Clinical study of apatinib plus temozolomide for the treatment of recurrent high-grade gliomas.

OBJECTIVES: Recurrent high-grade glioma, a malignant tumor of the brain or spinal cord associated with poor prognosis with a median survival of <6 months. Recurrent high-grade glioma does not have standard treatment even if some strategies have some effect in recurrent gliomas. Apatinib, as a tyrosine kinase inhibitor shown to be effective in treating the lung and gastric cancer. The present study investigated the efficacy and safety of apatinib in combination with dose-dense regimens of temozolomide for treating recurrent glioma. PATIENTS AND METHODS: Eighteen patients with recurrent high-grade glioma were enrolled and treated with apatinib (500 mg/day) and TMZ (50 mg/m2/day). Patients who achieved partial response or stable disease continued treatment. Administration of drug was terminated for patients with progressive disease, who could not tolerate toxicity, and who required discontinuation due to other medical conditions. RESULTS: From the 18 cases, only 17 were included in the evaluation of the curative effect of the drug and in that four showed partial responses, ten had stable disease, remaining three exhibited progressive disease. The disease control rate was 82.3% (14/17). Progression-free and overall survival was found to be 4 months and 9.1 months, respectively. Three patients became transiently capable of self-care (Karnofsky performance status >70). Cognition and quality of life improved after treatment and from the safety perspective, three most common adverse reactions included epilepsy (24.1%), hypertension (20.7%), and fatigue (17.2%). CONCLUSION: Apatinib and TMZ may represent an alternative treatment option for patients with recurrent high-gradeglioma, especially those with a low Karnofsky performance status. However, studies using a larger sample size are required to confirm these findings.

ABCG2 downregulation in glioma stem cells enhances the therapeutic efficacy of demethoxycurcumin.

We analyzed the role of ABCG2, a drug transporter, in determining the sensitivity of glioma stem cells (GSCs) to demethoxycurcumin (DMC). We first demonstrated that ABCG2 is more highly expressed in GSCs than primary astrocytes. Modulation of ABCG2 levels in GSCs by transfection of ABCG2 shRNA or a lentiviral vector encoding ABCG2 revealed an inverse relation between ABCG2 levels and DMC-induced GSC growth inhibition. Suppressing ABCG2 increased DMC-induced apoptosis and G0/G1 cell cycle arrest in GSCs. It also increased levels reactive oxygen species (ROS) in GSCs treated with DMC, resulting in increased cytochrome C and caspase-3 activity. When GSCs transfected with ABCG2 shRNA or overexpressing ABCG2 were xenografted and the tumor-bearing, immunodeficient mice were treated with DMC, ABCG2 expression suppressed the tumor proliferation rate (T/C %). These findings demonstrate that ABCG2 expression is critical for DMC resistance in GSCs and is a potential therapeutic target for GBM.

[Several monomes from Tripterygium wilfordii inhibit proliferation of glioma cells in vitro].

BACKGROUND AND OBJECTIVE: Researches indicated that Tripterygium wilfordii possess antitumor activity. The current study was designed to investigate inhibitive effect of several monomes of Tripterygium wilfordii on the proliferation of glioma cells. METHODS: The effect of three monomes from Tripterygium wilfordii on the proliferation of glioma cell lines SHG44, C6, and U251 in vitro was examined by using MTT assay. Immunohistochemistry was used to examine the expression of Bax, Bcl-2 after treatment of triptolide and celastrol. RESULT: The proliferation of glioma cells was remarkably inhibited by triptolide and celastrol. They both increased expression of Bax and decreased expression of Bcl-2 in the SHG44 cells. CONCLUSION: Triptolide and celastrol inhibit the proliferation of glioma cells in vitro, which was associated with promoting the expression of Bax and inhibiting the expression of Bcl-2 and accelerating cell apotosis.