Tadaaki Arizumi

Kinki University, Ōsaka, Ōsaka, Japan

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Publications (28)101.46 Total impact

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    Journal of Hepatology 04/2015; 62:S456. DOI:10.1016/S0168-8278(15)30596-1 · 11.34 Impact Factor
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    ABSTRACT: Most hepatocellular carcinomas (HCCs) develop in the context of chronic liver inflammation. Oxidative stress is thought to play a major role in the pathogenesis of HCC development. In this study, we examined whether cold-inducible RNA-binding protein (Cirp) controls reactive oxygen species (ROS) accumulation and development of HCC by using murine models of hepatocarcinogenesis and human liver samples. Cirp expression, ROS accumulation and CD133 expression were increased in the liver of tumor-harboring mice. Cirp-deficiency reduced production of IL-1β and IL-6 in Kupffer cells, ROS accumulation and CD133 expression, leading to attenuated hepatocarcinogenesis. Thioacetamide treatment enhanced hepatic expression of CD133 and phosphorylated STAT3, which was prevented by administration of the antioxidant butylated hydroxyanisole. Intriguingly, the risk of human HCC recurrence is positively correlated with Cirp expression in liver. Cirp appears to play a critical carcinogenic function and its expression might be a useful biomarker for HCC risk prediction.This article is protected by copyright. All rights reserved.
    Cancer Science 01/2015; 106(4). DOI:10.1111/cas.12611 · 3.52 Impact Factor
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    ABSTRACT: Trans-arterial chemoembolization (TACE) is used to treat hepatocellular carcinoma (HCC), but it is a challenge to predict patient survival. The hepatic arterial embolization prognostic (HAP) score has been shown to predict which patients will have shorter survival times and should not undergo TACE. We aimed to validate this scoring system in a prospective study of patients in Europe and Asia. We evaluated the prognostic accuracy of the HAP score in estimating overall survival (OS) of 126 patients with HCC who received TACE in the UK or Italy (training set) from 2001 through 2013. We also analyzed data from 723 patients treated in Korea and Japan (validation set), including 79 with newly diagnosed HCC, who underwent TACE in Korea or Japan from 2004 through 2013. Response to TACE was determined based on computed tomography analysis. OS was calculated from the time of the first TACE until death or the last follow-up evaluation. OS was associated with hypoalbuminaemia, alfa-fetoprotein (AFP) >400 ng/ml, and tumor size >7 cm at diagnosis (P<.01), but not bilirubin>17 umol/L (P>.05), in both datasets. The lack association between OS and bilirubin level was confirmed using receiver operating characteristic analysis. We developed a modified version of the HAP score (mHAP), based on level of albumin and AFP and tumor size, which predicted OS with increased accuracy in the training and validation cohorts. In a multi-center validation study, we developed an mHAP that predicts survival of patients with HCC treated with TACE in Europe and Asia. This system might be used to identify patients with HCC most likely to benefit from TACE in clinical practice. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Clinical Gastroenterology and Hepatology 12/2014; DOI:10.1016/j.cgh.2014.11.037 · 7.90 Impact Factor
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    ABSTRACT: Transcatheter arterial chemoembolization (TACE) failure or refractoriness is an indication for sorafenib therapy in patients with advanced hepatocellular carcinoma. The study evaluated the validity of the definition of TACE failure or refractoriness as proposed by the Liver Cancer Study Group of Japan (LCSGJ) through a retrospective analysis of sorafenib treatment. Out of 265 patients with advanced hepatocellular carcinoma who were treated with sorafenib at our hospital, 45 experienced TACE failure or refractoriness and were included in this study and retrospectively analyzed. Multivariate analysis only identified the number of ineffective TACE procedures performed before starting sorafenib treatment as significant factors. Overall survival (OS) after starting sorafenib was statistically longer in patients treated with ≤2 consecutive ineffective TACE procedures before sorafenib administration than in patients treated with ≥3 consecutive ineffective TACE procedures (p < 0.005). This result matched the LCSGJ criteria. In patients treated with sorafenib, OS was extended with ≤2 consecutive ineffective TACE procedures compared to that with ≥3 consecutive ineffective TACE procedures. Thus, if tumors are uncontrolled, TACE should not be repeated. The result of this study supports the definition of TACE failure or refractoriness proposed by the LCSGJ. © 2014 S. Karger AG, Basel.
