Search

Background: The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. Methods: Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. Results: Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. Conclusions: CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract Background Brain metastases (BM) from hepatocellular carcinoma (HCC) are extremely rare and are associated with a poor prognosis. The aim of this study was to define clinical outcome and prognostic determinants in patients with BM from HCC. Methods Between January 1994 and December 2009, all patients with HCC and BM treated in Sun Yat-sen University Cancer Center were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors. Results Forty-one patients were diagnosed with BM from HCC, an incidence of 0.47%. The median age at diagnosis of BM was 48.5 years. Thirty-three patients (80.5%) developed extracranial metastases at diagnosis of BM, and 30 patients (73.2%) had hepatitis B. Intracranial hemorrhage occurred in 19 patients (46.3%). BM were treated primarily either with whole brain radiation therapy (WBRT; 5 patients), stereotactic radiosurgery (SRS; 7 patients), or surgical resection (6 patients). The cause of death was systemic disease in 17 patients and neurological disease in 23. Patients in a high RPA (recursive partitioning analysis) class, treated with conservatively and without lung metastases, tended to die from neurological disease. Median survival after the diagnosis of BM was 3 months (95% confidence interval: 2.2-3.8 months). In multivariate analysis, the presence of extracranial metastases, a low RPA class and aggressive treatment, were positively associated with improved survival. Conclusions BM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive treatment. The clinical implication of extracranial metastases in HCC patients with BM needs further assessment.

Abstract Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment), the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas.