The Chinese Glioma Cooperative Group (CGCG) Guideline Panel for adult diffuse gliomas provided recommendations for diagnostic and therapeutic procedures. The Panel covered all fields of expertise in neuro-oncology, i.e. neurosurgeons, neurologists, neuropathologists, neuroradiologists, radiation and medical oncologists and clinical trial experts. The task made clearer and more transparent choices about outcomes considered most relevant through searching the references considered most relevant and evaluating their value. The scientific evidence of papers collected from the literature was evaluated and graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence and recommendations were given accordingly. The recommendations will provide a framework and assurance for the strategy of diagnostic and therapeutic measures to reduce complications from unnecessary treatment and cost. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China.

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Vasculogenic mimicry (VM) is known as non-endothelial tumor cell-lined microvascular channels in aggressive tumors. We have previously found the presence of VM in high-grade gliomas. In this study, we aimed to identify VM patterns in gliomas and to explore their clinical significance. Tumor samples as well as their detailed clinical/prognostic data were collected from 101 patients. Vasculogenic mimicry in the glioma samples was determined by dual staining for endothelial marker CD34 and periodic acid–Schiff (PAS). Tumor samples were also immunohistochemically stained for Ki-67, VEGF, COX-2 and MMP-9. The association between VM and the clinical characteristics of the patients were analyzed. A Kaplan–Meier survival analysis and log-rank tests were performed to compare survival times of the patients. Vasculogenic mimicry was present in 13 out of 101 samples. The higher grade gliomas had a higher incidence of VM than that of lower grade gliomas (P = 0.006). Vasculogenic mimicry channels were associated with the expression of COX-2 and MMP-9 (P < 0.05). While there was no association between the existence of VM and the sex, age and preoperative epilepsy of the patients, or expression of Ki-67 and VEGF. However, patients with VM-positive gliomas survived a shorter period of time than those with VM negative gliomas (P = 0.027). Interestingly, in high-grade gliomas, the level of microvascular density was lower in VM positive tumors than those VM negative tumors (P = 0.039). Our results suggest that VM channels in gliomas correlate with increasing malignancy and higher aggressiveness, and may provide a complementation to the tumor’s blood supply, especially in less vascularized regions, which may aid in the identification of glioma patients with a poorer prognosis.

SUMMARY Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM. Dibutyryl cyclic AMP (dbcAMP) reverses the Warburg effect, as evidenced by increased oxygen consumption and reduced lactate production. Mitochondrial biogenesis induced by activation of the CREB-PGC1α pathway triggers metabolic shift and differentiation. Blocking mitochondrial biogenesis using mdivi1 or by silencing PGC1α abrogates differentiation; conversely, overexpression of PGC1α elicits differentiation. In GBM xenograft models and patient-derived GBM samples, cAMP activators also induce tumor growth inhibition and differentiation. Our data show that mitochondrial biogenesis and metabolic switch to oxidative phosphorylation drive the differentiation of tumor cells.

BackgroundBrain 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.MethodsBetween 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.ResultsForty-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.ConclusionsBM 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.

TGM2 regulates ID1 expression in glioma-initiating cell lines high in CD44. Targeting TGM2 could be an effective strategy to treat gliomas with high CD44 expression.

miR-181b independently predicted chemoresponse to temozolomide and enhanced temozolomide sensitivity via MEK1 downregulation. A combination of miR-181b and temozolomide may be an effective therapeutic strategy for gliomas.

Glioma stem-like cells (GSCs) may be the initiating cells in glioblastoma (GBM) and contribute to the resistance of these tumors to conventional therapies. Development of novel chemotherapeutic agents and treatment approaches against GBM, especially those specifically targeting GSCs are thus necessary. In the present study, we found that a novel Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway inhibitor (WP1193) significantly decreased the proliferation of established glioma cell lines in vitro and inhibit the growth of glioma in vivo. To test the efficacy of WP1193 against GSCs, we then administrated WP1193 to GSCs isolated and expanded from multiple human GBM tumors. We revealed that WP1193 suppressed phosphorylation of JAK2 and STAT3 with high potency and demonstrated a dose-dependent inhibition of proliferation and neurosphere formation of GSCs. These effects were at least due in part to G1 arrest associated with down-regulation of cyclin D1 and up-regulation of p21( Cip1/Waf-1 ). Furthermore, WP1193 exposure decreased expression of stem cell markers including CD133 and c-myc, and induced cell death in GSCs through apoptosis. Taken together, our data indicate that WP1193 is a potent small molecule inhibitor of the JAK2/STAT3 pathway that shows promise as a therapeutic agent against GBM by targeting GSCs.