Home About us Contact | |||
Rat Glioma (rat + glioma)
Terms modified by Rat Glioma Selected AbstractsInterplay of constitutively released nucleotides, nucleotide metabolism, and activity of P2Y receptorsDRUG DEVELOPMENT RESEARCH, Issue 2-3 2001Eduardo R. Lazarowski Abstract At least six mammalian P2Y receptors exist that are specifically activated by ATP, UTP, ADP or UDP. Although the existence of ectoenzymes that rapidly metabolize extracellular nucleotides is well established, the relative flux of ATP and UTP through their extracellular metabolic products remains undefined. In addition, the existence of basal nucleotide release and the contribution of resting levels of ATP and UTP to P2 receptor activation are poorly understood. In the absence of exogenous agonists, an apyrase-sensitive inositol phosphate accumulation was observed in resting 16HBE14o, human bronchial epithelial cells endogenously expressing P2Y receptors and in 1321N1 human astrocytoma cells expressing a recombinant P2Y2 receptor. To test whether nucleotide release may account for basal P2 receptor activities, the rates of extracellular accumulation and metabolism of endogenous ATP were examined with resting 16HBE14o,, C6 rat glioma, and 1321N1 cell cultures. Although extracellular ATP concentrations (1-5 nM) remained unchanged for up to 12 h, [,32P] ATP included in the medium (as a radiotracer) was completely degraded within 120 min, indicating that ATP release balanced ATP hydrolysis. The calculated basal rates of ATP release ranged from 20 to 200 fmol/min per million cells. HPLC analysis during steady state revealed that the gamma-phosphate of ATP was reversibly transferred to species further identified as UTP and GTP, implicating ecto-nucleoside diphosphokinase (NDPK)-catalyzed phosphorylation of endogenous UDP and GDP. At steady state, the final 32P-products of [,32P]ATP metabolism were 32P-orthophosphoric acid and a species further purified and identified as 32P-pyrophosphate. Constitutive nucleotide release balanced by the concerted activities of ecto-ATPase, ecto-ATP pyrophosphatase, and ecto-NDPK may determine the resting levels of extracellular nucleotides and therefore, the basal activity of P2 receptors. Drug Dev. Res. 53:66,71, 2001. © 2001 Wiley-Liss, Inc. [source] Water diffusion in a rat glioma during ganciclovir-thymidine kinase gene therapy-induced programmed cell death in vivo: Correlation with cell densityJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2004Piia K. Valonen MSc Abstract Purpose To study the characteristics of diffusion magnetic resonance imaging (MRI) contrast in a rat brain BT4C glioma during progression of ganciclovir (GCV)-thymidine kinase gene therapy-induced programmed cell death (PCD) in vivo. Materials and Methods The trace of the diffusion tensor (Dav = 1/3Trace ), T2, and spin density were determined by MRI and the apparent diffusion coefficient (ADC) of water by diffusion nuclear MR (NMR) spectroscopy using largely varying b values and diffusion times (tD) at 4.7 T. Cell count and apoptotic cells were quantified by histological means. Results Decline in cell count was strongly associated with increase in both Dav and T2. Spin density ratio between tumor and contralateral parietal cortex increased with a very similar time course as Dav and T2, indicating net water gain into the eradicating tumor. Diffusion spectroscopy showed a nonmonoexponential signal decay at all tD values ranging from 14,192 msec. During PCD, the ADC of the component yielding fast diffusion coefficient (D1), as acquired with tD , 47 msec, increased with kinetics similar to those of Dav (tD = 4.8 msec). The fractional size of D1 increased by 10% to 15% throughout the entire tD range. Apparent water residence time of the slow diffusion component, D2, shortened from a value of 38.3 ± 1.7 msec on day 0 to 33.4 ± 0.5 msec by day 8. Conclusion The present results show that reduced cell density and increased water content, leading to altered water microenvironment, are associated with increased water diffusion coefficient in eradicating gliomas as a result of PCD. J. Magn. Reson. Imaging 2004;19:389,396. © 2004 Wiley-Liss, Inc. [source] Correlation between the occurrence of 1H-MRS lipid signal, necrosis and lipid droplets during C6 rat glioma developmentNMR IN BIOMEDICINE, Issue 4 2003Sonja Zoula Abstract The aim of this study was to investigate the possible correlation between the 1H MRS mobile lipid signal, necrosis and lipid droplets in C6 rat glioma. First, the occurrence of necrosis and lipid droplets was determined during tumor development, by a histological analysis performed on 34 rats. Neither necrosis nor lipid droplets were observed before 18 days post-implantation. At later stages of development, both necrosis and lipid droplets were apparent, the lipid droplets being mainly located within the necrotic areas. Using a second group of eight rats, a temporal correlation was evidenced between mobile lipid signal detected by in vivo single-voxel one- (136,ms echo time) and two-dimensional J -resolved 1H MR spectroscopy, and the presence of necrosis and lipid droplets on the histological sections obtained from the brains of the same rats. Finally, spatial distribution of the mobile lipid signal was analyzed by chemical-shift imaging performed on a third group of eight animals, at the end of the tumor growth. The spectroscopic image corresponding to the resonance of mobile lipids had its maximum intensity in the center of the tumor where necrotic regions were observed on the histological sections. These necrotic areas contained large amounts of lipid droplets. All these results suggest that mobile lipids detected in vivo by 1H MRS (136,ms echo time) in C6 rat brain glioma arise mainly from lipid droplets located in necrosis. Copyright © 2003 John Wiley & Sons, Ltd. [source] Therapeutic efficacy of 5-fluorouracil-loaded microspheres on rat glioma: a magnetic resonance imaging studyNMR IN BIOMEDICINE, Issue 6 2001L. Lemaire Abstract The aim of this work was to assess the therapeutic efficacy of an intratumoral bolus injection of 5-fluorouracil (FU) compared to that of drug loaded in biodegradable microspheres, for the treatment of brain tumour. Experiments were carried out using a fast-growing C6-glioma rat model. The therapeutic protocols were performed 12 days after the injection of glioma cells. At this stage, the tumours were installed and the mean volume was 13,±,2,µl as measured by proton magnetic resonance (MR) imaging. This technique was used for the follow-up of the tumour volume with respect to time and therapy. In terms of rat survival, both therapies induced a significant 50% increase in animal life span (p,<,0.05) compared to animals receiving no drug or unloaded microspheres. Whilst no cure was observed, analysis of the MR images showed that the local and sustained delivery of FU slowed the tumour development in the vicinity of the microspheres by a factor of 3, compared with the bolus intratumoral injection. Copyright © 2001 John Wiley & Sons, Ltd. [source] |