    Oncology 11/2014; 87 Suppl 1(s1):32-6. DOI:10.1159/000368143 · 2.42 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the usefulness of the combination guidance of contrast-enhanced US (CEUS) and fusion imaging in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with poor conspicuity on B-mode US and CEUS/fusion imaging. We conducted a retrospective cohort study, which included 356 patients with 556 HCCs that were inconspicuous on B-mode US. A total of 192 patients with 344 HCCs, 123 patients with 155 HCCs, and 37 patients with 57 HCCs underwent RFA under CEUS guidance, fusion imaging guidance, and the combination of CEUS and fusion imaging guidance. The average number of treatment sessions was 1.1 (range: 1-2) in the CEUS guidance group, 1.1 (range: 1-2) in the fusion imaging guidance group, and 1.1 (range: 1-3) in the combination of CEUS and fusion imaging guidance group. Treatment analysis did not reveal significantly more RFA treatment sessions in the combination guidance group than in the other groups (p = 0.97, Student's t test). During the follow-up period (1.1-85.3 months, mean ± SD, 43.2 ± 59.5), the 3-year local tumor progression rates were 4.9, 7.2, and 5.9% in the CEUS guidance group, the fusion imaging guidance group, and the combination guidance group, respectively (p = 0.84, log-rank test). In spite of selection bias, session frequency and local tumor progression were not different under the combination guidance with CEUS and fusion imaging in RFA. The combination of fusion imaging and CEUS guidance in RFA therapy is an effective treatment for HCC with poor conspicuity on B-mode US and CEUS/fusion imaging. © 2014 S. Karger AG, Basel.
    Oncology 11/2014; 87 Suppl 1(s1):55-62. DOI:10.1159/000368146 · 2.42 Impact Factor
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    ABSTRACT: Telaprevir-based antiviral therapy has been the primary treatment for chronic hepatitis C genotype 1 at a high viral load since November 2011. On the other hand, a number of patients have been reported to require withdrawal from or reduced doses of drugs due to side effects, such as eruptions, anemia, and renal dysfunction. In addition, as hepatitis C patients are growing older, it is imperative to investigate the tolerability of triple combination therapy for elderly patients. The study subjects comprised 35 patients who received telaprevir combination therapy after November 2011. They were divided into group A (age: <65 years; n = 21) and group B (age: ≥65 years; n = 14) in order to compare the treatment completion rate, sustained virological response at week 24 (SVR24), and adverse events between the groups. The treatment completion rate was 82.8% (29/35) in all subjects, 90.4% (19/21) in group A, and 78.5% (11/14) in group B. The rate was lower in group B but without a significant difference between the groups (p = 0.804). The SVR24 rate was 88.5% (31/35) in all subjects, 90.4% (19/21) in group A, and 85.7% (12/14) in group B, without a significant difference between the groups (p = 0.161). Although the incidence of anemia was higher in group B, there was no significant difference in the treatment completion or SVR24 rate between the groups. Telaprevir combination therapy is suggested to be tolerable for elderly hepatitis C patients. © 2014 S. Karger AG, Basel.
    Oncology 11/2014; 87 Suppl 1(s1):110-7. DOI:10.1159/000368154 · 2.42 Impact Factor
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    ABSTRACT: To investigate the relationship between tissue elasticity before and after antiviral therapy and shear wave as well as strain elastography. FibroScan and real-time tissue elastography were performed before and after antiviral therapy for chronic hepatitis C, and treatment efficacy and elastographic findings were comparatively analyzed. Elasticity was evaluated by measuring liver stiffness (LS) in kilopascals using FibroScan, and the liver fibrosis index (LFI) was assessed by real-time tissue elastography. LS and LFI correlated well before and after therapy (r = 0.567, p = 0.003 and r = 0.576, p = 0.002, respectively). In the group without a sustained virological response (SVR), LS increased in 4 of 5 patients. Patients with an increase in both LS and LFI were all in the non-SVR group (3/3, 100%). In addition, LS increased in all patients except 1 in the non-SVR group (4/5, 80%). In the SVR group, both LS and LFI decreased in all patients except 1 (18/19, 94.7%). In the patient with an increase in LS despite achieving SVR, LS decreased quickly after alcohol cessation. With a few exceptions, SVR improved LS. All patients with an increase in LFI were in the non-SVR group, even though LFI decreased in 2 patients. Our findings suggest that an LFI increase indicates lack of treatment efficacy with antiviral therapy. LFI may be useful for the assessment of treatment efficacy in patients with worsening of LS despite achieving SVR with antiviral therapy. © 2014 S. Karger AG, Basel.
