Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Research in Urology 2014

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 June 2014) | Viewed by 82787

Share This Special Issue

Special Issue Editors

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

Dr. Nees Matthias

E-Mail Website
Guest Editor

Medical Biotechnology Knowledge Centre, VTT Technical Research Centre of Finland, Turku, Finland

Special Issue Information

Dear Colleagues,

The unmet needs in prostate cancer diagnosis and therapy are diverse; there is an urgent need for biomarkers that can be used for the early diagnosis of patients with clinically significant prostate cancer. Significant steps forward have been made and are reviewed in this issue. Once metastasized, there is still no effective treatment, nor stand alone a curative therapy. However, an improved understanding of sustained androgen receptor signaling in CRPC has now led to more effective therapies. Apart from a better insight in the molecular aspects of prostate carcinogenesis and progression, we need to understand tumor cell biology. Identification of cancer initiating cells and therapies targeted to eradicate these population(s) are the way forward to combat this disease.

Prof. Dr. Jack A. Schalken
Dr. Nees Matthias
Guest Editors

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

biomarkers (diagnostic prognostic and predictive)
androgen receptor targeted therapy
novel targets for therapy
cancer initiating cells

Related Special Issue

Molecular Research in Urology in International Journal of Molecular Sciences (38 articles)

Published Papers (11 papers)

Download All Papers

Research

Jump to: Review, Other

4128 KiB

Open AccessArticle

Potential Therapeutic Roles of Tanshinone IIA in Human Bladder Cancer Cells

by Sheng-Chun Chiu, Sung-Ying Huang, Shu-Fang Chang, Shee-Ping Chen, Chi-Cheng Chen, Tien-Huang Lin, Hsin-Ho Liu, Tsung-Hsun Tsai, Shang-Sen Lee, Cheng-Yoong Pang and Teng-Fu Hsieh

Int. J. Mol. Sci. 2014, 15(9), 15622-15637; https://doi.org/10.3390/ijms150915622 - 04 Sep 2014

Cited by 32 | Viewed by 6375

Abstract

Tanshinone IIA (Tan-IIA), one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Figure 1

696 KiB

Open AccessArticle

Role of Serum Cholesterol and Statin Use in the Risk of Prostate Cancer Detection and Tumor Aggressiveness

by Juan Morote, Anna Celma, Jacques Planas, José Placer, Inés De Torres, Mireia Olivan, Juan Carles, Jaume Reventós and Andreas Doll

Int. J. Mol. Sci. 2014, 15(8), 13615-13623; https://doi.org/10.3390/ijms150813615 - 06 Aug 2014

Cited by 25 | Viewed by 6491

Abstract

The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p < 0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p < 0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p = 0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p = 0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p = 0.012). NSC men had a 53.8% rate of HGPCa, while the rate was only 27.6% in HSC men (p < 0.001). NSC men on statins had an HGPCa rate of 70.2%, while non-statin users had a rate of 41.2% (p < 0.001). The HGPCa rate for HSC men on statins was 18.8%, while the rate was 30.0% (p = 0.011) for non-users. Logistic regression analysis suggested that serum cholesterol levels could serve as an independent predictor of PCa risk, OR 1.87 (95% CI 1.56–2.24) and HGPCa risk, OR 0.31 (95% CI 0.23–0.44), while statin usage could not. Statin treatment may prevent PCa detection through serum cholesterol-mediated mechanisms. A disturbing increase in the HGPCa rate was observed in statin users who normalized their serum cholesterol. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Figure 1

731 KiB

Open AccessArticle

Comparative Evaluation of Urinary PCA3 and TMPRSS2: ERG Scores and Serum PHI in Predicting Prostate Cancer Aggressiveness

by Lucile Tallon, Devillier Luangphakdy, Alain Ruffion, Marc Colombel, Marian Devonec, Denis Champetier, Philippe Paparel, Myriam Decaussin-Petrucci, Paul Perrin and Virginie Vlaeminck-Guillem

