A5016366834- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- NF-κB Signaling Pathways
- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Research Studies
- Immune cells in cancer
- Occupational and environmental lung diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Pleural and Pulmonary Diseases
- Cancer Mechanisms and Therapy
- Respiratory and Cough-Related Research
- Neonatal Respiratory Health Research
- Respiratory Support and Mechanisms
- Developmental Biology and Gene Regulation
- Lung Cancer Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Cancer-related Molecular Pathways
- MicroRNA in disease regulation
- Radiopharmaceutical Chemistry and Applications
- Chemokine receptors and signaling
Tokushima University
2013-2024
Hamamatsu University School of Medicine
2021
Center for Rheumatology
2021
Showa University Fujigaoka Hospital
2021
Tokyo Metropolitan Komagome Hospital
2017-2018
Chiba University
2005
Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance treatment. Such can be regulated various factors, although underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive contribute acquired bevacizumab. In mouse models malignant pleural...
Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays pivotal role tumor progression; however, the mechanisms underlying this are not fully understood. Here, we found that TP-mediated catabolism could supply carbon source glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, was converted metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, serine, via both...
Recent clinical trials revealed that immune checkpoint inhibitors and antiangiogenic reagent combination therapy improved the prognosis of various cancers. We investigated roles fibrocytes, collagen-producing monocyte-derived cells, in immunotherapy. Anti-VEGF (vascular endothelial growth factor) antibody increases tumor-infiltrating fibrocytes enhances antitumor effects anti-PD-L1 (programmed death ligand 1) vivo. Single-cell RNA sequencing CD45+ cells identifies a distinct "fibrocyte...
Notch signaling regulates cell-fate decisions during development and postnatal life. Little is known, however, about the role of Delta-like-4 (Dll4)-Notch between cancer cells, or how this affects metastasis. We, therefore, assessed Dll4-Notch in We generated a soluble Dll4 fused to IgG1 constant region (Dll4-Fc) that acts as blocker introduced it into human small cell lung (SCLC) lines expressing either high levels (SBC-3 H1048) low (SBC-5) Dll4. The effects Dll4-Fc on metastasis SCLC were...
Fibrocytes, a distinct population of collagen-producing, monocyte-derived cells, are involved in wound healing as well fibrotic diseases. Recently, fibrocytes have been revealed to play role the tumor microenvironment, particularly under antiangiogenic therapy. In addition, combination cancer immunotherapy with immune checkpoint inhibitor and agents developed for various cancers clinical setting, although immunological background is not clear. current study, we aimed determine function...
Thymidine phosphorylase (TP) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) is induced by tumor necrosis factor α (TNFα) and other cytokines that have been reported to be major inflammation mediators RA. We previously demonstrated TP plays an important role angiogenesis growth, invasion, metastasis. The aim of this study was investigate whether the pathogenesis RA similar its tumors.In FLS obtained from 2 patients with RA, expression TP, interferon-γ (IFNγ)-inducible protein...
Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP identical to platelet-derived endothelial cell growth factor and contributes tumour angiogenesis. induces generation of reactive oxygen species (ROS) enhances expression oxidative stress-responsive genes, such as interleukin (IL)-8. However, mechanism underlying ROS induction by remains unclear. In present study, we demonstrated that promotes NADPH oxidase-derived signalling cancer cells. oxidase...
Abstract Myeloid‐derived suppressor cells (MDSCs) have been known to play a pivotal role in the induction of immune tolerance, which limits benefits checkpoint inhibitors (ICIs). Recent studies revealed that several chemotherapeutic agents decreased tumor‐infiltrating MDSCs. Therefore, combination therapy with cytotoxic and ICIs was approved for first‐line treatment lung cancer. However, impact on MDSCs an optimal partner has not fully investigated thoracic tumors, including cancer malignant...
Histological transformation to small-cell lung cancer (SCLC) is a well-known mechanism of acquired resistance epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and almost all patients receive EGFR-TKIs at the time transformation. We herein report three cases EGFR-mutated adenocarcinoma that transformed into SCLC long after cessation EGFR-TKIs. Rapid tumor progression elevated marker levels were observed Our case highlights importance considering throughout clinical...
Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and predictive biomarkers remain unclear. We report effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 inhibited angiogenesis induces net-like hypoxia only ICI-sensitive cell lines. tissue serum line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines...
Abstract Background Immune checkpoint inhibitors (ICIs) are a revolutionary paradigm in the treatment of thoracic malignancies and chemoimmunotherapy is current standard care this field. Chemotherapeutic agents known to induce not only direct cytotoxic effects on tumor cells but also immune modulating effects, such as stimulating immunogenic cell death (ICD). Currently, either pemetrexed (PEM) or taxane plus platinum combined with ICIs for patients non‐small lung cancer (NSCLC); however, it...
Abstract Combination immunotherapy with multiple immune checkpoint inhibitors (ICIs) has been approved for various types of malignancies, including malignant pleural mesothelioma (MPM). Podoplanin (PDPN), a transmembrane sialomucin‐like glycoprotein, investigated as diagnostic marker and therapeutic target MPM. We previously generated developed PDPN‐targeting Ab reagent high Ab‐dependent cellular cytotoxicity (ADCC) complement‐dependent (CDC). However, the effects anti‐PDPN Abs on...
Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm. S-1 has been developed as novel oral antineoplastic agent based on the modulation of 5-fluorouracil (5-FU) bioactivity. This study was conducted to investigate preclinical therapeutic effect MPM. We used three human MPM cell lines, Y-MESO-14, NCI-H290 and MSTO-211H. In vitro proliferation cells determined by MTT assay. Human were orthotopically implanted into thoracic cavity SCID mice. Tumor-bearing mice treated with or...
Pulmonary pleomorphic carcinoma is often refractory to chemotherapy and follows an aggressive clinical course. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced lung cancer, a few cases with been reported show tumor shrinkage after therapy ICIs. When treating patients ICIs, patient selection essential, monitoring management immune-related adverse events, including pneumonitis, are needed. We herein report case pulmonary preexisting interstitial pneumonia...
In this study we investigated the relationship between development of either HSILs (high-grade squamous intraepithelial lesions) or invasive cancers uterine cervix and p53 codon 72 polymorphisms consisting arginine (Arg)- proline (Pro)-encoded allele in Japanese populations. Furthermore, determined if intrinsic is affected by p53-degradation activities human papillomavirus type 16 (HPV 16)-E6 normal cervical keratinocytes with each genotype. Using PCR polymorphic allele-specific primers,...
Radiation therapy (RT) activates the antigen presentation of dendritic cells and priming cancer-specific cytotoxic CD8+ T cells, occasionally resulting in a systemic immune response to tumor outside treatment field. The phenomenon regression at site distant from irradiated fields is known as abscopal effect. Several case reports have indicated potential role RT overcoming primary acquired resistance against checkpoint inhibitors non-small cell lung cancer (NSCLC) melanoma patients. We herein...
A man with non-small-cell lung cancer who was negative for anti-nuclear antibodies admitted dyspnea after immune checkpoint inhibitor (ICI) administration. Computed tomography (CT) showed complexed radiologic features, including subpleural and basal predominant reticular shadow cystic structures peribronchovascular consolidation. Although we treated him high-dose steroid under a diagnosis of ICI-related pneumonitis, he developed acute exacerbation pneumonitis progressive fibrosis volume...
A non-smoker woman with advanced lung adenocarcinoma was referred to us. The Oncomine Dx target test (ODxTT), a next-generation sequencing (NGS)-based hot spots panel test, did not detect any driver mutations, so we treated her chemo-immunotherapy. After second-line chemotherapy, performed FoundationOne CDx, NGS-based comprehensive genomic profiling (CGP) and identified rare variant of epidermal growth factor receptor exon 19 deletion that had been covered by ODxTT. This case highlights the...
Abstract Background Osimertinib is a standard first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although malignant pleural effusion (PE) common clinical problem in NSCLC, information about the efficacy of osimertinib patients with PE limited, especially regarding its EGFR T790M-negative remains unclear. Methods We retrospectively reviewed medical records NSCLC mutations who were treated our institution between...