A5011349417- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Pancreatic and Hepatic Oncology Research
- Radiopharmaceutical Chemistry and Applications
- Melanoma and MAPK Pathways
- Lung Cancer Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- Phagocytosis and Immune Regulation
- Colorectal Cancer Treatments and Studies
- Cancer Mechanisms and Therapy
- Ubiquitin and proteasome pathways
- Cancer Immunotherapy and Biomarkers
- HER2/EGFR in Cancer Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Microtubule and mitosis dynamics
- Ferroptosis and cancer prognosis
- Pneumonia and Respiratory Infections
- Brain Metastases and Treatment
- Cancer Research and Treatments
- S100 Proteins and Annexins
- Neuroendocrine Tumor Research Advances
Kanazawa Medical University Hospital
2024-2025
Kanazawa University Hospital
2021-2025
Tokyo Dental College
2017-2025
Kanazawa University
2015-2024
Kyoto Prefectural University of Medicine
2021
Kanazawa Medical University
2021
Tokyo Metropolitan Komagome Hospital
2021
Kurashiki Central Hospital
2010-2020
Kobe City Medical Center General Hospital
2012
Katsushika Medical Center
2011
A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated was associated EGFR HER3 maintaining cell survival inducing the emergence of cells tolerant inhibition reduced viability cancer overexpressing were exposed The addition during either...
Abstract Background The ATLANTIC trial reported that higher PD-L1 expression in tumors was involved a objective response patients with EGFR + /ALK non-small cell lung cancer (NSCLC), indicating the possibility of anti-PD-1/PD-L1 therapy as third-line (or later) treatment for advanced NSCLC. Therefore, determination status and regulatory mechanisms mutant NSCLC before after acquired EGFR-TKIs resistance are meaningful. Methods correlation among PD-L1, c-MET, HGF analyzed based on TCGA...
BACKGROUND The secondary epidermal growth factor receptor (EGFR) mutation Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR‐tyrosine kinase inhibitor (TKI). Recent reports have demonstrated that the emergence T790M predicts a favorable prognosis and indolent progression. However, rebiopsy confirm status can be challenging due limited tissue availability procedural feasibility, little is known regarding differences among patients with or without mutation....
Abstract Purpose: Currently, an optimal therapeutic strategy comprising molecularly targeted agents for treating EGFR-mutated non–small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib is not available. Therefore, the initial intervention crucial prolonged survival of these patients. The activation anexelekto (AXL) signaling known be associated intrinsic and EGFR tyrosine kinase inhibitors (EGFR-TKIs). In this study, we investigated best combat AXL-induced tolerance...
Abstract Drug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including osimertinib, through mechanisms that still remain unclear. Here, we show while AXL-low expressing EGFR mutated lung cancer ( mut-LC) cells are more sensitive osimertinib than AXL-high mut-LC cells, a small population emerge tolerance. The mediated by increased expression and phosphorylation of insulin-like factor-1 receptor (IGF-1R), caused...
Abstract Mutations in the ALK gene are detectable approximately 40% of ALK-rearranged lung cancers resistant to inhibitors. Although epithelial-to-mesenchymal transition (EMT) is a mechanism resistance various targeted drugs, its involvement inhibitor largely unknown. In this study, we report that both ALK-mutant L1196M and EMT were concomitantly detected single crizotinib-resistant lesion patient with cancer. Digital PCR analyses combined microdissection after IHC staining for markers...
Molecularly targeted cancer therapy has improved outcomes for patients with targetable oncoproteins, such as mutant EGFR in lung cancer. Yet, the long-term survival of these remains limited, because treatment responses are typically incomplete. One potential explanation lack complete and durable is that oncogene-driven cancers activating mutations often harbor additional co-occurring genetic alterations. This hypothesis untested most alterations co-occur EGFR. Here, we report functional...
There have been few data on the chemotherapy in elderly advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS), and usefulness of for such remains unclear. The objective this study was to identify factors that predicted survival benefit chemotherapy.All consecutive (≥75 years) NSCLC, Eastern Cooperative Oncology Group PS ≥2, EGFR mutation wild type/unknown, newly diagnosed from January 2009 December 2012 at a tertiary hospital were retrospectively reviewed.We...
