Beyond Grade: Molecular Pathology of Malignant Gliomas

Sulman, Erik P.; Guerrero, Marisol; Aldape, Ken

doi:10.1016/j.semradonc.2009.02.001

Cited by 31 publications

(27 citation statements)

References 71 publications

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“…Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumor (1). Current therapy consists of surgical resection followed by radiation therapy and concomitant chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Cycling hypoxia increases U87 glioma cell radioresistance via ROS induced higher and long-term HIF-1 signal transduction activity

Hsieh¹,

Lee

Liang³

et al. 2010

Oncol Rep

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Abstract. Glioblastoma multiforme (GBM) tumors are the most common type of brain tumors and resistance to radiotherapy. This study aimed to investigate the differential effect and mechanism of tumor microenvironments, cycling hypoxia and non-interrupted hypoxia, on tumor cell radiosensitivity in the human U87 glioblastoma tumor model. We exposed U87 cells and mice bearing U87 glioma to experimentally imposed cycling or non-interrupted hypoxic stress in vitro and in vivo prior to treatment with ionizing irradiation. Clonogenic survival assay and tumor growth measurements were performed to determine tumor radiosensitivity. The differential regulation of non-interrupted vs. cycling hypoxia by hypoxia-inducible factor-1 (HIF-1) and the impact of HIF-1· on hypoxia-induced radioresistance were assessed by molecular assay and RNAiknockdown technology. Our results demonstrated that cycling hypoxia induced higher and longer term HIF-1 signal transduction activity via reactive oxygen species (ROS) in U87 cells compared with non-interrupted hypoxia. Cycling hypoxiainduced HIF-1· activation reflected ROS mediated HIF-1· synthesis and stabilization, whereas non-interrupted hypoxiainduced HIF-1· activation was due to decreased HIF-1· degradation resulting from decreased prolyl hydroxylation. With regard to tumor radiosensitivity, cycling hypoxia induced more tumor cell radioresistance and a decreased response to radiotherapy in U87 cells compared with non-interrupted hypoxia. HIF-1 knockdown during in vitro and in vivo hypoxic stresses combined with radiotherapy suppressed cycling and non-interrupted hypoxia-induced radioresistance while increasing overall tumor radiosensitivity. Our results suggest that cycling hypoxia induces more radioresistance than non-interrupted hypoxia in U87 gliomas, and ROS mediated HIF-1· activation is a crucial mechanism involved in hypoxia-induced differential radioresistant in U87 gliomas.

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Section: Introductionmentioning

confidence: 99%

Cycling hypoxia increases U87 glioma cell radioresistance via ROS induced higher and long-term HIF-1 signal transduction activity

Hsieh¹,

Lee

Liang³

et al. 2010

Oncol Rep

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“…Therefore it is thought that p53 mutations are a hallmark of low-grade gliomas and consequently also occur in secondary GBM that arise from lower grade gliomas (Noda et al, 2009). Loss of p53 is observed in grade II astrocytomas (35-60%), grade III astrocytomas (~50%), primary GBM (~30%), and secondary GBM (~60-65%) (Sulman et al, 2009;Bourne & Schiff, 2010;Gladson et al, 2010). Additionally, p53 mutations are found in ~44% of grade II oligoastrocytoma and ~13% of oligodendroglioma cases (Bourne & Schiff, 2010).…”

Section: Cell Cycle Regulation 221 P53mentioning

confidence: 99%

“…Deletion or mutation of p16INK4A as a consequence of loss of chromosome 9p or hypermethylation occurs in approximately 12-62.5% of anaplastic astrocytoma cases (Gladson et al, 2010). p16 loss has also been reported in 20-57% of GBM cases (Sulman et al, 2009;Kim et al, 2010). Interestingly, since cyclins and cyclin-dependent kinase (CDK) inhibitors are subject to proteosomal degradation, cell cycle regulation can be modified through proteasome inhibitors.…”

Section: Rb/p16ink4a/cdk4mentioning

confidence: 99%

“…In 1984, extra copies of chromosome 7 were identified in malignant gliomas, which resulted in EGFR amplification/overexpression (Van Meir et al, 2010). EGFR promotes cell proliferation, invasion and angiogenesis, induces resistance to apoptosis, and may mediate radiation resistance (Sulman et al, 2009;Gladson et al, 2010). EGFR amplification at 7p12 is the most commonly amplified and overexpressed gene in primary GBM (30-70%) (Fischer & Aldape, 2010;Gladson et al, 2010;Kim et al, 2010;Riemenschneider et al, 2010).…”

Section: Egfr/nfkbiamentioning

confidence: 99%

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Evolvement of Molecular Biomarkers in Targeted Therapy of Malignant Gliomas

Bell¹,

Hadziahmetovic²,

Chakravarti³

2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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“…For example, there is a great deal of interest in developing tumor-grading meth-ods based on the genetic states of tumors rather than their anatomical appearance. 86,122 These methods would use genetic markers as an adjunct to traditional grading of tumors by a pathology lab. There is also significant interest in developing tumor prognosis classifiers based on genetic markers, with some recent success.…”

Section: Diagnostics Tumor Grading and Prognosismentioning

confidence: 99%

Genome-wide association studies: a powerful tool for neurogenomics

Cowperthwaite

Mohanty

Burnett

2010

FOC

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As their power and utility increase, genome-wide association (GWA) studies are poised to become an important element of the neurosurgeon's toolkit for diagnosing and treating disease. In this paper, the authors review recent findings and discuss issues associated with gathering and analyzing GWA data for the study of neurological diseases and disorders, including those of neurosurgical importance. Their goal is to provide neurosurgeons and other clinicians with a better understanding of the practical and theoretical issues associated with this line of research. A modern GWA study involves testing hundreds of thousands of genetic markers across an entire genome, often in thousands of individuals, for any significant association with a particular disease. The number of markers assayed in a study presents several practical and theoretical issues that must be considered when planning the study. Genome-wide association studies show great promise in our understanding of the genes underlying common neurological diseases and disorders, as well as in leading to a new generation of genetic tests for clinicians.

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Beyond Grade: Molecular Pathology of Malignant Gliomas

Cited by 31 publications

References 71 publications

Cycling hypoxia increases U87 glioma cell radioresistance via ROS induced higher and long-term HIF-1 signal transduction activity

Cycling hypoxia increases U87 glioma cell radioresistance via ROS induced higher and long-term HIF-1 signal transduction activity

Evolvement of Molecular Biomarkers in Targeted Therapy of Malignant Gliomas

Genome-wide association studies: a powerful tool for neurogenomics

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