Combination of Intracranial Temozolomide With Intracranial Carmustine Improves Survival When Compared With Either Treatment Alone in a Rodent Glioma Model

Recinos, Violette Renard; Tyler, Betty; Bekelis, Kimon; Sunshine, Sarah B.; Vellimana, Ananth K.; Li, Khan Wayne; Brem, Henry

doi:10.1227/01.neu.0000365263.14725.39

Cited by 58 publications

(37 citation statements)

References 28 publications

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“…Glioblastoma multiforme (GBM), the most common and aggressive form of brain malignancies, remains mostly incurable and has about 1-year median survival postdiagnosis, despite considerable advances in diagnosis, therapies, and understanding of its molecular pathways (1)(2)(3)(4)(5). Recent studies have revealed that a cancer-cell subpopulation in brain tumors-glioma stem cells (GSC)-exhibits tumor-initiating ability, self-renewal, and aberrant differentiation and is responsible for glioma initiation and progression (6,7).…”

Section: Introductionmentioning

confidence: 99%

ID4 Imparts Chemoresistance and Cancer Stemness to Glioma Cells by Derepressing miR-9*–Mediated Suppression of SOX2

Jeon

Sohn²,

Oh³

et al. 2011

Cancer Research

183

108

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Glioma stem cells (GSC) possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Thus, they are considered to be major drivers for glioma initiation, progression, and recurrence. However, the precise mechanism governing acquisition of their drug resistance remains to be elucidated. Our previous study has shown that inhibitor of differentiation 4 (ID4) dedifferentiates Ink4a/Arf À/À mouse astrocytes and human glioma cells to glioma stem-like cells (induced GSCs or iGSCs). In this article, we report that ID4-driven iGSCs exhibit chemoresistant behavior to anticancer drugs through activation of ATPbinding cassette (ABC) transporters. We found that ID4 enhanced SOX2 protein expression by suppressing microRNA-9* (miR-9*), which can repress SOX2 by targeting its 3 0 -untranslated region. Consequently, ID4-mediated SOX2 induction enhanced ABCC3 and ABCC6 expression through direct transcriptional regulation, indicating that ID4 regulates the chemoresistance of iGSCs by promoting SOX2-mediated induction of ABC transporters. Furthermore, we found that short hairpin RNA-mediated knockdown of SOX2 in ID4-driven iGSCs resulted in loss of cancer stemness. Moreover, ectopic expression of SOX2 could dedifferentiate Ink4a/Arf À/À astrocytes and glioma cells to iGSCs, indicating a crucial role of SOX2 in genesis and maintenance of GSCs. Finally, we found that the significance of the ID4-miR-9*-SOX2-ABCC3/ABCC6 regulatory pathway is recapitulated in GSCs derived from patients with glioma. Together, our results reveal a novel regulatory mechanism by which ID4-driven suppression of miR-9* induces SOX2, which imparts stemness potential and chemoresistance to glioma cells and GSCs. Cancer Res; 71(9); 3410-21. Ó2011 AACR.

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Section: Introductionmentioning

confidence: 99%

ID4 Imparts Chemoresistance and Cancer Stemness to Glioma Cells by Derepressing miR-9*–Mediated Suppression of SOX2

Jeon

Sohn²,

Oh³

et al. 2011

Cancer Research

183

108

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“…Intracranial delivery of temozolomide (TMZ) polymers was found to be superior to oral administration in a gliosarcoma rat model [61] and was suggested to be well tolerated in humans [62,63]. Local delivery of TMZ and carmustine improved the survival of tumor-bearing animals in the 9 L and F98 glioma models [64]. Even by local delivery, systemic toxicity due to diffusion from the tumor site is a possibility.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells

et al. 2011

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Gliomas are the most common primary brain tumor, and their treatment is still a challenge. Here, we evaluated the antiproliferative effect of a novel combination of two potent oxidative stress enhancers: menadione (M) and sodium orthovanadate (SO). We observed both short-term and prolonged growth inhibitory effects of M or SO alone as well as in combination (M:SO) on DBTRG.05MG human glioma cells. A stronger antiproliferative effect was observed in the short-term proliferation assay with the M:SO combination compared to either investigated agent alone. In the long-term proliferation assay, a 10-day exposure to M:SO at concentrations of 10 μM:17.5 μM or 17.5 μM:10 μM was enough to kill 100% of the cells; no cell regrowth was observed after re-incubation in drug-free media. When used in combination, the single concentration of M and SO could be decreased by 2.5- to 5-fold of those used for each experimental drug alone and still obtain a similar antiproliferative effect. The underlying molecular mechanism was investigated by co-incubating M:SO with dithiothreitol (DTT) and genistein. Both substances partially neutralized the effects of the M:SO combination, showing additive effects. This observation suggests a role of oxidative stress and tyrosine kinase stimulation in the M:SO cytotoxic effect. Our results indicate that M:SO combination is an attractive alternative for glioma treatment that encourages further study. The neutralizing effects of genistein and DTT reveal a possibility for their use in the minimization of potential M:SO systemic toxicity.

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“…2a-b). Long-term survivors were defined as animals that survived for more than 120 days following 9L cell implantation [35]. Magnetic resonance imaging [36] …”

Section: Importance Of the Administration Route On The Activity Gradientmentioning

confidence: 99%

Tumor eradication in rat glioma and bypass of immunosuppressive barriers using internal radiation with 188Re-lipid nanocapsules

et al. 2011

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Combination of Intracranial Temozolomide With Intracranial Carmustine Improves Survival When Compared With Either Treatment Alone in a Rodent Glioma Model

Abstract: The survival of tumor-bearing animals in the 9L and F98 glioma models was improved with the local delivery of BCNU and TMZ combined with XRT when compared with either treatment alone or oral TMZ, local BCNU, and XRT.

Cited by 58 publications

References 28 publications

ID4 Imparts Chemoresistance and Cancer Stemness to Glioma Cells by Derepressing miR-9*–Mediated Suppression of SOX2

ID4 Imparts Chemoresistance and Cancer Stemness to Glioma Cells by Derepressing miR-9*–Mediated Suppression of SOX2

Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells

Tumor eradication in rat glioma and bypass of immunosuppressive barriers using internal radiation with 188Re-lipid nanocapsules

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