• Title, Summary, Keyword: CRPC

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Generation of Whole-Genome Sequencing Data for Comparing Primary and Castration-Resistant Prostate Cancer

  • Park, Jong-Lyul;Kim, Seon-Kyu;Kim, Jeong-Hwan;Yun, Seok Joong;Kim, Wun-Jae;Kim, Won Tae;Jeong, Pildu;Kang, Ho Won;Kim, Seon-Young
    • 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.

Precision Medicine in Castration-Resistant Prostate Cancer (거세저항성전립선암에서 정밀의학에 대한 고찰)

  • Kim, Won Tae;Yun, Seok Joong;Kim, Wun-Jae
    • The Korean Journal of Urological Oncology
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    • v.16 no.3
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    • pp.97-102
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    • 2018
  • Prostate cancer is usually managed by androgen deprivation therapy after failure of primary treatment. However, such therapies are only temporarily effective in prostate cancer patients, and the most patients experience the progression to castration-resistant prostate cancer (CRPC). Docetaxel chemotherapy is conventional effective treatment for CRPC but has many adverse effects. In CRPC patients, treatment decisions were not typically base on the recognitions of inter-individual differences. Therefore, there are growing interests for precision medicine in CRPC. In this review, we summarized the precision medicine such as candidate target genes and potential therapies in CRPC.

Application of Constant Rate of Velocity or Pressure Change Method to Improve Annular Jet Pump Performance

  • Yang, Xuelong;Long, Xinping;Kang, Yong;Xiao, Longzhou
    • International Journal of Fluid Machinery and Systems
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    • v.6 no.3
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    • pp.137-143
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    • 2013
  • To improve annular jet pump (AJP) performance, new ways named constant rate of velocity/pressure change method (CRVC/CRPC) were adopted to design its diffuser. The design formulas were derived according to the assumption of linear velocity/pressure variation in the diffuser. Based on the two-dimensional numerical simulations, the effect of the diffuser profile and the included angle on the pump performance and the internal flow details has been analyzed. The predicted results of the RNG k-epsilon turbulence model show a better agreement with the experiment data than that of the standard and the realizable k-epsilon turbulence models. The AJP with the CRPC diffuser produces a linear pressure increase in the CRPC diffuser as expected. The AJP with CRPC/CRVC diffuser has better performance when the diffuser included angle is greater or the diffuser length is shorter. Therefore, the AJP with CRPC/CRVC diffuser is suitable for applications requiring space limitation and weight restriction.

A Study on the Soyangin Pathologies that originate from a Common Root Pathologic Category (소양인 동출일속 병증에 관한 연구)

  • Kim, Yun-Hee;Hwang, Min-Woo
    • Journal of Sasang Constitutional Medicine
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    • v.23 no.3
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    • pp.285-293
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    • 2011
  • 1. Objectives: This study examines the pathologies that originate from a Common Root Pathologic Category(CRPC; 同出一屬) in the Soyangin that are suggested in the Sasang Constitutional Medicine(SCM). 2. Methods: The changes in concepts and perceptions on the Soyangin pathologies were compared across the different editions of Donguisusebowon, "Donguisusebowon, Gabo edition(東醫壽世保元甲午本) (DGO)" and "Donguisusebowon, Sinchuk edition (東醫壽世保元辛丑本) (DSC)". 3. Results and Conclusions: The Soyangin pathologies originating from a CRPC that are described in Donguisusebowon are actually detailed classifications of the Yin-deficiency Diurnal-heat symptomatology (陰虛午熱證) and the Chest-congestion symptomatology (結胸證). Lee Jema had introduced the concept of "Common Root Pathologic Category(CRPC)" to approach pathologies of similar exterior/interior classification or severity stage (mild/moderate/severe/critical) by combining them in a comprehensive, integrative pathology system. This comprehensive approach, which promotes better understanding of the Soyangin pathology and maximizes the therapeutic efficiency of SCM, constitutes the "Comprehensive Therapeutic Methodology" that is the hallmark of Sasang therapy.

Is it Time to Change the Control Placebo Arms in Phase III Trials of Metastatic Castration Resistant Prostate Cancer?

  • Dogan, Mutlu;Erdem, Gokmen Umut;Zengin, Nurullah
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6167-6169
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    • 2015
  • Prostate cancer is common all around the world. Hormonal therapy is the mainstay of therapy, however castration-resistant prostate cancer (CRPC) becomes a serious problem and needs further clinical trials with novel agents. Novel agents like cabazitaxel, abireterone acetate or enzalutamide are encouraging but we do not know which one is the best in metastatic CRPC. In here, treatment modalities for metastatic CRPC are discussed witha mini-review of the literature.

