18 results on '"Mitsuro, Kanda"'
Search Results
2. The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy
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Haruyoshi Tanaka, Chie Tanaka, Mitsuro Kanda, Suguru Yamada, Goro Nakayama, Hiroyuki Sugimoto, Masamichi Hayashi, Dai Shimizu, Masahiko Koike, Tsutomu Fujii, Daisuke Kobayashi, Naoki Iwata, Yasuhiro Kodera, Michitaka Fujiwara, Masahiro Shibata, and Hideki Takami
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Male ,0301 basic medicine ,Oncology ,Protein-Arginine N-Methyltransferases ,Cancer Research ,medicine.medical_treatment ,Cell ,Fluorescent Antibody Technique ,Kaplan-Meier Estimate ,Polymerase Chain Reaction ,0302 clinical medicine ,oncogene ,protein arginine methyltransferase 5 ,Aged, 80 and over ,Protein arginine methyltransferase 5 ,Liver Neoplasms ,Articles ,hepatocellular carcinoma ,Middle Aged ,Cell cycle ,Prognosis ,Phenotype ,Treatment Outcome ,medicine.anatomical_structure ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,biomarker ,Female ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Blotting, Western ,Biology ,03 medical and health sciences ,Cell Line, Tumor ,Internal medicine ,expression ,Biomarkers, Tumor ,medicine ,Hepatectomy ,Humans ,neoplasms ,Aged ,Oncogene ,Cancer ,medicine.disease ,Molecular medicine ,digestive system diseases ,030104 developmental biology ,Cancer research - Abstract
The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC.
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- 2017
3. Adherens junctions associated protein 1 serves as a predictor of recurrence of squamous cell carcinoma of the esophagus
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Suguru Yamada, Satoshi Sueoka, Hiroyuki Sugimoto, Kazuhiro Ezaka, Haruyoshi Tanaka, Ryoji Hashimoto, Naoki Iwata, Goro Nakayama, Chie Tanaka, Yasuhiro Kodera, Yuri Tanaka, Tsutomu Fujii, Mitsuro Kanda, Masahiko Koike, Hideki Takami, Michitaka Fujiwara, and Dai Shimizu
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Adult ,Male ,Cancer Research ,Esophageal Neoplasms ,Biology ,Disease-Free Survival ,Adherens junction ,Ezrin ,Transcription (biology) ,Cell Line, Tumor ,Biomarkers, Tumor ,Humans ,RNA, Messenger ,Promoter Regions, Genetic ,Gene ,Aged ,Oncogene ,Promoter ,DNA Methylation ,Middle Aged ,Cell cycle ,Gene Expression Regulation, Neoplastic ,Oncology ,DNA methylation ,Carcinoma, Squamous Cell ,Cancer research ,CpG Islands ,Female ,Esophageal Squamous Cell Carcinoma ,Neoplasm Recurrence, Local ,Cell Adhesion Molecules - Abstract
Esophageal squamous cell carcinoma (ESCC), the most common esophageal cancer in East Asia, is among the six cancers with the highest fatality rates worldwide. Unfortunately, multidisciplinary treatment strategies have not achieved satisfactory outcomes. Therefore, novel insights into the molecular biology of ESCC are required to improve treatment. The gene encoding the transmembrane adherens junctions-associated protein-1 (AJAP1) expressed by epithelial cells resides in chromosome 1p36, which is frequently lost or epigenetically silenced in several malignancies. Here, we investigated the expression levels and regulatory mechanism of AJAP1 transcription. We determined the levels of AJAP1 mRNA and the genes encoding potentially interacting proteins expressed by ESCC cell lines, as well as the chromosomal copy number of AJAP1 and the methylation status of its promoter region. AJAP1 mRNA levels of 78 pairs of surgically resected specimens were determined to evaluate the association of AJAP1 expression and clinicopathological factors. Nine ESCC cell lines differentially expressed AJAP1 mRNA, and demethylation of hypermethylated AJAP1 genomic DNA reactivated AJAP1 mRNA expression. The copy number of sequences upstream or downstream of the AJAP1 transcriptional start site was not detectably altered. AJAP1 mRNA levels correlated inversely with those of ezrin (EZR) and were significantly lower in ESCC tissues compared with adjacent normal tissues. AJAP1 mRNA levels decreased gradually with increasing tumor stage. Patients with downregulated AJAP1 transcription were more likely to experience shorter overall and disease-free survival. Multivariate analysis of disease-free survival identified downregulated AJAP1 transcription as an independent prognostic factor. These results suggest that in ESCC, AJAP1 acts as a putative tumor suppressor and that AJAP1 transcription is regulated by promoter hypermethylation. These findings indicate that downregulated AJAP1 transcription may serve as a novel tumor biomarker to predict recurrence of ESCC after esophagectomy.
