A5058882740- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Neuroblastoma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Sarcoma Diagnosis and Treatment
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Congenital Diaphragmatic Hernia Studies
- Tracheal and airway disorders
- Childhood Cancer Survivors' Quality of Life
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Influenza Virus Research Studies
- Platelet Disorders and Treatments
- Retinoids in leukemia and cellular processes
- Renal and related cancers
- Mesenchymal stem cell research
- Medical Imaging and Pathology Studies
- Respiratory viral infections research
- Congenital Anomalies and Fetal Surgery
- Viral-associated cancers and disorders
The University of Tokyo
2015-2024
Karolinska Institutet
2020-2024
Nagoya University
2024
Tohoku Medical and Pharmaceutical University Hospital
2020-2022
University of Tokyo Hospital
2018-2022
Tohoku Medical and Pharmaceutical University
2020
Japan Society of Chemotherapy
2020
Graduate School USA
2017
Tokyo Medical and Dental University
2017
Kyoto University
1962-2016
Abstract Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel genetic/epigenetic basis of RMS. On methylation patterns, RMS clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes clinical behaviours. A1 A2 especially A1, largely correspond alveolar histology frequent PAX3/7...
Abstract Rare multipotent stem cells replenish millions of blood per second through a time-consuming process, passing multiple stages increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight need for more rapid replenishment from cells, established models hematopoiesis implicate only one mandatory differentiation pathway each cell lineage. Here, we establish nonhierarchical relationship between distinct that all lineages and almost exclusively...
Pleuropulmonary blastoma (PPB) is a rare pediatric malignancy whose pathogens are poorly understood. Recent reports suggest that germline mutations in the microRNA-processing enzyme DICER1 may contribute to PPB development. To investigate genetic basis of this cancer, we performed whole-exome sequencing or targeted deep multiple cases PPB. We found biallelic be very common, more common than TP53 also many tumors. Somatic ribonuclease III (RNase IIIb) domain were identified all evaluable...
Neuroblastoma (NB) is the most common solid tumor found in children, and deletions within 11q region are observed 11% to 48% of these tumors. Notably, such tumors associated with poor prognosis; however, little known regarding molecular targets located 11q.Genomic alterations ATM , DNA damage response (DDR)-associated genes ( MRE11A, H2AFX CHEK1 ), BRCA1, BARD1, CHEK2, MDM2 TP53 were investigated 45 NB-derived cell lines 237 fresh samples. PARP (poly [ADP-ribose] polymerase) inhibitor...
Abstract Although hepatoblastoma is the most common pediatric liver cancer, its genetic heterogeneity and therapeutic targets are not well elucidated. Therefore, we conducted a multiomics analysis, including mutatome, DNA methylome, transcriptome analyses, of 59 samples. Based on methylation patterns, was classified into three clusters exhibiting remarkable correlation with clinical, histological, features. Cluster F largely composed cases fetal histology good outcomes, whereas E1 E2...
Abstract Recent genetic studies using high-throughput sequencing have disclosed alterations in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, their effects on clinical outcomes not been fully investigated. To address this, we comprehensively examined and prognostic impact a large series of pediatric B-ALL cases. We performed targeted capture total 1003 patients with from 2 Japanese cohorts. Transcriptome (n = 116) and/or array-based gene expression analysis 120) were also...
KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover molecular heterogeneity this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with Our multi-omics clustering followed by single-sample single-cell inference hematopoietic differentiation establishes five robust integrative clusters (ICs) different master transcription factors, fusion partners...
ELEVATED serum potassium levels usually result from deranged metabolic processes in renal or adrenal dysfunction whose detection often involves extensive laboratory investigation. Clinical and electrocardiographic findings are corroborative these cases. Increased values without such corollaries occur with the thrombocytosis of some myeloproliferative diseases.1 2 3 4 5 Appreciation extent to which is released under certain conditions during thrombocyte degradation may prevent needless...
Abstract Translocations of retinoic acid receptor-α (RARA), typically PML–RARA, are a genetic hallmark acute promyelocytic leukemia (APL). However, because small fraction APL lack translocations RARA, we focused here on cases without RARA translocation to elucidate the molecular etiology RARA-negative APL. We performed whole-genome sequencing, PCR, and FISH for five translocations. Four had involving receptor-β (RARB) translocations, TBL1XR1–RARB was identified as an in-frame fusion in three...
