• Title/Summary/Keyword: Prostate model

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Association of rs1042522 Polymorphism with Increased Risk of Prostate Adenocarcinoma in the Pakistani Population and its HuGE Review

  • Khan, Mohammad Haroon;Rashid, Hamid;Mansoor, Qaiser;Hameed, Abdul;Ismail, Muhammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3973-3980
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    • 2014
  • Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX. In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostate adenocarcinoma in the Pakistani population (p=0.000).

Effects of the Korean Medicinal Herbs for Treatment of Benign Prostatic Hyperplasia Induced in Rat Models: A Review (양성 전립선 비대증 유발 쥐에 단미 한약재가 미치는 영향에 관한 연구 분석)

  • Bae, In-suk;Jung, Seung-hyun
    • The Journal of Internal Korean Medicine
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    • v.39 no.4
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    • pp.592-604
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    • 2018
  • Objectives: This study is to review the effect of Korean medicinal herbs on treatment of benign prostatic hyperplasia induced in rat models, as reported in domestic and foreign journals. Methods: Six electronic databases (EMBASE, PubMed, Oasis, RISS, CENTRAL, and Koreankt) were searched with terms including benign prostatic hyperplasia to identify study reports on treatment of benign prostatic hyperplasia impairment with Korean medicinal herbs. After selecting several studies, the analysis focused on items reflected in the diagnosis of benign prostatic hyperplasia, such as prostate weight, thickness of the prostate epithelium, and prostate specific antigen. Results: Six studies were reviewed. Testosterone propionate was used as a benign prostatic hyperplasia induction material in all the included studies. Cinnamomum verum (CV), Cynanchum wilfordii (CW), Ponciri fructus (PF), Quisqualis indica (QI), Acorus gramineus (AG), and Melandrium firmum (MF) had reduced prostate weight statistically significantly. The QI gave a better response than finasteride in terms of reducing epithelium thickness, and the response was statistically significant. The prostate specific antigen level was lower in the group treated with CV than in the control group. Conclusions: CV, CW, PF, QI, AG, and MF had distinct therapeutic effects. However it is difficult to determine which of these is better by comparing them numerically because the observation items evaluated in a rat model of benign prostatic hyperplasia.

Association Between Single Nucleotide Polymorphisms in the XRCC1 Gene and Susceptibility to Prostate Cancer in Chinese Men

  • Zhou, Yun-Feng;Zhang, Guang-Bo;Qu, Ping;Zhou, Jian;Pan, Hui-Xin;Hou, Jian-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5241-5243
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    • 2012
  • Background: Prostate cancer (Pca) is one of the most common complex and polygenic diseases in men. The X-ray repair complementing group 1 gene (XRCC1) is an important candidate in the pathogenesis of Pca. The purpose of this study was to evaluate the association between single nucleotide polymorphisms in the XRCC1 gene and susceptibility to Pca. Materials and Methods: XRCC1 gene polymorphisms and associations with susceptibility to Pca were investigated in 193 prostate patients and 188 cancer-free Chinese men. Results: The c.910A>G variant in the exon9 of XRCC1 gene could be detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods. Significantly increased susceptibility to prostate cancer was noted in the homozygote comparison (GG versus AA: OR=2.95, 95% CI 1.46-5.42, ${\chi}^2$=12.36, P=0.001), heterozygote comparison (AG versus AA: OR=1.76, 95% CI 1.12-2.51, ${\chi}^2$=4.04, P=0.045), dominant model (GG/AG versus AA: OR=1.93, 95% CI 1.19-2.97, ${\chi}^2$=9.12, P=0.003), recessive model (GG versus AG+AA: OR=2.17, 95% CI 1.33-4.06, ${\chi}^2$=8.86, P=0.003) and with allele contrast (G versus A: OR=1.89, 95% CI 1.56-2.42, ${\chi}^2$=14.67, P<0.000). Conclusions: These findings suggest that the c.910A>G polymorphism of the XRCC1 gene is associated with susceptibility to Pca in Chinese men, the G-allele conferring higher risk.

6-sialyllactose ameliorates dihydrotestosterone-induced benign prostatic hyperplasia through suppressing VEGF-mediated angiogenesis

  • Kim, Eun-Yeong;Jin, Bo-Ram;Chung, Tae-Wook;Bae, Sung-Jin;Park, Hyerin;Ryu, Dongryeol;Jin, Ling;An, Hyo-Jin;Ha, Ki-Tae
    • 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.

A semiparametric method to measure predictive accuracy of covariates for doubly censored survival outcomes

  • Han, Seungbong;Lee, JungBok
    • Communications for Statistical Applications and Methods
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    • v.23 no.4
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    • pp.343-353
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    • 2016
  • In doubly-censored data, an originating event time and a terminating event time are interval-censored. In certain analyses of such data, a researcher might be interested in the elapsed time between the originating and terminating events as well as regression modeling with risk factors. Therefore, in this study, we introduce a model evaluation method to measure the predictive ability of a model based on negative predictive values. We use a semiparametric estimate of the predictive accuracy to provide a simple and flexible method for model evaluation of doubly-censored survival outcomes. Additionally, we used simulation studies and tested data from a prostate cancer trial to illustrate the practical advantages of our approach. We believe that this method could be widely used to build prediction models or nomograms.

The MTHFR C677T Polymorphism and Prostate Cancer Risk: New Findings from a Meta-analysis of 7306 Cases and 8062 Controls

  • Zhang, Wei-Bing;Zhang, Jun-Hong;Pan, Zheng-Qi;Yang, Qi-Sheng;Liu, Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2597-2604
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    • 2012
  • Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P < 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P < 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P < 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.

