A5077877614- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Extracellular vesicles in disease
- Lung Cancer Research Studies
- Lung Cancer Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- Neuroendocrine Tumor Research Advances
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Angiogenesis and VEGF in Cancer
- Immune cells in cancer
- Medical Imaging and Pathology Studies
- Autophagy in Disease and Therapy
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Sarcoidosis and Beryllium Toxicity Research
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Esophageal Cancer Research and Treatment
- interferon and immune responses
Osaka University
2016-2025
Takeda (United States)
2022
Weatherford College
2022
Azabu University
2015
National Institute of Allergy and Infectious Diseases
2011-2013
National Institutes of Health
2011-2013
Office of Extramural Research
2013
Cytokinetics (United States)
2013
Tokushima University
2006-2012
Sakai Municipal Hospital
2011
Objectives: Hypoxia-inducible factor 1α (HIF-1α) is a transcription that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows marked inhibition HIF-1α expression; however, the association between 1 (HDAC1), metastasis-associated protein (MTA1) not fully understood. Methods: 1α, HDAC1, MTA1 expressions were detected by immunohistochemistry 39 pancreatic carcinoma patients. The correlations expression HIF-1α, or clinical features prognosis analyzed....
Abstract The aim of this study was to investigate the clinical impact sarcopenia on efficacy programmed death (PD)-1 inhibitors. We retrospectively reviewed medical records all patients treated with nivolumab or pembrolizumab between January 2016 and September 2018 for previously advanced non–small cell lung cancer (NSCLC). cross-sectional area psoas muscle at level third lumbar vertebra baseline computed tomography assessed calculate index (PMI). Sarcopenia defined based PMI cut-off values...
Autophagy is an evolutionarily conserved cellular recycling mechanism that occurs at a basal level in all cells. It can be further induced by various stimuli including starvation, hypoxia, and treatment with cytokines such as IFNG/IFNγ TGFB/TGFβ. Type I IFNs are proteins induce antiviral state They also have antiproliferative, proapoptotic immunomodulatory activities. We investigated whether type IFN autophagy multiple human cell lines. found IFNA2c/IFNα2c IFNB/IFNβ induces 24 h Daudi B...
Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms mice, although role of human Sema4A tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non–small cell lung (NSCLC) responded significantly better to anti–programmed death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly,...
BackgroundNovel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes.ObjectiveWe sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs).MethodsWe performed data-independent acquisition of EVs 4 healthy controls, noneosinophilic (NEA) patients, eosinophilic (EA) patients BA. We confirmed EA-specific via validation in 61 BA 23 controls. To further validate these findings, we 6 chronic rhinosinusitis...
Abstract Chronic obstructive pulmonary disease (COPD) has been recently characterized as a of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with COPD-like phenotype progressively developed syndrome resembling human including cataracts, hair loss, atrophy various organs, thymus, muscle, testis, resulting shorter survival than wild-type (WT) mice....
Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by Mycobacterium avium complex (MAC), and tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made sputum culture. To investigate potential serum biomarkers, we conducted non-targeted proteome analysis on extracellular vesicles (EVs) collected 10 patients with MAC (MAC-PD), 7 TB,...
Although responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) are initially positive, 30%-40% of patients with EGFR-mutant tumors do not respond well EGFR-TKIs, and most lung cancer harboring mutations experience relapse resistance. Therefore, it is necessary identify only the mechanisms underlying EGFR-TKI resistance, but also potentially novel therapeutic targets and/or predictive biomarkers for adenocarcinoma. We found that GPI-anchored protein semaphorin 7A (SEMA7A) highly induced by...
Abstract Background Cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) (K3)—a novel synthetic single-stranded DNA immune adjuvant for cancer immunotherapy—induces a potential Th1-type response against cells. We conducted phase I study of CpG ODN (K3) in patients with lung to assess its safety and patients’ responses. Methods The primary endpoint was the proportion dose-limiting toxicities (DLTs) at each dose level. Secondary endpoints included profile, an response, including dynamic...
The methyltransferase-like 3 (METTL3)-/METTL14-containing complex predominantly catalyzes N6-methyladenosine (m6A) modification, which affects mRNA stability. Although the METTL14 R298P mutation is found in multiple cancer types, its biological effects are not completely understood. Here, we show that heterozygous promotes cell proliferation, whereas homozygous reduces proliferation. Methylated RNA immunoprecipitation sequencing analysis indicates m6A modification at canonical motifs....
