Цинк как возможная мишень терапии при заболеваниях простаты

Prostate Specific Antigen and Human Glandular Kallikrein 2 in Early Detection of Prostate Cancer

Malignant transformation of the prostate and progression of carcinoma appear to be the consequence of a complex series of initiation and promotional events under genetic and environmental influences. Increased incidence of the condition may be the result of improved detection, greater awareness of the condition, and possibly an increased life expectancy accompanied by a decrease in competing causes of death rather than a true increase in the prevalence of the disease. The marked racial and geographic differences are probably multifactorial, with genetic, environmental, and possibly social influences affecting progression of the disease. Among several risk factors, evidence for the familial inheritance of some prostate cancers is compelling. Dietary influences, hormonal milieu, and the role of environmental carcinogens are currently under intense investigation. As further risk factors are identified, it will become increasingly important to identify individuals at increased risk for the disease. These men should undergo regular evaluation with state-of-the-art methods.

Objective To investigate the relationship between iron metabolism disorder and the development and progression of prostate cancer. Methods From May 2014 to May 2017, 80 patients with prostate cancer in our hospital were selected as the experimental group, and 80 patients with benign prostatic hyperplasia were selected as the control group. The two groups were collected by centrifugation to separate blood serum, detect serum total prostate specific antigen (PSA), free prostate specific antigen (free PSA), serum ferritin levels and high blood protein in proportion. The expressions of Hepcidin, IL-6, soluable transferritin recptor(sTfR) and bone morphogenebic protein-6(BMP6) in serum of two groups were measured by ELISA method. Correlation between serum markers and prognostic factors, correlation between serum markers and risk of prostate cancer, and correlation between Hepcidin and variables were analyzed. Results There was no significant difference between the two groups in age (P>0.05), but compared with the patients with benign prostatic hyperplasia and prostate cancer patients serum ferritin, total PSA, free PSA and free PSA/and total PSA were significantly increased, the proportion of patients with high blood protein increased significantly (P<0.05). Gleason scores, total PSA levels and serum ferritin levels were positively correlated with patient stage, lymph node invasion, and distant metastasis in patients with prostate cancer. Elevated serum ferritin levels were significantly associated with elevated serum total PSA and increased prostate cancer risk (P<0.05). At the same time, high blood pressure was associated with elevated serum total PSA and risk of prostate cancer (P<0.05). The expression of Hepcidin, IL-6 and BMP6 in serum of patients with prostate cancer were significantly higher than those in patients with benign prostatic hyperplasia (P<0.05), the expression of sTfR was significantly lower than that of patients with benign prostatic hyperplasia (P<0.05), there was no significant difference in HB expression between the two groups (P<0.05). The expression of Hepcidin was positively correlated with the expression of IL-6 and BMP6 in prostate cancer patients, and negatively correlated with the expression of sTfR, which was not related to the expression of HB. The expression of Hepcidin was not correlated with the expression of IL-6, sTfR, BMP6 and HB in BPH patients. Conclusions The occurrence and development of prostate cancer can be predicted by detecting the expression of Hepcidin in serum and serum ferritin levels. Serum ferritin is positively correlated with pathological stage, lymph node invasion and distant metastasis of prostate cancer. Elevated serum ferritin levels increase the risk of prostate cancer. Key words: Prostatic Neoplasms; Iron Metabolism Disorders

Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells.

RATIO OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN IN SERUM CANNOT DISTINGUISH PATIENTS WITH PROSTATE CANCER FROM THOSE WITH CHRONIC INFLAMMATION OF THE PROSTATE

Objective To observe the changes of serum ferritin (SF), interleukin-6 (IL-6), and soluble transferrin receptor (sTfR) in prostate cancer patients with bone metastasis, analyze the correlation among three indexes, and to explore the role of SF in prostate cancer with bone metastasis. Methods From 2011 January to 2014 June, 25 cases of prostate cancer with bone metastasis, 30 cases of prostate cancer without bone metastasis, and 30 patients with benign prostatic hyperplasia (BPH) were included. The age of patients ranged from 55 to 75 years (mean 67). In the group of prostate cancer with bone metastasis, the baseline prostate specific antigen (PSA) was more than 20 μg/L, ranging from 20.0-1 500 μg/L (mean 138.0 μg/L), serum PSA ranged from 3.5-28.2 μg/L (mean 10.2 μg/L) in the group of prostate cancer without bone metastasis, and serum PSA ranged from 0.3-14.2 μg/L (mean 3.7 μg/L) in the group of BPH. In the morning fasting venous blood was taken out, and serum was isolated. The competitive in-phase enzyme-linked immunoassay (ELISA) was used to determine serum SF, IL-6 and sTfR. Results The expression of SF was (330.0±61.9) μg/L in prostate cancer with bone metastasis group, (140.1±17.1) μg/L in prostate cancer without bone metastasis group, and (128.3±12.7) μg/L in BPH grou. There was significant difference between prostate cancer with bone metastasis group and protate cancer without bone metastasis group or BPH group (P<0.05). In prostate cancer with bone metastasis group, SF was significantly correlated with IL-6 [(22.5±22.1) μg/L] and sTfR [(5.7±2.6) μg/L] expression with the correlation coefficients being 0.972, -0.987, 0.971 respectively (P<0.05) Conclusion Serum SF expression, which increased in prostate cancer with bone metastasis, can be used as a sensitive index for diagnosis and prognosis evaluation of advanced prostate cancer with bone metastasis. Key words: Serum ferritin; Prostate cancer; Bone metastasis

