[Novel biomarkers in renal cell carcinoma. Identification and functional characterization]. / Biomarker in Nierenzellkarzinomen. Identifikation und funktionelle Charakterisierung.

Due to advanced imaging techniques, renal cell carcinoma (RCC) is now identified earlier, often in localized stages. As a result, nephron-sparing surgical resection is possible in most cases. The development of new targeted therapies has changed the way metastatic RCC is treated. Despite this positive trend with improved survival rates and expanding treatment options, reliable biomarkers for better predicting disease course are lacking. These are urgently needed to enable personalized therapy based on the treatment-associated risks, the presence of comorbidities, and molecular tumor characteristics. We were able to show that proteins with a regulatory influence on apoptotic signal cascades represent not only promising prognostic markers, but also interesting targets for new therapeutic approaches. Furthermore, our data demonstrate that molecular tests are necessary to correctly classify a RCC with Xp11.2 translocation, since in addition to translocation, amplification can also result in TFE3 activation. Translational research with RCC biomarker identification and establishment, as well as molecular characterization and subtyping of RCCs is required to guide therapeutic decisions and enable personalized medicine in RCC patients.

Contrast-enhanced ultrasonography in the early period after kidney transplantation predicts long-term allograft function.

INTRODUCTION: Real-time contrast-enhanced sonography (CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The purpose of the study was to evaluate the feasibility of early CES in predicting long-term kidney allograft function in comparison to color Doppler ultrasonography (CDUS). METHODS: We prospectively studied 68 consecutive kidney transplant recipients using CES and conventional CDUS investigation 1 week after transplantation. Transplant tissue perfusion imaging was performed by low-power imaging during intravenous administration of the sonocontrast SonoVue. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow (RBF). The obtained sonography values were correlated with clinical data 1 week up to 1 year after transplantation. RESULTS: In contrast with conventional CDUS resistive indices, RBF estimated by CES 1 week posttransplantation significantly correlated with kidney function after 1 year (r = 0.67; P < .001). Determination of RBF by CES revealed a significant correlation with donor age but not recipient age, whereas conventional CDUS resistive index was significantly correlated to recipient age (r = 0.54; P < .001) but not donor age. Furthermore RBF was associated with vascular fibrosis and intimal thickening of the engraftment biopsies. CONCLUSION: This is the first prospective study demonstrating the prognostic value of CES early after kidney transplantation. In contrast with CDUS, CES reveals information about kidney allograft perfusion independent of recipient vascular compliance.

[High-resolution imaging of the layers of the gastrointestinal wall of pig and human specimens using an endoluminal MR receiver coil: correlation to histology]. / Hochauflösende Bildgebung der gastrointestinalen Wandschichten von Schweine- und Humanpräparaten mittels endoluminaler MR-Spule: Korrelation zur Histologie.

PURPOSE: High-resolution MR imaging of the layers of the gastrointestinal wall to provide a foundation for tumor staging based on morphological criteria. MATERIALS AND METHODS: Over a period of 12 months, miscellaneous parts of the gastrointestinal tract of 15 human specimens and 30 porcine specimens were scanned using a 1.5 Tesla clinical MRI scanner combined with an endoluminal receiver coil. The sequences used were T 1-weighted opposed-phase, T 2-weighted turbo spin echo with fat saturation and fast T 2-weighted inversion recovery. The number of differentiable layers, their width and the signal intensity were documented. Then, the results were compared with histological specimens in order to link the imaged wall layers to the anatomical layers. Spearman's Rank Correlation was used to determine the soundness of the link between the images and their related histology. RESULTS: For both human and animal specimens, the MRI scanning produced 3 to 5, maximum 6 (pig), differentiable layers. The mucosa, submucosa and muscularis could be differentiated with a hyperintense, hypointense and intermediary signal, respectively. The subserosal layer displayed a hypointense signal. CONCLUSION: High-resolution MRI is able to produce differentiable images of the anatomical layers of the gastrointestinal wall in both humans and pigs. Accordingly, it is possible to use MR imaging to diagnose the extent of local tumor infiltration of the gastrointestinal wall.

Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney.

The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms alpha and beta were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.