Substrates for Astrocytoma Invasion

Giese, Alf; Loo, Melinda A.; Rief, Monique D.; Tran, Nhan L.; Berens, Michael E.

doi:10.1097/00006123-199508000-00015

Cited by 32 publications

(38 citation statements)

References 47 publications

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“…The explanation for these observations is not entirely clear and bears further investigation. Migration and invasion of glioma cells into normal brain are complex processes involving a wide variety of molecules including proteases, adhesion molecules, small G-proteins, cytoskeletal proteins, cytoskeleton associating proteins, extracellular matrix molecules, growth factors, and guidance molecules [26]. In general, glioma cell invasion can be considered to consist of three interrelated processes.…”

Section: Discussionmentioning

confidence: 99%

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

et al. 2008

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Photodynamic therapy (PDT) has been investigated as a postoperative treatment in patients with high grade gliomas. The purpose of this in vitro investigation was to determine whether motexafin gadolinium (MGd), a known radiation sensitizer, could potentiate the effects of 5-aminolevulinic acid (ALA)-PDT. Human glioma (ACBT) spheroids (250 μm diameter) were incubated in 5-aminolevulinic acid (ALA) with and without MGd and irradiated with 635 nm light for a total light fluence of 6, 12, or 18 J cm−2 delivered at a fluence rate of 5 mW cm−2. Spheroid growth was monitored for a period of 4 weeks following each treatment. In another set of experiments, 400–500 μm diameter ACBT spheroids were implanted into a gel collagen matrix and subjected to ALA-PDT (fluence: 3 or 6 J cm−2), MGd, or a combination of ALA-PDT and MGd. The migration distance of surviving glioma cells in each treatment group was recorded over a 5-day period. The results showed that MGd interacted with PDT in a synergistic manner resulting in greater cytotoxicity than that achievable with either treatment modality alone. The degree of synergism was shown to increase with increasing light fluence. At the highest light fluence investigated (18 J cm−2), the percentage of spheroids demonstrating growth 4 weeks following exposure to MGd, ALA-PDT, or MGd + ALA-PDT was 100%, 75%, and 15%, respectively. The results of cell migration studies revealed that the combination of PDT and MGd produced a significant inhibitory effect on glioma cell migration: the addition of MGd resulted in an approximately three times reduction in migration distance compared with PDT alone. Overall, the results suggest that MGd can potentiate both the cytotoxic and migration inhibitory effects of ALA-PDT and hence, this combined therapeutic approach has the potential to extend treatment volumes in patients with malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

et al. 2008

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“…The pro-apoptotic disposition of a cell is positively correlated with the proliferative activity of a cell population [2,44]. On the other hand there is increasing evidence that migration and proliferation may be antagonistic cellular behaviors [16,18,19]. This may have important implications for the treatment of invasive cells.…”

Section: Discussionmentioning

confidence: 99%

“…The migration characteristics [15,16,19] of the cell lines and the synthesis profiles for thromboxane synthase have been demonstrated earlier [20]. For selected experiments G-44 was used because it demonstrates expression of thromboxane synthase, COX-1 and COX-2 under standard tissue culture conditions.…”

Section: Cells and Cell Culturementioning

confidence: 99%

Cyclo-Oxygenase Inhibitors and Thromboxane Synthase Inhibitors Differentially Regulate Migration Arrest, Growth Inhibition and Apoptosis in Human Glioma Cells

Kürzel

Hagel

Zapf

et al. 2002

Acta Neurochirurgica

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We have previously identified thromboxane synthase as an important regulator of glioma cell migration. Inhibitors of this enzyme abrogate cell motility and induce apoptosis. However, the formation rate of thromboxanes is indirectly dependent on the activity of cyclo-oxygenase, which represents the rate-limiting step in the synthesis of prostaglandins and thromboxanes. In this study we have analyzed the expression of COX-1 and COX-2 in glioma cell lines and biopsies of glial tumors. In normal glia no expression of both COX isoforms was present, however, reactive astrocytes and glial tumors of all grades demonstrated expression of both COX-1 and COX-2. In contrast to inhibitors of thromboxane synthase, selective and non-selective cyclo-oxygenase inhibitors did not block cell motility. Specific COX-2 inhibitors resulted in growth inhibition and induction of intracellular DNA fragmentation indicative of apoptotic cell death. Treatment of glioma cells with thromboxane synthase inhibitors had a synergistic effect on induction of apoptosis by camptothecin, whereas COX inhibitors had not. Furthermore, combined treatment using COX-2 inhibitors and specific thromboxane synthase inhibitors did not show a synergistic increase of apoptosis. These data indicate that COX inhibitors and thromboxane synthase inhibitors influence apoptosis in glioma cells through different pathways. We hypothesize that, in contrast to the COX-2 inhibitors, thromboxane synthase inhibitors block the invasive phenotype of glioma cells and therefore increase the pro-apoptotic disposition of the cells and increase the susceptibility to induced apoptosis. This effect may be independent of prostaglandin synthesis controlled by cyclo-oxygenases.

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“…From the highly cellular tumor a gradient of invasive tumor cells can be found extending several centimeters into the adjacent brain. The path of individual invasive tumor cells follows preformed anatomical structures, predominantly the myelinated fiber tracts, but also structures such as the basement membrane of blood vessels, the pial lining of the brain surface and the walls of the ventricular system (8,9,11,10). Because of this diffuse growth pattern and a low inherent contrast of highly cellular tumor, invaded brain, and adjacent normal brain the detection of residual tumor during neurosurgical resections remains an important challenge.…”

Section: Introductionmentioning

confidence: 99%

Non-invasive intraoperative optical coherence tomography of the resection cavity during surgery of intrinsic brain tumors

Giese¹,

Böhringer²,

Leppert³

et al. 2006

SPIE Proceedings

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Optical coherence tomography (OCT) is a non-invasive imaging technique with a micrometer resolution. It allows noncontact / non-invasive analysis of central nervous system tissues with a penetration depth of 1-3,5 mm reaching a spatial resolution of approximately 4-15 µm. We have adapted spectral-domain OCT (SD-OCT) and time-domain OCT (TD-OCT) for intraoperative detection of residual tumor during brain tumor surgery. Human brain tumor tissue and areas of the resection cavity were analyzed during the resection of gliomas using this new technology. The site of analysis was registered using a neuronavigation system and biopsies were taken and submitted to routine histology. We have used post image acquisition processing to compensate for movements of the brain and to realign A-scan images for calculation of a light attenuation factor. OCT imaging of normal cortex and white matter showed a typical light attenuation profile. Tumor tissue depending on the cellularity of the specimen showed a loss of the normal light attenuation profile resulting in altered light attenuation coefficients compared to normal brain. Based on this parameter and the microstructure of the tumor tissue, which was entirely absent in normal tissue, OCT analysis allowed the discrimination of normal brain tissue, invaded brain, solid tumor tissue, and necrosis. Following macroscopically complete resections OCT analysis of the resection cavity displayed the typical microstructure and light attenuation profile of tumor tissue in some specimens, which in routine histology contained microscopic residual tumor tissue. We have demonstrated that this technology may be applied to the intraoperative detection of residual tumor during resection of human gliomas.

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Substrates for Astrocytoma Invasion

Cited by 32 publications

References 47 publications

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

Cyclo-Oxygenase Inhibitors and Thromboxane Synthase Inhibitors Differentially Regulate Migration Arrest, Growth Inhibition and Apoptosis in Human Glioma Cells

Non-invasive intraoperative optical coherence tomography of the resection cavity during surgery of intrinsic brain tumors

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