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- 2015
4. Effectiveness of plasma treatment on pancreatic cancer cells
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Hiroaki Kajiyama, Goro Nakayama, Hiroyuki Sugimoto, Michitaka Fujiwara, S. Takeda, Norifumi Hattori, Suguru Yamada, Tsutomu Fujii, Masahiko Koike, Masaru Hori, Masaaki Mizuno, Hiromasa Tanaka, Shuji Nomoto, Yasuhiro Kodera, Mitsuro Kanda, Koji Torii, and Kae Nakamura
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Cancer Research ,Pathology ,medicine.medical_specialty ,Plasma Gases ,pancreatic cancer ,Cell ,xenograft model antitumor assays ,Biology ,Mice ,In vivo ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,Cell Proliferation ,Cell Nucleus ,reactive oxygen species ,Cell growth ,apoptosis ,Cancer ,Articles ,Cell cycle ,medicine.disease ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Oncology ,Apoptosis ,Cell culture ,non-thermal atmospheric pressure plasma ,Cancer research - Abstract
Non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. We explored the indirect effect of NEAPP through plasma-activated medium (PAM) on pancreatic cancer cells in vitro and in vivo. In this study, four pancreatic cancer cell lines were used and the antitumor effects of PAM treatment were evaluated using a cell proliferation assay. To explore functional mechanisms, morphological change and caspase-3/7 activation in cells were also assessed. Furthermore, reactive oxygen species (ROS) generation in cells was examined and N-acetyl cysteine (NAC), an intracellular ROS scavenger, was tested. Finally, the antitumor effect of local injection of PAM was investigated in a mouse xenograft model. We found that PAM treatment had lethal effect on pancreatic cancer cells. Typical morphological findings suggestive of apoptosis such as vacuolization of cell membranes, small and round cells and aggregation of cell nuclei, were observed in the PAM treated cells. Caspase-3/7 activation was detected in accordance with the observed morphological changes. Additionally, ROS uptake was observed in all cell lines tested, while the antitumor effects of PAM were completely inhibited with NAC. In the mouse xenograft model, the calculated tumor volume on day 28 in the PAM treatment group was significantly smaller compared with the control group [28 ± 22 vs. 89 ± 38 (mm(3) ± SD), p=0.0031]. These results show that PAM treatment of pancreatic cancer might be a promising therapeutic strategy.
