Radiotherapy and concomitant/adjuvant therapy with temozolomide are a common treatment regimen for children and adults with high-grade glioma. Although temozolomide is generally safe, it can rarely cause life-threatening complications. Here we report a case of a 31-year-old female patient who underwent surgical resection followed by radiotherapy plus concomitant temozolomide. She developed panc...

Glioblastoma (GBM) is often treated with the cytotoxic drug temozolomide, but the disease inevitably recurs in a drug-resistant form after initial treatment. Here, we report that in GBM cells, even a modest decrease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sensitivity. RNAi-mediated attenuation of MSH2 and MSH6 showed that such modest decreases...

PURPOSE This phase II trial was designed to define the role of O(6)-benzylguanine (O(6)-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administering O(6)-BG in combination with temozolomide. PATIENTS AND METHODS Patients were accrued into two independent strata on the basis of histology...

PURPOSE The objective of the study was to determine whether astrocytes and brain endothelial cells protect glioma cells from temozolomide through an endothelin-dependent signaling mechanism and to examine the therapeutic efficacy of the dual endothelin receptor antagonist, macitentan, in orthotopic models of human glioblastoma. EXPERIMENTAL DESIGN We evaluated several endothelin receptor anta...

Temozolomide is an alkylating agent used frequently in the management of gliomas. Although temozolomide is generally safe, rarely it can cause life threatening complications. Here we report the cases of two patients who developed prolonged and severe pancytopenia after low dose continuous temozolomide concurrently with cranial radiotherapy. The pancytopenia lasted two to six months. Both the pa...

Temozolomide is used widely to treat malignant glioma, but the overall response to this agent is generally poor. Resistance to DNA-damaging drugs such as temozolomide has been related to the induction of antiapoptotic proteins. Specifically, the transcription factor NF-κB has been suggested to participate in promoting the survival of cells exposed to chemotherapy. To identify factors that modul...

Glioblastoma multiforme (GM) is an aggressive malignant tumor of the brain. The standard treatment of GM is surgical resection with consequent radio- and chemotherapy with temozolomide. The prognosis is unfavorable, with a survival time of 12-14 months. The phenomenon of targeted migration to the tumor in the brain opens novel possibilities for the treatment of GM. Multipotent mesenchymal strom...

BACKGROUND/AIM Lobarstin is a metabolite occurring from the Antarctic lichen Stereocaulon alpnum. Human glioblastoma is highly resistant to chemotherapy with temozolomide. Lobarstin was examined for its effect on glioblastoma. MATERIALS AND METHODS Temozolomide-resistant T98G cells were subjected to toxicity test with temozolomide and/or lobarstin. DNA damage and recovery was assessed by the ...

QUESTIONS What is the role of single-agent temozolomide in the treatment of patients with metastatic melanoma? In comparison with single-agent temozolomide, does the addition of interferon-alpha to temozolomide improve disease-free survival, overall survival, or response rates? In comparison with single-agent temozolomide, does the addition of thalidomide to temozolomide improve disease-free su...

PURPOSE Previous preclinical studies have shown that regional temozolomide therapy via isolated limb infusion is more effective than melphalan, the current drug of choice for regional chemotherapy for advanced extremity melanoma. The aim of this study was to determine whether hyperthermia could further augment the efficacy of temozolomide, an alkylating agent, against melanoma and improve its t...