- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Bladder and Urothelial Cancer Treatments
- Renal and related cancers
- Cancer-related molecular mechanisms research
- Urinary and Genital Oncology Studies
- Liver Disease Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Urological Disorders and Treatments
- MicroRNA in disease regulation
- Pancreatic and Hepatic Oncology Research
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- BRCA gene mutations in cancer
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Neuroendocrine Tumor Research Advances
- Gastric Cancer Management and Outcomes
- Urologic and reproductive health conditions
- Nutrition and Health in Aging
- IgG4-Related and Inflammatory Diseases
- Molecular Biology Techniques and Applications
Keio University
2016-2025
National Center of Neurology and Psychiatry
2025
Hokkaido University
2022-2024
Keio University Hospital
2017-2022
University of Pennsylvania
2017-2021
Bryn Mawr College
2018
Japan Agency for Medical Research and Development
2018
UPMC Hillman Cancer Center
2017
Cancer Research Institute
2017
Japan Science and Technology Agency
2014
Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, neuroendocrine carcinoma of ampulla Vater. These organoids BTCs were cultured stably for >1 year closely recapitulated histopathology, gene expression, genetic alterations evident in primary tumors. Gene expression profiling revealed that SOX2 could be potential prognostic...
Abstract Renal cell carcinoma (RCC) is the most common histological type of adult kidney cancer. In this study, we obtained lipidomic profiles clear RCC (ccRCC), a major subtype, by performing analysis specimens cancerous tissue and surrounding normal renal cortex from same patients ( N = 49). We also compared with lipogenic transcriptome for an additional set patient samples 95). Overall, detected 326 lipids, including phospholipids, sphingolipids, neutral eicosanoids. The levels more than...
Tumor cells are thought to evade immune surveillance through interaction with cells. Much recent attention has focused on the modification of responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon its ligand CD47 expressed surface target Here, we show highly human renal cell carcinoma and melanoma. Furthermore, anti-SIRPα Ab blocks markedly suppressed tumor formation by or melanoma immunocompetent syngeneic mice. This...
To clarify the significance of DNA methylation alterations during renal carcinogenesis, methylome analysis using single-CpG-resolution Infinium array was performed on 29 normal cortex tissue (C) samples, 107 non-cancerous (N) samples obtained from patients with clear cell carcinomas (RCCs) and 109 tumorous (T) samples. levels at 4830 CpG sites were already altered in N compared C Unsupervised hierarchical clustering based 801 sites, where had occurred inherited by strengthened T clustered...
Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction renal proximal tubules rodents that ultimately leads to high incidence cell carcinoma (RCC) after repeated treatments. We performed high-resolution microarray comparative genomic hybridization identify characteristics the profiles this oxidative stress-induced rat RCCs. The results revealed extensive large-scale alterations preference for...
Non-alcoholic steatohepatitis (NASH) has emerged as a common cause of chronic liver disease and virus-independent hepatocellular carcinoma (HCC) in patients with obesity, diabetes, metabolic syndrome. To reveal the molecular mechanism underlying hepatocarcinogenesis from NASH, microRNA (miRNA) expression profiles were analyzed STAM mice, NASH-HCC animal model. MicroRNA was also examined 42 clinical samples HCC tissue. Histopathological images mice at ages 6, 8, 12, 18 weeks showed findings...
The aim of this study was to clarify the significance DNA methylation alterations during non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Single-CpG-resolution genome-wide analysis performed on 264 liver tissue samples using Illumina Infinium HumanMethylation450 BeadChip. After Bonferroni correction, 3331 probes showed significant in 113 non-cancerous showing NASH (NASH-N) as compared with 55 normal (NLT). Principal component revealed distinct profiles NASH-N that were...
BackgroundCentenarians and supercentenarians with exceptional longevity are excellent models for research towards improvements of healthy life expectancy. Extensive regarding the maintenance reduction epigenetic age has provided insights into increasing longevity. To this end, we explored signatures reflecting hallmarks longevity, including avoidance age-related diseases cognitive functional decline.MethodsIn cross-sectional study, enrolled Japanese non-centenarians (eligible participants...