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- 2015
5. B-cell translocation gene 1 serves as a novel prognostic indicator of hepatocellular carcinoma
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Mitsuro Kanda, Hiroyuki Sugimoto, Ryoji Hashimoto, Suguru Yamada, Goro Nakayama, S. Nomoto, Yasuhiro Kodera, Yukiyasu Okamura, Hisaharu Oya, Michitaka Fujiwara, Soki Hibino, Dai Shimizu, Masahiko Koike, Tsutomu Fujii, and Hideki Takami
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Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cell ,Kaplan-Meier Estimate ,Biology ,medicine.disease_cause ,Downregulation and upregulation ,Biomarkers, Tumor ,medicine ,Humans ,Promoter Regions, Genetic ,Aged ,Aged, 80 and over ,Regulation of gene expression ,Oncogene ,Cell growth ,Liver Neoplasms ,Hep G2 Cells ,Hematology ,DNA Methylation ,Middle Aged ,Cell cycle ,Microarray Analysis ,Prognosis ,medicine.disease ,Molecular biology ,digestive system diseases ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Reverse transcription polymerase chain reaction ,medicine.anatomical_structure ,Oncology ,Hepatocellular carcinoma ,DNA methylation ,Cancer research ,Female ,Carcinogenesis ,BTG1 - Abstract
Aim: Although B-cell translocation gene 1 (BTG1) plays an important role in apoptosis and negatively regulates cell proliferation, BTG1 expression in hepatocellular carcinoma (HCC) has not been evaluated. The aim of this study was to clarify the role of BTG1 in the initiation of HCC carcinogenesis and progression. Methods: BTG1 mRNA expression levels were determined for HCC cell lines and 151 surgical specimen pairs using a quantitative real-time reverse transcription polymerase chain reaction assay. The mutational and methylation statuses of HCC cell lines were analyzed via high-resolution melting analysis and direct sequencing analysis to explore the regulatory mechanisms of BTG1 expression. The expression and distribution of the BTG1 protein in liver tissues were evaluated using immunohistochemistry. Results: Decreased expression of BTG1 mRNA was confirmed in the majority of HCC cell lines (89%) and clinical HCC tissues (85%) compared with non-cancerous liver tissues. Mutations or promoter hypermethylation of BTG1 were not identified in HCC cell lines. BTG1 mRNA expression levels were not influenced by background liver status. The pattern of BTG1 protein expression was consistent with that of BTG1 mRNA. Downregulation of BTG1 mRNA in HCC was significantly associated with shorter disease-specific and recurrence-free survival rates. Multivariate analysis of disease-specific survival rates identified BTG1 mRNA downregulation as an independent prognostic factor for HCC (hazard ratio 2.12, 95% confidence interval 1.12 – 4.04, P = 0.022). Conclusions: Our results indicate that altered BTG1 expression might affect hepatocarcinogenesis and may represent a novel biomarker for HCC carcinogenesis and progression. Disclosure: All authors have declared no conflicts of interest.
- Published
- 2014
6. Downregulation of DENND2D by promoter hypermethylation is associated with early recurrence of hepatocellular carcinoma
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Hiroyuki Sugimoto, Yoshikuni Inokawa, Hideki Takami, Mitsuhiro Hishida, Yoko Nishikawa, Mitsuro Kanda, Tsutomu Fujii, Masaya Suenaga, Mikako Asai, Yasuhiro Kodera, Soki Hibino, Shuji Nomoto, Suguru Yamada, and Hisaharu Oya
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Adult ,Male ,Cancer Research ,Carcinoma, Hepatocellular ,Tumor suppressor gene ,Biology ,medicine ,Guanine Nucleotide Exchange Factors ,Humans ,Gene silencing ,Promoter Regions, Genetic ,Aged ,Aged, 80 and over ,Oncogene ,Tumor Suppressor Proteins ,Liver Neoplasms ,Hep G2 Cells ,DNA Methylation ,Middle Aged ,Cell cycle ,Prognosis ,medicine.disease ,Candidate Tumor Suppressor Gene ,Molecular biology ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Real-time polymerase chain reaction ,Oncology ,Hepatocellular carcinoma ,DNA methylation ,Cancer research ,Female ,Neoplasm Recurrence, Local - Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and its prognosis is poor. Novel targets for treating recurrence and progression along with associated biomarkers are urgently required. In this study, the expression and regulatory mechanism of DENN/MADD domain containing 2D (DENND2D) were investigated in an attempt to identify a tumor suppressor gene for HCC regulated by silencing through promoter hypermethylation. The levels of DENND2D expression in HCC cell lines and surgical specimens were determined using a quantitative polymerase chain reaction assay and the relationship between the expression levels of DENND2D mRNA and clinicopathological factors was evaluated. The expression and distribution of DENND2D were determined using immunohistochemistry. DNA methylation analysis was performed to determine the regulatory mechanisms of DENND2D expression in HCC. Most HCC cell lines (89%) and surgical specimens (78%) expressed lower levels of DENND2D mRNA compared with normal liver tissue. In contrast, there was no significant difference in the expression levels of DENND2D mRNA between normal tissues of HCC patients with and without cirrhosis. The expression patterns of DENND2D protein and mRNA were consistent. Patients with significantly lower levels of DENND2D mRNA in HCC tissues had remarkably earlier recurrences after hepatectomy and their prognosis worsened. The DENND2D promoter was methylated in eight out of nine HCC cell lines and DNA demethylation reactivated DENND2D mRNA expression. Hypermethylation of DENND2D was frequently detected in HCC tissues (75%) and was significantly associated with downregulation of DENND2D mRNA expression. DENND2D is a candidate tumor suppressor gene that is inactivated by promoter hypermethylation in patients with HCC and may serve as a novel biomarker of early recurrence of HCC.
