• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9439-9444
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• 2014

Purpose: To identify prostate cancer lncRNAs using a pipeline proposed in this study, which is applicable for the identification of lncRNAs that are differentially expressed in prostate cancer tissues but have a negligible potential to encode proteins. Materials and Methods: We used two publicly available RNA-Seq datasets from normal prostate tissue and prostate cancer. Putative lncRNAs were predicted using the biological technology, then specific lncRNAs of prostate cancer were found by differential expression analysis and co-expression network was constructed by the weighted gene co-expression network analysis. Results: A total of 1,080 lncRNA transcripts were obtained in the RNA-Seq datasets. Three genes (PCA3, C20orf166-AS1 and RP11-267A15.1) showed a significant differential expression in the prostate cancer tissues, and were thus identified as prostate cancer specific lncRNAs. Brown and black modules had significant negative and positive correlations with prostate cancer, respectively. Conclusions: The pipeline proposed in this study is useful for the prediction of prostate cancer specific lncRNAs. Three genes (PCA3, C20orf166-AS1, and RP11-267A15.1) were identified to have a significant differential expression in prostate cancer tissues. However, there have been no published studies to demonstrate the specificity of RP11-267A15.1 in prostate cancer tissues. Thus, the results of this study can provide a new theoretic insight into the identification of prostate cancer specific genes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6929-6933
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• 2013

Background: Multiple etiologies have been hypothesized for prostate cancer, including genetic defects and infectious agents. A recently reported gamaretrovirus, xenotropic murine leukemia virus-related virus (XMRV) has been reported to be detected in prostate cancer. However, this virus has not been detected in similar groups of patients in other studies. Herein, we sought to detect XMRV in prostate cancers and benign controls in Sanandaj, west of Iran. Materials and Methods: In a case-control study, genomic DNA was extracted from formalin fixed and paraffin embedded prostate tissues from a total of 163 Iranian patients. We developed a conventional and a nested PCR assay using primers targeting to an env specific sequence of XMRV. PCR assays were carried out on 63 prostate cancers and 100 benign prostate hyperplasias. Results: Beta-actin sequences were successfully detected in the DNA extracts from all prostate tissues, confirming DNA extraction integrity. We did not detect XMRV in samples either from prostate cancers or benign prostate hyperplasias using XMRV specific primers. Conclusions: We conclude that in our population XMRV does not play a role in genesis of prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2023-2028
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• 2013

A number of studies have indicated that Nurr1, which belongs to a novel class of orphan nuclear receptors (the NR4A family), is important for carcinogenesis. Here we investigated expression of Nurr1 protein in benign and malignant human prostate tissues and association with clinicopathologic features using immunohistochemical techniques. Moreover, we also investigated the ability of Nurr1 to influence proliferation, migration, invasion and apoptosis of human prostate cancer cells using small interfering RNA silencing. Immunohistochemical analysis revealed that the expression of Nurr1 protein was higher in prostate cancer tissues than in benign prostate tissue (P<0.001), levels being positively correlated with tumor T classification (P = 0.003), N classification (P = 0.017), M classification (P = 0.011) and the Gleason score (P = 0.020) of prostate cancer patients. In vitro, silencing of endogenous Nurr1 attenuated cell proliferation, migration and invasion, and induced apoptosis of prostate cancer cells. These results suggest that Nurr1 may be used as an indicator for prostate cancer progression and be useful for novel potential therapeutic strategies.

• Journal of the Korean Magnetic Resonance Society
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• v.23 no.1
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• pp.12-19
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• 2019

A former study has shown that the spin-lattice relaxation time ($T_1$) in cancerous prostate tissue had enhanced contrast at an ultra-low magnetic field, $132{\mu}T$. To study the field dependence and the origin of the contrast we measured $T_1$ in pairs of ex-vivo prostate tissues at the Earth's magnetic field. A portable and coil-based nuclear magnetic resonance (NMR) system was adopted for $T_1$ measurements at $40{\mu}T$. The $T_1$ contrast, ${\delta}=1-T_1$ (more cancer)/$T_1$(less cancer), was calculated from each pair. Additionally, we performed pathological examinations such as Gleason's score, cell proliferation index, and micro-vessel density (MVD), to quantify correlations between the pathological parameters and $T_1$ of the cancerous prostate tissues.

• Current Optics and Photonics
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• v.4 no.1
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• pp.31-43
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• 2020

The feasibility of the application of terahertz electromagnetic waves in the diagnosis of prostate cancer was examined. Four samples of incomplete cancerous prostatic paraffin-embedded tissues were examined using terahertz spectral imaging (TPI) system and the results obtained by comparing the absorption coefficient and refractive index of prostate tumor, normal prostate tissue and smooth muscle from one of the paraffin tissue masses examined were reported. Three hundred and sixty cases of absorption coefficients from one of the paraffin tissues examined were used as raw data to classify these three tissues using the Principal Component Analysis (PCA) and Least Squares Support Vector Machine (LS-SVM). An excellent classification with an accuracy of 92.22% in the prediction set was achieved. Using the distribution information of THz reflection signal intensity from sample surface and absorption coefficient of the sample, an attempt was made to use the TPI system to identify the boundaries of the different tissues involved (prostate tumors, normal and smooth muscles). The location of three identified regions in the terahertz images (frequency domain slice absorption coefficient imaging, 1.2 THz) were compared with those obtained from the histopathologic examination. The tissue tumor region had a distinctively visible color and could well be distinguished from other tissue regions in terahertz images. Results indicate that a THz spectroscopy imaging system can be efficiently used in conjunction with the proposed advanced computer-based mathematical analysis method to identify tumor regions in the paraffin tissue mass of prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6639-6643
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• 2015

