Aldo-keto reductase family 1 (AKR1) enzymes play a crucial role in diabetic complications. Since type 2 diabetes (T2D) is associated with cancer progression, we investigated the impact of diabetes on AKR1 gene expression in the context of prostate cancer (PCa) development. In this study, we analyzed benign (BEN) prostate and PCa tissue of patients with and without T2D. Furthermore, to replicate hyperglycemia in vitro, we treated the prostate adenocarcinoma cell line PC3 with increasing glucose concentrations. Gene expression was quantified using real-time qPCR. In the prostate tissue of patients with T2D, AKR1C1 and AKR1C2 transcripts were higher compared to samples of patients without diabetes. In PC3 cells, high glucose treatment induced the gene expression levels of AKR1C1, C2, and C3. Furthermore, both in human tissue and in PC3 cells, the transcript levels of AKR1C1, C2, and C3 showed positive associations with oncogenes, which are involved in proliferation processes and HIF1α and NFκB pathways. These results indicate that in the prostate glands of patients with T2D, hyperglycemia could play a pivotal role by inducing the expression of AKR1C1, C2, and C3. The higher transcript level of AKR1C was furthermore associated with upregulated HIF1α and NFκB pathways, which are major drivers of PCa carcinogenesis.

Subfamily

10.3390/jpm10030124

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PO-1194: MR-based adaptive IGRT of prostate cancer: feasibility, plan adaptation and acute toxicity

Radiotherapy and Oncology (2020)

Daniel Wegener Finn‐Ole Paulsen Chiara De‐Colle D. Thorwart Ulrich Grosse

Image-guided radiation therapy

10.1016/s0167-8140(21)01212-3

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Systematic Review and Cumulative Analysis of Oncologic and Functional Outcomes After Robot-assisted Radical Cystectomy

European Urology (2015)

Bertram Yuh Timothy G. Wilson Bernard H. Bochner Kevin Chan Joan Palou

Lymphadenectomy

10.1016/j.eururo.2014.12.008

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Citations (218)

Immuncheckpointinhibition beim metastasierten Urothelkarzinom

Aktuelle Urologie (2018)

Jens Bedke Tilman Todenhöfer Arnulf Stenzl

The treatment of metastatic urothelial carcinoma is characterized by the administration of combinatory regimes of chemotherapy. In the first-line treatment theses regimes demonstrate relatively good objective response rates and prolongation of overall survival. The prognosis declines if the patient is refractory to platin in the second- or third-line treatment or if the patient is ineligible for cisplatin in the first-line setting. Cisplatin ineligibility is defined by a poor renal function or subsequent comorbidities. The new class of immune checkpoint inhibitors (ICI) has led to an impressive improvement in the therapy of mUC in platin-refractory or cisplatin-ineligible patients. Currently, the EMA has approved Atezolizumab, Nivolumab and Pembrolizumab based on phase II and III trial data. Future developments focus on first-line and adjuvant treatment of ICI with PD-L1/PD-1 as a backbone and in combination with either other ICI or chemotherapy. The prognostic use of biomarkers in ICI is still a medical need as the currently available results with regard to the PD-L1 status are heterogeneous.Die Behandlung des metastasierten Urothelkarzinoms (mUC) erfolgte standardmäßig durch die Applikation chemotherapiehaltiger Regime. Während in der Erstlinienbehandlung durch cisplatinbasierte Kombinationen noch relativ gute Ansprechraten und eine Verlängerung des Gesamtüberlebens erzielt werden kann, verringert sich dieses in der platinrefraktären Situation und wenn − aufgrund einer eingeschränkten Nierenfunktion oder Komorbiditäten − kein Cisplatin mehr gegeben werden kann. Die neue Substanzklasse der Immuncheckpointinhibitoren (ICI) hat die Therapie beim mUC deutlich verbessert, sowohl nach platinhaltiger Therapie als auch bei cisplatin-ungeeigneten Patienten. Aktuell sind durch die EMA Atezolizumab, Nivolumab und Pembrolizumab basierend auf Phase II- und III-Daten für die Therapie des mUC zugelassen. Zukünftige Entwicklungen fokussieren auf die Anwendung in der Erstlinie und der adjuvanten Therapie, auch in der Kombination von PD-L1-/PD-1-Antikörpern mit zusätzlichen ICI-Targets und der Kombination mit Chemotherapie. Klinischer Bedarf besteht in der Etablierung von Biomarkern in der ICI-Therapie, da die derzeitigen Ergebnisse für den PD-L1-Status heterogen sind.