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- 2013
7. Estrogen receptor 1 gene as a tumor suppressor gene in hepatocellular carcinoma detected by triple-combination array analysis
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Shin Takeda, Suguru Yamada, Goro Nakayama, Mitsuhiro Hishida, Yoko Nishikawa, Shuji Nomoto, Mitsuro Kanda, Yasuhiro Kodera, Daisuke Kobayashi, Masamichi Hayashi, Masahiko Koike, Chie Tanaka, Michitaka Fujiwara, Hiroyuki Sugimoto, Yukiyasu Okamura, Yoshikuni Inokawa, and Tsutomu Fujii
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Adult ,Male ,Cancer Research ,Candidate gene ,Carcinoma, Hepatocellular ,Tumor suppressor gene ,Biology ,Polymorphism, Single Nucleotide ,Cell Line, Tumor ,Gene expression ,medicine ,Humans ,Genes, Tumor Suppressor ,Promoter Regions, Genetic ,Aged ,Oligonucleotide Array Sequence Analysis ,Oncogene ,Liver Neoplasms ,Estrogen Receptor alpha ,DNA Methylation ,Middle Aged ,medicine.disease ,Molecular biology ,Candidate Tumor Suppressor Gene ,Gene Expression Regulation, Neoplastic ,Real-time polymerase chain reaction ,Oncology ,Hepatocellular carcinoma ,Female ,Transcriptome ,Estrogen receptor alpha - Abstract
Hepatocellular carcinoma (HCC) is one of the top five causes of cancer-related deaths worldwide. Recent developments in the treatment of HCC remain insufficient to cure unresectable disease or to prevent HCC. Consistent efforts are, therefore, needed to deepen understanding of pathogenesis of the disease. Genome-wide gene expression profile analyses can now detect various candidate genes that are modified by HCC. We have developed a new technique to identify tumor suppressor genes, triple-combination array analysis, which combines gene expression profiles, single nucleotide polymorphism and methylation arrays to identify genes with altered expression. Using HCC tissue samples, triple-combination array analysis was performed to identify a candidate tumor suppressor gene. Subsequently, samples from 48 HCC patients were subjected to quantitative polymerase chain reaction (qPCR) and methylation-specific PCR to further elucidate clinical relevance of the gene. Estrogen receptor 1 (ESR1) was detected as a candidate tumor suppressor gene. Of the 48 clinical samples, 40 (83.3%) showed ESR1 promoter hypermethylation. In 24 (50%) HCC samples, the expres- sion levels of the ESR1 gene was decreased by >90%. The decreased expression was significantly related to high liver damage score, pathological invasion of the intrahepatic portal vein, the size of tumor (>3 cm in diameter) and hepatitis B virus infection. The present study represents another example that triple-combination array is a convenient technique for detecting genes with altered expression in disease. The ESR1 gene was identified as a candidate tumor suppressor gene in HCC and further validation is warranted.