Background: Prostate cancer is a major concern of public health. Microvascular density (MVD) is one of the prognostic markers for various solid cancers. Matrix metalloproteinase 11 (MMP11) plays an important role in angiogenesis and changes in its expression level are known to be associated with tumor progression and clinical outcome. Aim: To investigate the relationship between MVD and MMP11 expression in prostatic adenocarcinoma tissues. Materials and Methods: The expression levels of MMP11 and MVD were analyzed immunohistochemically for 50 specimens of prostatic adenocarcinoma. Results: MMP11 was mainly expressed in stromal cells but rarely seen in epithelial cells. Mean MVD was $36/mm^2$, and it was correlated significantly only with bone metastases. MVD was also significantly correlated with MMP11 expression (r=0.29, p=0.044). Conclusions: MMP11 may alter the stromal microenvironment of prostate cancer to stimulate tumor angiogenesis.

• BMB Reports
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• v.53 no.12
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• pp.634-639
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• 2020

In prostate cancer, the androgen receptor (AR) transcription factor is a major regulator of cell proliferation and metastasis. To identify new AR regulators, we focused on Mixed lineage leukemia 5 (MLL5), a histone-regulating enzyme, because significantly higher MLL5 expression was detected in prostate cancer tissues than in matching normal tissues. When we expressed shRNAs targeting MLL5 gene in prostate cancer cell line, the growth rate and AR activity were reduced compared to those in control cells, and migration ability of the knockdown cells was reduced significantly. To determine the molecular mechanisms of MLL5 on AR activity, we proved that AR physically interacted with MLL5 and other co-factors, including SET-1 and HCF-1, using an immunoprecipitation method. The chromatin immunoprecipitation analysis showed reduced binding of MLL5, co-factors, and AR enzymes to AR target gene promoters in MLL5 shRNA-expressing cells. Histone H3K4 methylation on the AR target gene promoters was reduced, and H3K9 methylation at the same site was increased in MLL5 knockdown cells. Finally, xenograft tumor formation revealed that reduction of MLL5 in prostate cancer cells retarded tumor growth. Our results thus demonstrate the important role of MLL5 as a new epigenetic regulator of AR in prostate cancer.

• Genomics & Informatics
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• v.16 no.3
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• pp.71-74
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• 2018

Because castration-resistant prostate cancer (CRPC) does not respond to androgen deprivation therapy and has a very poor prognosis, it is critical to identify a prognostic indicator for predicting high-risk patients who will develop CRPC. Here, we report a dataset of whole genomes from four pairs of primary prostate cancer (PC) and CRPC samples. The analysis of the paired PC and CRPC samples in the whole-genome data showed that the average number of somatic mutations per patients was 7,927 in CRPC tissues compared with primary PC tissues (range, 1,691 to 21,705). Our whole-genome sequencing data of primary PC and CRPC may be useful for understanding the genomic changes and molecular mechanisms that occur during the progression from PC to CRPC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5229-5235
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• 2016

Prostate cancer (PCa) remains one of the most widespread and perplexing of all human malignancies. Assessment of gene expression is thought to have an important impact on cancer diagnosis, prognosis and therapeutic decisions. In this context, we explored combined expression of PCa related target genes AMACR and PCA3 in 126 formalin fixed paraffin embedded prostate tissues (FFPE) from Moroccan patients, using quantitative real time reverse transcription-PCR (RT-qPCR). This quantification required data normalization accomplished using stably expressed reference genes (RGs). A panel of twelve RG was assessed, data being analyzed using GenEx V6 based on geNorm, NormFinder and statistical methods. Accordingly, the hnRNP A1 gene was identified and selected as the most stably expressed RG for reliable and accurate gene expression quantification in prostate tissues. The ratios of both PCA3 and AMACR gene expression relative to that of the hnRNP A1 gene were calculated and the performance of each target gene for PCa diagnosis was evaluated using receiver-operating characteristics. PCA3 and AMACR mRNA quantification based on RT-qPCR may prove useful in PCa diagnosis. Of particular interesting, combining PCA3 and AMACR quantification improved PCa prediction by increasing sensitivity with retention of good specificity.

• BMB Reports
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• v.52 no.9
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• pp.560-565
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• 2019

Benign prostatic hyperplasia (BPH), a common disease in elderly males, is accompanied by non-malignant growth of prostate tissues, subsequently causing hypoxia and angiogenesis. Although VEGF-related angiogenesis is one of the therapeutic targets of prostate cancer, there is no previous study targeting angiogenesis for treatment of BPH. Dihydrotestosterone (DHT)-induced expressions of vascular endothelial growth factor (VEGF) in prostate epithelial RWPE-1 cells and human umbilical vascular endothelial cells (HUVECs). Conditioned media (CM) from DHT-treated RWPE-1 cells were transferred to HUVECs. Then, 6SL inhibited proliferation, VEGFR-2 activation, and tube formation of HUVECs transferred with CM from DHT-treated RWPE-1 cells. In the rat BPH model, 6SL reduced prostate weight, size, and thickness of the prostate tissue. Formation of vessels in prostatic tissues were also reduced with 6SL treatment. We found that 6SL has an ameliorative effect on in vitro and in vivo the BPH model via inhibition of VEGFR-2 activation and subsequent angiogenesis. These results suggest that 6SL might be a candidate for development of novel BPH drugs.