    Oncology 11/2014; 87 Suppl 1(s1):118-23. DOI:10.1159/000368155 · 2.42 Impact Factor
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    ABSTRACT: Background: Sorafenib is a multikinase inhibitor targeting Raf and protein tyrosine kinases, which are involved in cell growth and tumor angiogenesis. Sorafenib administration induces temporary inhibition of tumor growth and a decrease in arterial blood flow in a considerable number of hepatocellular carcinoma (HCC) patients. We retrospectively evaluated the association between decreased blood flow and the overall survival (OS) of HCC patients after the initiation of sorafenib therapy. Patients and methods: Therapeutic responses of 158 advanced HCC patients with hypervascular tumors who had received sorafenib for more than 1 month were analyzed. To assess their therapeutic response, patients underwent radiological evaluation before and every 4-6 weeks after the initiation of sorafenib treatment. After the classification of patients into three groups based on the change in arterial enhancement during treatment (no change, decrease and disappearance), the OS of each group was compared using the Kaplan-Meier method. Results: Statistically significant differences in OS were observed among the three groups (p < 0.001). A decrease or disappearance of arterial enhancement was significantly associated with improved OS compared to patients with no change in arterial enhancement; the median OS was 19.9 months (95% confidence interval, CI, 16.4-24.5 months) and 6.0 months (95% CI, 4.0-8.8 months), respectively (p < 0.001). However, there was no difference in OS between the decrease and disappearance groups (p = 0.88). Conclusion: We conclude that decreased arterial enhancement during sorafenib treatment was associated with the longest OS and could therefore reflect an effective response.
    Digestive Diseases 10/2014; 32(6):733-9. DOI:10.1159/000368013 · 2.18 Impact Factor
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    ABSTRACT: Background: Sorafenib is a molecular-targeting agent showing improved overall survival (OS) for advanced hepatocellular carcinoma (HCC). Although tumor dormancy, characterized by stable tumor status or stable disease (SD) without tumor regression, is a unique feature of sorafenib treatment, the contribution of SD to OS remains debatable. This study aimed to clarify the correlation between SD periods and OS in patients with HCC treated with sorafenib. Methods: From May 2009 to January 2013, 269 patients with advanced-stage HCC were treated with sorafenib at the Kinki University Hospital. The antitumor response of sorafenib was evaluated in 158 patients using the modified Response Evaluation Criteria in Solid Tumors, and patients with SD were divided into two subgroups according to the median duration of SD: short SD (<3 months) and long SD (≥3 months). The relationship between the duration of SD and OS was analyzed among patients with complete (CR) and partial response (PR), and long and short SD using the Kaplan-Meier method. Results: The median OS was 5.7 months in the short SD, 20.8 months in the long SD and 17.9 months in the CR + PR group. Although the duration of OS was significantly longer in the long SD group than the short SD group, no difference in OS was detected between the patients with CR + PR and patients with long SD. The impact of long SD on OS could be as strong as that of CR + PR. Conclusion: Achievement of long SD is one of the important goals for improving survival in patients with HCC treated with sorafenib.
    Digestive Diseases 10/2014; 32(6):705-10. DOI:10.1159/000368006 · 2.18 Impact Factor
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    ABSTRACT: Background Transarterial chemoembolisation (TACE) is a standard treatment for unresectable, intermediate stage hepatocellular carcinoma (HCC). Survival after TACE, however, can be highly variable, with no suitable biomarker predicting therapeutic outcome. The inflammation-based index (IBI) has previously been shown to independently predict overall survival (OS) in all stages of HCC.AimTo explore the prognostic ability of IBI as a predictor of survival after TACE.Methods Baseline staging, biochemical and clinicopathological features including IBI were studied in a derivation set of 64 patients undergoing TACE for intermediate stage HCC. Dynamic changes in IBI before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model and further validated in two independent patient cohorts from Korea (n = 76) and Japan (n = 577).ResultsPre-treatment IBI predicted for OS in the derivation set (P = 0.001). Other univariate predictors of OS included radiological response to TACE (P < 0.001), pre-TACE CLIP score (P < 0.01), tumour diameter >5 cm (P = 0.05) and AFP ≥400 (P < 0.001). Normalisation of IBI post-TACE was associated with radiological response by mRECIST criteria and improved OS (P < 0.001). Normalisation of IBI remained a significant multivariate predictor of OS in both the derivation and validation sets (P < 0.001).Conclusions Normalisation of IBI after TACE is shown to be an independent predictor of survival and may be integrated into the retreatment criteria for repeat TACE in intermediate stage HCC. IBI and its dynamic changes after treatment are validated as a biomarker allowing the stratification of patients with a significant survival advantage following initial TACE.
