A5001467370- Gastric Cancer Management and Outcomes
- Gastrointestinal disorders and treatments
- Gastrointestinal Tumor Research and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Liver physiology and pathology
- Cholangiocarcinoma and Gallbladder Cancer Studies
- MicroRNA in disease regulation
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Endoplasmic Reticulum Stress and Disease
- Helicobacter pylori-related gastroenterology studies
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Cancer Mechanisms and Therapy
- Colorectal Cancer Treatments and Studies
- Liver Disease and Transplantation
Kyoto University
2015-2024
Osaka Red Cross Hospital
2009-2011
Background: Combination therapy with anti-programmed death-ligand 1 monoclonal antibody atezolizumab plus anti-vascular endothelial growth factor agent bevacizumab (Atezo/Bev) was approved in 2020 as a first-line treatment for unresectable hepatocellular carcinoma (HCC). Atezo/Bev is relatively well tolerated; however, factors that can predict its response have not yet been reported. Thus, we aimed to investigate whether the pretreatment neutrophil-to-lymphocyte ratio (NLR) could therapeutic...
Hepatocellular carcinoma (HCC) originates from regenerating liver cells with genetic alterations in chronically inflamed liver. Ductal and hepatocytes proliferate for regeneration, proliferating ductal (PDC) derived bile ductules have long been considered putative stem/progenitor candidate cellular origins of HCC. The potential PDC as tumor-originating cells, however, remains controversial contrast to accumulating evidence that HCC hepatocytes. Here, we demonstrate PDCs expressing the...
Abstract Background Although atezolizumab plus bevacizumab (Atezo/Bev) therapy has been used as the preferred first-line treatment for advanced hepatocellular carcinoma (HCC), up to 26% of patients do not achieve disease control, suggesting alternative treatments might be more beneficial such patients. We investigated key predictors refractoriness Atezo/Bev therapy, particularly in setting. Methods retrospectively analyzed 302 with HCC who received between October 2020 and September 2022...
Abstract Telomerase reverse transcriptase ( TERT ) gene aberration is detectable in >80% of cases with hepatocellular carcinoma (HCC). reactivation essential for cellular immortalization because it stabilizes telomere length, although the role hepatocarcinogenesis remains unelucidated. To elucidate significance aberrant expression hepatocytes inflammation‐associated hepatocarcinogenesis, we generated Alb‐Cre;Tert Tg mice, which overexpress liver and examined their phenotype during chronic...
Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility genetic aberrations. The mechanism underlying the enhanced instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFα stimulation induced transcriptional downregulation of MSH2, member mismatch repair family, via NF-κB-dependent miR-21 expression hepatocytes. Liver cancers developed ALB-MSH2(-) (/) (-)AID(+), (-), and ALB-AID(+) mice, which MSH2 deficient and/or...
Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment various types cancers. However, RDI may not accurately reflect lenvatinib, it is first oral MTA where based on patient's weight. We aimed to evaluate utility 2M-DBR (the delivered intensity/body surface area ratio at 60 days) by comparing relationship between 2M-DBR, 2M-RDI (RDI...
Abstract Intestinal metaplasia (IM) is a risk factor for gastric cancer following infection with Helicobacter pylori. To explore the susceptibility of pure IM to development, we investigated genetic alterations in single glands. We isolated 50 or non-IM glands from inflamed mucosa 11 patients intramucosal carcinoma (IGC) and 4 without IGC; 19 noninflamed individuals our cohort previous dataset were also included as controls. Whole-exome sequencing revealed significantly higher accumulation...
Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown.The sera of patients PSC and controls were subjected to enzyme-linked immunosorbent assays detect using recombinant integrin proteins. Integrin αvβ6 expression in bile duct tissues was examined immunofluorescence. The blocking activity solid-phase binding assays.Anti-integrin antibodies detected 49/55 (89.1%) 5/150 (3.3%) (P < 0.001), a...
Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). In patients who became refractory to TACE, a switch tyrosine kinase inhibitors (TKIs) needs be considered. However, TACE could worsen liver function, thereby narrowing time window TKIs because are with Child-Pugh grade A (CP-A). We investigated factors associated CP deterioration after TACE. Among underwent 125 CP-A were enrolled. The cumulative rates 20.3%,...
Recent genetic analyses revealed heterogeneity in hepatocellular carcinoma (HCC), although it remains unclear how alterations contribute to the multistage progression of HCC, especially early step from hypovascular liver nodules hypervascular HCC. We conducted multiregional whole-genome sequencing on HCCs with a nodule-in-nodule appearance, consisting inner HCC surrounded by arising common origin, and identified point mutations, structural variations, copy-number variations each specimen....
<i>Background/Aims:</i> To clarify risk factors and clinical features of both hepatitis B surface antigen anti-HCV negative hepatocellular carcinoma (NBNC-HCC). <i>Methods:</i> HCC patients (n = 1,109) diagnosed at a single center were categorized based on the presence serum HCVAb. Clinical characteristics 127 NBNC-HCC evaluated. <i>Results:</i> stratified as those with alcoholic liver disease (ALD-HCC, n 42) alcohol-unrelated (non-ALD-HCC, 85). Compared...
Abstract Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into close association between mutation pattern cancers and specific mutagens led us to investigate possible involvement activation-induced cytidine deaminase (AID), a DNA editing enzyme, pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression...
Contrast-enhanced ultrasonography (US) has improved the detection and characterization of focal hepatic lesions. Recently, importance obtaining high-quality samples in biopsy lesions been increasing not only field pathological diagnosis but also molecular analysis for predicting effectiveness anticancer agents targeted drugs. We evaluated utility Sonazoid-enhanced (SEUS) guiding percutaneous by comparing results histopathological between B-mode US SEUS guidance.This retrospective study...
The emergence of hepatitis C virus (HCV) with resistance-associated substitution (RAS), produced by mutations in the HCV genome, is a major problem direct acting antivirals (DAA) treatment. This study aimed to clarify mutational spectrum HCV-RNA and pattern for RASs patients chronic infection. from two replicon cell lines serum four non-liver transplant post-liver unsuccessful DAA treatment were analyzed using high-accuracy single-molecule real-time long-read sequencing. Transition...
Most hepatocellular carcinomas (HCCs) develop on the basis of chronic hepatitis, but mechanism epigenetic regulation in inflammatory hepatocarcinogenesis has yet to be elucidated. Among de novo DNA methyltransferases (DNMTs), DNMT3B lately been reported act specifically actively transcribed genes, suggesting possibility that it plays a role pathogenesis cancer. We confirmed isoforms lacking its catalytic domain were highly expressed HCCs compared with non-tumorous liver tissue. To elucidate...
Chronic inflammation triggers the aberrant expression of a DNA mutator enzyme, activation-induced cytidine deaminase (AID), and contributes to tumorigenesis through accumulation genetic aberrations. To gain further insight into inflammation-mediated genotoxic events required for carcinogenesis, we examined role chronic in emergence aberrations liver with constitutive AID expression. Treatment thioacetamide (TAA) at low-dose concentrations caused minimal hepatic both wild-type (WT) transgenic...