The prognostic implications of miR-21, miR-17-92 and miR-155 were evaluated in diffuse large B-cell lymphoma (DLBCL) patients, and novel mechanism by which miR-21 contributes to the oncogenesis of DLBCL by regulating FOXO1 and PI3K/AKT/mTOR pathway was investigated. The expressions of miR-21, miR-17-92 and miR-155 measured by quantitative reverse-transcription-PCR were significantly up-regulated in DLBCL tissues (n=200) compared to control tonsils (P=0.012, P=0.001 and P<0.0001). Overexpression of miR-21 and miR-17-92 was significantly associated with shorter progression-free survival (P=0.003 and P=0.014) and overall survival (P=0.004 and P=0.012). High miR-21 was an independent prognostic factor in DLBCL patients treated with rituximab-combined chemotherapy. MiR-21 level was inversely correlated with the levels of FOXO1 and PTEN in DLBCL cell lines. Reporter-gene assay showed that miR-21 directly targeted and suppressed the FOXO1 expression, and subsequently inhibited Bim transcription in DLBCL cells. MiR-21 also down-regulated PTEN expression and consequently activated the PI3K/AKT/mTOR pathway, which further decreased FOXO1 expression. Moreover, miR-21 inhibitor suppressed the expression and activity of MDR1, thereby sensitizing DLBCL cells to doxorubicin. These data demonstrated that miR-21 plays an important oncogenic role in DLBCL by modulating the PI3K/AKT/mTOR/FOXO1 pathway at multiple levels resulting in strong prognostic implication. Therefore, targeting miR-21 may have therapeutic relevance in DLBCL.

We found that cells resembling MSCs indeed exist in an independent cohort of glioma patients, as presented in western populations. We could presume that the possible location of KGS-MSLCs was in perivascular area or in glioma stroma that was a disorganized vascular niche. It might be possible that KGS-MSLCs could be one of constituent of stroma of glioma microenvironment.

No abstract

The aims of our study were (1) to describe the ultrasonographic findings of the injured medial collateral ligament of the knee and (2) to assess the usefulness of ultrasonography in both evaluating the presence and location of the medial collateral ligament injuries and predicting the prognoses for the patients. The study group consisted of 16 patients with the clinical diagnosis of medial collateral ligament injury. We also examined 20 knee joints in 10 volunteers who had no history of injury to the knee. To predict prognoses, we divided the patients into two groups on the basis of the location of medial collateral ligament injuries. A thickened and heterogeneously hypoechoic appearance of the medial collateral ligament was considered abnormal. The normal medial collateral ligament was a thin and moderately homogeneous hypoechoic band with an average thickness of 4.3 mm (range, 3.3 to 5.6 mm) at the femoral attachment and of 2.3 mm (range, 1.3 to 3.2 mm) at the tibial attachment. All injured medial collateral ligament structures were thickened and heterogeneously hypoechoic. According to the criteria for grading of medial collateral ligament injury with stress view, 10 patients had grade III medial collateral ligament tears, three had grade II tears, and none had grade I injuries. In 15 (94%) of 19 knees, a correct diagnosis could be made with ultrasonography. Ultrasonography is useful in evaluating isolated medial collateral ligament injuries and in predicting patient outcome on the basis of the location of the medial collateral ligament injuries.

Syntenin is a PDZ domain-containing adaptor protein that has been recently shown to regulate migration and invasion in several tumors. Small cell lung cancer (SCLC) is notorious for its invasiveness and strong potential for metastasis. We therefore studied the influence of syntenin on the invasiveness of SCLC. Immunohistochemistry in tumor tissues showed that syntenin was more frequently expressed in small cell carcinomas than other neuroendocrine tumors, such as carcinoids and neuroblastomas, suggesting that syntenin expression may be related to more aggressive forms of neuroendocrine tumors. In SCLC patients, syntenin overexpression in tumor cells was significantly associated with more extensive and advanced disease at the time of diagnosis (P=0.029). Overexpression of syntenin in SCLC cells that were intrinsically syntenin-low increased the invasiveness of cells and led to the induction of extracellular matrix (ECM)-degrading membrane type 1-matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase 2 (MMP2). In contrast, suppression of syntenin in syntenin-high cells was associated with the downregulation of MT1-MMP. Contrary to the results of previous studies using malignant melanomas and breast carcinomas, signaling cascades were shown to be further transduced through p38 MAPK and PI3K/AKT, with activation of SP1 rather than NF-κB, under circumstances not involving ECM interaction. In addition, the upstream molecule focal adhesion kinase was induced by syntenin activation, in spite of the absence of ECM interaction. These results suggest that syntenin might contribute to the invasiveness of SCLC and could be utilized as a new therapeutic target for controlling invasion and metastasis in SCLC.

No abstract

We report a case of solitary primary leptomeningeal glioma. The mass was totally removed under awake surgery. Intraoperatively, no parenchymal involvement was noted. Histopathological study revealed a predominant anaplastic oligodendroglioma component and a focal anaplastic astrocytoma component, which was consistent with an anaplastic oligoastrocytoma. Adjuvant tomotherapy was followed and the tumor has not recurred until 12 months after surgery. A focal type of primary leptomeningeal glioma is extremely rare. We report a rare case of solitary primary leptomeningeal anaplastic oligoastrocytoma.

No abstract