Bayesian Clustering of Prostate Cancer Patients by Using a Latent Class Poisson Model (잠재그룹 포아송 모형을 이용한 전립선암 환자의 베이지안 그룹화)

  • Oh Man-Suk
    • The Korean Journal of Applied Statistics
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    • v.18 no.1
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    • pp.1-13
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    • 2005
  • Latent Class model has been considered recently by many researchers and practitioners as a tool for identifying heterogeneous segments or groups in a population, and grouping objects into the segments. In this paper we consider data on prostate cancer patients from Korean National Cancer Institute and propose a method for grouping prostate cancer patients by using latent class Poisson model. A Bayesian approach equipped with a Markov chain Monte Carlo method is used to overcome the limit of classical likelihood approaches. Advantages of the proposed Bayesian method are easy estimation of parameters with their standard errors, segmentation of objects into groups, and provision of uncertainty measures for the segmentation. In addition, we provide a method to determine an appropriate number of segments for the given data so that the method automatically chooses the number of segments and partitions objects into heterogeneous segments.

Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor

  • Hyun Hwangbo;Min Yeong Kim;Seon Yeong Ji ;Beom Su Park;TaeHee Kim;Seonhye Yoon;Hyunjin Kim;Sung Yeon Kim ;Haeun Jung;Taeiung Kim;Hyesook Lee;Gi-Young Kim;Yung Hyun Choi
    • Nutrition Research and Practice
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    • v.17 no.1
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    • pp.32-47
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    • 2023
  • BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. RESULTS: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. CONCLUSIONS: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

Evaluation of Biochemical Recurrence-free Survival after Radical Prostatectomy by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) Score

  • Aktas, Binhan Kagan;Ozden, Cuneyt;Bulut, Suleyman;Tagci, Suleyman;Erbay, Guven;Gokkaya, Cevdet Serkan;Baykam, Mehmet Murat;Memis, Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2527-2530
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    • 2015
  • Background: The cancer of the prostate risk assessment (CAPRA) score has been defined to predict prostate cancer recurrence based on the pre-clinical data, then pathological data have also been incorporated. Thus, CAPRA post-surgical (CAPRA-S) score has been developed based on six criteria (prostate specific antigen (PSA) at diagnosis, pathological Gleason score, and information on surgical margin, seminal vesicle invasion, extracapsular extension and lymph node involvement) for the prediction of post-surgical recurrences. In the present study, biochemical recurrence (BCR)-free probabilities after open retropubic radical prostatectomy (RP) were evaluated by the CAPRA-S scoring system and its three-risk level model. Materials and Methods: CAPRA-S scores (0-12) of our 240 radical prostatectomies performed between January 2000-May 2011 were calculated. Patients were distributed into CAPRA-S score groups and also into three-risk groups as low, intermediate and high. BCR-free probabilities were assessed and compared using Kaplan-Meier analysis and Cox proportional hazards regression. Ability of CAPRA-S in BCR detection was evaluated by concordance index (c-index). Results: BCR was present in 41 of total 240 patients (17.1%) and the mean follow-up time was $51.7{\pm}33.0$ months. Mean BCR-free survival time was 98.3 months (95% CI: 92.3-104.2). Of the patients in low, intermediate and high risk groups, 5.4%, 22.0% and 58.8% had BCR, respectively and the difference among the three groups was significant (P = 0.0001). C-indices of CAPRA-S score and three-risk groups for detecting BCR-free probabilities in 5-yr were 0.87 and 0.81, respectively. Conclusions: Both CAPRA-S score and its three-risk level model well predicted BCR after RP with high c-index levels in our center. Therefore, it is a clinically reliable post-operative risk stratifier and disease recurrence predictor for prostate cancer.

Effects of Paljeong-san Pharmacopuncture on Experimental Rat Model of Benign Prostatic Hyperplasia (팔정산약침이 실험적으로 유발된 전립선 비대증 Rat에 미치는 영향)

  • Kim, Chae Weon;Lee, Kwang Ho
    • Journal of Acupuncture Research
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    • v.31 no.1
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    • pp.95-103
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    • 2014
  • Objectives : The aim of this study is to evaluate the effect of Paljeong-san pharmac-opuncture(PJS) on the rat model of benign prostatic hyperplasia(BPH). Methods : Rats were divided into 5 groups, with 6 rats in each group. The 5 groups included sham-operated group(sham group), BPH model group(BPH group), finasteride-treated group (fina group), PJS-treated groups(PJS 10 and PJS 100 group). Testosterone was injected subcutaneously to the castrated rats except sham group for BPH model. During 4-week experimental period, finasteride(5 mg/kg) was administrated orally once daily in fina group, PJS in PJS 10(10 mg/kg) and PJS 100(100 mg/kg) group and normal saline in sham and BPH group were injected subcutaneously once daily at Jungwan($CV_{12}$). We checked prostate weights, serum concentration of dihydrotestosterone(DHT), morphologic changes of the prostate, and the amount of expression of the proliferating cell nuclear antigen(PCNA) and $5{\alpha}$-reductase gene to evaluate the effect of PJS after 4-week experimental period. Results : 1. PJS and finasteride treatment reduced prostate weights comparing with BPH group, but PJS-treated groups showed no significant changes, unlikely fina group. 2. PJS-treated groups showed significant degreases in concentration of DHT. 3. PJS-treated groups showed significant degreases concentration-dependently in the amount of expression of the PCNA and $5{\alpha}$-reductase gene. 4. PJS treatment showed shrinking of thickness in the prostatic epithelial tissue. Conclusions : PJS has the effects that improve the symptoms of BPH through inhibiting proliferation of the prostatic tissues.