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- 2013
8. Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer
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Yasuhiro Kodera, Goro Nakayama, Masahiko Koike, Hiroyuki Sugimoto, Mitsuro Kanda, Masahiro Shibata, Daisuke Kobayashi, Naoki Iwata, Haruyoshi Tanaka, Michitaka Fujiwara, Chie Tanaka, Tsutomu Fujii, Masamichi Hayashi, Dai Shimizu, and Suguru Yamada
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0301 basic medicine ,Male ,Cancer Research ,Protein-Arginine N-Methyltransferases ,Cell ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,Peritoneal Neoplasms ,Cell Proliferation ,Gene knockdown ,Oncogene ,Protein arginine methyltransferase 5 ,Gene Expression Profiling ,Cancer ,Cell cycle ,medicine.disease ,Survival Analysis ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Cancer research ,Female ,Carcinogenesis - Abstract
Identification of novel gastric cancer (GC)-related molecules is necessary to improve management of patients with GC in both diagnostic and therapeutic aspects. The aim of the present study was to determine whether protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in the progression of GC and whether it serves as a novel diagnostic marker and therapeutic target. We conducted global expression profiling of GC cell lines and RNA interference experiments to evaluate the effect of PRMT5 expression on the phenotype of GC cells. We analysed tissues of 179 patients with GC to assess the association of PRMT5 mRNA levels with clinicopathological factors. Differential expression of PRMT5 mRNA by GC cell lines correlated positively with the levels of GEMIN2, STAT3 and TGFB3. PRMT5 knockdown reduced the proliferation, invasion and migration of a GC cell line. PRMT5 mRNA levels were significantly higher in GC tissues than the corresponding adjacent normal tissues and were independent of tumour depth, differentiation and lymph node metastasis. High PRMT5 expression was an independent risk factor of positive peritoneal lavage cytology (odds ratio 3.90, P=0.003) and decreased survival. PRMT5 enhances the malignant phenotype of GC cell lines and its expression in gastric tissues may serve as a biomarker for patient stratification and a potential target of therapy.
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- 2016
9. Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma
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Hideki Takami, Yasuhiro Kodera, Satoshi Sueoka, Chie Tanaka, Michitaka Fujiwara, Mitsuro Kanda, Goro Nakayama, Dai Shimizu, Yuri Tanaka, Tsutomu Fujii, Ryoji Hashimoto, Naoki Iwata, Shuji Nomoto, Hiroyuki Sugimoto, Yukiyasu Okamura, Masahiko Koike, Suguru Yamada, and Kazuhiro Ezaka
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Adult ,Male ,Cancer Research ,Carcinoma, Hepatocellular ,Nerve Tissue Proteins ,Biology ,Downregulation and upregulation ,Cell Line, Tumor ,Gene expression ,Cell Adhesion ,Humans ,Epigenetics ,Promoter Regions, Genetic ,Aged ,Aged, 80 and over ,Extracellular Matrix Proteins ,Oncogene ,Liver Neoplasms ,Promoter ,Cell cycle ,DNA Methylation ,Middle Aged ,Molecular medicine ,Survival Analysis ,digestive system diseases ,Cytoskeletal Proteins ,Oncology ,Liver ,Protein Biosynthesis ,DNA methylation ,Cancer research ,Female - Abstract
Accumulation of epigenetic alterations causes inactivation of tumor suppressors and contributes to the initiation and progression of hepatocellular carcinoma (HCC). Identification of methylated genes is necessary to improve our understanding of the pathogenesis of HCC and develop novel biomarkers and therapeutic targets. The Kallmann syndrome-1 (KAL1) gene encodes an extracellular matrix-related protein with diverse oncological functions. However, the function of KAL1 in HCC has not been examined. We investigated the methylation status of the KAL1 promoter region in HCC cell lines, and evaluated KAL1 mRNA levels and those of genes encoding potential interacting cell adhesion factors. KAL1 mRNA expression level was heterogeneous in nine HCC cell lines, and reactivation of KAL1 mRNA expression was observed in cells with promoter hypermethylation of KAL1 gene