Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.
Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; China ; Docetaxel/therapeutic use* ; Humans ; Kallikreins/blood* ; Kaplan-Meier Estimate ; Leukocyte Count ; Lymphocyte Count ; Male ; Middle Aged ; Neoplasm Metastasis ; Neutrophils ; Prognosis ; Proportional Hazards Models ; Prostate-Specific Antigen/blood* ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Retrospective Studies ; Survival Rate ; Time Factors

Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P<0.001). According to receiver operating characteristics curve analysis, the sensitivity of hMOB3B expression for PCa diagnosis was 84.7%, with a specificity of 86% (AUC=0.910; 95% CI=0.869-0.941; P<0.001). hMOB3B expression was significantly lower in patients with elevated prostate specific antigen (PSA) levels (> or =10 ng/mL), a Gleason score> or =8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and non-metastatic disease (each P<0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa.
Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Case-Control Studies ; Disease Susceptibility ; Gene Expression ; Humans ; Kallikreins/blood ; Male ; Microtubule-Associated Proteins/*metabolism ; Middle Aged ; Neoplasm Grading ; Polymerase Chain Reaction ; Prostate/*pathology/surgery ; Prostate-Specific Antigen/blood ; Prostatic Hyperplasia/blood/pathology ; Prostatic Neoplasms/blood/*pathology/surgery

The purpose of this study was to determine whether contemporary active surveillance (AS) protocols could sufficiently discriminate significant from indolent tumors in men with low-risk prostate cancer. We retrospectively analyzed 312 patients with low-risk prostate cancer treated with radical prostatectomy. After exclusion of patients with fewer than 10 cores taken at biopsy and those who received neo-adjuvant treatment, 205 subjects satisfied the final inclusion criteria. Five widely accepted AS protocols were employed in this study. A total of 82.0% of the patients met the inclusion criteria of at least one protocol, and 18% did not meet any criteria of published AS protocols. A significant proportion of patients had non-organ-confined disease (8.6% to 10.6%) or a Gleason score of 7 or greater (18.6% to 23.9%) between the different AS criteria. Among patients who did not meet any AS criteria, 32.4% of patients had a pathologically insignificant cancer. Our results indicated a significant adverse pathology in patients who met the contemporary AS protocols. On the other hand, some patients in whom expectant management would be appropriate did not meet any criteria of published AS protocols. None of the clinical or histological criteria reported to date is able to sufficiently discriminate aggressive tumors from indolent ones.
Aged ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Prostate/*pathology ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies ; Risk Assessment ; Treatment Outcome ; *Watchful Waiting

PURPOSE: Prostate cancer is the most frequent cancer in men in Europe. A major focus in urology is the identification of new biomarkers with improved accuracy in patients with low-risk prostate cancer. Here, we evaluated two-dimensional neovascular complexity in prostate tumor and nontumor biopsy cores by use of a computer-aided image analysis system and assessed the correlations between the results and selected clinical and pathological parameters of prostate carcinoma. MATERIALS AND METHODS: A total of 280 prostate biopsy sections from a homogeneous series of 70 patients with low-risk prostate cancer (Gleason score 3+3, prostate-specific antigen [PSA]<10 ng/mL, and clinical stage T1c) who underwent systematic biopsy sampling and subsequent radical prostatectomy were analyzed. For each biopsy, 2-microm sections were treated with CD34 antibodies and were digitized by using an image analysis system that automatically estimates the surface fractal dimension. RESULTS: Our results showed that biopsy sections without cancer were significantly more vascularized than were tumors. No correlations were found between the vascular surface fractal dimension and patient's age, PSA and free-to-total PSA ratios, pathological stage, Gleason score, tumor volume, vascular invasion, capsular penetration, surgical margins, and biochemical recurrence. CONCLUSIONS: The value of angiogenesis in prostate cancer is still controversial. Our findings suggest that low-risk prostate cancer tissues are less vascularized than are nontumor tissues. Further studies are necessary to understand whether angiogenesis is a hallmark of intermediate- and high-risk prostate cancer.
Adult ; Aged ; Biopsy, Needle ; Fractals ; Humans ; Image Processing, Computer-Assisted/methods ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neovascularization, Pathologic/*pathology ; Prostate/*blood supply ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*blood supply/pathology/surgery ; Retrospective Studies

PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients.
Aged ; Biopsy, Needle/methods ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Precancerous Conditions/*pathology/surgery ; Predictive Value of Tests ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*pathology/surgery ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies

