79

The human melanoma antigen (MAGE) gene family encode tumor-specific antigens recognized by autologous cytotoxic T lymphocytes. Some of these antigens may be potentially useful for cancer-specific immunotherapy. The expression of MAGE genes has been reported not only in melanoma but also in various other malignant tumors. However, little is known about the expression of these genes in human hepatocellular carcinoma (HCC). We therefore analyzed, by means of a reverse transcription-polymerase chain reaction (RT-PCR), the expression of MAGE-1, MAGE-2, and MAGE-3 genes in 60 tissue samples resected from HCCs. The MAGE-1, MAGE-2, and MAGE-3 genes were expressed in 18 (30.0%), 9 (15.0%), and 15 (25.0%), respectively, of the 60 tumor-tissue samples. Nineteen (31.7%) samples expressed at least one of the three MAGE genes, and 8 (13.3%) expressed all three genes. In contrast, none of the MAGE genes was expressed in any of the 60 adjacent non-tumorous liver samples. The age of patients was significantly older in at least one MAGE-positive group (MAGE-positive groups) than in the MAGE-negative ones (p<0.05). The tumor size was significantly larger in MAGE-positive groups than in the negative ones (p<0.05). The serum alpha-fetoprotein level was significantly lower in MAGE-positive groups than in negative ones (p<0.05). Patients with tumors expressing at least one MAGE gene showed a better recurrence-free survival rate than those with tumors showing no MAGE gene expression (p<0.05). These results indicated that the MAGE genes were exclusively expressed in cancerous tissues of a considerable proportion of patients affected by HCC, and that some of these patients might be potential candidates for tumor-specific immunotherapy using the MAGE encoded antigens.
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PMID:Expression of MAGE genes and survival in patients with hepatocellular carcinoma. 1056 32

MAGE gene family encodes peptides recognized by autologous cytotoxic T lymphocytes in a major histocompatibility complex (MHC) class-I restricted fashion. In the present study, we have performed reverse-transcription polymerase chain reaction (RT-PCR) for the genes, as well as immunohistochemical analysis and Western blotting of MAGE-1 and -3 proteins in 33 surgically resected hepatocellular carcinomas (HCCs). MAGE-1 and -3 mRNAs were constitutively expressed exclusively in 78 and 42% of HCCs respectively. On immunohistochemistry with monoclonal antibodies, 77B for MAGE-1 and 57B for MAGE-3, MAGE-1 and -3 proteins were recognized in cytoplasm of only six among 33 (18%) and two of 29 HCCs (7%) respectively. The distribution pattern was mostly focal in HCC nodules. By contrast, the Western blot analysis revealed that the MAGE-1 (46 kDa) and -3 proteins (48 kDa) were expressed in 80 and 60% of 15 HCCs examined respectively. The proteins of MAGE-1 and -3 were also expressed exclusively in HCCs regardless of the histological grading and clinical staging. Our results indicate that the detection of the genes by RT-PCR or the proteins by Western blotting is useful for differentiating early HCCs from non-cancerous lesions, and that the peptides derived from MAGE-1 and -3 proteins might be suitable targets for immunotherapy of human HCC.
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PMID:Expression of MAGE-1 and -3 genes and gene products in human hepatocellular carcinoma. 1057 68

We investigated the expression of several candidate gene markers: MAGE-1, MAGE-3, cytokeratin-20 (CK-20), and alpha-fetoprotein (AFP) in tumor tissue and blood specimens from patients with hepatocellular carcinoma to develop a multiple marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for detection of micrometastasis in circulation. In 24 tumor specimens, the positivity for MAGE-1, MAGE-3, AFP, and CK-20 genes was 71, 67, 88, and 79% respectively, and all specimens expressed at least one marker. Although AFP and CK-20 transcripts were also detected in corresponding noncancerous liver specimens, none of the 22 corresponding normal specimens or seven normal livers were positive for MAGE-1 or MAGE-3 transcripts. In addition, MAGE-1 and MAGE-3 gene transcripts were not detected in any peripheral blood specimens from 31 normal healthy volunteers. MAGE-1, MAGE-3, and AFP transcripts were detected in 9 (12.7%), 3 (4.8%), and 10 (15.9%) of 71 blood specimens from 11 hepatocellular carcinoma patients, respectively, while 19 specimens (26.8%) were positive for at least one marker. Our results indicate that a multimarker RT-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a liver-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients with better sensitivity and specificity.
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PMID:Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma. 1096 17

