A5003384343- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Cardiac Valve Diseases and Treatments
- Chronic Myeloid Leukemia Treatments
- RNA modifications and cancer
- Cancer therapeutics and mechanisms
- Infective Endocarditis Diagnosis and Management
- Colorectal Cancer Treatments and Studies
- Cardiac Imaging and Diagnostics
- Neuroendocrine Tumor Research Advances
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Cardiovascular Function and Risk Factors
- Diabetes Management and Research
- Epigenetics and DNA Methylation
- Coronary Interventions and Diagnostics
- DNA Repair Mechanisms
- Pancreatic function and diabetes
- Electromagnetic Scattering and Analysis
- Cardiac electrophysiology and arrhythmias
- Atrial Fibrillation Management and Outcomes
- Diabetes and associated disorders
- Aortic Disease and Treatment Approaches
- Dialysis and Renal Disease Management
National Cancer Center Hospital East
2022-2025
Tohoku University
1971-2025
Center for Cancer Research
2018-2024
Aichi Medical University
2024
National Cancer Institute
2018-2024
Himeji Medical Center
2023-2024
National Center for Global Health and Medicine
2014-2024
National Institutes of Health
2018-2024
Kansai Medical University
2009-2023
Tokyo Women's Medical University
1999-2023
Abstract Immune checkpoint blockade (ICB) benefits only a small subset of patients with cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors clinical to ICB, we performed immunogenomic profiling tumor samples from relapsed SCLC. Tumors who derive ICB exhibit cytotoxic T-cell infiltration, high expression antigen processing and presentation machinery (APM) genes, low neuroendocrine (NE) differentiation. However, elevated Notch signaling,...
Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade the 'don't-eat-me' cell-surface molecule CD47 in small cell lung (SCLC), highly metastatic form cancer. potently enhances local antitumor effects preclinical models SCLC. Notably, also stimulates off-target 'abscopal' inhibiting non-irradiated SCLC tumors mice receiving radiation. These abscopal are independent T cells require macrophages that...
Abstract Molecular subtypes of small cell lung cancer (SCLC) defined by the expression key transcription regulators have recently been proposed in lines and limited number primary tumors. The clinical biological implications neuroendocrine (NE) metastatic SCLC, extent to which they vary within between patient tumors patient-derived models is not known. We integrate histology, transcriptome, exome, treatment outcomes SCLC from a range sites, revealing complex intra- intertumoral heterogeneity...
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine cancer. Oncogenic MYC amplifications drive SCLC heterogeneity, but the genetic mechanisms of amplification and phenotypic plasticity, characterized by nonneuroendocrine cell states, are not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA fluorescence in situ hybridization to find extrachromosomal (ecDNA) as a primary source oncogene driver fusions. ecDNAs bring proximity enhancer...
Matsuo, Kiyoshi M.D; Hirose, Takeshi Tomono, Tokio Iwasawa, Motonao Katohda, Susumu Takahashi, Nobuyuki Koh, Buon M.D. Author Information
Abstract Although several ATR inhibitors are in development, there unresolved questions regarding their differential potency, molecular signatures of patients with cancer for predicting activity, and most effective therapeutic combinations. Here, we elucidate how to improve ATR-based chemotherapy the newly developed inhibitor, M4344 using vitro vivo models. The potency was compared clinically BAY1895344, berzosertib, ceralasertib. anticancer activity investigated as monotherapy combination...
Full-color fluorescent display devices are demonstrated using a near-UV (n-UV) light-emitting diode (LED) and various films. ZnS:Ag (blue), ZnS:Cu,Al (green) ZnCdS:Ag (red) powdered fluors mixtures of them dispersed in poly-vinyl-alcohol aqueous solutions, films prepared by spin coating the suspensions to glass slides. The n-UV light emitted from blue LED with high injection current is irradiated onto films, three primary colors white color easily obtained.
Tegoprazan [(<i>S</i>)-4-((5,7-difluorochroman-4-yl)oxy)-<i>N</i>,<i>N</i>,2-trimethyl-1<i>H</i>-benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB), is novel potent and highly selective inhibitor of gastric H<sup>+</sup>/K<sup>+</sup>-ATPase. inhibited porcine, canine, human H<sup>+</sup>/K<sup>+</sup>-ATPases in vitro with IC<sub>50</sub> values ranging from 0.29 to 0.52 <i>μ</i>M, while that for canine kidney Na<sup>+</sup>/K<sup>+</sup>-ATPase was more than 100...
