Bone marrow‐derived mesenchymal stem or stromal cells (MSC) have been shown to be recruited to various types of tumor tissues, where they interact with tumor cells to promote their proliferation, survival, invasion and metastasis, depending on the type of the tumor. We have previously shown that Ror2 receptor tyrosine kinase and its ligand, Wnt5a, are expressed in MSC, and Wnt5a‐Ror2 signaling in MSC induces expression of CXCL16, which, in turn, promotes proliferation of co–cultured MKN45 gastric cancer cells via the CXCL16‐CXCR6 axis. However, it remains unclear how CXCL16 regulates proliferation of MKN45 cells. Here, we show that knockdown of CXCL16 in MSC by siRNA suppresses not only proliferation but also migration of co–cultured MKN45 cells. We also show that MSC‐derived CXCL16 or recombinant CXCL16 upregulates expression of Ror1 through activation of STAT3 in MKN45 cells, leading to promotion of proliferation and migration of MKN45 cells in vitro. Furthermore, co–injection of MSC with MKN45 cells in nude mice promoted tumor formation in a manner dependent on expression of Ror1 in MKN45 cells, and anti–CXCL16 neutralizing antibody suppressed tumor formation of MKN45 cells co–injected with MSC. These results suggest that CXCL16 produced through Ror2‐mediated signaling in MSC within the tumor microenvironment acts on MKN45 cells in a paracrine manner to activate the CXCR6‐STAT3 pathway, which, in turn, induces expression of Ror1 in MKN45 cells, thereby promoting tumor progression.
Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer’s disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry. We found that a unique mannosylated-glycan is carried by a Tf isoform in CSF (Man-Tf). The cerebral cortex contained Man-Tf as a major isofom, suggesting that CSF Man-Tf is, at least partly, derived from the cortex. Man-Tf levels were analyzed in CSF of patients with neurological diseases. Concentrations of Man-Tf were significantly increased in AD and mild cognitive impairment (MCI) comparing with other neurological diseases, and the levels correlated well with those of phosphorylated-tau (p-tau), a representative AD marker. Consistent with the observation, p-tau and Tf were co-expressed in hippocampal neurons of AD, leading to the notion that a combined p-tau and Man-Tf measure could be a biomarker for AD. Indeed, levels of p-tau x Man-Tf showed high diagnostic accuracy for MCI and AD; 84% sensitivities and 90% specificities for MCI and 94% sensitivities and 89% specificities for AD. Thus Man-Tf could be a new biomarker for AD.
Background and study aims: It is difficult to perform endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of small gastrointestinal (GI) subepithelial lesions (SELs) approximately 10 mm in diameter. This study was undertaken to evaluate the feasibility, safety, and diagnostic ability of EUS-FNA with a forward-viewing and curved linear-array echoendoscope (FVCLA-ES) that has a cap for small SELs.
Patients and methods: The study enrolled 8 patients who had small upper GI SELs approximately 10 mm in diameter. To fix the SELs during FNA, a cap device was attached to the scope tip.
Results: The mean (standard deviation [SD]) diameter of the SELs was 10.6 mm (2.94). Even small lesions were well targeted for FNA when the FVCLA-ES with a cap device was used. The mean (SD) number of passes was 4.6 (1.59). Adequate samples were obtained from 7 patients (87.5 %) – in 6 (75 %) for cytology and in 4 (50 %) for histologic examination with immunohistochemical (IHC) staining. No complication occurred. Gastrointestinal stromal tumor (GIST) in 2 patients and leiomyoma in 2 patients were definitively diagnosed with IHC staining.
Conclusions: EUS-FNA with an FVCLA-ES that has a cap device is feasible and safe. This technique is expected to contribute to histologic diagnosis, even in small SELs.
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