In ALK-rearranged non-small cell lung cancer (NSCLC), impacts of concomitant genetic alterations on targeted therapies with ALK-tyrosine kinase inhibitors (ALK-TKI) are not yet well understood. Here, we investigated related to ALK-TKI resistance using clinico-genomic data and explored effective overcome the in preclinical models through identification underlying molecular mechanisms.We used integrated clinical next-generation sequencing generated a nationwide genome screening project...
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The clinical development of Kirsten rat sarcoma virus (KRAS)-G12C inhibitors for the treatment KRAS-mutant lung cancer is limited by presence co-mutations, intrinsic resistance, and emergence acquired resistance. Therefore, innovative strategies enhancing apoptosis in KRAS-mutated non-small cell (NSCLC) are urgently needed. Through CRISPR-Cas9 knockout screening using a library 746 crRNAs drug with custom 432 compounds, we discover that WEE1 kinase potent enhancers apoptosis, particularly...
The aims of this study were to retrospectively review Japanese consecutive cases polymyositis (PM), dermatomyositis (DM), and clinically amyopathic (CADM), focusing on interstital lung disease (ILD) malignancy, document any differences in the incidence, clinical features, impact prognosis among patients with PM, DM, CADM. We reviewed 62 diagnosed CADM according Bohan Peter's criteria (PM/DM) Sontheimer's Gerami's ILD malignancy. occurrence rates 48 % (11/23) 46 (11/24) 100 (15/15) Malignancy...
Abstract Patient‐derived xenograft ( PDX ) models are a useful tool in cancer biology research. However, the number of lung is limited. In present study, we successfully established 10 , including three adenocarcinoma AD ), six squamous cell carcinoma SQ and one large LA from 30 patients with non‐small NSCLC (18 2 mainly SCID hairless outbred SHO mice (Crlj: ‐Prkdc scid Hr hr ). Histology advanced clinical stage III ‐ IV status lymph node metastasis (N2‐3), maximum standardized uptake value...
Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) harboring BIM deletion polymorphism (BIM deletion) have poor responses to EGFR TKI. Mechanistically, the induces preferential splicing of non-functional exon 3-containing isoform over functional 4-containing isoform, impairing TKI-induced, BIM-dependent apoptosis. Histone deacetylase inhibitor, vorinostat, resensitizes deletion-containing NSCLC cells EGFR-TKI. In present study, we determined...
IntroductionLeptomeningeal carcinomatosis (LMC) occurs frequently in anaplastic lymphoma kinase (ALK)–rearranged NSCLC and develops acquired resistance to ALK tyrosine inhibitors (ALK TKIs). This study aimed clarify the mechanism alectinib, a second-generation TKI, LMC test novel therapeutic strategy.MethodsWe induced alectinib an mouse model with ALK-rearranged cell line, A925LPE3, by continuous oral treatment, established A925L/AR cells. Resistance mechanisms were analyzed using several...
Osimertinib monotherapy is currently the standard of care as a first-line treatment for patients harboring epidermal growth factor receptor (EGFR) mutations; however, some EGFR-mutated non-small cell lung cancer (NSCLC) exhibit primary resistance and an insufficient response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Elevated programmed death-ligand 1 (PD-L1) expression in tumors was reported negative predictive outcomes first- or second-generation EGFR-TKIs.We prospectively assessed...
For non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, the initial therapeutic interventions will have crucial impacts on their clinical outcomes. Drug tolerant factors reportedly an impact EGFR-tyrosine kinase inhibitor sensitivity. This prospective study investigated of drug tolerant-related protein expression in tumors based efficacy osimertinib first-setting EGFR-mutated advanced NSCLC patients. A total 92 or postoperative recurrent were...
Abstract Introduction Tooth extraction is one of the clinical internship requirements in Japan. Human posture during tooth important since poor can cause failure safe operation and musculoskeletal injuries. Only a few studies aimed to evaluate posture, but most them used manual or complex measurement methods which lead some inconvenient problems such as subjective biases, quantitativeness, device availability. Thanks recent advancement computer vision technology, pose estimation has been...