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Laboratory of, Japan

Peng W.,Nanjing Medical University | Fan H.,Laboratory of Cancer Research | Wu G.,Nanjing Southeast University | Wu J.,Nanjing Medical University | Feng J.,Nanjing Medical University
Clinical and Experimental Medicine | Year: 2015

Diffuse large B cell lymphoma (DLBCL) is one of the most common malignancies worldwide. To date, there has been little progress in improving the overall survival of DLBCL patients. Emerging evidences have implicated that long noncoding RNAs (lncRNAs) have important regulatory roles in fundamental biological processes, and some of them are involved in cancer initiation, development and progression. This study was to investigate the expression of lncRNA PEG10 in a cohort of DLBCL patients to assess its clinical value and biological function in DLBCL. We first found that the expression of PEG10 was upregulated in DLBCL tumorous tissues and that cell lines compared with the normal. Moreover, we illustrated that PEG10 was significantly correlated with B symptoms, IPI score, CHOP-like treatment and rituximab. In addition, ROCAUC of PEG10 was up to 0.8228, implicating that PEG10 could be a diagnostic marker for distinguishing DLBCL from normal. Importantly, we verified that PEG10 was a key independent predictive factor for DLBCL prognosis from sizable samples through the longtime follow-ups. Furthermore, we revealed that knockdown of PEG10 expression by siRNA could lead to growth arrest and cell apoptosis in vitro. Our results suggested that PEG10 could represent a novel indicator of poor prognosis and might be served as a potential target for the diagnosis and gene therapy of DLBCL. © 2015 Springer-Verlag Italia

Matsui Y.,Hokkaido University | Ikesue M.,Hokkaido University | Danzaki K.,Hokkaido University | Morimoto J.,Hokkaido University | And 5 more authors.
Circulation Research | Year: 2011

Rationale: Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan, has been detected in the infarct region after myocardial infarction (MI), but its functional significance has not been elucidated. Objective: We examined whether and how Syn4 regulates the cardiac healing process after MI. Methods and results: Although the heart in Syn4-deficient (Syn4) mice was morphologically and functionally normal, Syn4 mice exhibited impaired heart function and increased mortality rate as a result of cardiac ruptures after MI. Cardiac ruptures in Syn4 mice were associated with reduced inflammatory reaction and impaired granulation tissue formation during the early phase of MI, as evidenced by reduced numbers of leukocytes, fibroblasts, myofibroblasts, macrophages, and capillary vessels, along with reduced extracellular matrix protein deposition in the infarct region after MI. Transforming growth factor-β1-dependent cell signaling was preserved, whereas cell migration, fibronectin-induced cell signaling, and differentiation into myofibroblasts were defective in Syn4 cardiac fibroblasts. We also found that Syn4 was involved in basic fibroblast growth factor-dependent endothelial cell signaling, cell proliferation, and tube formation. Finally, overexpression of the shed form of Syn4 before MI creation led to an increase in mortality due to cardiac rupture via its action as a dominant-negative inhibitor of endogenous Syn4 signaling, which suggested a protective role of Syn4 signaling in MI. Conclusions: These results suggest that Syn4 plays an important role in the inflammatory response and granulation tissue formation, thereby preventing cardiac rupture and dysfunction after MI. © 2011 American Heart Association, Inc.

Kanno H.,Laboratory of Cancer Research | Nishihara H.,Laboratory of Translational Pathology | Wang L.,Laboratory of Translational Pathology | Yuzawa S.,Laboratory of Cancer Research | And 7 more authors.
Neuro-Oncology | Year: 2013

Background: CD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients' poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression. Methods: First, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated its roles in tumor progression in vitro and in vivo. Results: Immunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore, CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Conclusions: To our knowledge, this is the first report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma. © 2013 The Author(s).

Kanno H.,Laboratory of Cancer Research | Nishihara H.,Hokkaido University | Hara K.,Nakamura Memorial Hospital | Ozaki Y.,Nakamura Memorial Hospital | And 5 more authors.
Brain Tumor Pathology | Year: 2011

Lymphoplasmacyte-rich meningioma (LPRM), the most rare variant of meningiomas, features extensive lymphoplasmacytic infiltrates. Although the jugular foramen (JF) is occasionally involved by several types of tumor, such as paragangliomas and schwannomas, meningioma in the JF is an infrequent disease. Here we present an extremely rare case of LPRM found in the JF. A 55-year-old woman complained of paresis in her right eyelid and palsy in the right side of her lip. Hoarseness and dysphagia also occurred in the following month. Radiologic examinations disclosed a mass lesion in the right JF, and the tumor was operatively removed. Microscopically, the tumor was composed of extensive lymphoplasmacytic infiltration with mild vascular proliferation and scattered sheets of epithelioid cells with plump cytoplasm. Although the obvious whorl formation or psammoma bodies were not observed, by immunochemistry the epithelioid cells were positive for epithelial membrane antigen and also progesterone receptor, indicating a meningothelial cell origin. Considering the histological and radiologic findings, we finally diagnosed the case as LPRM, making this the second reported case of LPRM in the JF. © 2011 The Japan Society of Brain Tumor Pathology.

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