Predictive Factors for Neutropenia after Docetaxel-Based Systemic Chemotherapy in Korean Patients with Castration-Resistant Prostate Cancer

  • Kwon, Whi-An;Oh, Tae Hoon;Lee, Jae Whan;Park, Seung Chol
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3443-3446
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    • 2014
  • The aim of this study was to determine predictive factors for neutropenia after docetaxel-based systemic chemotherapy in patients with castration-resistant prostate cancer (CRPC). The study included 40 Korean CRPC patients who were treated with several cycles of docetaxel plus prednisolone from May 2005 to May 2012. Patients were evaluated for neutropenia risk factors and for the incidence of neutropenia. In this study, nine out of forty patients (22.5%) developed neutropenia during the first cycle of docetaxel-based systemic chemotherapy. Four experienced grade 2, three grade 3, and one grade 4 neutropenia. Multivariate analysis showed that pretreatment white blood cell (WBC) count (p=0.042), pretreatment neutrophil count (p=0.015), pretreatment serum creatinine level (p=0.027), and pretreatment serum albumin level (p=0.017) were significant predictive factors for neutropenia. In conclusion, pretreatment WBC counts, neutrophil counts, serum creatinine levels, and serum albumin levels proved to be significant independent risk factors for the development of neutropenia induced by docetaxel-based systemic chemotherapy in patients with CRPC.

Abiraterone for Treatment of Metastatic Castration-resistant Prostate Cancer: a Systematic Review and Meta-analysis

  • Zhou, Zhi-Rui;Liu, Shi-Xin;Zhang, Tian-Song;Xia, Jun;Li, Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1313-1320
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    • 2014
  • Introduction: Although most prostate cancers initially respond to castration with luteinizing hormonereleasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Methods: Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Results: Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. Conclutios: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-na$\ddot{i}$ve, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.

Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies

  • Qi, Wei-Xiang;Fu, Shen;Zhang, Qing;Guo, Xiao-Mao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8177-8182
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    • 2014
  • Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

Prostatectomy Provides Better Symptom-Free Survival Than Radiotherapy Among Patients With High-Risk or Locally Advanced Prostate Cancer After Neoadjuvant Hormonal Therapy

  • Kim, Sung Han;Song, Mi Kyung;Park, Weon Seo;Joung, Jae Young;Seo, Ho Kyung;Chung, Jinsoo;Lee, Kang Hyun
    • The Korean Journal of Urological Oncology
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    • v.16 no.3
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    • pp.126-134
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    • 2018
  • Purpose: The purpose of this study is to compare the radiation therapy (RT) and radical prostatectomy (RP) of high-risk or locally advanced prostate cancer (PC) patients after neoadjuvant hormonal therapy (NHT). Materials and Methods: This retrospective study evaluated patients underwent RT (42 patients) or RP (152 patients) after NHT at a single center during 2003-2014. Times to biochemical recurrence (BCR), pelvic local recurrence (PLR), metastasis, clinical painful symptom progression (CPSP), castration-resistant PC (CRPC), and overall survival were compared between the RT and RP groups, after adjustment for TN stage, using the Kaplan-Meier method and log-rank test. Results: Significant inter-group differences were observed for age, Gleason score, initial PSA, and clinical and pathological T stages (all p<0.05). During a median follow-up of 71.7 months, the overall incidences of BCR, PLR, metastasis, CPSP, CRPC, and death were 49.5%, 16.5%, 8.3%, 7.7%, 7.7%, and 17.5%, respectively. The median times to BCR were 100 months for RT and 36.2 months for RP (p=0.004), although the median times were not reached for the other outcomes (all p>0.05). The independent predictor of CPSP was RP (hazard ratio, 0.291; p=0.013). Conclusions: Despite significantly different baseline parameters, RP provided better CPSP-free survival than RT among patients with localized high-risk or locally advanced PC.

Ultrasound Targeted Microbubble Destruction for Novel Dual Targeting of HSP72 and HSC70 in Prostate Cancer

  • Wang, Hang-Hui;Song, Yi-Xin;Bai, Min;Jin, Li-Fang;Gu, Ji-Ying;Su, Yi-Jin;Liu, Long;Jia, Chao;Du, Lian-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1285-1290
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    • 2014
  • The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.