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Molecular Research of Urology 2022
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Molecular Research of Urology 2022

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 9631

Special Issue Editor

Prof. Dr. Jack A. Schalken

E-Mail Website
Guest Editor
Research Director Urology, Dept. of Urology, University Hospital Nijmegen, Box 9101, NL-6500 HB Nijmegen, The Netherlands
Interests: molecular and cellbiology of oncological diseases; cadherine mediated interactions and signal transductions; molecular diagnostics; urogenital oncology; veterinary oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Molecular technology platforms have exponentially developed to a status where pathologies can be profiled at various levels. In this Special Issue, we invite you to submit manuscripts related new progress of urology research. We invite both oncological and non-oncological papers. Topics to be considered include, but are not limited to, precision medicine in GU oncology, new molecular therapeutical targets, biomarkers for non-oncological bladder disease, and advances in molecular tissue engineering.

The investigations we will focus our attention on are fundamentally cellular/molecular studies, papers only contain clinical trials/data are not acceptable.

Prof. Dr. Jack A. Schalken
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • precision medicine in GU oncology
  • new molecular therapeutical targets
  • biomarkers for non-oncological bladder disease
  • advances in molecular tissue engineering

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Published Papers (4 papers)

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Research

10 pages, 1110 KiB  
Communication
A Compendium of AR Splice Variants in Metastatic Castration-Resistant Prostate Cancer
by Khrystany T. Isebia, Martijn P. Lolkema, Guido Jenster, Ronald de Wit, John W. M. Martens and Job van Riet
Int. J. Mol. Sci. 2023, 24(6), 6009; https://doi.org/10.3390/ijms24066009 - 22 Mar 2023
Cited by 1 | Viewed by 2055
Abstract
Treatment-induced AR alterations, including AR alternative splice variants (AR-Vs), have been extensively linked to harboring roles in primary and acquired resistance to conventional and next-generation hormonal therapies in prostate cancer and therefore have gained momentum. Our aim was to uniformly determine recurrent AR-Vs [...] Read more.
Treatment-induced AR alterations, including AR alternative splice variants (AR-Vs), have been extensively linked to harboring roles in primary and acquired resistance to conventional and next-generation hormonal therapies in prostate cancer and therefore have gained momentum. Our aim was to uniformly determine recurrent AR-Vs in metastatic castration-resistant prostate cancer (mCRPC) using whole transcriptome sequencing in order to assess which AR-Vs might hold potential diagnostic or prognostic relevance in future research. This study reports that in addition to the promising AR-V7 as a biomarker, AR45 and AR-V3 were also seen as recurrent AR-Vs and that the presence of any AR-V could be associated with higher AR expression. With future research, these AR-Vs may therefore harbor similar or complementary roles to AR-V7 as predictive and prognostic biomarkers in mCRPC or as proxies for abundant AR expression. Full article
(This article belongs to the Special Issue Molecular Research of Urology 2022)
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23 pages, 4516 KiB  
Article
Comprehensive Evaluation of Multiple Approaches Targeting ABCB1 to Resensitize Docetaxel-Resistant Prostate Cancer Cell Lines
by Dinah Linke, Lukas Donix, Claudia Peitzsch, Holger H. H. Erb, Anna Dubrovska, Manuel Pfeifer, Christian Thomas, Susanne Fuessel and Kati Erdmann
Int. J. Mol. Sci. 2023, 24(1), 666; https://doi.org/10.3390/ijms24010666 - 30 Dec 2022
Cited by 11 | Viewed by 2335
Abstract
Docetaxel (DTX) is a mainstay in the treatment of metastatic prostate cancer. Failure of DTX therapy is often associated with multidrug resistance caused by overexpression of efflux membrane transporters of the ABC family such as the glycoprotein ABCB1. This study investigated multiple approaches [...] Read more.
Docetaxel (DTX) is a mainstay in the treatment of metastatic prostate cancer. Failure of DTX therapy is often associated with multidrug resistance caused by overexpression of efflux membrane transporters of the ABC family such as the glycoprotein ABCB1. This study investigated multiple approaches targeting ABCB1 to resensitize DTX-resistant (DTXR) prostate cancer cell lines. In DU145 DTXR and PC-3 DTXR cells as well as age-matched parental controls, the expression of selected ABC transporters was analyzed by quantitative PCR, Western blot, flow cytometry and immunofluorescence. ABCB1 effluxing activity was studied using the fluorescent ABCB1 substrate rhodamine 123. The influence of ABCB1 inhibitors (elacridar, tariquidar), ABCB1-specific siRNA and inhibition of post-translational glycosylation on DTX tolerance was assessed by cell viability and colony formation assays. In DTXR cells, only ABCB1 was highly upregulated, which was accompanied by a strong effluxing activity and additional post-translational glycosylation of ABCB1. Pharmacological inhibition and siRNA-mediated knockdown of ABCB1 completely resensitized DTXR cells to DTX. Inhibition of glycosylation with tunicamycin affected DTX resistance partially in DU145 DTXR cells, which was accompanied by a slight intracellular accumulation and decreased effluxing activity of ABCB1. In conclusion, DTX resistance can be reversed by various strategies with small molecule inhibitors representing the most promising and feasible approach. Full article
