GliaSite Brachytherapy for Treatment of Recurrent Malignant Gliomas: A Retrospective Multi-institutional Analysis

Gabayan, Arash; Green, Sylvan B.; Sanan, Abhay; Jenrette, Joseph M.; Schultz, Christopher J.; Papagikos, Michael A.; Tatter, Stephen B.; Patel, Apurva; Amin, Pradip; Lustig, Robert A.; Bastin, Kenneth; Watson, Gordon A.; Burri, Stuart H.; Stea, Baldassarre

doi:10.1227/01.neu.0000194836.07848.69

Cited by 125 publications

(77 citation statements)

References 30 publications

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“…In spite of the enormous improvements made in neurosurgery, chemotherapy, and radiotherapy, the prognosis of malignant gliomas has remained poor over the last decades in the United States and Europe (1). The cumulative 1-year survival rate is <30%, and the median survival time of the grade 4 glioma, glioblastoma multiforme (GBM), is only 15 months (2,3). Such suboptimal efficacy in the management of glioma is largely attributable to the highly invasive nature of glioma cells capable of diffusely infiltrating and widely migrating in the surrounding brain tissue, leading to restricted and incomplete surgical resection and, thus, high recurrence rates (1,4).…”

Section: Introductionmentioning

confidence: 99%

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

et al. 2010

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The poor prognosis of malignant gliomas is largely attributed to their highly invasive nature. The molecular mechanism underlying the invasiveness of glioma cells, however, remains to be elucidated. The present study found that astrocyte elevated gene-1 (AEG-1) was upregulated in human glioma cell lines and glioma tissues compared with normal astrocytes and brain tissues. AEG-1 was found to be upregulated in 265 of 296 (89.5%) glioma sections, and the AEG-1 expression level significantly correlated with clinicopathologic stages of gliomas. Ectopic expression or short hairpin RNA silencing of AEG-1 significantly enhanced or inhibited, respectively, the invasive ability of glioma cells. At the molecular level, we showed that upregulated AEG-1 in glioma cells interacted with matrix metalloproteinase-9 (MMP-9) promoter and transactivated MMP-9 expression, whereas knockdown of AEG-1 expression reduced the level of MMP-9. Two regions in MMP-9 promoter were found to be involved in the interaction with AEG-1. Suppression of endogenous MMP-9 abrogated the effects of AEG-1 on invasiveness. Consistent with these observations, immunostaining analysis revealed a significant correlation between the expressions of AEG-1 and MMP-9 in a cohort of clinical glioma samples. Moreover, intracranial xenografts of glioma cells engineered to express AEG-1 were highly invasive compared with the parental cells and expressed high level of MMP-9. Collectively, these findings provide evidence that AEG-1 contributes to glioma progression by enhancing MMP-9 transcription and, hence, tumor cell invasiveness, and underscore the importance of AEG-1 in glioma development and progression. Cancer Res; 70(9); 3750-9. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

et al. 2010

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“…Despite the advances in surgery, radiation therapy, and chemotherapy, the 1-year overall survival rate is less than 30%, and the median survival time of patients with high-grade glioma is only approximately 15 months (1,2). To develop more optimized and effective treatment strategies for glioblastomas, it is critical to gain deeper understanding of the molecular mechanisms underlying gliomagenesis and to identify targets for therapeutic intervention (3,4).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-221/222 sensitizes glioma cells to temozolomide by regulating apoptosis independently of p53 status

