Leuchtend: Eine von einem G‐Quartett inspirierte Fluoreszenzsonde (APD), die aus zwei acetylenverbrückten Purinen besteht, wurde synthetisiert. APD leuchtet in Gegenwart paralleler DNA‐ (z. B. c‐MYC) oder RNA‐G‐Quadruplexe, während es keine Fluoreszenzverstärkung in Gegenwart von doppelsträngiger DNA, antiparallelen oder gemischten (z. B. h‐Telo) G‐Quadruplexen zeigt. APD wurde auch zur bevorzugten Anfärbung von G‐Quadruplexen verwendet.

Purpose: Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans.Experimental Design: ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis.Results: Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA-and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype.Conclusions: Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease.

It has been hypothesized that patients with bladder cancer (BCa) might suffer from subsequent upper tract urothelial carcinoma (UTUC) if hydronephrosis is managed via US. We analyzed the impact of several factors at transurethral resection of bladder tumor (TURBT) on the occurrence of metachronous UTUC.METHODS: Retrospective analysis of 545 patients with BCa presenting with hydronephrosis and managed with US or PN. All the patients underwent TURBT and subsequent radical cystectomy between 1990 and 2019 at 23 tertiary care centers. Patients without hydronephrosis, not undergoing UUT decompression or without concomitant UTUC were excluded from the study. A 1:1 propensity score matching (PSM) estimated using logistic regression was performed using preoperative parameters such as: age, ASA score, clinical T stage, tumor multifocality, CIS at TURBT. Univariable and multivariable Cox regression analyses were used to predict the occurrence of metachronous UTUC after BCa diagnosis, adjusting for clinicopathological variables. Kaplan-Meier analyses predicted recurrence, cancer specific mortality (CSM) and overall mortality (OM) according to the drainage modality.RESULTS: After PSM we obtained 125 (50%) BCa patients managed with US and 125 (50%) with PN. Hydronephrosis was due to direct BCa obstruction in 193 (77%) cases. US and PN were maintained in situ for a mean of 130 and 71 days, respectively (p<0.001). Patients receiving PN had a higher rate of muscle invasive BCa (74 vs 36%, p<0.001) at TURBT in comparison with the US cohort. On univariable and multivariable analysis we found no statistically significant association between clinico-pathological features at TURBT and the occurrence of metachronous UTUC. Similarly, the presence of hydronephrosis due to BCa obstruction and the duration of indwelling US were not statistically associated with the development of metachronous UTUC. Lastly, the two cohorts didn't show differences in terms of CSM and OM (Log-rank 0.6 and 0.5, respectively).CONCLUSIONS: Ureteral stenting does not increase the risk of developing metachronous UTUC in patients with BCa presenting with hydronephrosis requiring UUT decompression. The choice of managing the hydronephrosis in patients with BCa should not be based on concerns of developing metachronous UTUC.

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