Critical Appraisal of Prostate-specific Antigen in Prostate Cancer Screening: 20 Years Later

Objective To investigate characteristics of serum prostate specific antigen (PSA) in HGPIN patients and the effect of the number of the first time biopsy high grade prostatic intraepithelial neoplasia (HGPIN) positive needles on the detection rate of secondary biopsy prostate cancer (PCa). Methods A total of 320 patients who underwent prostate biopsy in our hospital from February 2013 to December 2015 were selected. Ultrasound guided prostate biopsy was performed in all patients, and the differences of serum PSA was analyzed, non PCa patients after 6 months of treatment underwent the secondary biopsy. Results All patients for the first time biopsy results showed: 80 patients with HGPIN ( 51 cases of solitary type and 29 cases of multifocal type ), 45 cases of low grade prostatic intraepithelial neoplasia (LGPIN), 128 cases of benign prostatic hyperplasia (BPH), 67 cases of PCa. Serum PSA of patients with PCa was significantly higher than that of BPH, LGPIN, solitary and multifocal HGPIN patients (P 0.05). PCa proportion of secondary biopsy in multifocal HGPIN patients was 38.46%, significantly higher than BPH, LGPIN and solitary HGPIN patients (P 0.05). Conclusions Serum PSA level of multifocal HGPIN patients is higher than solitary HGPIN, BPH and LGPIN, but still lower than PCa. Detection rates of secondary biopsy PCa in multifocal HGPIN patients are significantly higher than other patients. Key words: Prostatic Neoplasms; Prostate-Specific Antigen; Biopsy, Needle

This study is conducted to clarify the correlation between serum and urinary prostate-specific antigen (PSA) and to find the difference in urinary PSA between patients with prostate cancer (CaP) and those with benign prostatic hyperplasia (BPH). PSA levels of 20 patients with prostatic cancer and 78 patients with BPH were determined using the ELSA-PSA2 kit. For the first 14 patients, the PSA of serum and first-voided urine in the morning were detected. For the following 20 patients, serum PSA, as well as morning and evening midstreamurinary PSA were examined. Serum PSA and 24-h urinary PSA were measured for the remaining 64 patients. PSA levels of spot midstream urine specimens were highly variable between morning and evening urine, but they were usually higher than and poorly correlated with those of serum. PSA levels of morning first-voided, evening urine, and serum were 336±233,443±208, and 11.7±4.4ng/ml, respectively. For the remaining 64 patients, serum PSA levels of BPH and CaP patients were 9.9±1.6and 25.7±8.2ng/ml, respectively;while, their 24-h urinary PSA amounts were 243±38 and 125±46 ug, respectively (p=0.059). The correlation between serum PSA and 24-h urinary PSA amounts was poor as well. For either spot or 24-h urine, urinary PSA is highly variable and is usually higher than serum PSA. However, 24-h urine specimens can precisely determine the level of PSA secretion of the lower urinary tract. The 24-h urinary PSA amounts of BPH patients were higher than those of CaP patients, but the overlapping area between these 2 groups was very large. Therefore it is not suitable to use urinary PSA as a substitute for serum PSA for clinical application in prostatic diseases. (J Rrol R.O.C., 9:132-137,1998)

Society of Interventional Radiology Research Reporting Standards for Prostatic Artery Embolization

