A5044383315- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Protein Tyrosine Phosphatases
- Protein Kinase Regulation and GTPase Signaling
- Cancer Genomics and Diagnostics
- Head and Neck Cancer Studies
- Digestive system and related health
- Pancreatic and Hepatic Oncology Research
- Genetic factors in colorectal cancer
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- PI3K/AKT/mTOR signaling in cancer
- Colorectal and Anal Carcinomas
- Hepatocellular Carcinoma Treatment and Prognosis
- ATP Synthase and ATPases Research
- Hippo pathway signaling and YAP/TAZ
- Helicobacter pylori-related gastroenterology studies
- Cancer Research and Treatments
- Biochemical and Molecular Research
- Cytokine Signaling Pathways and Interactions
- Tumors and Oncological Cases
Tokyo Medical and Dental University
2012-2025
The University of Tokyo
2023-2024
Shanghai Institute for Science of Science
2024
University of Toronto
2014-2022
Tokyo Medical and Dental University Hospital
2021-2022
Canada Research Chairs
2015-2016
Tokyo University of Pharmacy and Life Sciences
2012
Tsuchiura Kyodo General Hospital
2008
Abstract Ras is phosphorylated on a conserved tyrosine at position 32 within the switch I region via Src kinase. This phosphorylation inhibits binding of effector Raf while promoting engagement GTPase-activating protein (GAP) and GTP hydrolysis. Here we identify SHP2 as ubiquitously expressed phosphatase that preferentially binds to dephosphorylates increase its association with activate downstream proliferative Ras/ERK/MAPK signalling. In comparison normal astrocytes, activity elevated in...
The transcription factor Atoh1/Hath1 plays crucial roles in the differentiation program of human intestinal epithelium cells (IECs). Although previous studies have indicated that Notch signal suppresses IEC, mechanism by which it does so remains unknown. This study shows undifferentiated state is maintained suppression Hath1 gene intestine. To assess effect signaling, doxycycline-induced expression intracellular domain (NICD) and Hes1 were generated LS174T. was analyzed quantitative...
Significance Despite the well-established connection between Ras and Src, there currently is no evidence of direct interaction these two proteins. We show here that Src binds to phosphorylates GTP-loaded on a conserved Y32 residue within switch I region. It has been shown Raf with an affinity 1,000-fold greater than GAP. However, it remained unclear how GAP able outcompete for upon displacement. phosphorylation inhibits binding concomitantly promotes association GTP hydrolysis, thereby...
Abstract Deregulation of the RAS GTPase cycle due to mutations in three genes is commonly associated with cancer development. Protein tyrosine phosphatase SHP2 promotes RAF-to-MAPK signaling pathway and an essential factor RAS-driven oncogenesis. Despite emergence inhibitors for treatment cancers harbouring mutant KRAS, mechanism underlying activation KRAS remains unclear. Here we report tyrosyl-phosphorylation endogenous demonstrate that phosphorylation via Src on Tyr32 Tyr64 alters...
Survival for high-risk neuroblastoma remains poor and treatment relapsed disease rarely leads to long-term cures. Large sequencing studies of tumors from diagnosis have not identified common targetable driver mutations other than the 10% that harbor in anaplastic lymphoma kinase (ALK) gene. However, at recurrence, more frequent genes RAS-MAPK pathway been detected. The PTPN11-encoded tyrosine phosphatase SHP2 is an activator RAS pathway, we others shown pharmacologic inhibition suppresses...
Abstract Background The programmed cell death-1 (PD-1) receptor and its ligands PD-L1 PD-L2 are immune checkpoints that suppress anti-cancer immunity. Typically, cancer cells express the PD-Ls bind PD-1 on cells, inhibiting their activity. Recently, expression has also been found in cells. Here, we analysed functions of thyroid (TC). Methods was evaluated by immunohistochemistry human TC samples RT-PCR, western blot FACS lines. Proliferation migration culture were assessed BrdU incorporation...
Introduction Clinical sequencing has provided molecular and therapeutic insights into the field of clinical oncology. However, despite its significance, utility in Japanese patients remains unknown. Here, we examined tissue-based with FoundationOne ® CDx Heme. Between August 2018 2019, 130 pretreated advanced solid tumors were tested or Results The median age was 60.5 years (range: 3 to 84 years), among them, 64 males 66 females. Major cancer types gastrointestinal (23 cases) hepatic,...
