Malignant glioma: patterns of failure following individually tailored limited volume irradiation

Hess, Clemens F.; Schaaf, J; Kortmann, Rolf Dieter; Schabet, Martin; Bamberg, M.

doi:10.1016/0167-8140(94)90044-2

Cited by 124 publications

(66 citation statements)

References 15 publications

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“…The limitations of conventional treatment modalities at adequately treating infiltrative tumor cells are highlighted by the observation that 80% of malignant gliomas recur within 2 to 3 cm of the original tumor mass. 4 Herpes simplex virus-1 (HSV-1) is a large, naturally neurotropic, double-stranded DNA virus that is actively being developed into useful replication-selective (oncolytic) and replication-defective gene therapy vectors. 5 To date, two replication-selective viral constructs have reached clinical trials in patients with malignant gliomas.…”

Section: Introductionmentioning

confidence: 99%

Evaluation and optimization of the administration of a selectively replicating herpes simplex viral vector to the brain by convection-enhanced delivery

et al. 2011

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The direct intraparenchymal administration of oncolytic viral vectors by convection-enhanced delivery (CED) represents a promising new treatment strategy for malignant gliomas. However, there is no evidence to suggest that oncolytic viruses as large as herpes simplex virus-1 (HSV-1) can be administered by CED, as this has not been systematically examined in an animal model. In this study, the administration of a herpes simplex viral vector, HSV1, has been evaluated in detail in the gray and white matter of both rat and pig models, using high flow-rate infusions, co-infusing heparin or preinfusing the tissue with an isotonic albumin solution. Rat HSV-1 infusions at both slow (0.5 ml min À1 ) and high infusion rates (2.5 ml min À1 ) led to extensive tissue damage and negligible cell transduction. Co-infusion with heparin led to extensive hemorrhage. Preinfusion of tissue with an isotonic albumin solution facilitated widespread vector distribution and cell transduction in white matter only. Using this approach in pig brain led to widespread vector distribution with extensive transduction of astrocytes and activated microglia. In rat brain, enhanced green fluorescent protein expression peaked 48 h after vector administration and was associated with a vigorous immune response. These findings indicate that direct infusions of HSV-1-based viral vectors into the brain lead to minimal vector distribution, negligible cell transduction and extensive damage. Tissue preinfusion with an isotonic solution prior to vector administration represents an effective technique for achieving widespread HSV-1 distribution.

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Section: Introductionmentioning

confidence: 99%

Evaluation and optimization of the administration of a selectively replicating herpes simplex viral vector to the brain by convection-enhanced delivery

et al. 2011

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“…In the last few years, many attempts were made for optimizing radiotherapy, such as increasing the dose (over 60Gy yield), whole brain irradiation, and the adoption of a stereotactic therapy [28,29]. Unfortunately, all these therapy concepts led to an increase of recrudescences in the surrounding area and a combination with chemotherapy must be discussed.…”

Section: Discussionmentioning

confidence: 99%

The Radiation Induced Migration of Human Malignant Glioma Cells can be Blocked by Inhibition of the EGFR Downstream Pathways

Margraf¹

2012

J Nucl Med Radiat Ther

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Background: It is well documented that low dose ionizing radiation induces migration of glioma cells, but the mechanisms are still poorly understood. The aim of the current study was to elucidate the intracellular signal transduction pathways of radiation induced migration in human glioma cells. Methods:Migration was assessed via a wound healing assay. In addition, tumor cell proliferation was evaluated with a MTT colorimeritric assay using 3 glioma cell lines (LN18, LN229, LNZ308). The cells were treated with increasing doses of irradiation (2Gy, 5Gy, 8Gy) in the presence or absence of EGF or inhibitors of the EGFR or downstream pathways (AG1478, LY294002, PD98059). Biochemical activation of EGFR, Akt/PKB and MAPK/ERK was examined by Western blot analysis.Results: Irradiation induced a dose dependant intense increase of migrating cells and a decrease of proliferation. The inhibition of PI3K by LY294002 (50 µmol/L) reduced the radiation-induced migration (LN18: p<0.001, LN229: p=0.16, LNZ308: p=0.13), the blockade of MEK1 by PD98059 (50 µmol/L) was also effective (LN18: p=0.036, LN229: p=0.021, LNZ308: p=0.021). After irradiation, no effect on EGFR or the downstream pathways was observed in Western blot analysis. Conclusion:Our results demonstrate that the downstream pathways of EGFR are involved in radiation induced migration of glioma cells.

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“…It was not until the early 1970's that partial brain treatment became a viable option with the introduction of CT which heralded a dramatic change in the diagnostic evaluation and treatment principles of gliomas. The correlation of CT imaging and histological data in conjunction with clinical data demonstrating 80% of local recurrence arising within 2 cm of the original tumor as defined by CT, paved the foundation for successful partial brain treatment [2,3,5,14,[23][24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Comparison of T2 and FLAIR Imaging for Target Delineation in High Grade Gliomas

Stall

Zach

Ning

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Malignant glioma: patterns of failure following individually tailored limited volume irradiation

Cited by 124 publications

References 15 publications

Evaluation and optimization of the administration of a selectively replicating herpes simplex viral vector to the brain by convection-enhanced delivery

Evaluation and optimization of the administration of a selectively replicating herpes simplex viral vector to the brain by convection-enhanced delivery

The Radiation Induced Migration of Human Malignant Glioma Cells can be Blocked by Inhibition of the EGFR Downstream Pathways

Comparison of T2 and FLAIR Imaging for Target Delineation in High Grade Gliomas

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