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• W2911372238 abstract "554 Glioblastoma is the deadliest and most prevalent brain tumor. Currently, there is no cure for glioblastona. However, the general strategy for the treatment of glioblastoma involves surgery, radiotherapy, and/or chemotherapy. There are various adjuvant and chemotherapeutic drugs, which are often used in combination with a hope of better outcome. Dexamethasone (DXM) is a steroid commonly used for treatment of glioblastoma patients for alleviation of pain and vasogenic edema prior to treatment with chemotherapeutic drugs. Temozolomide (TMZ), an alkylating chemotherapeutic drug, has recently been introduced in clinical trials for treatment of glioblastoma. This investigation was designed to determine the modulatory effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells. Freshly grown cells were treated with different doses of DXM or TMZ for 6 h followed by incubation in drug-free medium for 48 h. Wright staining and ApopTag assay showed no apoptosis in U87MG cells treated with 40 μM DXM but significant amounts of apoptosis in cells treated with 100 μM TMZ. Apoptosis in TMZ treated U87MG was associated with an increase in intracellular free [Ca2+], as determined by fura-2 assay. Western blot analyses showed alterations in the levels of Bax (pro-apoptotic) and Bcl-2 (anti-apoptotic) proteins with an increase in Bax/Bcl-2 ratio in TMZ treated cells, indicating a commitment to apoptosis. Western blot analyses also detected overexpression of calpain and caspase-3, which cleaved 230 kD a-spectrin at specific sites for generation of 145 and 120 kD spectrin break down products (SBDPs), respectively. However, 1-h pretreatment of U87MG cells with 40 μM DEX dramatically decreased TMZ induced apoptosis, decreasing Bax/Bcl-2 ratio and SBDPs. Thus, our results revealed that DXM was antagonistic to TMZ induced apoptosis in human glioblastoma U87MG cells. This study has yet to be substantiated in the xenografted and allografted animal models of glioblastoma. This investigation, however, strongly implies that treatment of glioblastoma patients with DXM prior to chemotherapy with TMZ may result in an undesirable clinical outcome. Supported in part by five R01 grants from the National Cancer Institue (NCI) and National Institue of Neurological Disorders ans Stroke (NINDS) of the National Institutes of Health (NIH), and also a grant from the state of SC." @default.
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• W2911372238 date "2004-04-01" @default.
• W2911372238 modified "2023-09-24" @default.
• W2911372238 title "Modulatory effect of dexamethasone on temozolomide induced apoptosis in human glioblastoma U87MG cells" @default.
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