A5040795325- Gastric Cancer Management and Outcomes
- Esophageal Cancer Research and Treatment
- Metastasis and carcinoma case studies
- Telomeres, Telomerase, and Senescence
- Gastrointestinal Tumor Research and Treatment
- Extracellular vesicles in disease
- Cancer-related Molecular Pathways
- Esophageal and GI Pathology
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- Neuroendocrine Tumor Research Advances
- RNA regulation and disease
- Cancer Cells and Metastasis
- Lung Cancer Research Studies
- Cancer Research and Treatments
- Dental materials and restorations
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- Dental Research and COVID-19
- Helicobacter pylori-related gastroenterology studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Retinoids in leukemia and cellular processes
- Circular RNAs in diseases
Japanese Foundation For Cancer Research
2014-2024
Saku Central Hospital
2013-2024
The University of Tokyo
2024
Japan Agency for Medical Research and Development
2019-2023
Saitama Cancer Center
2018-2023
Nippon Medical School
2015-2022
Japan Science and Technology Agency
2019-2021
Kitasato University Hospital
2020
National Cancer Center Hospital East
2013-2017
Sapporo Medical University
2012-2013
Abstract Emerging evidence is revealing that exosomes contribute to many aspects of physiology and disease through intercellular communication. However, the biological roles exosome secretion in exosome-secreting cells have remained largely unexplored. Here we show plays a crucial role maintaining cellular homeostasis cells. The inhibition results accumulation nuclear DNA cytoplasm, thereby causing activation cytoplasmic sensing machinery. This event provokes innate immune response, leading...
Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation. However, altered secretome senescent can promote growth surrounding cancer cells. Although extracellular vesicles (EVs) have emerged as new players in intercellular communication, their role function cell has been largely unexplored. Here, we show that exosome-like small EVs (sEVs) are important mediators pro-tumorigenic sEV-associated EphA2 secreted from binds to ephrin-A1, is, highly expressed...
Abstract Accumulating evidence indicates that the senescence-associated secretory phenotype (SASP) contributes to many aspects of physiology and disease. Thus, controlling SASP will have tremendous impacts on our health. However, understanding regulation is far from complete. Here, we show cytoplasmic accumulation nuclear DNA plays key roles in onset SASP. Although both DNase2 TREX1 rapidly remove fragments emanating nucleus pre-senescent cells, expression these DNases downregulated...
Although radical surgery is recommended for patients not meeting the curative criteria endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) because potential risk lymph node metastasis (LNM), this recommendation may be overestimated and excessive. We aimed to establish a simple scoring system decision making after ESD.This multicenter retrospective study consisted two stages. First, risk-scoring LNM was developed using multivariate logistic regression analysis in 1,101 who...
Abstract Although cellular senescence acts primarily as a tumour suppression mechanism, the accumulation of senescent cells in vivo eventually exerts deleterious side effects through inflammatory/tumour-promoting factor secretion. Thus, development new drugs that cause specific elimination cells, termed senolysis, is anticipated. Here, by an unbiased high-throughput screening chemical compounds and bio-functional analysis, we identify BET family protein degrader (BETd) promising senolytic...
Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little currently known about whether and how causally CRC development. Here we show 12 faecal bacterial taxa enriched patients two independent cohort studies. Among them, 2 Porphyromonas species capable of inducing cellular senescence, an oncogenic stress response, through the secretion metabolite, butyrate. Notably, invasion these bacteria observed tissues, coinciding...
In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated phenotype (SASP) leads to cancer progression and chemoresistance. However, role of CAFs in metastatic lesions molecular mechanism inflammation-related SASP induction are not well understood. We show that pro-inflammatory cytokine-driven EZH2 downregulation maintains by demethylating H3K27me3 marks...