PURPOSE: Few data are available concerning the clinical outcome of abiraterone acetate treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) in terms of the duration of androgen deprivation therapy (ADT) before diagnosis of CRPC. We investigated the clinical efficacy of abiraterone acetate according to the duration of ADT. MATERIALS AND METHODS: We reviewed the medical records of 20 patients with mCRPC who received abiraterone acetate after failure of docetaxel chemotherapy from May 2012 to March 2014 at Seoul National University Bundang Hospital. Clinical factors including prostate-specific antigen (PSA) nadir level, time to PSA nadir, PSA doubling time, PSA response, and modes of progression (PSA, radiologic, clinical) were analyzed. Disease progression was classified according to the Prostate Cancer Working Group 2 criteria. RESULTS: The mean age and PSA value of the entire cohort were 76.0+/-7.2 years and 158.8+/-237.9 ng/mL, respectively. The median follow-up duration was 13.4+/-6.7 months. There were no statistically significant differences in clinical characteristics between patients who received abiraterone acetate with ADT duration<35 months and those who received abiraterone acetate with ADT duration> or =35 months. There were also no significant differences in terms of PSA progression-free survival, radiologic progression-free survival, and clinical progression-free survival between patients with ADT duration<35 months and those with ADT duration > or =35 months. CONCLUSIONS: Although this was a retrospective study with a small sample size, we did not observe any statistically significant differences in the clinical response to abiraterone acetate between mCRPC patients with long ADT duration and those with short ADT duration in terms of disease progression-free survival.
Abiraterone Acetate/administration & dosage ; Aged ; Aged, 80 and over ; Androgen Receptor Antagonists/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease Progression ; Drug Administration Schedule ; Humans ; Kallikreins/blood ; Male ; Neoplasm Metastasis ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms, Castration-Resistant/*drug therapy ; Retrospective Studies ; Taxoids/administration & dosage ; Treatment Outcome

PURPOSE: To evaluate the relationship between levels of total testosterone and total prostate-specific antigen (PSA) in healthy men with PSA<4 ng/mL. MATERIALS AND METHODS: The study comprised 179 men with a mean age of 59.19+/-12 years who visited Osmaniye State Hospital, Osmaniye, Turkey, between January 2006 and January 2007 for a routine checkup. The patients were divided into two subgroups: patients with PSA<2.5 mg/ml (group I, n=160 patients) and patients with PSA of 2.5 to 4 ng/mL (group II, n=19 patients). The relationship between PSA and testosterone levels was investigated in both groups and in patients aged <60 years. The mean testosterone level was calculated for patients aged <50 years and was compared with the mean value of patients aged > or =50 years. RESULTS: In all patients, the mean values for serum PSA and total testosterone were 1.27+/-0.88 ng/mL and 404.04+/-158.86 ng/mL, respectively. No correlation was detected between serum PSA and testosterone levels in either subgroup (group I, r=0.072, p=0.363; group II, r=0.031, p=0.900) or in patients aged <60 years (r=0.032, p=0.72). The mean values of testosterone in patients aged > or =50 years and in patients aged <50 years were 417.01+/-163.35 and 344.16+/-120.21 ng/dL, respectively (p=0.02). CONCLUSIONS: No impact of testosterone was found on the PSA level in healthy men with PSA <4 ng/mL. Therefore, a high serum testosterone level may not mandate adjustment of PSA values. This serum sex hormone showed a significant increment after the age of 50 years. Further studies including a larger number of patients should be carried out to confirm these findings.
Aged ; Aging/blood ; Humans ; Kallikreins/*blood ; Male ; Middle Aged ; Prostate-Specific Antigen/*blood ; Reference Values ; Testosterone/*blood ; Tumor Markers, Biological/blood

PURPOSE: This study aimed to improve prostate biopsy compliance by analyzing the factors that influence the acceptance of prostate biopsy by patients to whom transrectal ultrasound (TRUS)-guided prostate biopsy is recommended for suspected prostate cancer. MATERIALS AND METHODS: The subjects of this study were 268 patients to whom TRUS-guided prostate biopsy was recommended from January to June 2011 and who completed a questionnaire. Patients who showed a prostate-specific antigen (PSA) increase to more than 4.0 ng/mL or abnormal findings on a digital rectal examination and TRUS were recommended to undergo prostate biopsy. The questionnaire consisted of 9 questions about the subjects' demographic characteristics and 15 questions that assessed their knowledge of prostate disease. Fisher exact probability test was conducted to assess the influence of the demographic characteristics and levels of knowledge of prostate disease on acceptance of prostate biopsy. RESULTS: The mean age of the subjects was 66.2 years (range, 43-83 years). Of the cohort, 188 patients (70.7%) agreed to the prostate biopsy and 78 patients (29.3%) refused. In terms of demographic characteristics, the patients' acceptance of prostate biopsy was associated only with education level. Patients with relatively lower education levels had a higher acceptance rate for prostate biopsy (80.0% vs. 65.9%, p=0.018). Other demographic factors, as well as the degree of knowledge of prostate disease, had no significant effect on the acceptance rate. CONCLUSIONS: The patients' acceptance of prostate biopsy can be influenced by demographic characteristics, especially education level. Therefore, when prostate biopsy is recommended to patients, their demographic characteristics should be taken into consideration.
Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle/methods/psychology ; Health Knowledge, Attitudes, Practice ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; *Patient Acceptance of Health Care ; Prospective Studies ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/*pathology/psychology/ultrasonography ; Republic of Korea ; Socioeconomic Factors ; Ultrasonography, Interventional