after demethylation. In addition, KAL1 mRNA levels inversely correlated with those of ezrin in all nine HCC cell lines. KAL1 expression levels in 144 pairs of surgically-resected tissues were determined and correlated to clinicopathological parameters. KAL1 mRNA level was independent of the background liver status, whereas HCC tissues showed significantly lower KAL1 mRNA levels than corresponding noncancerous liver tissues. Downregulation of KAL1 mRNA in HCC was significantly associated with malignant phenotype characteristics, including elevated tumor markers, larger tumor size, vascular invasion, and hypermethylation of KAL1. Patients with downregulation of KAL1 were more likely to have a shorter overall survival than other patients, and multivariate analysis identified downregulation of KAL1 as an independent prognostic factor (hazard ratio 2.04, 95% confidence interval 1.11-3.90, P=0.022). Our results indicated that KAL1 may act as a putative tumor suppressor in HCC and is inactivated by promoter hypermethylation. KAL1 may serve as a biomarker of malignant phenotype of HCC.
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- 2015
10. CCNJ detected by triple combination array analysis as a tumor-related gene of hepatocellular carcinoma
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Goro Nakayama, Masamichi Hayashi, Mitsuhiro Hishida, Yoko Nishikawa, Shuji Nomoto, Michitaka Fujiwara, Yasuhiro Kodera, Masahiko Koike, Tsutomu Fujii, Mitsuro Kanda, Chie Tanaka, Daisuke Kobayashi, Suguru Yamada, Yoshikuni Inokawa, Hiroyuki Sugimoto, Naoki Iwata, and Nao Takano
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Adult ,Male ,Cancer Research ,Carcinoma, Hepatocellular ,Biology ,Methylation ,Polymorphism, Single Nucleotide ,Young Adult ,Cyclins ,Carcinoma ,medicine ,Tumor Cells, Cultured ,Humans ,Aged ,Regulation of gene expression ,Oncogene ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Liver Neoplasms ,DNA, Neoplasm ,Sequence Analysis, DNA ,DNA Methylation ,Middle Aged ,medicine.disease ,Molecular biology ,Molecular medicine ,Neoplasm Proteins ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,Oncology ,Tissue Array Analysis ,Hepatocellular carcinoma ,DNA methylation ,Female - Abstract
Hepatocellular carcinoma (HCC) has a high likelihood of recurrence and a poor prognosis. To detect cancer-related genes of HCC, we developed a new technique: triple combination array analysis, consisting of a methylation array, a gene expression array and a single nucleotide polymorphism array. A surgical specimen obtained from a 68-year-old female HCC patient was analyzed using triple combination array, which identified cyclin J (CCNJ) as a candidate cancer-related gene of HCC. Subsequently, samples from 85 HCC patients were evaluated for CCNJ promoter hypermethylation and expression status using methylation-specific PCR (MSP) and quantitative reverse transcriptase RT-PCR, respectively. CCNJ was found to be hypermethylated (methylation value, 0.906; range, 0-1.0) in cancer tissue, compared with adjacent non-cancerous tissue (0.112) using a methylation array. MSP revealed that CCNJ was hypermethylated in 67 (78.8%) of the tumor samples. CCNJ expression was significantly decreased in cases with hypermethylation (P
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- 2014
11. Clinical utility of PDSS2 expression to stratify patients at risk for recurrence of hepatocellular carcinoma
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Fuminori Sonohara, Hideki Takami, Hisaharu Oya, Yasuhiro Kodera, Michitaka Fujiwara, Shuji Nomoto, Hiroyuki Sugimoto, Dai Shimizu, Yukiyasu Okamura, Ryoji Hashimoto, Masahiko Koike, Suguru Yamada, Goro Nakayama, Mitsuro Kanda, and Tsutomu Fujii