Abstract Cancer cells bearing distinct KRAS mutations exhibit variable sensitivity to SHP2 inhibitors (SHP2i). Here we show that harboring Q61H are uniquely resistant SHP2i, and investigate the underlying mechanisms using biophysics, molecular dynamics, cell-based approaches. mutation impairs intrinsic GAP-mediated GTP hydrolysis, impedes activation by SOS1, but does not alter tyrosyl phosphorylation. Wild-type Q61H-mutant both phosphorylated Src on Tyr32 Tyr64 dephosphorylated SHP2,...
Abstract Objectives An understanding of the tumor immune microenvironment is required to improve treatment, especially selection checkpoint inhibitors (ICIs). In this study, we stratified immunotypes tongue squamous cell carcinoma (TSCC) based on results comprehensive profiling. Methods We enrolled 87 therapy-naïve TSCC and 17 ICI-treated patients who underwent glossectomy without any other prior therapy. Comprehensive profile analyses employed multiplex immunofluorescence tissue imaging....
Comprehensive genomic profiling (CGP) provides information regarding cancer-related genetic aberrations. However, its clinical utility in recurrent/metastatic head and neck cancer (R/M HNC) remains unknown. Additionally, predictive biomarkers for immune checkpoint inhibitors (ICIs) should be fully elucidated because of their low response rate. Here, we analyzed the CGP identified that respond to ICIs R/M HNC. We evaluated over 1100 cases HNC using nationwide database established by Center...
Abstract Clear cell renal carcinoma (ccRCC) is the most common form of kidney cancer and major cause mortality for individuals with von Hippel-Lindau (VHL) disease. ccRCC characterized frequently by inactivation VHL tumor suppressor protein that mediates degradation alpha subunit hypoxia-inducible factor (HIF) transcription family. HIF has been implicated in disease progression aim this study was to identify novel target genes may contribute ccRCC. We show GAL3ST1, an enzyme catalyzes...
The emerging concepts of fetal-like reprogramming following tissue injury have been well recognized as an important cue for resolving regenerative mechanisms intestinal epithelium during inflammation. We previously revealed that the remodeling mesenchyme with collagen fibril induces YAP/TAZ-dependent fate conversion intestinal/colonic epithelial cells covering wound bed towards progenitors. To fully elucidate underlying link between extracellular matrix (ECM) and cells, it is critical to...
Patients with inflammatory bowel disease ( IBD ) have an increased risk of developing colitis‐associated colorectal cancer CAC ). cells often develop chemoresistance, resulting in a poorer prognosis than that sporadic CRC The mechanism by which enhances malignant potential remains unknown. We previously reported the proteasomal degradation transcription factor Atonal homolog 1 (Atoh1) protein results non‐mucinous form . It also unknown whether Atoh1 is expressed Therefore, present study, we...
Abstract Aim The use of immune checkpoint inhibitors (ICIs) has increased remarkably, and immune‐related adverse events (irAEs) have also increased. This study aimed to identify factors associated with liver injury (irLI), the relationship between grades irLI overall survival (OS) in patients treated ICIs. Methods A total 571 who had been for advanced malignancies ICIs January 2015 March 2022 were retrospectively recruited. presence was determined by aspartate aminotransferase alanine...
This study aimed to investigate the clinical usefulness of comprehensive genomic profiling (CGP) in patients with unresectable hepatocellular carcinoma who received multiple systemic therapies real-world practice. In this study, all nine had gene alterations, and seven were candidates eligible for trials based on results CGP. The median number alterations per patient was four, blood sample used five extrahepatic metastasis. We revealed information reported utility samples Furthermore, status...
Immune checkpoint inhibitors (ICIs) are effective in treating recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but only 20% of patients achieve durable responses. This study evaluated circulating tumor DNA (ctDNA) as a real-time biomarker for monitoring treatment response HNSCC. The SHIZUKU-HN prospectively collected analyzed serial plasma samples (n = 27) from HNSCC undergoing ICIs, using Guardant360 to assess ctDNA variant allele frequency (VAF) genetic mutations. Tumor...
Background and Objectives: Adenoid cystic carcinoma (ACC) of the head neck is generally slow-growing but has a high potential for local recurrence metastasis to distant organs. There currently no standard pharmacological treatment recurrent/metastatic (R/M) ACC, there are cases in which immune checkpoint inhibitors (ICIs) administered ACC according squamous cell (HNSCC). However, efficacy ICIs remains unclear, predictive biomarkers need be elucidated. Materials Methods: The Center Cancer...