Objective To investigate the serum prostate specific antigen tPSA),ratio of serum free PSA to total PSA (f/t),prostate volume (PV) and prostate specific antigen density (PSAD),their correlation with prostatic intraepithelial neoplasia (PIN) and their clinical diagnostic significance. Methods Retrospectively evaluate 165 cases of patients with PIN ( including 31 cases of LGPIN,134 cases of HGPIN),which confirmed by pathology,and 252 cases of benign prostatic hyperplasia (BPH),49 patients with prostate cancer (PCa),both diagnosed by pathology,as control.The average age of BPH,LGPIN,HGPIN,PCa groups were 70.13 ± 0.43,70.97 ± 1.28,70.74 ± 0.64,70.37 ± 1.40,the International Prostate Symptom Score (IPSS) were 20.20 ± 0.88,14.71 ± 3.42,20.19 ± 1.239,19.27 ± 2.73,and the PV were 58.07 ± 3.58,56.01 ± 7.52,60.74 ± 4.81,47.56 ± 6.54,respectively.The data of PSA,f/t,PV and PSAD were analyzed and compared within the four groups. Results Age,IPSS score and PV had no significant difference among the four groups (P ＞ 0.05).The PSA level of BPH,LGPIN,HGPIN,PCa groups were 5.65 ±0.38,5.86 ±0.81,8.91 ±0.71,13.80 ±1.83,the f/t ratio were 0.26 ±0.01,0.24 ±0.02,0.22 ±0.01,0.167 ± 0.01,and the PSAD level were 0.11 ± 0.01,0.10 ± 0.02,0.19 ±0.03,0.48 ±0.12,respectively.PSA,f/t and PSAD were not significantly different between HGPIN and LGPIN ( P ＞ 0.05 ),and likewise between LGPIN and BPH patients ( P ＞ 0.05 ).PSA,f/t and PSAD were significantly different between LGPIN and PCa patients ( P ＜ 0.05),and likewise between HGPIN and BPH patients (P ＜ 0.05 ).PSA and PSAD were significantly different between HGPIN and PCa (P ＜ 0.05 ).The areas under the ROC curve of PSA and PSAD of HGPIN were 0.6281 (P ＜0.01 ) and 0.5919 (P ＜0.05).Conclusions PSA and PSAD are correlated with HGP1N and can predict the existence of HGPIN early;PSAD can identify HGPIN and PCa,when PSA and f/t are normal.The clinical features of LGPIN are similar to BPH,and HGPIN is easy to develop to PCa. Key words: Prostatic intraepithelial neoplasia; Benign prostatic hyperplasia; Prostate cancer; Retrospective study

Interleukin-6 (IL-6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate-specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL-6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL-6 levels as a marker of disease progression. MATERIALS AND METHODS Serum IL-6, prostate specific antigen (PSA), percent free PSA (%fPSA), and prostate-specific membrane antigen (PSMA) were measured using commercially available assays in 407 men, including 15 controls. The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). None had history of concurrent malignancy or acute inflammatory condition. Kruskal-Wallis analysis of variance and Spearman's correlation analysis were used for statistical analyses. Serum levels of IL-6 were significantly elevated in patients with clinically evident hormone refractory disease (5.7 +/- 1.9 pg/ml) and statistical significance was seen when comparing the elevated serum IL-6 levels to those in normal controls, prostatitis, BPH, and localized and recurrent disease, (P values < 0.01). Compared to serum levels of controls and BPH, PSA was significantly elevated in advanced untreated disease and hormone refractory groups (P < 0.05). Percent fPSA was significantly lower in all cancer patients but the hormone refractory. Serum PSMA was elevated in advanced untreated prostate cancer. Serum IL-6 showed positive correlation with PSMA and negative correlation with serum PSA but did not attain statistical significance. Serum IL-6 levels are significantly elevated in hormone-refractory prostate cancer patients and may be a surrogate marker of the androgen independent phenotype.

The case for prostate‐specific antigen screening starting at age 40

EVALUATION OF THE BACTERIAL FLORA OF THE PROSTATE USING A 16S rRNA GENE BASED POLYMERASE CHAIN REACTION

Objective: Prostate-specific antigen (PSA) is a marker used to detect prostate cancer. When high PSA values are detected, a prostate biopsy is performed considering the possibility of prostate cancer. PSA elevation is not specific to prostate cancer, but may also be caused by conditions such as benign prostatic hyperplasia (BPH), urinary tract infection, and chronic prostatitis. Prostate cancer is not detected in approximately 66% of patients undergoing a biopsy, and patients are exposed to unnecessary biopsy and biopsy complications. Chronic prostatitis is detected in approximately 40% of these biopsies. The two-glass test is based on examining urine before and after rectal examination, which is used in diagnosing chronic prostatitis. In this study, we aimed to reveal the two-glass test’s effectiveness in predicting the incidence of prostatitis and inflammation in patients with a PSA value of 2.5-10 ng/ml and who underwent prostate needle biopsy. Methods: Fifty-two male patients, aged between 50 and 78 years, with PSA values between 2.5 and 10 ng/ml, who applied to our clinic were included in the study. EPS-two-glass test and prostate biopsy were applied to all patients. EPS; is a sample obtained by removing the fluid from the urethra after a prostate massage; VB-3; shows the urine produced by taking about 10 ml of urine voided after massage. EPS and VB3 detect prostate infection. Under the microscope, ≥10 leukocytes were considered significant for prostate inflammation. According to the pathology results, the patients were divided into 3 groups; prostate cancer, BPH, and chronic prostatitis. The chronic prostatitis group was classified according to the histopathological calcification described by Nickel. Results: In this study, the ratio of chronic prostatitis was found to be 38%. VB3 positivity was found to be statistically significant in the chronic prostatitis group compared to the other groups (p = 0.028). Although there was no statistically significant difference between the prevalence of inflammation and PSA elevation, PSA was found to be higher in the multifocal inflammation subgroup than in the focal inflammation patient group. Conclusion: The relationship between chronic prostatitis and PSA elevation remains a mystery. Although no statistical relationship was found between inflammation and PSA elevation in this study, the significant correlation between chronic prostatitis and VB3 positivity reinforces the possibility of this relationship. We believe that our results will form the basis for further studies to avoid unnecessary biopsies.