Chen

Zhang²,

Han³

et al. 2011

Oncol Rep

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Abstract.A previous study showed that miR-221/222 can regulate cell apoptosis. p53 is a well known tumor suppressor which can influence the chemosensitivity of glioma cells. However, the effect of miR-221/222 in gliomas with different p53 status is unknown. Here, we demostrate that knockdown of miR-221/222 increases apoptosis in human gliomas of different p53 types (U251 cells, p53 mutant-type; LN308 cells, p53 null-type; and U87 cells, p53 wild-type). Furthermore, the effect of miR-221/22 caused no change of p53 expression in the glioma cells studied. In addition, when a specific siRNA against p53 was employed in U87 cells, no attenuation of apoptosis was found after knockdown of miR-221/222. Importantly, we found that As-miR-221/222-treated cells increased expression of Bax, cytochrome c, Apaf-1 and cleaved-caspase-3. Our results showed that low expression of miR-221/222 sensitized glioma cells to temozolomide (TMZ); in addition, ectopic expression of PUMA by pcDNA-PUMA had a similar effect. Taken together, our study indicates that downregulated miR-221/222 can sensitize glioma cells to TMZ by regulating apoptosis independently of p53 status. IntroductionGlioblastoma, the most aggressive type of tumor arising in the central nervous system (CNS), is considered to be one of the deadliest of human cancers. Despite the advances in surgery, radiation therapy, and chemotherapy, the 1-year overall survival rate is less than 30%, and the median survival time of patients with high-grade glioma is only approximately 15 months (1,2). To develop more optimized and effective treatment strategies for glioblastomas, it is critical to gain deeper understanding of the molecular mechanisms underlying gliomagenesis and to identify targets for therapeutic intervention (3,4).MicroRNAs are small regulatory RNA molecules that in recent years have been identified in the progression of various cancers and proposed as novel targets for anticancer therapies (5,6). By negatively regulating their mRNA targets to either degradation or translational repression, they can act as both tumor suppressors and oncogenes (7). Recent studies showed frequent deregulation of miR-221/222 in glioblastoma and astrocytoma cell lines (8). Overexpression of miR-221/222 increased glioma cell proliferation and invasion in vitro and induced glioma growth in a subcutaneous mouse model (9). In addition, blockade of miR-221/222 cluster suppressed human glioma cell growth, suggesting the cosuppression of miR-221/222 cluster might be a potential therapeutic strategy in glioma (10). Our previous study demostrated that miR-221/222 can directly target PUMA inducing apoptosis (11). p53, an upstream gene of PUMA, is a well known tumor-suppressor. However, the role of miR-221/222 in glioma of different p53 status is not well elucidated.In this study, we identified the involvement of miR-221/-222 in mediating apoptosis in glioma regardless of p53 status. Furthermore, we confirmed that low expression of miR-221/222 sensitizes glioma cells to the alkylating agent TMZ partly...

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“…Nonetheless, clinical and survival benefit is dependent on patient and tumor characteristics, which need to be considered before pursuing a second surgery. The most consistently demonstrated prognostic factor is favorable PS (KPS ≥ 70), which associates with significantly improved PFS and OS, following salvage therapy (70)(71)(72)(73)(74)(75)(76). Younger age is the second most frequently reported prognostic factor associated with improved survival (70,72,77,78).…”

Section: Surgery At Recurrencementioning

confidence: 99%

Current Standards of Care in Glioblastoma Therapy

et al. 2017

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Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Regardless of ideal multidisciplinary treatment, including maximal surgical resection, followed by radiotherapy plus concomitant and maintenance temozolomide (TMZ), almost all patients experience tumor progression with nearly universal mortality and a median survival of less than 15 months. The addition of bevacizumab to standard treatment with TMZ revealed no increase in overall survival (OS) but improved progression-free survival (PFS). In newly diagnosed GBM, methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been shown to predict response to alkylating agents, as well asgnosis. Therefore, MGMT promoter status may have a crucial role in the choice of single modality treatment in fragile elderly population. No standard of care is established in recurrent or progressive GBM. Treatment alternatives may include supportive care, surgery, re-irradiation, systemic therapies, and combined modality therapy. Despite numerous clinical trials, the identification of effective therapies is complex because of the lack of appropriate control arms, selection bias, small sample sizes, and disease heterogeneity. Tumor-treating fields plus TMZ represent a major advance in the field of GBM therapy, and should be Standards of Care in Glioblastoma Therapy 198 considered for patients with newly diagnosed GBM with no contraindications. As a disease with such a poor prognosis, treatment of GBM should go beyond improving survival and aim at preserving and even improving the quality of life of both the patient and the caregiver.

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GliaSite Brachytherapy for Treatment of Recurrent Malignant Gliomas: A Retrospective Multi-institutional Analysis

Cited by 125 publications

References 30 publications

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

Downregulation of miR-221/222 sensitizes glioma cells to temozolomide by regulating apoptosis independently of p53 status

Current Standards of Care in Glioblastoma Therapy

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