To evaluate the significance of altered DNA methylation during renal tumorigenesis, tumorous tissues (T) and corresponding nontumorous (N) from 94 patients with tumors, normal (C) 16 without tumors were investigated. status on CpG islands p16, human MutL homologue 1 (hMLH1), von-Hippel Lindau (VHL) thrombospondin-1 (THBS-1) genes methylated in tumor (MINT) -1, -2, -12, -25 -31 clones methyltransferase (DNMT) expression examined by bisulfite modification immunohistochemistry, respectively....
The aim of this study was to identify pathways that have a significant impact during renal carcinogenesis. Sixty-seven paired samples both noncancerous cortex tissue and cancerous from patients with clear cell carcinomas (RCCs) were subjected whole-exome, methylome transcriptome analyses using Agilent SureSelect All Exon capture followed by sequencing on an Illumina HiSeq 2000 platform, Infinium HumanMethylation27 BeadArray SurePrint Human Gene Expression microarray, respectively. Sanger...
We identify clinicopathological variables predicting overall survival in patients with recurrent bladder urothelial carcinoma after radical cystectomy.We retrospectively collected data on 114 treated cystectomy for who subsequently had remote metastasis and/or local recurrence. The Kaplan-Meier method the log rank test and multivariate Cox regression models were used to address recurrence.During followup 99 of died. Median was 11.2 months. One 3-year rates 48.0% 12.1%, respectively. On...
The aim of this study was to clarify the significance DNA methylation alterations during lung carcinogenesis. Infinium assay performed using 139 paired samples non-cancerous tissue (N) and tumorous (T) from a learning cohort patients with adenocarcinomas (LADCs). Fifty N T validation were also analyzed. on 1,928 probes occurred in relative normal without primary tumors, inherited by, or strengthened in, samples. Unsupervised hierarchical clustering levels all 26,447 subclustered into Cluster...
Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification therapeutic targets for diseases such as cancers. In this connection, Japanese Society Pathology (JSP) has developed “The JSP Guidelines on Handling Pathological Tissue Samples Genomic Research” based an abundance data from empirical analyses stored under various conditions. should be appropriate sites within surgically resected...
The aim of this study was to clarify the significance DNA methylation alterations at precancerous stages lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide analysis performed in 36 samples normal tissue obtained from patients without any primary tumor, 145 non-cancerous (N) with adenocarcinomas, and tumorous (T). Stepwise progression then samples, observed 3,270 CpG sites, suggesting that adenocarcinomas alterations. At sites 2,083 genes, status significantly...
The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide analysis and targeted sequencing tumor-related genes were using Infinium MethylationEPIC BeadChip Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples normal control tissue from patients without cancer 81 tissue. Principal component revealed that tumor had a profile distinct samples. Gene Ontology enrichment significant differences at 1034...
The aim of this study was to investigate DNA methylation alterations in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinomas (HCCs).Genome-wide analysis performed using the Infinium Human Methylation 450 K BeadChip, and levels mRNA expression were analyzed by quantitative reverse transcription-PCR.Compared 36 samples normal control liver tissue (C), observed on 19,281 probes 22 cancerous (T) obtained from patients showing histological features compatible with NASH their...
Induced pluripotent stem cells (iPSCs) are capable of providing an unlimited source from all three germ layers and cells. The derivation usage iPSCs various animal models may facilitate cell-based therapy, gene-modified production, evolutionary studies assessing interspecies differences. However, there is a lack species-wide methods for deriving iPSCs, in particular by means non-viral non-transgene-integrating (NTI) approaches. Here, we demonstrate the iPSC somatic fibroblasts multiple...
To clarify genome-wide DNA methylation profiles during hepatocarcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed on 126 tissue samples. The average numbers of BAC clones showing hypo- or hypermethylation increased from noncancerous liver obtained patients with hepatocellular carcinomas (HCCs) (N) to HCCs. N appeared be at the precancerous stage, alterations that were correlated future development HCC. Using Wilcoxon test, 25...
The CpG island methylator phenotype (CIMP) of clear cell renal carcinomas (ccRCCs) is characterized by accumulation DNA methylation at islands and poorer patient outcome. aim this study was to establish criteria for prognostication patients with ccRCCs using the ccRCC-specific CIMP marker genes. levels 299 sites in 14 genes were evaluated quantitatively tissue specimens 88 CIMP-negative CIMP-positive a learning cohort MassARRAY system. An additional 100 also analyzed as validation cohort....