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,Epigenetics ,RNA, Messenger ,Promoter Regions, Genetic ,Aged ,Aged, 80 and over ,Alkyl and Aryl Transferases ,Oncogene ,business.industry ,Liver Neoplasms ,Methylation ,Cell cycle ,DNA Methylation ,Middle Aged ,medicine.disease ,Prognosis ,Molecular medicine ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Hepatocyte nuclear factors ,Hepatocellular carcinoma ,DNA methylation ,Cancer research ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Identification of novel genetic and epigenetic alterations is required for optimal stratification of patients with hepatocellular carcinoma (HCC) at risk for recurrence and adverse prognosis. Coenzyme Q10 (CoQ10), which mediates apoptosis, is synthesized by prenyl diphosphate synthase subunit 2 (PDSS2). In the present study we evaluated the clinical significance and regulatory mechanisms of PDSS2 expression in HCC. PDSS2 expression levels and those of genes encoding potentially interacting proteins as well as the methylation status of the PDSS2 promoter region were analyzed in HCC cell lines. PDSS2 mRNA levels in 151 pairs of resected specimens were determined to evaluate the association of PDSS2 expression and clinicopathological factors. The expression and distribution of PDSS2 were determined using immunohistochemistry. PDSS2 mRNA expression was decreased in six of nine HCC cell lines and significantly correlated with those of hepatocyte nuclear factor 4α. PDSS2 transcription in HCC cells with decreased PDSS2 expression accompanying hypermethylation was reactivated after treating these cells with a methylation inhibitor. Mean expression levels of PDSS2 mRNA relative to that of uninvolved liver diminished gradually in the order of chronic hepatitis to cirrhosis, and each was significantly higher than those of HCCs. PDSS2 and PDSS2 mRNA levels were consistent. Decreased PDSS2 mRNA levels were detected in HCC tissues of 56 patients, correlated with shorter disease-specific survival, and was identified as an independent prognostic factor. PDSS2 is a putative tumor suppressor, and promoter hypermethylation is a key regulatory mechanism in HCC. Decreased levels of PDSS2 mRNA expression may represent a novel biomarker of HCC.
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- 2014
12. Detection of metallothionein 1G as a methylated tumor suppressor gene in human hepatocellular carcinoma using a novel method of double combination array analysis
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Hiroyuki Sugimoto, Shin Takeda, Naohito Kanazumi, Yukiyasu Okamura, Mitsuro Kanda, Yoko Nishikawa, Akimasa Nakao, and Shuji Nomoto
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Cancer Research ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Tumor suppressor gene ,Kaplan-Meier Estimate ,Biology ,Polymorphism, Single Nucleotide ,Loss of heterozygosity ,Biomarkers, Tumor ,medicine ,Humans ,Gene silencing ,Genes, Tumor Suppressor ,Gene Silencing ,Promoter Regions, Genetic ,Aged ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Oncogene ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Liver Neoplasms ,DNA Methylation ,Hepatitis C, Chronic ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Reverse transcription polymerase chain reaction ,Oncology ,DNA methylation ,Female ,Metallothionein - Abstract
Gene expression profiling or karyotyping analysis has made it possible to identify novel genes with altered expressions or copy numbers that have not been previously reported in liver cancer. On the same HCC sample, we performed double array analysis, both expression profiling and karyotyping analysis using a single nucleotide polymorphism (SNP) array in an attempt to find a novel tumor suppressor gene for its prognostic marker. We conducted expression array and SNP chip array using tumor and corresponding non-tumor tissues from the resected liver specimen of a 68-year-old woman who had chronic hepatitis type C. Additionally, we performed quantitative real-time reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR (MSP) for gene detection using specimens from 48 patients with HCC, and investigated their correlation with the prognosis. Metallothionein (MT) 1G gene located on 16q13 showed a decreased expression in tumor tissue. The copy number by SNP chip array revealed no loss of heterozygosity since no deletions were detected in 16q13, and HCC tissue showed AB call in both SNPs next to MT1G. In quantitative real-time PCR using 48 HCC clinical samples, mRNA expression of MT1G decreased significantly compared with that in corresponding non-cancerous liver tissues (p
