Special Issue "Molecular Research in Urology"
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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology".
Deadline for manuscript submissions: closed (20 April 2013)
Special Issue Editor
Guest Editor
Prof. Dr. Jack A. Schalken
Research Director Urology, Dept. of Urology, University Hospital Nijmegen, Box 9101, Nijmegen NL-6500 HB, The Netherlands
Website: http://www.narcis.nl/person/RecordID/PRS1239673/Language/en
E-Mail: j.schalken@uro.umcn.nl
Interests: molecular and cellbiology of oncological diseases; cadherine mediated interactions and signal transductions; molecular diagnostics; urogenital oncology; veterinary oncology
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 are made and are reviewed in this issue. Once metastasized, there is still no effective treatment, let stand alone a curative therapy. A better 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 the 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
Guest Editor
Submission
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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF.
Keywords
- biomarkers (diagnostic prognostic and predictive)
- androgen receptor targeted therapy
- novel targets for therapy
- cancer initiating cells
Published Papers (6 papers)
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Received: 18 January 2013; in revised form: 3 March 2013 / Accepted: 5 March 2013 / Published: 15 March 2013
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Abstract: Given that podocalyxin (PCX) and nestin play important roles in podocyte morphogenesis and the maintenance of structural integrity, we examined whether the expression and localization of these two podocyte proteins were influenced in the early stage of various hemodynamic conditions. Mice kidney tissues were prepared by in vivo cryotechnique (IVCT). The distribution of glomeruli and podocyte proteins was visualized with DAB staining, confocal laser scanning microscopy and immunoelectron microscopy. The mRNA levels were examined by real-time quantitative PCR. The results showed the following: Under the normal condition, PCX stained intensely along glomerular epithelial cells, whereas nestin was clearly staining in the endothelial cells and appeared only weakly in the podocytes. Under the acute hypertensive and cardiac arrest conditions, PCX and nestin staining was not clear, with a disarranged distribution, but the colocalization of PCX and nestin was apparent under this condition. In addition, under the acute hypertensive and cardiac arrest conditions, the mRNA levels of PCX and nestin were significantly decreased. Collectively, the abnormal redistribution and decreased mRNA expressions of PCX and nestin are important molecular events at the early stage of podocyte injury during hemodynamic disorders. IVCT may have more advantages for morphological analysis when researching renal diseases.
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Received: 16 February 2013; in revised form: 20 March 2013 / Accepted: 22 March 2013 / Published: 10 April 2013
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Abstract: MicroRNAs (miRNAs) have emerged as key regulators of numerous biological processes, and increasing evidence suggests that circulating miRNAs may be useful biomarkers of clinical disease. In this study, we sought to identify plasma miRNAs that differentiate patients with metastatic castration resistant prostate cancer (mCRPC) from those with localized prostate cancer (PCa). Pooled plasma samples from patients with localized PCa or mCRPC (25 per group) were assayed using the Exiqon miRNA qPCR panel, and the differential expression of selected candidates was validated using qRT-PCR. We identified 63 miRNAs upregulated in mCRPC versus localized PCa, while only four were downregulated. Pearson’s correlation analysis revealed two highly correlated groups: one consisting of miR-141, miR375 and miR-200c and the other including miR151-3p, miR423-3p, miR-126, miR152 and miR-21. A third group, containing miR-16 and miR-205, showed less correlation. One miRNA from each group (miR-141, miR151-3p and miR-16) was used for logistic regression analysis and proved to increase the sensitivity of the prostate-specific antigen (PSA) test alone. While no miRNA alone differentiated localized PCa and mCRPC, combinations had greater sensitivity and specificity. The expression of these 10 candidates was assayed for association with clinical parameters of disease progression through the cBio portal. Our results demonstrate that plasma levels of selected miRNAs are potential biomarkers to differentiate localized PCa and mCRPC.
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Yang Jiao, Li Wang, Xin Gu, Sha Tao, Lu Tian, Rong Na, Zhuo Chen, Jian Kang, Siqun L. Zheng, Jianfeng Xu, Jielin Sun and Jun Qi
Received: 21 February 2013; in revised form: 21 March 2013 / Accepted: 8 April 2013 / Published: 24 April 2013
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Abstract: A recent prostate cancer (PCa) genome-wide association study (GWAS) identified rs103294, a single nucleotide polymorphism (SNP) located on LILRA3, a key component in the regulation of inflammatory inhibition, to be significantly associated with PCa risk in a Chinese population. Because inflammation may be a common etiological risk factor between PCa and benign prostatic hyperplasia (BPH), the current study was conducted to investigate the association of rs103294 with BPH risk. rs103294 was genotyped in a Chinese population of 426 BPH cases and 1,008 controls from Xinhua Hospital in Shanghai, China. Association between rs103294, BPH risk and clinicopathological traits were tested with adjustment for age. rs103294 was significantly associated with BPH risk with a p-value of 0.0067. Individuals with risk allele “C” had increased risk for BPH (OR = 1.34, 95% CI: 1.09–1.66). Stratified analysis revealed a stronger association risk for younger patients who are below 72 years old (OR = 1.51, 95% CI: 1.06–2.16). Our study represents the first effort to demonstrate that LILRA3 gene is significantly associated with BPH risk in a Chinese population. Our results support a common role of inflammation in the development of PCa and BPH. Additional studies are needed to further evaluate our results.
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Received: 29 March 2013; in revised form: 26 April 2013 / Accepted: 2 May 2013 / Published: 8 May 2013
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Abstract: Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate cancer cells (PC3 and DU145) at noncytotoxic concentrations. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. Treatment of prostate cancer cells with D-pinitol reduced mRNA and cell surface expression of αvβ3 integrin. In addition, D-pinitol exerted its inhibitory effects by reducing focal adhesion kinase (FAK) phosphorylation, c-Src kinase activity and NF-kB activation. Thus, D-pinitol may be a novel anti-metastasis agent for the treatment of prostate cancer metastasis.
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Received: 15 April 2013; in revised form: 8 May 2013 / Accepted: 8 May 2013 / Published: 21 May 2013
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Abstract: Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via a novel binding sequence in an androgen-independent manner. Further understanding of PAcP function and regulation of expression will have a significant impact on understanding PCa progression and therapy.
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Received: 16 February 2013; in revised form: 14 March 2013 / Accepted: 6 May 2013 / Published: 21 May 2013
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Abstract: The C-C chemokine ligand 2 (CCL2) stimulates migration, proliferation, and invasion of prostate cancer (PCa) cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area of intense research. The objective of our study was to investigate the efficacy of CCL2 blockade by neutralizing antibodies to inhibit the growth of PCa in bone. We used a preclinical model of cancer growth in the bone in which PCa C4-2B cells were injected directly into murine tibiae. Animals were treated for ten weeks with neutralizing anti-CCL2 antibodies, docetaxel, or a combination of both, and then followed an additional nine weeks. CCL2 blockade inhibited the growth of PCa in bone, with even more pronounced inhibition in combination with docetaxel. CCL2 blockade also resulted in increases in bone mineral density. Furthermore, our results showed that the tumor inhibition lasted even after discontinuation of the treatment. Our data provide compelling evidence that CCL2 blockade slows PCa growth in bone, both alone and in combination with docetaxel. These results support the continued investigations of CCL2 blockade as a treatment for advanced metastatic PCa.
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Last update: 30 October 2012