    Alimentary Pharmacology & Therapeutics 10/2014; 40(11). DOI:10.1111/apt.12992 · 5.73 Impact Factor
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    ABSTRACT: Objective: The purpose of this study was to evaluate the risk factors for local recurrence with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) measuring ≤2 cm. Methods: This study involved 234 patients with 274 HCCs measuring ≤2 cm who had undergone RFA as the initial treatment. The mean tumor diameter was 1.478 cm. The median follow-up period was 829 days. We evaluated the post-RFA cumulative local recurrence rate and analyzed the risk factors contributing to clinical outcomes. Results: Cumulative local recurrence rates were 9, 19 and 19% at 1, 2 and 3 years, respectively. Among the 145 cases with a complete safety margin (SM) after RFA, only 4 developed local tumor recurrence and the cumulative rates of local tumor recurrence at 1, 2 and 3 years were 2, 3 and 3%, respectively. Among the 129 cases with incomplete SM, local tumor recurrence developed in 34 and the cumulative rates of local tumor progression at 1, 2 and 3 years were 14, 36 and 36%, respectively. In multivariate analysis, significant risk factors were tumor location (liver surface), irregular gross type and SM <5 mm. Conclusion: Even with HCC measuring ≤2 cm, location and gross type of tumor should be carefully evaluated before RFA is performed.
    Digestive Diseases 10/2014; 32(6):670-7. DOI:10.1159/000367999 · 2.18 Impact Factor
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    ABSTRACT: Objective: To clarify the progression pattern of abnormal DNA methylation during the development of hepatocellular carcinoma (HCC) using a comprehensive methylation assay. Methods: We used an Infinium HumanMethylation450 BeadChip array that can analyze >485,000 CpG sites distributed throughout the genome for a comprehensive methylation study of 117 liver tissues consisting of 59 HCC and 58 noncancerous livers. Altered DNA methylation patterns during tumor progression were also analyzed. Results: We identified 38,330 CpG sites with significant differences in methylation levels between HCCs and noncancerous livers (DM-CpGs) using strict criteria. Of the DM-CpGs, 92% were hypomethylated and only 3,051 CpGs (8%) were hypermethylated in HCC. The DM-CpGs were more prevalent within intergenic regions with isolated CpGs. In contrast, DM-CpGs that were hypermethylated in HCC were predominantly located within promoter regions and CpG islands (p < 0.0001). The association between methylation profiles of DM-CpGs and tumor size was statistically significant, especially in hepatitis C virus (HCV)-positive cases (p = 0.0001). Conclusions: We clarified the unique characteristics of DM-CpGs in human HCCs. The stepwise progression of alterations in DNA methylation was a common feature of HCV-related hepatocarcinogenesis.
    Digestive Diseases 10/2014; 32(6):658-63. DOI:10.1159/000367982 · 2.18 Impact Factor
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    ABSTRACT: Objectives: DNA methylation-dependent transcriptional inactivation of tumor suppressor genes (TSGs) is critical for the pathogenesis of hepatocellular carcinoma (HCC). This study identifies potential TSGs in HCCs using methylation profiling and pharmacological unmasking of methylated TSGs. Methods: Methylation profiling was performed on 22 pairs of HCCs and their corresponding noncancerous liver tissues using the Infinium HumanMethylation27 BeadChip. We also determined the gene reexpression after treatment with 5-aza-2'-deoxycytidine (5-Aza-dC) and trichostatin A (TSA) in 5 HCC cell lines. Results: We selected CpGs that exhibited a significant increase in methylation in HCC tissues compared with that of the noncancerous control group. Two hundred and thirteen CpGs on different gene promoters with a mean difference in the β value ≥0.15 and a value of p < 0.05 were selected. Of the 213 genes, 45 genes were upregulated in 3 or more HCC cell lines with multiplier value of differences ≥2.0 after 5-Aza-dC and TSA treatment. Conclusions: We identified several potential TSGs that participate in transcription inactivation through epigenetic interactions in HCC. The results of this study are important for the understanding of functionally important epigenetic alterations in HCC.