- Published
- 2009
13. The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy.
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DAI SHIMIZU, MITSURO KANDA, HIROYUKI SUGIMOTO, MASAHIRO SHIBATA, HARUYOSHI TANAKA, HIDEKI TAKAMI, NAOKI IWATA, MASAMICHI HAYASHI, CHIE TANAKA, DAISUKE KOBAYASHI, SUGURU YAMADA, GORO NAKAYAMA, MASAHIKO KOIKE, MICHITAKA FUJIWARA, TSUTOMU FUJII, and YASUHIRO KODERA
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- 2017
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14. Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer.
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MITSURO KANDA, DAI SHIMIZU, TSUTOMU FUJII, HARUYOSHI TANAKA, MASAHIRO SHIBATA, NAOKI IWATA, MASAMICHI HAYASHI, DAISUKE KOBAYASHI, CHIE TANAKA, SUGURU YAMADA, GORO NAKAYAMA, HIROYUKI SUGIMOTO, MASAHIKO KOIKE, MICHITAKA FUJIWARA, and YASUHIRO KODERA
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- 2016
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15. Adherens junctions associated protein 1 serves as a predictor of recurrence of squamous cell carcinoma of the esophagus.
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HARUYOSHI TANAKA, MITSURO KANDA, MASAHIKO KOIKE, NAOKI IWATA, DAI SHIMIZU, KAZUHIRO EZAKA, SATOSHI SUEOKA, YURI TANAKA, HIDEKI TAKAMI, RYOJI HASHIMOTO, CHIE TANAKA, SUGURU YAMADA, TSUTOMU FUJII, GORO NAKAYAMA, HIROYUKI SUGIMOTO, MICHITAKA FUJIWARA, and YASUHIRO KODERA
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- 2015
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16. Effectiveness of plasma treatment on pancreatic cancer cells.
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NORIFUMI HATTORI, SUGURU YAMADA, KOJI TORII, SHIGEOMI TAKEDA, KAE NAKAMURA, HIROMASA TANAKA, HIROAKI KAJIYAMA, MITSURO KANDA, TSUTOMU FUJII, GORO NAKAYAMA, HIROYUKI SUGIMOTO, MASAHIKO KOIKE, SHUJI NOMOTO, MICHITAKA FUJIWARA, MASAAKI MIZUNO, MASARU HORI, and YASUHIRO KODERA
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- 2015
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17. B-cell translocation gene 1 serves as a novel prognostic indicator of hepatocellular carcinoma.
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MITSURO KANDA, HIROYUKI SUGIMOTO, SHUJI NOMOTO, HISAHARU OYA, SOKI HIBINO, DAI SHIMIZU, HIDEKI TAKAMI, RYOJI HASHIMOTO, OKAMURA, YUKIYASU, SUGURU YAMADA, TSUTOMU UJII, GORO NAKAYAMA, MASAHIKO KOIKE, MICHITAKA FUJIWARA, and YASUHIRO KODERA
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- 2015
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18. Clinical utility of PDSS2 expression to stratify patients at risk for recurrence of hepatocellular carcinoma.
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MITSURO KANDA, HIROYUKI SUGIMOTO, SHUJI NOMOTO, HISAHARU OYA, DAI SHIMIZU, HIDEKI TAKAMI, RYOJI HASHIMOTO, FUMINORI SONOHARA, YUKIYASU OKAMURA, SUGURU YAMADA, TSUTOMU FUJII, GORO NAKAYAMA, MASAHIKO KOIKE, MICHITAKA FUJIWARA, and YASUHIRO KODERA
- Published
- 2014
- Full Text
- View/download PDF
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