A5088002604- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Long-Term Effects of COVID-19
- Cancer therapeutics and mechanisms
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Diagnosis and Treatment
- RNA modifications and cancer
- Quinazolinone synthesis and applications
- Liver physiology and pathology
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
- Fibroblast Growth Factor Research
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- COVID-19 and Mental Health
- Cancer Mechanisms and Therapy
- COVID-19 Clinical Research Studies
- Gastric Cancer Management and Outcomes
- Glycosylation and Glycoproteins Research
- Tuberculosis Research and Epidemiology
- Congenital Diaphragmatic Hernia Studies
Keio University
2016-2025
Keio University Hospital
2025
University Kebangsaan Malaysia Medical Centre
2021
Nihon University
2021
Hyogo Medical University
2021
Pulmonary Associates
2018
Saiseikai Central Hospital
2018
Jikei University School of Medicine
2015
University of Chicago
2011-2014
University of Toyama
2012
// Toshiyuki Hirano 1, * , Hiroyuki Yasuda 1 Tetsuo Tani Junko Hamamoto Ayano Oashi Kota Ishioka Daisuke Arai Shigenari Nukaga Masayoshi Miyawaki Ichiro Kawada Katsuhiko Naoki 2 Daniel B. Costa 3 Susumu S. Kobayashi Tomoko Betsuyaku Kenzo Soejima Division of Pulmonary Medicine, Department Keio University, School Medicine 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan Cancer Center, Hematology/Oncology, Beth Israel Deaconess Medical Harvard School, Boston, MA, USA These authors have contributed...
Alterations in the processing of genetic information carcinogenesis result from stable mutations or epigenetic modifications. It is becoming clear that nucleosomal histones are central to proper gene expression and aberrant DNA methylation genes histone plays important roles tumor progression. To date, several lysine methyltransferases (HKMTs) have been identified now considered be a critical regulator transcription. However, still relatively little known about role HKMTs tumorigenesis.We...
EGFR-mutated lung cancers account for a significant subgroup of non-small cell overall. Third-generation EGFR tyrosine kinase inhibitors (TKI) are mutation-selective with minimal effects on wild-type EGFR. Acquired resistance develops to these agents, however, the mechanisms as yet uncharacterized. In this study, we report that Src-AKT pathway contributes acquired TKI. addition, amplification alleles but not mutant was sufficient confer resistance. These findings underscore importance...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir orally administrable antiviral drug whose mechanism action to selectively inhibit RNA-dependent polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude clinical parameters, but these findings have not been confirmed adequate well-controlled trial. We conducted randomized, single-blind,...
Human lung cancer is a constellation of tumors with various histological and molecular properties. To build preclinical platform that covers this broad disease spectrum, we obtained specimens from multiple sources, including sputum circulating tumor cells, generated living biobank consisting 43 lines patient-derived organoids. The organoids recapitulated the hallmarks original tumors. Phenotypic screening niche factor dependency revealed EGFR mutations in adenocarcinoma are associated...
Abstract Activation of the EGFR pathway is one mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine inhibitors (TKI) such as crizotinib and alectinib. Ceritinib a highly selective ALK inhibitor shows promising efficacy in non–small cell lung cancers (NSCLC) harboring gene rearrangement. However, precise mechanism underlying ceritinib not well-defined. This study set out clarify ALK-translocated cancer find preclinical rationale overcoming pathway–induced...
Background Multiple prolonged symptoms observed in patients who recovered from COVID-19 are defined as long COVID. Although diverse phenotypic combinations possible, they remain unclear. This study aimed to perform a cluster analysis of COVID Japan and clarify the association between its characteristics background factors quality life (QOL). Methods multicentre prospective cohort collected various QOL after January 2020 February 2021. included 935 aged ≥18 years with at 26 participating...
Alectinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the EML4-ALK gene rearrangement. The precise mechanism of acquired resistance to alectinib not well defined. purpose this study was clarify ALK-translocated cancer cells. We established alectinib-resistant cells (H3122-AR) from H3122 NSCLC line, rearrangement, by long-term exposure alectinib. H3122-AR evaluated phospho-receptor tyrosine kinase (phospho-RTK) array...
Lung cancer is a heterogeneous disease encompassing wide array of genetic abnormalities. The MET receptor tyrosine kinase altered in many lung cancers, especially non-small cell (NSCLC), and clinical trials inhibitors that are under way documenting cases acquired resistance. On the basis evidence RON can also be overexpressed NSCLC, we evaluated potent MET/RON dual inhibitor LY2801653 this setting. was more efficacious than MET/ALK/RON/ROS crizotinib with distinct pattern downstream...
Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis. Studies have shown that both MET and its key downstream intracellular signaling partners, PI3K mTOR, are overexpressed in MPM. Here we determined the combinatorial therapeutic efficacy of new generation small molecule inhibitor MET, ARQ 197, dual PI3K/mTOR inhibitors NVP-BEZ235 GDC-0980 cell mouse xenograft models. Cell viability results show lines were sensitive to inhibitors. The combined use 197 either or...
// Keita Masuzawa 1 , Hiroyuki Yasuda Junko Hamamoto Shigenari Nukaga Toshiyuki Hirano Ichiro Kawada Katsuhiko Naoki 2 Kenzo Soejima and Tomoko Betsuyaku Division of Pulmonary Medicine, Department Keio University School Tokyo 160-8582, Japan Cancer Center, Correspondence to: Yasuda, email: hiroyukiyasuda@a8.keio.jp Keywords: EGFR tyrosine kinase inhibitors; mutations; osimertinib; nazartinib; lung cancer Received: July 12, 2017 Accepted: August 26, Published: November 06, ABSTRACT...
Significance A variety of rare mutations account for 10–20% EGFR in nonsmall cell lung cancer. However, due to high diversity, proper medication patients with such is impossible daily clinic. To appropriately treat cancer harboring mutations, a robust prediction model predict sensitivities mutants existing drugs strongly needed. Using molecular dynamics simulation-based model, we successfully predicted diverse exon 20 insertion inhibitors. The findings suggest the usefulness silico...
Abstract EGFR-mutated lung cancer accounts for a significant proportion of cases worldwide. For these cases, osimertinib, third-generation EGFR tyrosine kinase inhibitor, is extensively used as first-line or second-line treatment. However, cells acquire resistance to osimertinib in 1 2 years. Thus, thorough clarification mechanisms highly anticipated. Recent next-generation sequencing (NGS) samples identified several genetically defined such C797S MET amplification. nongenetically are not...
Esophageal cancer incidence is increasing and has few treatment options. In studying receptor tyrosine kinases associated with esophageal cancers, we have identified EPHB4 to be robustly overexpressed in cell lines primary tumor tissues. total, 94 squamous carcinoma, 82 adenocarcinoma, 25 dysplasia, 13 Barrett esophagus, adjacent or unrelated normal tissues were evaluated by immunohistochemistry. expression was significantly higher all the different histologic categories than lines, 3 of 9...
Prognostic understanding in advanced cancer patients and their caregivers may have an impact on the delivery of effective care. The aims this study were to explore prognostic at diagnosis both with lung investigate correlates understanding.A total 193 newly diagnosed 167 enrolled 16 hospitals Japan. We assessed perceptions prognosis goals therapy examined associations sociodemographic characteristics, clinical status, quality life, mood symptoms, status disclosure information by treating...
Abstract Background: Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use biomarkers, have not yet been fully investigated. This study aimed to evaluate (1) relationship between exposure osimertinib, especially its active metabolites (AZ5104 AZ7550), AEs, (2) germline polymorphisms AEs. Methods: We conducted a prospective, longitudinal observational 53 patients with advanced non-small cell lung cancer receiving...
Abstract Background Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes little understanding its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung...
Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue frequently with COVID during and post-acute phases. This study aimed to identify the specific risk factors for general
Abstract Background Companion diagnostic tests play a crucial role in guiding treatment decisions for patients with non‐small cell lung cancer (NSCLC). The Oncomine Dx Target Test (ODxTT) Multi‐CDx System has emerged as prominent companion method. However, its efficacy detecting driver gene mutations, particularly rare warrants investigation. Aims This study aimed to assess the performance of ODxTT mutations NSCLC patients. Specifically, we evaluate sensitivity epidermal growth factor...
Cytoskeletal and focal adhesion abnormalities are observed in several types of cancer, including lung cancer. We have previously reported that paxillin (PXN) was mutated, amplified, overexpressed a significant number cancer patient samples, PXN protein upregulated more advanced stages compared with lower stages, the gene also amplified some pre-neoplastic lesions. Among mutations investigated, we found variant A127T cells enhanced cell proliferation formation colocalized anti-apoptotic B...
Abstract Multiple epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) have been developed to effectively inhibit EGFR-derived signals in non–small cell lung cancer (NSCLC). In this study, we assessed the efficacy of EGFR-TKIs, including a novel third-generation inhibitor naquotinib (ASP8273), clinically relevant EGFR mutations, L858R, exon 19 deletion, L858R+T790M, deletion+T790M with or without C797S mutation, and several 20 insertion mutations. Using structural...