    Digestive Diseases 10/2014; 32(6):740-6. DOI:10.1159/000368015 · 2.18 Impact Factor
  • Masatoshi Kudo · Tadaaki Arizumi · Kazuomi Ueshima
    Hepatology 06/2014; 59(6). DOI:10.1002/hep.26760 · 11.06 Impact Factor
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    ABSTRACT: To test the hypothesis that use of the response evaluation criteria in cancer of the liver (RECICL), an improved evaluation system designed to address the limitations of the response evaluation criteria in solid tumors 1.1 (RECIST1.1) and modified RECIST (mRECIST), provides for more accurate evaluation of response of patients with hepatocellular carcinoma (HCC) to treatment with sorafenib, a molecularly targeted agent, as assessed by overall survival (OS). The therapeutic response of 156 patients with advanced HCC who had been treated with sorafenib therapy for more than 1 month was evaluated using the RECIST1.1, mRECIST, and RECICL. After categorization as showing progressive disease (PD), stable disease (SD), or objective response, the association between OS and categorization was examined using the Kaplan-Meier method to develop survival curves. The 141 cases categorized as PD or SD by the RECIST1.1, but objective response by the mRECIST and RECICL, were further analyzed for determination of the association between OS and categorization. Only categorization using the RECICL was found to be significantly correlated with OS (p = 0.0033). Among the patients categorized as SD or PD by the RECIST1.1, reclassification by the RECICL but not the mRECIST was found to be significantly associated with OS and allowed for precise prediction of prognosis (p = 0.0066). Only the use of the RECICL allowed for identification of a subgroup of HCC patients treated with sorafenib with improved prognosis. The RECICL should, therefore, be considered a superior system for assessment of therapeutic response.
    Journal of Gastroenterology 02/2014; 49(12). DOI:10.1007/s00535-014-0936-0 · 4.52 Impact Factor
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    ABSTRACT: Chronic hepatitis C (CHC) triggers oxidative stress and contributes to the emergence of hepatocellular carcinoma (HCC). We previously reported that tumor suppressor gene (TSG) methylation is a critical factor during the early stages of hepatocarcinogenesis. In this study, we clarify the association between oxidative stress and epigenetic alterations during hepatocarcinogenesis. We examined DNA oxidation and methylation profiles in 128 liver biopsy samples from CHC patients. The DNA oxidation and methylated TSG numbers were quantified using immunohistochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and quantitative PCR for 11 TSGs, respectively. The quantitative chromatin immunoprecipitation-PCR (ChIP-qPCR) assay in HepG2 and fetal liver Hc cells treated with H2O2 was used to quantify trimethyl-H3K4, acetylated-H4K16 (an active chromatin marker), trimethyl-H3K27 (a repressive chromatin marker) and 8-OHdG. We analyzed 30 promoters of 25 different TSGs by qPCR. The high levels of 8-OHdG was the only variable that was significantly associated with the increased number of methylated TSGs in CHC (p < 0.0001). The ChIP-qPCR revealed that after H2O2 treatment of the cell lines, the 8-OHdG-bound promoters showed a modification from an active chromatin (trimethyl-H3K4 and acetylated-H4K16 dominant) to a repressive chromatin (trimethyl-H3K27 dominant) status. We conclude that oxidative stress alters the chromatin status, which leads to abnormal methylation of TSGs, and contributes to hepatocarcinogenesis in CHC patients. © 2013 S. Karger AG, Basel.
    Digestive Diseases 11/2013; 31(5-6):459-66. DOI:10.1159/000355245 · 2.18 Impact Factor
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    ABSTRACT: Objective: Mild hypothermia (32-33°C) shows protective effects in patients with brain damage and cardiac arrest. Although cold-inducible RNA-binding protein (CIRP) contributes to the protective effects of hypothermia through extracellular signal-regulated kinase activation in fibroblasts, the effects of hypothermia in the liver remain unclear. Methods: We analysed the effects of cold temperature on fulminant hepatitis, a potentially fatal disease, using the D-galactosamine (GalN)/lipopolysaccharide (LPS) and concanavalin (con) A-induced hepatitis models in mice. After GalN/LPS administration and anaesthesia, mice in the hypothermia group were kept at 25°C and those in control group were kept at 35°C. After concanavalin A (con A) administration, the mice in the hypothermia group were placed in a chamber with an ambient temperature of 6°C for 1.5 h. Results: Hypothermia attenuated liver injury and prolonged survival. Activation of c-Jun N-terminal kinase and Akt, which are involved in reactive oxygen species (ROS) accumulation, was suppressed by low temperature. Hypothermia significantly decreased oxidized protein levels, and treatment with N-acetyl-L-cysteine, an antioxidant, attenuated GalN/LPS-induced liver injury. In con A-induced hepatitis, CIRP expression was upregulated and Bid expression was downregulated, resulting in decreased apoptosis of hepatocytes in the hypothermia group. Conclusions: These data suggest that hypothermia directly protects hepatocytes from cell death via reduction of ROS production in fulminant hepatitis.