Calcium-dependent activator protein for secretion 1 (CAPS1) plays a distinct role in the priming step of dense core vesicle (DCV) exocytosis. CAPS1 pre-mRNA is known to undergo adenosine-to-inosine RNA editing its coding region, which results glutamate-to-glycine conversion at site C-terminal region. However, physiological significance remains elusive. Here, we created mutant mice edited was solely expressed. These were lean due increased energy expenditure caused by physical hyperactivity....
Messenger RNA (mRNA) vaccines that protect against COVID-19 are widely used in many countries owing to their high efficacy and safety profiles. Recently, few severe adverse events, such as anaphylaxis myocarditis, were reported healthy individuals. The of mRNA has not been adequately studied patients with interstitial lung disease. We report 2 cases acute exacerbation preexisting pneumonia associated vaccination. In both cases, disease was stable before the Initial responses steroid therapy...
Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection patients at risk PPF, we performed a proteomic analysis serum extracellular vesicles (EVs). Notably, identified candidate were enriched lung-derived proteins participating in fibrosis-related pathways. Among them, surfactant-associated protein B (SFTPB) EVs could predict ILD progression better than...
The present study investigates the expression of VLA-4 on thymocytes at various stages maturation and their capacity to adhere thymic stromal cells. Whole were stained with anti-CD4 anti-CD8, as well anti-VLA-4 antibodies. Flow microfluorometric analyses revealed that a) most CD4-8- (double negative DN) CD4-8intermediate thymocyte populations expressed large amounts VLA-4, b) levels considerably markedly reduced CD4+8+ positive DP) single (SP) (CD4+8- or CD4-8+) populations, respectively....
Abstract Thymic shared antigen-1 (TSA-1) is a glycosyl-phosphatidylinositol (GPI)-anchored differentiation Ag expressed on murine lymphocytes, and identical to stem cell Ag-2 (Sca-2). Using newly established mAb against TSA-1/Sca-2, we have previously shown that surface TSA-1 expression induced upon activation in T cells, anti-TSA-1 inhibits IL-2 production by anti-CD3 stimulation hybridomas. In the present study, analyzed functional role of during using normal hybridomas, transfected Jurkat...
There is an unmet need for novel biomarkers in the diagnosis of multifactorial COPD. We applied next-generation proteomics to serum extracellular vesicles (EVs) discover COPD biomarkers. EVs from 10 patients with and six healthy controls were analysed by tandem mass tag-based non-targeted proteomics, those elastase-treated mouse models emphysema also proteomics. For validation, 23 20 validated targeted Using we identified 406 proteins, 34 which significantly upregulated Of note, EV protein...
Abstract Coronavirus disease 2019 (COVID‐19) can cause severe lymphopenia and respiratory failure requiring prolonged invasive mechanical ventilation (MV). COVID‐19 patients with or are at risk of developing secondary infections. Here, we present the needle autopsy findings a critically ill patient who required reintubation MV, eventually died cytomegalovirus (CMV) pneumonia. This case highlights potential long‐term steroid use need for routine monitoring CMV infection in COVID‐19.
Abstract Cancer immunotherapy has shown great promise as a new standard therapeutic strategy against cancer. However, the response rate and survival benefit remain unsatisfactory because most current approaches, such use of immune checkpoint inhibitors, depend on spontaneous antitumor responses. One possibility for improving efficacy is to promote immunity using adjuvants or specific cytokines actively. IL-33 been candidate cytokine therapies, but it remains unclear how in which situations...
Abstract Small-cell lung cancer (SCLC) easily recurs with a multidrug resistant phenotype. However, standard therapeutic strategies for relapsed SCLC remain unestablished. We found that human epidermal growth factor receptor 2 (HER2) is not only expressed in pretreated specimens, but also upregulated when HER2-positive cells acquire chemoresistance. Trastuzumab induced differential levels of antibody-dependent cell-mediated cytotoxicity (ADCC) to cells. Furthermore, as mechanism the ADCC, we...
This is the first report of COVID-19 in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. HTLV-1 infection can cause immune dysfunction even asymptomatic carriers. case highlights need for guidance on management COVID-19-HTLV-1 coinfection, specifically appropriate use corticosteroid treatment while considering secondary infection.
Abstract Sarcoidosis is a complex, polygenic, inflammatory granulomatous multi-organ disease of unknown cause. The inflammation in sarcoidosis driven by the interplay between T cells and macrophages. Extracellular vesicles (EVs) play important roles intercellular communication. We subjected serum EVs, isolated size exclusion chromatography, from seven patients with five control subjects to non-targeted proteomics analysis. Non-targeted, label-free analysis detected 2292 proteins EVs; 42 were...