Int. J. Mol. Sci. 2014, 15(8), 13299-13316; https://doi.org/10.3390/ijms150813299 - 30 Jul 2014

Cited by 32 | Viewed by 5615

Abstract

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Figure 1

4712 KiB

Open AccessArticle

Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model

by Deying Zhang, Xing Liu, Jinpu Peng, Dawei He, Tao Lin, Jing Zhu, Xuliang Li, Yuanyuan Zhang and Guanghui Wei

Int. J. Mol. Sci. 2014, 15(8), 13151-13165; https://doi.org/10.3390/ijms150813151 - 24 Jul 2014

Cited by 73 | Viewed by 8667

Abstract

Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit) were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Graphical abstract

745 KiB

Open AccessArticle

Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

by Samanta Salvi, Daniele Calistri, Giorgia Gurioli, Elisa Carretta, Luigi Serra, Roberta Gunelli, Wainer Zoli and Valentina Casadio

Int. J. Mol. Sci. 2014, 15(7), 12458-12468; https://doi.org/10.3390/ijms150712458 - 14 Jul 2014

Cited by 12 | Viewed by 5338

Abstract

Patients with non-muscle invasive bladder cancer (NMIBC) generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs) of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF) using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB) were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023). Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041). Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Figure 1

1041 KiB

Open AccessArticle

Protein Tyrosine Kinase 7 (PTK7) as a Predictor of Lymph Node Metastases and a Novel Prognostic Biomarker in Patients with Prostate Cancer

by Hongtuan Zhang, Andi Wang, Shiyong Qi, Shang Cheng, Bing Yao and Yong Xu

Int. J. Mol. Sci. 2014, 15(7), 11665-11677; https://doi.org/10.3390/ijms150711665 - 01 Jul 2014

Cited by 36 | Viewed by 6464

Abstract

Protein tyrosine kinase 7 (PTK7) has been studied in various tumors, but its role in prostate cancer remains unknown. This study is aimed to investigate the prognostic and predictive significance of PTK7 in patients with prostate cancer. PTK7 expression was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis in 20 pairs of benign prostatic hyperplasia specimens and prostate cancer specimens. Then, we examined the immunohistochemical expression of PTK7 in 180 prostate cancer specimens and evaluated its clinical significances. Elevated PTK7 expression was significantly associated with lymph node metastases, seminal vesicle invasion, prostate cancer stage, the higher preoperative prostate-specific antigen, the higher Gleason score, angiolymphatic invasion, and biochemical recurrence. The results revealed that the overexpression of PTK7 in prostate cancer was an independent prognostic factor for poor overall survival and biochemical recurrence-free survival. The present data provide evidence that PTK7 predicts lymph node metastasis and poor overall survival and biochemical recurrence-free survival, highlighting its potential function as a therapeutic target for prostate cancer. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Figure 1

1557 KiB

Open AccessArticle

PSMA, EpCAM, VEGF and GRPR as Imaging Targets in Locally Recurrent Prostate Cancer after Radiotherapy

by Maxim Rybalov, Hildo J. K. Ananias, Hilde D. Hoving, Henk G. Van der Poel, Stefano Rosati and Igle J. De Jong

Int. J. Mol. Sci. 2014, 15(4), 6046-6061; https://doi.org/10.3390/ijms15046046 - 10 Apr 2014