    Digestive Diseases 11/2013; 31(5-6):440-6. DOI:10.1159/000355242 · 2.18 Impact Factor
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    ABSTRACT: Global DNA hypomethylation is a characteristic feature of cancer cells that closely associates with chromosomal instability (CIN). However, the association between these characteristics during hepatocarcinogenesis remains unclear. Herein, we determined the relationship between hypomethylation and CIN in human hepatocellular carcinoma (HCC) by analyzing 179 HCCs, 178 matched non-tumor livers and 23 normal liver tissues. Hypomethylation at three different repetitive DNA (rDNA) sequences and hypermethylation of 12 CpG loci, including 11 tumor suppressor gene (TSG) promoters, were quantified using MethyLight or combined bisulfite restriction analysis. Fractional allelic loss (FAL) was used as a marker for CIN, calculated by analyzing 400 microsatellite markers. Gains and losses at each chromosome were also determined using semi-quantitative microsatellite analysis. The associations between rDNA hypomethylation and FAL, as well as between TSG hypermethylation and FAL were investigated. Significantly more hypomethylation was observed in HCC tissues than in normal liver samples. Progression of hypomethylation during carcinogenesis was more prominent in hepatitis C virus (HCV)-negative cases, which was in contrast to our previous reports of significantly increased TSG methylation levels in HCV-positive tumors. Absence of liver cirrhosis and higher FAL scores were identified as independent contributors to significant hypomethylation of rDNA in HCC. Among the chromosomal alterations frequently observed in HCC, loss of 8p, which was unique in the earliest stages of hepatocarcinogenesis, was significantly associated with hypomethylation of rDNA by multivariable analysis (p = 0.0153). rDNA hypomethylation was also associated with a high FAL score regardless of tumor differentiation (p = 0.0011, well-differentiated; p = 0.0089, moderately/poorly-differentiated HCCs). We conclude that DNA hypomethylation is an important cause of CIN in the earliest step of HCC, especially in a background of non-cirrhotic liver.
    PLoS ONE 09/2013; 8(9):e72312. DOI:10.1371/journal.pone.0072312 · 3.23 Impact Factor
  • Ultrasound in Medicine & Biology 05/2013; 39(5):S24-S25. DOI:10.1016/j.ultrasmedbio.2013.02.131 · 2.21 Impact Factor
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    ABSTRACT: Objectives: Hepatocellular carcinoma (HCC) is one of the common cancers worldwide. Accurate diagnosis of tumor progression is critical for the appropriate management of HCC. Here, we established a sensitive assay to detect and quantify tumor-derived DNA in the serum of HCC patients. Methods: Aberrant methylation of the APC gene was quantified in 23 HCC patients and 8 healthy volunteers using 100 µl of serum. For sensitive detection and accurate quantification of tumor DNA, we combined seminested polymerase chain reaction (PCR) with TaqMan PCR, which could amplify the APC gene regardless of the methylation status and detect the methylated and unmethylated sequences separately. The ratio of methylated to unmethylated sequences was quantified. Results: The methylated APC gene was detected in all HCC patients examined, but no healthy volunteers showed amplification of methylated sequences in serum. HCC patients with portal vein thrombosis showed a significantly higher methylated to unmethylated APC gene ratio in serum than those without portal vein thrombosis (p = 0.0029). Conclusions: Considering the strong association between the ratio of the methylated to unmethylated APC sequences in serum and the presence of portal vein thrombosis, methylation status of APC sequences could be a promising marker for improving HCC management.
    Oncology 02/2013; 84 Suppl 1:82-7. DOI:10.1159/000345895 · 2.42 Impact Factor

Publication Stats

64 Citations
101.46 Total Impact Points


  • 2011–2015
    • Kinki University
      • • Department of Gastroenterology and Hepatology
      • • Department of Internal Medicine
      Ōsaka, Ōsaka, Japan