The members of MAGE gene family are highly expressed in human hepatocellular carcinoma (HCC). In the present study, we tested the tumour-specific MAGE-1 and MAGE-3 transcripts in the peripheral blood of HCC patients by nested RT-PCR to detect the circulating tumour cells and evaluate their potential clinical implication. Of 30 HCC patients, the positive rate of MAGE-1 and MAGE-3 transcripts was 43.3% (13 out of 30) and 33.3% (10 out of 30) in PBMC samples, whilst the positive rate was 70% (21 out of 30) and 53.3% (16 out of 30) in the resected HCC tissue samples, respectively. The positivity for at least one MAGE gene transcript was 63.3% (19 out of 30) in PBMC samples of HCC patients and 83.3% (25 out of 30) in the resected HCC tissue samples. MAGE-1 and/or MAGE-3 mRNA were not detected in the PBMC of those patients from whom the resected HCC tissues were MAGE-1 or MAGE-3 mRNA negative, nor in the 25 PBMC samples from healthy donors. The detection of MAGE transcripts in PBMC was correlated with the advanced stages and tumour size of the HCC, being 82.4% (14 out of 17) in tumour stages III and IVa, 56.6% (five out of nine) in stage II, and null (nought out of four) in stage I. The serum alpha-FP in 33.3% (10 out of 30) of HCC patients was normal or slightly elevated (< 40 ng ml(-1)). However, six of these 10 patients (alpha-FP < 40 ng ml(-1)) were MAGE-1 and /or MAGE-3 mRNA positive in their PBMC. The follow-up survey of MAGE mRNA in PBMC was performed in 12 patients. Seven patients with persistent MAGE-1 and/or MAGE-3 mRNA positive or from negative turned to positive died because of metastasis and/or recurrence. In striking contrast, all four patients with MAGE-1 and/or MAGE-3 mRNA from positive turned to negative and one patient with persistent MAGE-3 transcript negative are alive after last test. Collectively, detection of MAGE transcripts with follow-up survey in PBMC is a feasible and reliable assay for the early prediction of the relapse and prognosis of the HCC patients.
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PMID:Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells. 1185 21

Hepatocellular carcinoma ranks among the most common malignancies in Southeast Asia and South Africa. Although there are many modalities of treatment, the recurrence and metastasis rates are high, and the prognosis is unsatisfactory. Gankyrin, a recently found oncoprotein, is a promising target for drug therapy because it is overexpressed in all studied hepatocellular carcinomas. Gankyrin contains six ankyrin repeats and interacts with Rb, Cdk4, and the S6 ATPase of the 26 S proteasome. In this study, a yeast two-hybrid screen with gankyrin has identified MAGE-A4 as another interacting protein. The interaction, mediated by the C-terminal half of MAGE-A4, was reproduced in mammalian cells. The interaction was specific to MAGE-A4, because other MAGE family proteins structurally similar to MAGE-A4, i.e. MAGE-A1, MAGE-A2, and MAGE-A12, did not bind to gankyrin. MAGE-A4 partially suppressed both anchorage-independent growth in vitro and tumor formation in athymic mice of gankyrin-overexpressing cells. The ability of mutant MAGE-A4 to interact with gankyrin correlated with the ability to suppress the anchorage-independent growth. These results demonstrate that MAGE-A4 binds to gankyrin and suppresses its oncogenic activity. So far, the major focus of studies on the MAGE proteins has been on their potential for cancer immunotherapy. Our results may also shed light on novel functions for MAGE-A proteins.
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PMID:MAGE-A4 interacts with the liver oncoprotein gankyrin and suppresses its tumorigenic activity. 1252 3

Cancer-testis (CT) genes are expressed in a variety of human cancers, but not in normal tissues except for testis, and represent promising targets for immunotherapy and gene therapy. We investigated the expression of 10 CT genes (MAGE-1, MAGE-3, MAGE-4, GAGE, NY-ESO-1, SSX-1, HOM-MEL-40/SSX-2, SSX-4, HOM-TES-14/SCP-1, and HOM-TES-85) in 21 hepatocellular carcinoma (HCC) biopsy specimens. The most frequently expressed CT genes were SSX-1 and GAGE, which were found in 8/21 (38%) HCC samples, followed by HOM-TES-14/SCP-1 (6/21 or 29%), MAGE-3 (5/21 or 24%), HOM-TES-85 and MAGE-1 (4/21 or 19% each), whereas SSX-4 and HOM-MEL-40/SSX-2 were only expressed in 2/21 cases each, MAGE-4 in one case, and NY-ESO-1 not at all. Of the 21 HCC cases investigated, only four did not express any of the CT genes tested, 17 (81%) expressed at least one, 9 (43%) coexpressed two, four (19%) coexpressed four, three (14%) coexpressed five and one coexpressed 8 of the 10 CT genes tested. We conclude that a majority of HCC cases might be amenable to specific immunotherapeutic interventions. However, the identification of additional tumor-specific antigens with a frequent expression in HCCs is warranted to develop widely applicable, polyvalent HCC vaccines.
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PMID:Expression of cancer-testis genes in human hepatocellular carcinomas. 1274 56

MAGE is a family of genes specifically associated to human melanoma, but also found in hepatocellular carcinoma (HCC). In this study we evaluated the expression of such genes in 41 HCC patients, their correlation with pathological and clinical aspects of cancer, and the impact on prognosis. MAGE are expressed in most of HCC samples (28/41), no correlation was found with type and stage but they may be used as potential target for IT.
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PMID:[Gene expression of the MAGE-1, -3, and -6 antigens in hepatic carcinoma]. 1290 61

MAGE-n is a new member of MAGE gene family and has been demonstrated closely associated with hepatocellular carcinoma (HCC). In this study, MAGE-n-derived peptide-specific cytotoxic T lymphocytes (CTL) were induced from the peripheral blood mononuclear cells of healthy donors by multiple stimulations with HLA-A2-restricted MAGE-n peptide-pulsed T2 cells. The induced CTLs exhibited specific lysis against T2 cells pulsed with the peptide and HLA-A2+ HCC cells expressing MAGE-n, while HLA-A2+ HCC cell lines that did not express MAGE-n could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-MHC class I monoclonal antibody. These results suggested the MAGE-n peptide could be a potential target of specific immunotherapy for HLA-A2 patients with HCC.
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PMID:Efficient induction of cytotoxic T lymphocytes specific to hepatocellular carcinoma using HLA-A2-restricted MAGE-n peptide in vitro. 1521 45


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