Aims: Oral administration of probiotics has been known to improve inflammatory responses against infectious diseases. Here, we describe the inhibitory effect oral intake heat-killed Lactobacillus pentosus strain b240 (b240) on pneumococcal pneumonia in a murine experimental model. Method and Results: The mice treated with for 21 days before Streptococcus pneumoniae infection exhibited prolonged survival time less body weight loss, compared saline-treated control mice. Mild significantly...
Pancreatoblastoma is a rare pediatric pancreatic malignancy for which the molecular pathogenesis not understood. In this study, we report findings of an integrated multiomics study whole-exome and RNA sequencing as well genome-wide copy number methylation analyses ten pancreatoblastoma cases. The genome was characterized by high frequency aberrant activation Wnt signaling pathway, either via somatic mutations CTNNB1 (90%) copy-neutral loss heterozygosity (CN-LOH) APC (10%). addition,...
Molecular mechanisms involved in the relapse of T‐cell acute lymphoblastic leukemia (T‐ ALL ) are not fully understood, although activating NOTCH 1 signaling due to 1/ FBXW 7 alterations is a major oncogenic driver. To unravel relevance mutations associated with relapse, we performed whole–exome sequencing 30 pediatric T‐ cases, among which 11 diagnosis‐relapse paired cases were further investigated track clonal evolution using amplicon–based deep sequencing. detected 73.3% (diagnosis) and...
Abstract Children with Down syndrome ( DS ) are at a 20‐fold increased risk for acute lymphoblastic leukemia ALL ). Compared to children and no (non‐ ‐ ), those harbor uncommon genetic alterations, suggesting could have distinct biological features. Recent studies implicated several genes on chromosome 21 in , but the precise mechanisms predisposing remain unknown. Our integrated genetic/epigenetic analysis revealed that was highly heterogeneous many subtypes. Although each subtype had...
Kasabach-Merritt phenomenon (KMP) is a rare condition and optimal treatments have not yet been established, especially for cases that are unresponsive to first-line therapy. We retrospectively reviewed 11 KMP treated over the past 13 years in our institute.With exception of 1 case, steroids were administered as Eight required second-line or third-line The effective salvage therapies include interferon (n=1), radiotherapy chemotherapy (n=5). One case continues depend upon chemotherapy. Three...
To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeted-deep sequencing for 10 neuroblastoma-related genes and SNP arrays analysis. ALK expression was evaluated immunohistochemical analysis in 259 samples. Based on alterations, following 6 subgroups were identified: groups A (ALK abnormalities), B (other gene mutations), C (MYCN amplification), D (11q loss heterozygosity [LOH]), E (at least 1 copy...
Abstract Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed DNA methylation and expression datasets neuroblastomas, extracted a candidate gene characterizing aggressive features, conducted functional studies. Based data, identified subgroup neuroblastoma cases with 11q loss heterozygosity extremely poor prognosis. PHGDH , serine metabolism-related gene, was as strong characteristic in well MYCN...
We previously reported that supplementation of a cationic liposome with transferrin (Tf) greatly enhanced lipofection efficiency (P.-W. Cheng, Hum. Gene Ther. 1996;7:275-282). In this study, we examined the efficacy p53 and PTEN tumor suppressor gene therapy in mouse xenograft model human prostate PC-3 carcinoma cells, using vector consisting dimyristoyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE)-cholesterol (DC) Tf. When volume tumors grown subcutaneously athymic nude mice...
Abstract In the silkworm, Bombyx mori (female, ZW; male, ZZ), femaleness is determined by presence of a single W chromosome, irrespective number autosomes or Z chromosomes. The chromosome devoid functional genes, except putative female‐determining gene ( Fem ). However, there are strains in which chromosomal fragments containing autosomal markers have been translocated on to W. this study, we analysed regions Zebra‐W strain (T(W;3) Ze chromosome) and Black‐egg‐W (T(W;10)+ w−2 at molecular...