Atezolizumab

10.1055/a-0581-4395

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Data from Simultaneous Infiltration of Polyfunctional Effector and Suppressor T Cells into Renal Cell Carcinomas

Sebastian Attig Jörg Hennenlotter Graham Pawelec Gerd Klein Sven D. Koch

<div>AbstractRenal cell carcinoma is frequently infiltrated by cells of the immune system. This makes it important to understand interactions between cancer cells and immune cells so they can be manipulated to bring clinical benefit. Here, we analyze subsets and functions of T lymphocytes infiltrating renal cell tumors directly ex vivo following mechanical disaggregation and without any culture step. Subpopulations of memory and effector CD4+ Th1, Th2, and Th17 and CD8+ Tc1 cells were identified based on surface phenotype, activation potential, and multicytokine production. Compared with the same patient's peripheral blood, T lymphocytes present inside tumors were found to be enriched in functional CD4+ cells of the Th1 lineage and in effector memory CD8+ cells. Additionally, several populations of CD4+ and CD8+ regulatory T cells were identified that may synergize to locally dampen antitumor T-cell responses. [Cancer Res 2009;69(21):8412–9]</div>

Tumor-infiltrating lymphocytes

10.1158/0008-5472.c.6499599.v1

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Somatostatin analogs for the treatment of advanced, hormone-refractory prostate cancer

Der Urologe (2008)

David Schilling R. Küfer Stephan Kruck Arnulf Stenzl M.A. Kuczyk

10.1007/s00120-008-1781-7

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Citations (3)

Reconstructive Urology

International braz j urol (2007)

Karl‐Dietrich Sievert Arnulf Stenzl

Purpose: Management for posterior urethral disruption and concurrent bladder neck incompetence is controversial.Some groups recommend treatment with a Mitrofanoff catheterizable stoma, while others advocate urethral reconstruction with delayed placement of an artificial urinary sphincter.We report our experience with the latter strategy.Materials and Methods: We reviewed the records of all patients with the above injury who were treated with end-to-end urethroplasty followed by delayed bladder neck artificial urinary sphincter placement from 1986 to 2006.Results: Five patients had videourodynamic evidence of bladder neck incompetence coexisting with traumatic posterior urethral disruption.The etiology of bladder neck incompetence in all 5 patients was a known longitudinal tear through the bladder neck that occurred at the time of trauma.Each patient underwent end-to-end urethroplasty.Six to 12 months later the patients had persistent incontinence.Bladder function and urethral patency were documented by urodynamic, radiographic and endoscopic studies.A bladder neck artificial urinary sphincter was subsequently placed.Each operation was technically demanding due to fibrosis in the pelvis and around the bladder neck.All patients were initially continent but erosion of the artificial urinary sphincter into the bladder neck in 4, and the bladder neck and rectum in 1 occurred at a mean of 3 years (range 6 months to 8 years).Conclusions: Placement of a bladder neck artificial urinary sphincter for managing urinary incontinence due to concurrent posterior urethral disruption and bladder neck incompetence is difficult and it risks delayed erosion.In this patient population we would strongly consider urinary diversion with a Mitrofanoff catheterizable stoma.

10.1590/s1677-55382007000400029

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Radical cystectomy for muscle-invasive bladder cancer

Georgios Gakis Arnulf Stenzl

10.2217/fmeb2013.13.4

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Targeted vs systematic robot‐assisted transperineal magnetic resonance imaging‐transrectal ultrasonography fusion prostate biopsy

BJU International (2017)

Johannes Mischinger Sascha Kaufmann Giorgio Ivan Russo Niklas Harland Steffen Rausch

Objective To evaluate the performance of transperineal robot‐assisted ( RA ) targeted ( TB ) and systematic ( SB ) prostate biopsy in primary and repeat biopsy settings. Patients and Methods Patients underwent RA biopsy between 2014 and 2016. Before RA ‐ TB , multiparametric magnetic resonance imaging (mp MRI ) was performed. Prostate lesions were scored (Prostate Imaging, Reporting and Data System, version 2) and used for RA ‐ TB planning. In addition, RA ‐ SB was performed. Available, whole‐gland pathology was analysed. Results In all, 130 patients were biopsy naive and 72 had had a previous negative transrectal ultrasonography‐guided biopsy. In total, 202 patients had suspicious mp MRI lesions. Clinically significant prostate cancer was found in 85% of all prostate cancer cases ( n = 123). Total and clinically significant prostate cancer detection rates for RA ‐ TB vs RA ‐ SB were not significantly different at 77% vs 84% and 80% vs 82%, respectively. RA ‐ TB demonstrated a better sampling performance compared to RA ‐ SB (26.4% vs 13.9%; P < 0.001). Conclusion Transperineal RA ‐ TB and ‐ SB showed similar clinically significant prostate cancer detection rates in primary and repeat biopsy settings. However, RA ‐ TB offered a 50% reduction in biopsy cores. Omitting RA ‐ SB is associated with a significant risk of missing clinically significant prostate cancer.

Transrectal ultrasonography

Prostate biopsy

10.1111/bju.14089

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PEDICLES OF THE FEMALE URETHRA

The Journal of Urology (1999)

Elizabeth Kavaler Hannes Strasser Arnulf Stenzl Georg Bartsch Helga Fritsch

Female urethra

Male urethra

10.1097/00005392-199904020-00232

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