(This article belongs to the Special Issue Molecular Research of Urology 2022)
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26 pages, 4596 KiB  
Article
Identification of the Regulatory Targets of miR-3687 and miR-4417 in Prostate Cancer Cells Using a Proteomics Approach
by Simone Venz, Heike Junker, Erik Ultsch, Franziska Hetke, Elke Krüger, Martin Burchardt, Pedro Caetano-Pinto and Cindy Roennau
Int. J. Mol. Sci. 2022, 23(18), 10565; https://doi.org/10.3390/ijms231810565 - 12 Sep 2022
Cited by 3 | Viewed by 1927
Abstract
MicroRNAs (miRNA) are ubiquitous non-coding RNAs that have a prominent role in cellular regulation. The expression of many miRNAs is often found deregulated in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). Although their expression can be associated with PCa and CRPC, their [...] Read more.
MicroRNAs (miRNA) are ubiquitous non-coding RNAs that have a prominent role in cellular regulation. The expression of many miRNAs is often found deregulated in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). Although their expression can be associated with PCa and CRPC, their functions and regulatory activity in cancer development are poorly understood. In this study, we used different proteomics tools to analyze the activity of hsa-miR-3687-3p (miR-3687) and hsa-miR-4417-3p (miR-4417), two miRNAs upregulated in CRPC. PCa and CRPC cell lines were transfected with miR-3687 or miR-4417 to overexpress the miRNAs. Cell lysates were analyzed using 2D gel electrophoresis and proteins were subsequently identified using mass spectrometry (Maldi-MS/MS). A whole cell lysate, without 2D-gel separation, was analyzed by ESI-MS/MS. The expression of deregulated proteins found across both methods was further investigated using Western blotting. Gene ontology and cellular process network analysis determined that miR-3687 and miR-4417 are involved in diverse regulatory mechanisms that support the CRPC phenotype, including metabolism and inflammation. Moreover, both miRNAs are associated with extracellular vesicles, which point toward a secretory mechanism. The tumor protein D52 isoform 1 (TD52-IF1), which regulates neuroendocrine trans-differentiation, was found to be substantially deregulated in androgen-insensitive cells by both miR-3687 and miR-4417. These findings show that these miRNAs potentially support the CRPC by truncating the TD52-IF1 expression after the onset of androgen resistance. Full article
(This article belongs to the Special Issue Molecular Research of Urology 2022)
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14 pages, 3445 KiB  
Article
Flavonoid Nobiletin Attenuates Cyclophosphamide-Induced Cystitis in Mice through Mechanisms That Involve Inhibition of IL-1β Induced Connexin 43 Upregulation and Gap Junction Communication in Urothelial Cells
by Jin Kono, Masakatsu Ueda, Atsushi Sengiku, Sylvia O. Suadicani, Je Tae Woo, Takashi Kobayashi, Osamu Ogawa and Hiromitsu Negoro
Int. J. Mol. Sci. 2022, 23(9), 5037; https://doi.org/10.3390/ijms23095037 - 1 May 2022
Cited by 9 | Viewed by 2502
Abstract
Bladder inflammatory diseases cause various urinary symptoms, such as urinary frequency and painful urination, that impair quality of life. In this study, we used a mouse model of cyclophosphamide (CYP)-induced bladder inflammation and immortalized human urothelial (TRT-HU1) cells to explore the preventive potential [...] Read more.
Bladder inflammatory diseases cause various urinary symptoms, such as urinary frequency and painful urination, that impair quality of life. In this study, we used a mouse model of cyclophosphamide (CYP)-induced bladder inflammation and immortalized human urothelial (TRT-HU1) cells to explore the preventive potential of nobiletin (NOB), a polymethoxylated flavone enriched in citrus fruit peel, and investigate its mechanism of action in the bladder. Prophylaxis with PMF90 (60% NOB) attenuated the development of bladder inflammation and urinary symptoms in CYP-treated mice. PMF90 also reduced the upregulation of connexin 43 (Cx43), a major component of gap junction channels, in the bladder mucosa of CYP-treated mice. Stimulation of TRT-HU1 cells with the pro-inflammatory cytokine IL-1β increased Cx43 mRNA and protein expression and enhanced gap junction coupling—responses that were prevented by pre-treatment with NOB. In urothelium-specific Cx43 knockout (uCx43KO) mice, macroscopic signs of bladder inflammation and changes in voiding behavior induced by CYP treatment were significantly attenuated when compared to controls. These findings indicate the participation of urothelial Cx43 in the development of bladder inflammation and urinary symptoms in CYP-treated mice and provide pre-clinical evidence for the preventive potential of NOB through its anti-inflammatory effects on IL-1β signaling and urothelial Cx43 expression. Full article
(This article belongs to the Special Issue Molecular Research of Urology 2022)
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