Background and Aim: No studies have previously described the learning curve for colonic endoscopic submucosal dissection (ESD). The aim of present study was to describe ESD large colorectal tumors based on a single colonoscopist's experience. Methods: carried out 120 in 115 patients (68 males, median age 70 years). All procedures were by experienced colonoscopist. cases grouped chronologically into three periods: (1st): 1–40; (2nd): 41–80; (3rd): 81–120. Results: changes proficiency over...
IntroductionThe information regarding therapeutically relevant genomic alterations in small cell lung cancer (SCLC) is not well developed. We analyzed the SCLC genome using an integrative approach to stratify targetable alterations.MethodsWe performed whole exon sequencing (n = 51) and copy number analysis =47) on surgically resected tumors matched normal tissue samples from treatment-naive Japanese patients.ResultsThe demographics of 51 patients included this study were as follows: median...
Expression of the p16Ink4a tumor suppressor gene, a sensor oncogenic stress, is up-regulated by variety potentially stimuli in cultured primary cells. However, because expression also induced tissue culture physiological mechanisms regulating remain unclear. To eliminate any potential problems arising from culture–imposed we used bioluminescence imaging for noninvasive and real-time analysis under various conditions living mice. In this study, show that insults such as ras activation provoke...
Abstract γ‐Glutamyltranspeptidase (GGT) is overexpressed in several types of cancer. Existing GGT‐targeting fluorescence probes can image these cancers, but the fluorescent hydrolysis product leaks from target cancer cells during prolonged incubation or fixation. Here, we present a functionalized probe for GGT, 4‐CH 2 F‐HMDiEtR‐gGlu, which designed to generate an azaquinone methide intermediate activation by GGT; this reacts with intracellular nucleophiles adduct that trapped inside cells,...
Several human cancers have been found to contain cancer stem-like cells (CSCs) having cancer-initiating ability. However, only a few reports shown the existence of CSCs in bone and soft tissue sarcomas. In this study, we identified characterised side population (SP) that showed drug-resistant features sarcoma cell lines. seven osteosarcoma lines (OS2000, KIKU, NY, Huo9, HOS, U2OS Saos2) one malignant fibrous histiocytoma (MFH) line (MFH2003), frequency SP was analysed. Tumourigenicity...
Abstract Although the p16INK4a and p21Waf1/Cip1 cyclin-dependent kinase (CDK) inhibitors are known to play key roles in cellular senescence vitro, their remain rather poorly understood vivo. This situation is partly due possibility of compensatory effect(s) between or upregulation functionally related CDK inhibitors. To directly address cooperative vivo, we generated a mouse line simply lacking both genes [double-knockout (DKO)]. Mouse embryonic fibroblasts (MEF) derived from DKO mice...
Abstract Cancer/testis ( CT ) antigens encoded by genes are immunogenic antigens, and the expression of gene is strictly restricted to only testis among mature organs. Therefore, promising candidates for cancer immunotherapy. In a previous study, we identified novel antigen, DNAJB8 . was found be preferentially expressed in stem‐like cells CSCs )/cancer‐initiating CICs ), it thus CSC antigen. this hypothesized that / rather than non‐ /‐ examined The 74 evaluated side population SP (= main MP...
Cell-cycle arrest in quiescence and senescence is largely orchestrated by the retinoblastoma (Rb) tumor-suppressor pathway, but mechanisms underlying quiescence-senescence switch remain unclear. Here, we show that crosstalk between Rb-AKT-signaling pathways forms this controlling overlapping functions of FoxO3a FoxM1 transcription factors cultured fibroblasts. In absence mitogenic signals, although expression repressed Rb prevents reactive oxygen species (ROS) production maintaining SOD2...
Abstract The p16 INK4a tumour suppressor has an established role in the implementation of cellular senescence stem/progenitor cells, which is thought to contribute organismal ageing. However, since knockout mice die prematurely from cancer, whether reduces longevity remains unclear. Here we show that, mutant homozygous for a hypomorphic allele α-klotho ageing-suppressor gene ( kl kl/kl ), accelerated ageing phenotypes are rescued by ablation. Surprisingly, this due restoration expression and...