In shallow subduction zones, fluid behavior impacts various geodynamic processes capable of regulating slip behaviors and forming mud volcanoes. However, evidence of structures that control the fluid transfer within an overriding plate is limited and the physical properties at the source faults of slow earthquakes are poorly understood. Here we present high-resolution seismic velocity models and reflection images of the Hyuga-nada area, Japan, where the Kyushu-Palau ridge subducts.
View Article and Find Full Text PDFThe capture of tumour-derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably to the formation of the pre-metastatic niche (PMN). However, due to the challenges associated with modelling release of small EVs in vivo, the kinetics of PMN formation in response to endogenously released TEVs have not been examined. Here, we have studied the endogenous release of TEVs in mice orthotopically implanted with metastatic human melanoma (MEL) and neuroblastoma (NB) cells releasing GFP-tagged EVs (GFTEVs) and their capture by host cells to demonstrate the active contribution of TEVs to metastasis.
View Article and Find Full Text PDFBackground: In Japan, public dialogue on allocation of life-saving medical resources remains taboo, and discussion largely has been avoided.
Research Question: Do Japanese health care workers and the general public agree with principles of ventilator allocation developed internationally?
Study Design And Methods: A four-point Likert scale questionnaire was used to assess the extent of agreement or disagreement with internationally developed triage principles for rationing mechanical ventilators during pandemics. Questionnaires were distributed in person or online, and generalized linear models were used to analyze quantitative data.
Background.: Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4 plasma cells.
View Article and Find Full Text PDFEpidermal growth factor receptor (EGFR) mutations are associated with responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC). Our previous study revealed a rapid point-of-care system for detecting EGFR mutations. This system analyzes cell pellets from cytology specimens using droplet-polymerase chain reaction (d-PCR), and has a reaction time of 10 min.
View Article and Find Full Text PDFThe detection of epidermal growth factor receptor () mutations is necessary for the selection of suitable patients with non-small cell lung cancer (NSCLC) for treatment with EGFR tyrosine kinase inhibitors. Cytology specimens are known to be suitable for mutation detection, although tissue specimens should be prioritized; however, there are limited studies that examine the utility of bronchial lavage fluid (BLF) in mutation detection. The purpose of the present study was to investigate the utility of BLF specimens for the detection of mutations using a conventional quantitative polymerase chain reaction (PCR) assay.
View Article and Find Full Text PDFTumor-associated macrophages (TAMs) are strongly associated with poor survival in neuroblastomas that lack amplification. To study TAM action in neuroblastomas, we used a novel murine model of spontaneous neuroblastoma lacking amplification, and observed recruitment and polarization of TAMs, which in turn enhanced neuroblastoma proliferation and growth. In both murine and human neuroblastoma cells, we found that TAMs increased STAT3 activation in neuroblastoma cells and transcriptionally up-regulated the oncogene.
View Article and Find Full Text PDFThe bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines.
View Article and Find Full Text PDFCancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship with MSCs is not clear. Here, we have isolated from primary human neuroblastoma tumors a population of αFAP- and FSP-1-expressing CAFs that share phenotypic and functional characteristics with bone marrow-derived MSCs (BM-MSC). Analysis of human neuroblastoma tumors also confirmed the presence of αFAP- and FSP-1-positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages.
View Article and Find Full Text PDFEpidermal growth factor receptor gene (EGFR) mutations are associated with response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). We developed a novel, rapid EGFR mutation assay using a real-time droplet-polymerase chain reaction machine (EGFR d-PCR assay). The purpose of this study was to validate the performance of the EGFR d-PCR assay using fresh liquid cytology specimens.
View Article and Find Full Text PDFType 1 autoimmune pancreatitis (AIP-1) is an immunoglobulin G (IgG)-4-related disease (IgG4-RD), characterized by elevated serum immunoglobulin G4 (IgG4) and infiltration by IgG4(+) plasma cells. Pancreatic carcinoma (PC) sometimes shows infiltration by IgG4(+) plasma cells, but details have been unclear. We compared pathological findings and expression of IgG4 and IgG in fibroses in 18 PC patients to those from 9 AIP-1 patients.
View Article and Find Full Text PDFDrug resistance is a major cause of treatment failure in cancer. Here, we have evaluated the role of STAT3 in environment-mediated drug resistance (EMDR) in human neuroblastoma. We determined that STAT3 was not constitutively active in most neuroblastoma cell lines but was rapidly activated upon treatment with interleukin (IL)-6 alone and in combination with the soluble IL-6 receptor (sIL-6R).
View Article and Find Full Text PDFInterleukin-6 (IL-6) is a pleiotropic cytokine with a broad range of physiologic and pathologic functions. Because in cancer, IL-6 contributes to a microenvironment that promotes tumor cell survival, angiogenesis, and inflammation, understanding the mechanism responsible for its production is important. In neuroblastoma, the second most common solid tumor in children, IL-6 is produced not by tumor cells but by stromal cells such as monocytes and bone marrow mesenchymal stem cells (BMMSC).
View Article and Find Full Text PDFUsing an organelle proteomics approach, we previously studied the rat peroxisome in order to characterize the proteins participating in its biogenesis. A peroxisome-specific isoform of Lon (pLon) protein was accordingly identified. However, the precise role of pLon in peroxisomes remains to be elucidated.
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