Influences of brain tumor-associated pH changes and hypoxia on epileptogenesis

Schaller, Bernhard

doi:10.1111/j.1600-0404.2004.00355.x

Cited by 58 publications

(42 citation statements)

References 75 publications

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“…Despite increasing experimental research regarding the pathophysiological mechanism of primary or secondary central nervous system (CNS) tumors in recent years, the underlying molecular and cellular changes (both in the tumor area and its surrounding tissue) remain only partially understood (1)(2)(3)(4)(5)(6). To date, very little work has been done for spinal tumors (7)(8)(9)(10); consequently most of our knowledge about spinal tumors is adapted from similar tumors in the brain; however, it is well documented that there are substantial molecular and cellular differences between brain and spine (7).…”

Section: Introductionmentioning

confidence: 99%

Current Molecular Imaging of Spinal Tumors in Clinical Practice

Sandu

Pöpperl²,

Toubert

et al. 2011

Mol Med

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Energy metabolism measurements in spinal cord tumors, as well as in osseous spinal tumors/metastasis in vivo, are rarely performed only with molecular imaging (MI) by positron emission tomography (PET). This imaging modality developed from a small number of basic clinical science investigations followed by subsequent work that influenced and enhanced the research of others. Apart from precise anatomical localization by coregistration of morphological imaging and quantification, the most intriguing advantage of this imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, MI represents one of the key technologies in translational molecular neuroscience research, helping to develop experimental protocols that may later be applied to human patients. PET may help monitor a patient at the vertebral level after surgery and during adjuvant treatment for recurrent or progressive disease. Common clinical indications for MI of primary or secondary CNS spinal tumors are: (i) tumor diagnosis, (ii) identification of the metabolically active tumor compartments (differentiation of viable tumor tissue from necrosis) and (iii) prediction of treatment response by measurement of tumor perfusion or ischemia. While spinal PET has been used under specific circumstances, a question remains as to whether the magnitude of biochemical alterations observed by MI in CNS tumors in general (specifically spinal tumors) can reveal any prognostic value with respect to survival. MI may be able to better identify early disease and to differentiate benign from malignant lesions than more traditional methods. Moreover, an adequate identification of treatment effectiveness may influence patient management. MI probes could be developed to image the function of targets without disturbing them or as treatment to modify the target's function. MI therefore closes the gap between in vitro and in vivo integrative biology of disease. At the spinal level, MI may help to detect progression or recurrence of metastatic disease after surgical treatment. In cases of nonsurgical treatments such as chemo-, hormone-or radiotherapy, it may better assess biological efficiency than conventional imaging modalities coupled with blood tumor markers. In fact, PET provides a unique possibility to correlate topography and specific metabolic activity, but it requires additional clinical and experimental experience and research to find new indications for primary or secondary spinal tumors.

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Section: Introductionmentioning

confidence: 99%

Current Molecular Imaging of Spinal Tumors in Clinical Practice

Sandu

Pöpperl²,

Toubert

et al. 2011

Mol Med

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“…Such pathological features are thought to be due to tissue hypoxia. Therefore hypoxia is a critical aspect of the surrounding microenvironment of brain tumors and is generally associated with unfavorable clinical outcomes (3,4,(8)(9)(10)(11)(12). Cells that are under hypoxic stress can develop an adaptive response that includes increased rates of glycolysis and angiogenesis or undergo cell death by promoting apoptosis and/or necrosis (3,8,13).…”

Section: The Microenvironment Of Brain Tumorsmentioning

confidence: 99%

“…Cytolytic viruses and genes coding for antitumor cytokines, prodrug-converting enzymes and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors (1). Novel brain tumor treatment strategies that involve transplantation or infusion of cells that seek out invading tumor cells demand thorough in vivo monitoring (3)(4)(5)(6)(7)(8)15,16). In particular, NSCs have attracted great interest because they have demonstrated tropism to tumor cells and even long-distance migration to single tumor cells (17,18).…”

Section: The Microenvironment Of Brain Tumorsmentioning

confidence: 99%

“…Therefore hypoxia is a critical aspect of the surrounding microenvironment of brain tumors and is generally associated with unfavorable clinical outcomes (3,4,(8)(9)(10)(11)(12). Cells that are under hypoxic stress can develop an adaptive response that includes increased rates of glycolysis and angiogenesis or undergo cell death by promoting apoptosis and/or necrosis (3,8,13). The ability of tumor cells to maintain a balance between adaptation to hypoxia and cell death is regulated by hypoxiainducing factors, a family of transcription factors that are essential for the regulation of the expression of a large number of hypoxia-responsive genes (13,14).…”

Section: The Microenvironment Of Brain Tumorsmentioning

confidence: 99%

“…Tumor hypoxia is hypothesized to facilitate metastases, tumor recurrence, invasive potential and resistance to chemotherapy and radiotherapy, which culminate in decreased patient survival. For this reason, effective targeting of hypoxic areas in brain tumors remains a significant therapeutic challenge (3,4,(8)(9)(10). New NSC therapeutic options for tumor-targeted drug delivery show promise in treatment of brain tumors that are refractory to traditional therapies (1,3,4,9).…”

Section: The Microenvironment Of Brain Tumorsmentioning

confidence: 99%

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Sandu¹,

Schaller²

2010

Mol. Med.

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Neural stem cells have been proposed as a new and promising treatment modality in various pathologies of the central nervous system, including malignant brain tumors. However, the underlying mechanism by which neural stem cells target tumor areas remains elusive. Monitoring of these cells is currently done by use of various modes of molecular imaging, such as optical imaging, magnetic resonance imaging and positron emission tomography, which is a novel technology for visualizing metabolism and signal transduction to gene expression. In this new context, the microenvironment of (malignant) brain tumors and the blood-brain barrier gains increased interest. The authors of this review give a unique overview of the current molecular-imaging techniques used in different therapeutic experimental brain tumor models in relation to neural stem cells. Such methods for molecular imaging of gene-engineered neural stem/progenitor cells are currently used to trace the location and temporal level of expression of therapeutic and endogenous genes in malignant brain tumors, closing the gap between in vitro and in vivo integrative biology of disease in neural stem cell transplantation.

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