Cited by 50 | Viewed by 8845

Abstract

In this retrospective pilot study, the expression of the prostate-specific membrane antigen (PSMA), the epithelial cell adhesion molecule (EpCAM), the vascular endothelial growth factor (VEGF) and the gastrin-releasing peptide receptor (GRPR) in locally recurrent prostate cancer after brachytherapy or external beam radiotherapy (EBRT) was investigated, and their adequacy for targeted imaging was analyzed. Prostate cancer specimens were collected of 17 patients who underwent salvage prostatectomy because of locally recurrent prostate cancer after brachytherapy or EBRT. Immunohistochemistry was performed. A pathologist scored the immunoreactivity in prostate cancer and stroma. Staining for PSMA was seen in 100% (17/17), EpCAM in 82.3% (14/17), VEGF in 82.3% (14/17) and GRPR in 100% (17/17) of prostate cancer specimens. Staining for PSMA, EpCAM and VEGF was seen in 0% (0/17) and for GRPR in 100% (17/17) of the specimens’ stromal compartments. In 11.8% (2/17) of cases, the GRPR staining intensity of prostate cancer was higher than stroma, while in 88.2% (15/17), the staining was equal. Based on the absence of stromal staining, PSMA, EpCAM and VEGF show high tumor distinctiveness. Therefore, PSMA, EpCAM and VEGF can be used as targets for the bioimaging of recurrent prostate cancer after EBRT to exclude metastatic disease and/or to plan local salvage therapy. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

1761 KiB

Open AccessArticle

Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1

by Tao Zhang, Shanna Qu, Qi Shi, Dalin He and Xunbo Jin

Int. J. Mol. Sci. 2014, 15(2), 3154-3171; https://doi.org/10.3390/ijms15023154 - 21 Feb 2014

Cited by 41 | Viewed by 7651

Abstract

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone or in combination with other anti-cancer agents, has been considered as a new strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine, a quinolone alkaloid isolated from the fruit of Evodia fructus, induced apoptosis and enhanced TRAIL-induced apoptosis in human bladder cancer cells. To elucidate the underlying mechanism, we found that evodiamine significantly reduced the protein levels of Mcl-1 in 253J and T24 bladder cancer cells, and overexpression of this molecule attenuated the apoptosis induced by evodiamine alone, or in combination with TRAIL. Further experiments revealed that evodiamine did not affect the mRNA level, proteasomal degradation and protein stability of Mcl-1. On the other hand, evodiamine inhibited the mTOR/S6K1 pathway, which usually regulates protein translation; moreover, knockdown of S6K1 with small interfering RNA (siRNA) effectively reduced Mcl-1 levels, indicating evodiamine downregulates c-FLIP through inhibition of mTOR/S6K1 pathway. Taken together, our results indicate that evodiamine induces apoptosis and enhances TRAIL-induced apoptosis possibly through mTOR/S6K1-mediated downregulation of Mcl-1; furthermore, these findings provide a rationale for the combined application of evodiamine with TRAIL in the treatment of bladder cancer. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Review

Jump to: Research, Other

799 KiB

Open AccessReview

Prognostic DNA Methylation Markers for Prostate Cancer

by Siri H. Strand, Torben F. Orntoft and Karina D. Sorensen

Int. J. Mol. Sci. 2014, 15(9), 16544-16576; https://doi.org/10.3390/ijms150916544 - 18 Sep 2014

Cited by 86 | Viewed by 9292

Abstract

Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

897 KiB

Open AccessReview

Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

by Ilaria Marech, Cosmo Damiano Gadaleta and Girolamo Ranieri

Int. J. Mol. Sci. 2014, 15(7), 13060-13076; https://doi.org/10.3390/ijms150713060 - 23 Jul 2014

Cited by 33 | Viewed by 12215

Abstract

Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Figure 1

Other

Jump to: Research, Review

1728 KiB

Open AccessLetter

Molecular Research in Urology 2014: Update on PET/MR Imaging of the Prostate

by Axel Wetter

Int. J. Mol. Sci. 2014, 15(8), 13401-13405; https://doi.org/10.3390/ijms150813401 - 31 Jul 2014

Cited by 3 | Viewed by 5072

Abstract

This article gives an overview of recent publications and potential indications of Positron emission tomography/ Magnetic resonance (PET/MR) imaging of prostate cancer. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Molecular Research in Urology 2014

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Related Special Issue

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI