A5044742615- Sarcoma Diagnosis and Treatment
- Pharmacy and Medical Practices
- Musculoskeletal synovial abnormalities and treatments
- Soft tissue tumors and treatment
- Pharmaceutical Practices and Patient Outcomes
- HER2/EGFR in Cancer Research
- BRCA gene mutations in cancer
- Safe Handling of Antineoplastic Drugs
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Cancer Treatment and Pharmacology
- Adipose Tissue and Metabolism
- Advanced Breast Cancer Therapies
- Endometrial and Cervical Cancer Treatments
- Lung Cancer Treatments and Mutations
- Breast Cancer Treatment Studies
- Cancer Immunotherapy and Biomarkers
- Palliative Care and End-of-Life Issues
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Inflammatory Biomarkers in Disease Prognosis
- Phytochemicals and Antioxidant Activities
- Statistical Methods in Clinical Trials
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Tumors and Oncological Cases
National Cancer Center
2015-2024
National Cancer Centre Japan
2022-2024
Institut Gustave Roussy
2019-2024
National Cancer Center Hospital East
2015-2023
Inserm
2019
Tokyo National Hospital
2017-2018
Prevention Group
2018
Kyushu University of Health and Welfare
2007-2017
University of Tsukuba
2016
Saitama Medical University
2014
Uterine cervical adenocarcinoma is rare, but its prevalence has increased. To improve outcomes and ensure the suitability of recent immunotherapies, aim this study was to evaluate clinicopathological impact tumor immune microenvironment uterine adenocarcinoma. We investigated 148 cases, including 21 cases in situ ( AIS ) 127 invasive adenocarcinoma, using immunohistochemistry detect tumor‐infiltrating cells expression programmed cell death 1 ligand‐1 PD ‐L1) p16 on cells. then carried out...
Clinical and epidemiological studies have indicated that the consumption of green tea has a number beneficial effects on health. Epigallocatechin-3-gallate (EGCg), major polyphenolic compound present in tea, received much attention as an active ingredient. Among numerous promising profiles EGCg, study focused anticancer effects. Apoptosis induced by EGCg subsequent cell growth suppression been demonstrated culture studies. However, underlying mechanism apoptotic death remains unclear. Thus,...
Abstract Many disease-associated genomic variants disrupt gene function through abnormal splicing. With the advancement of medicine, identifying splicing associated has become more important than ever. Most bioinformatics approaches to detect require both genome and transcriptomic data. However, there are not many datasets where them available. In this study, we develop a methodology that cause changes (more specifically, intron retention), using transcriptome sequencing data alone. After...
Triple-negative breast cancer (TNBC) is negative for hormone receptors and human epidermal growth factor receptor 2 (HER2). In stage I TNBC, adjuvant therapy or follow-up are performed according to risk factors, but clinical trial data scarce. recent years, it has been reported that HER2-low cases (1+/2+ in situ hybridization negative) have different prognoses than HER2-0 cases. However, the of recurrence factors this population TNBC not yet investigated.Herein, out 174 patients with who...
<p>EWS–WT1 drives enhanced DNA replication stress and R-loops, which contribute to DSRCT cells’ sensitivity PARPi ATRi. <b>A,</b> Assessment of fork speed (kb/minute) in JN1 cells subjected siRNA-mediated silencing EWS–WT1 or CCND1. A minimum 50 forks was analyzed per condition. Mean ± SD; each dot represents a single fork; <i>n</i> = 2, one-way ANOVA <i>post hoc</i> Dunnett test. <b>B,</b> exposed DMSO control, combination talazoparib...
<p>PARPi and ATRi have synergistic cytotoxic effects in models of DSRCT with high PARP1 expression. <b>A</b> <b>B,</b> expression (<b>A</b>) PARylation levels (<b>B</b>) as assessed by IHC a cohort 16 samples, compared those the JN1 R cell lines (PARP1 PAR are shown H-scores). Representative cases (PARP1-high vs. PARP1-low tumors; PAR-high PAR-low tumors) to right, cells. <b>C</b> <b>D,</b> Surface plots Bliss...
<p>EWS–WT1 is a determinant of DSRCT cells’ sensitivity to PARPi and ATRi. <b>A,</b> Western blot EWS–WT1 in JN1 R cells transfected with either siCNTRL or siEWS–WT1. Whole-cell lysates were generated 48 hours after transfection. <b>B–E,</b> Dose–response survival curves exposed talazoparib (<b>B</b> <b>C</b>) ATRi M4344 (<b>D</b> <b>E</b>) for 7 days the presence absence siRNA-mediated silencing EWS–WT1. Mean ±...
<div>Abstract<p>Desmoplastic small round cell tumor (DSRCT) is an aggressive sarcoma subtype that driven by the EWS–WT1 chimeric transcription factor. The prognosis for DSRCT poor, and major advances in treating have not occurred over two decades. To identify effective therapeutic approaches to target DSRCT, we conducted a high-throughput drug sensitivity screen line assessing chemosensitivity profiles 79 small-molecule inhibitors. cells were sensitive PARP inhibitors (PARPi)...
<p>The combination of PARPi and ATRi elicits a cGAS–STING–mediated cell-autonomous immune response. <b>A,</b> Western blots pTBK1, TBK, pIRF3, IRF3 in JN1 cells exposed to DMSO control, talazoparib (Tala), M4344, or both for 72 hours. <b>B</b> <b>C,</b> RT-qPCR analysis RNA isolated from talazoparib, CCL5 (<b>B</b>) CXCL10 (<b>C</b>) mRNA were analyzed separately relative RPLP0. Box whisker plots show arbitrary units gene...
<p>Supplementary File containing methods, figures and uncropped membranes.</p>
<p>PARPi and ATRi combination elicits DNA damage, replication stress, genomic instability in DSRCT cells. <b>A–D,</b> Quantification of γH2AX (<b>A</b> <b>B</b>) or RAD51 foci (<b>C</b> <b>D</b>) JN1 <b>C</b>) R (<b>B</b> cells exposed to DMSO control, PARPi talazoparib (Tala), M4344, a both for 72 hours. Cisplatin was used as the positive control. A minimum 500 nuclei analyzed per condition. Violin...
<p>A small-molecule inhibitor and drug screen identifies PARPi ATRi as candidate therapies for DSRCT. <b>A,</b> Schematic illustration of the workflow performed on JN1 cell line. <b>B,</b> Waterfall plot displaying difference in AUC between line (AUC<sub>JN1</sub>) panel 92 lines used comparison (AUC<sub>median</sub>) 79 evaluated inhibitors or drugs. Red, PARPi; blue, ATRi; green, conventional cytotoxic. <b>C–F,</b>...
Introduction: Next-generation sequencing (NGS) is commonly used in clinical practice to decide treatment based on genomic information. This study was performed optimize the proportion of actionable gene profiling and genetic alterations breast cancer at one centers Japan. Methods: Patients with who reported NGS results Japan from August 2019 December 2023 were retrospectively investigated by reviewing their electronic medical records. examined using OncoGuideTM NCC Oncopanel System,...
ABSTRACT Background Adenoid cystic carcinoma (ACC) is the second most common and treatment‐resistant salivary gland (SGC). Although platinum‐based therapies are effective, efficacy of eribulin, a microtubule inhibitor with an 18% response rate in Phase II trial involving recurrent/metastatic SGC, patients advanced ACC after platinum therapy remains unclear. Methods We retrospectively analyzed 19 unresectable/metastatic treated between December 2015 January 2023 at National Cancer Center...
Telomerase reverse transcriptase (TERT) promoter mutations have been discovered in solid and hematological malignancies, where they reflect TERT activation cell-cycle progression. In melanoma, glioma, thyroid cancers, are associated with a poor prognosis. However, no studies evaluated the prevalence prognostic significance of breast cancer. We analyzed hotspot (C228T C250T) using direct sequencing DNA from 319 tumor tissues. also collected clinical data cases that were positive for...
Abstract Prognostic value of hematologic indices and their association with the tumor microenvironment (TME) remain unclear in advanced soft tissue sarcoma (STS). We aimed to evaluate prognostic correlation TME status STS treated first-line doxorubicin (DXR) therapy. Clinical data three hematological indices, including lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte were collected from 149 patients STS. The was pathologically examined by CD3, CD68,...
Evidence on the association between BMI, height, and endometrial cancer risk, including by subtypes, among Asian populations remains limited. We evaluated impact of BMI height risk cancer, overall histological subtype. prospectively investigated 53 651 Japanese women aged 40-69 years. With an average follow-up duration 18.6 years, 180 newly diagnosed cancers were reported, 119 type 1 21 2. The was assessed using a Cox proportional hazards regression model with adjustment for potential...
Abstract Introduction: Antibody-drug conjugates (ADCs) targeting trophoblast cell surface antigen 2 (TROP2), such as sacituzumab-govitecan and datopotamab-deruxtecan, have recently been developed. A preclinical study has reported the efficacy of anti-human epidermal growth factor receptor (HER2) TROP2 bispecific ADCs in treating HER2 co-expressing tumors, including HER2-low tumors various solid (Chengzhang Shang et al: AACR 2023). In this study, we aimed to evaluate expression by...
Interstitial lung disease is a serious drug‐related condition that can cause life threatening organ failure. The incidence and risk factors of drug‐induced interstitial ( DILD ) are unknown in oncology phase I trials. This study analyzed clinical information from 8906 patients with malignancies who were enrolled 470 trials sponsored by the Cancer Therapy Evaluation Program, National Institute, 1988 to 2014. Logistic Cox statistical analyses utilized determine differences between developed...