Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target

Purpose  To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Methods  Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. Results  FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Conclusion  Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging.     

Overexpression Of GPR7 In Schwann Cells From Patients With Peripheral Neuropathies

The identification of regulated gene products that play a role in Schwann cell-axon contact after nerve injuries may have important implications for pain mechanisms and nerve repair processes. Schwann cell-intrinsic defects have been recently shown to cause neuropathies associated with pain (Gillespie et al., 2000). The 7TM GPR7, originally described by O'Dowd et al. (1995) as a likely G-protein coupled receptor, is a human orphan receptor expressed in the nervous system with sequence similarity to both somatostatin and opioid receptors. Using real time quantitative PCR^TM we evaluated the expression of GPR7 in sural nerve biopsies from patients with different kinds of peripheral neuropathies. We observed that GPR7 expression was significantly (p < 0.001) increased in sural nerves when an epineurial and endoneurial perivascular inflammatory infiltration was present. The overexpression was particularly noted in patients with painful peripheral neuropathies with an inflammatory, immuno and vasculitic etiology. In order to confirm changes in GPR7 expression at the protein level, we performed immunofluorescence staining on sections of neuropathic human sural nerves. A comparative analysis of rat injured sciatic nerves was also performed. We observed that GPR7 receptor is expressed by Schwann cells and that the amount of Schwann cell-staining in both human and rat nerve is increased in conditions of inflammatory neuropathy. In addition, we observed that the expression of GPR7 was significantly decreased in severe axonal neuropathies, suggesting that GPR7 expression is axon dependent. Immunofluorescence staining in rat cultured Schwann cells suggested that the expression GPR7 increased during Schwann-axon interaction. Taken together these results suggest that molecules such as GPR7 whose expression in Schwann cells varies under pathological conditions may play a role in the pathogenesis of human neuropathies. Altered GPR7 expression may disrupt myelination leading to progression of the neuropathy. Alternatively, GPR7 may play a role in Schwann cell-axon signaling and thereby influence axonal function in neuropathies leading to a painful phenotype.     

Accuracy of three cone-beam CT devices and two software systems in the detection of vertical root fractures

Objectives :The aim of this study was to compare the accuracy of vertical root fracture (VRF) detection using three tomography devices and two software systems in teeth with different endodontic fillings.Methods:The sample consisted of 45 premolars divided into 3 groups: No filling (NF, n=15); Gutta percha (GP, n=15) and Metallic Post (MP, n=15). Cone-beam computed tomography (CBCT) images were acquired in Kodak 9000 3D, Orthopantomography 300 (OP300) and PreXion 3D devices, before and after induced root fractures. Two oral radiologists analyzed all images using InVivoDental and e-Vol DX software systems. The analysis was repeated after 15 days in 30% of the sample. Data analysis compared receiver operating characteristic (ROC) curves, as well the areas under the ROC curves. Accuracy, sensitivity, specificity, positive and negative predictive value were calculated according to each tomographic device and software. Intra- and interexaminer reliability were tested using the Kappa coefficient.Results:The highest accuracy was seen in the image set from the PreXion 3D, using InVivo (0.96) or e-Vol DX (0.92) in image analysis. The OP300 device presented a similar performance of the PreXion 3D in teeth with different endodontic fillings. When using e-Vol DX, the accuracy of Kodak 9000 3D improved from 0.62 to 0.74.Conclusions:The PreXion 3D device is the most accurate when detecting VRF, with a performance similar to the OP300 in endodontic filled teeth. Kodak 9000 3D is indicated for teeth without fillings, with better accuracy using e-Vol DX software.