Coronary protection with guidewires and an undeployed coronary balloon or stent positioned in the artery is a pre-emptive technique to manage obstruction during transcatheter aortic valve implantation (TAVI). We investigated feasibility safety of left main (LM) TAVI.Twenty-five out 623 patients who underwent TAVI at our institute were deemed be increased risk LM compromise mainly due low ostium height, significant disease previous bioprosthetic valve. A was therefore used these cases. Five...
Because tobacco is a potent carcinogen, secondary causes of lung cancer are often diminished in perceived importance. To assess the extent inherited susceptibility to small cell (SCLC), most lethal type cancer, we sequenced germline exomes 87 patients (77 SCLC and 10 extrapulmonary cell) considered 607 genes, discovering 42 deleterious variants 35 cancer-predisposition genes among 43.7% patients. These findings were validated an independent cohort 79 with SCLC. Loss heterozygosity was...
Endogenous replication stress is a major driver of genomic instability. Current assessments are low throughput precluding its comprehensive assessment across tumors. Here we develop and validate transcriptional profile by leveraging established cellular characteristics that portend stress. The repstress gene signature defines subset tumors lineages characterized activated oncogenes, aneuploidy, extrachromosomal DNA amplification, immune evasion, high instability, poor survival, importantly...
Patients with relapsed small cell lung cancer (SCLC), a high replication stress tumor, have poor prognoses and few therapeutic options. A phase 2 study showed antitumor activity the addition of ataxia telangiectasia Rad3-related kinase inhibitor berzosertib to topotecan.
Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted delivery might enable clinical translation such combinations.In a phase I trial, we combined sacituzumab govitecan, antibody-drug conjugate (ADC) delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia Rad3-related (ATR) berzosertib. Twelve patients were enrolled across three dose...
Abstract Small‐cell lung cancer (SCLC) is the most lethal type of cancer. Specifically, MYC‐driven non‐neuroendocrine SCLC particularly resistant to standard therapies. Lurbinectedin was recently approved for treatment relapsed SCLC, but combinatorial approaches are needed increase depth and duration responses lurbinectedin. Using high‐throughput screens, we found inhibitors ataxia telangiectasia mutated rad3 related (ATR) as effective agents augmenting lurbinectedin efficacy. First‐in‐class...
Patients with small-cell lung cancer (SCLC) have poor prognosis and typically experience only transient benefits from combined immune checkpoint blockade (ICB) chemotherapy. Here, we show that inhibition of ataxia telangiectasia rad3 related (ATR), the primary replication stress response activator, induces DNA damage–mediated micronuclei formation in SCLC models. ATR activates stimulator interferon genes (STING)–mediated signaling, recruits T cells, augments antitumor programmed death-ligand...
We assessed the geometry of transcatheter heart valve (THV) and function associated with SAPIEN 3 implantation in patients bicuspid aortic (BAV) stenosis.We included 280 consecutive who had a contrast computed tomography (CT) before after (TAVI) our institution. Each THV was by CT at five cross-sectional levels: inflow, annulus, mid, sinus, outflow. The for eccentricity (1 - minimum diameter/maximum diameter) expansion (CT derived external area/nominal area). measurements transthoracic...
Stent-frame morphology of the newer-generation, balloon-expandable transcatheter heart valve (THV), SAPIEN 3 (S3), after aortic implantation (TAVI) is unknown. We evaluated THV stent-frame post TAVI S3 using multi-slice computed tomography (MSCT) compared with prior-generation THV, XT (S-XT). A total 94 consecutive participants RESOLVE registry (NCT02318342) had MSCT (S3 = 39 and S-XT 55). The was for expansion area eccentricity at THV-inflow, native annulus, mid-THV THV-outflow levels. Mean...
Small-cell lung cancer (SCLC) is the most fatal form of cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but cell-extrinsic drivers SCLC plasticity are poorly understood. To map landscape tumor microenvironment (TME), we apply spatially resolved transcriptomics quantitative mass spectrometry-based proteomics to metastatic tumors obtained via rapid autopsy. The phenotype overall composition non-malignant cells in TME...