PURPOSE: We are often confronted with patients in the "gray zone" (prostate-specific antigen [PSA]<10 ng/mL) whose biopsies reveal no malignancy but only inflammation. We investigated the relationship between histological inflammation and total PSA (tPSA), free PSA (fPSA), and percentage of free PSA (f/tPSA) levels in patients without prostate cancer (PC). MATERIALS AND METHODS: We studied 106 men with tPSA<10 ng/mL who had undergone biopsy that was negative for PC and who had no clinical prostatitis. Inflammation observed at biopsies was scored for inflammation type in each biopsy core by use of a four-point scale and was then correlated with tPSA, fPSA, and f/tPSA. RESULTS: Different patterns of inflammation were found in each set of biopsies. Regression factor analysis was used to form two groups according to inflammation type: more chronic and more acute. Median tPSA, fPSA, and f/tPSA levels in the more chronic and more acute inflammation groups were 6.4 ng/mL, 1.09 ng/mL, and 15%, and 7.3 ng/mL, 0.79 ng/mL, and l2%, respectively. A significant difference was found in fPSA (p=0.003) and f/tPSA (p<0.001), whereas the difference in tPSA was not significant (p=0.200). Total PSA correlated with fPSA (r=0.4, p<0.001) but not with inflammation type (r=0.12, p>0.010). A correlation existed between inflammation type and fPSA (r=-0.31, p=0.001) and f/tPSA (r=-0.43, p<0.001) in that the fPSA and f/tPSA were lower in the group with more acute inflammation. CONCLUSIONS: Subclinical inflammation has a significant influence on fPSA in patients with tPSA<10 ng/mL but without PC or clinical prostatitis. Subclinical inflammation is not characterized by elevated tPSA alone but also by a decreased fPSA, a tendency similar to that in PC.
Acute Disease ; Aged ; Aged, 80 and over ; Asymptomatic Diseases ; Biopsy, Large-Core Needle ; Chronic Disease ; Diagnosis, Differential ; Humans ; Kallikreins/*blood ; Male ; Middle Aged ; Prostate/pathology ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/blood/diagnosis ; Prostatitis/*blood/diagnosis/pathology

To investigate the effect of losartan on the axis of prolylcarboxypeptidase (PRCP)--kallikrein of the two-kidney, one-clipped (2K1C) hypertensives rats, and explore the novel protection mechanism of losartan on the kidney. Sprague-Dawley (SD) rats were used to develop the 2K1C hypertensive rats. Then, the rats were treated with prazosin (5 mg x kg(-1) x d(-1)) or losartan (5, 15 and 45 mg x kg(-1) x d(-1)) or vehicle, separately. At the same time, the blood pressures were observed. After treated for four weeks, the ratio of right kidney weight and body weight, the change of glomerular morphology, and K+, Na+, creatinine and blood urea nitrogen (BUN) of the serum were used for evaluation of kidney. The expressions of PRCP mRNA in the kidneys were determined by RT-PCR. The protein levels of PRCP, tissue kallikrein, plasma kallikrein, TGF-beta1 in kidney or plasma were measured by Western blotting. Results showed that the changes of body weight and kidney weight ratio, glomerular fibrosis degree and the biochemistrical index of serum induced by hypertension were relieved when the hypertensive rats treated with losartan for four weeks. Meanwhile, treatment of losartan also significantly decreased expression of TGF-beta1 and increased expressions of PRCP, plasma kallikrein and tissue kallikrein. The protective effects of losartan on the kidney of 2K1C hypertensive rats are activation of the axis of PRCP-kallikrein and reducing the expression of TGF-beta1.
Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Carboxypeptidases ; genetics ; metabolism ; Hypertension, Renovascular ; metabolism ; pathology ; physiopathology ; Kallikreins ; blood ; metabolism ; Kidney ; metabolism ; pathology ; Kidney Glomerulus ; pathology ; Losartan ; pharmacology ; Male ; Organ Size ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; blood ; metabolism