Study on the influence of urban tree canopy on thermal environment in Luoping County.

Urban forest is an integral part of the complex urban ecosystem, and tree canopy plays a key role in improving urban climatic environment. Urban Tree Canopy (UTC) is strongly linked to urban thermal environment and living quality of residents. In this study, Luoping County, a mountainous county in southwest China, was selected as the study area to uncover the inner connections between tree canopy and thermal environment, and provide relevant scientific references for the construction of livable forest cities in similar areas. Through eCongnition Developer, ENVI and ArcGIS software, the distribution of Land Surface Temperature (LST) and land cover types in the study area was extracted, 63 patches with super-large and extra-large tree canopy coverage selected, to explore the regulatory effect of UTC patches on urban thermal environment based on SPSS software. Results showed that the highest LST in the research area was 37.63 â„ƒ, the lowest 24.73 â„ƒ, and the average 30.83 â„ƒ. Among the land cover types, the area of buildings and impervious surfaces was 1615.71 hm2, accounting for 55.76% of the total study area, which was the largest proportion and with widespread distribution; the area of grassland and water body was 57.48 hm2 and 12.35 hm2, respectively, taking up 1.98% and 0.43%, with a smaller proportion. Mean LST: impervious surface > bare land > grassland > tree canopy > water body. By increasing the area and perimeter of the patch covered by tree canopy, the cooling rate of the patch can be increased while the temperature inside the patch can be reduced. The relationship between the area and cooling rate is closer than that between perimeter and cooling rate. The increase of perimeter has a stronger alleviation effect on the internal temperature of the patch, whereas, the increase of area has a weaker effect in this respect.

The novel transcriptomic signature of angiogenesis predicts clinical outcome, tumor microenvironment and treatment response for prostate adenocarcinoma.

Angiogenesis plays the critical roles in promoting tumor progression, aggressiveness, and metastasis. Although few studies have revealed some angiogenesis-related genes (ARGs) could serve as prognosis-related biomarkers for the prostate cancer (PCa), the integrated role of ARGs has not been systematically studied. The RNA-sequencing data and clinical information of prostate adenocarcinoma (PRAD) were downloaded from The Cancer Genome Atlas (TCGA) as discovery dataset. Twenty-three ARGs in total were identified to be correlated with prognosis of PRAD by the univariate Cox regression analysis, and a 19-ARG signature was further developed with significant correlation with the disease-free survival (DFS) of PRAD by the least absolute shrinkage and selection operator (LASSO) Cox regression with tenfold cross-validation. The signature stratified PRAD patients into high- and low-ARGs signature score groups, and those with high ARGs signature score were associated with significantly poorer outcomes (median DFS: 62.71 months vs unreached, p < 0.0001). The predicting ability of ARGs signature was subsequently validated in two independent cohorts of GSE40272 & PRAD_MSKCC. Notably, the 19-ARG signature outperformed the typical clinical features or each involved ARG in predicting the DFS of PRAD. Furthermore, a prognostic nomogram was constructed with three independent prognostic factors, including the ARGs signature, T stage and Gleason score. The predicted results from the nomogram (C-index = 0.799, 95%CI = 0.744-0.854) matched well with the observed outcomes, which was verified by the calibration curves. The values of area under receiver operating characteristic curve (AUC) for DFS at 1-, 3-, 5-year for the nomogram were 0.82, 0.83, and 0.83, respectively, indicating the performance of nomogram model is of reasonably high accuracy and robustness. Moreover, functional enrichment analysis demonstrated the potential targets of E2F targets, G2M checkpoint pathways, and cell cycle pathways to suppress the PRAD progression. Of note, the high-risk PRAD patients were more sensitive to immune therapies, but Treg might hinder benefits from immunotherapies. Additionally, this established tool also could predict response to neoadjuvant androgen deprivation therapy (ADT) and some chemotherapy drugs, such as cisplatin, paclitaxel, and docetaxel, etc. The novel ARGs signature, with prognostic significance, can further promote the application of targeted therapies in different stratifications of PCa patients.

Combination of Androgen Deprivation Therapy with Radical Local Therapy Versus Androgen Deprivation Therapy Alone for Newly Diagnosed Oligometastatic Prostate Cancer: A Phase II Randomized Controlled Trial.

BACKGROUND: Previous studies suggested that men with metastatic prostate cancer might benefit from local treatment of the primary tumor. OBJECTIVE: To determine whether radical local therapy (RLT) improves survival for men with oligometastatic prostate cancer (OMPCa). DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized controlled trial included patients with newly diagnosed OMPCa defined as five or fewer bone or extrapelvic lymph node metastases and no visceral metastases. INTERVENTION: Patients were randomly allocated to androgen deprivation therapy (ADT) or ADT and RLT. Men allocated RLT received either cytoreductive radical prostatectomy (RP) or prostate radiation therapy (RT) with a radical dose schedule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was radiographic progression-free survival (rPFS). Secondary outcomes were overall survival (OS) and prostate-specific antigen (PSA) progression-free survival. RESULTS AND LIMITATIONS: Between September 2015 and March 2019, 200 patients were randomized, with 100 men allocated to each group. The median age was 68 yr and the median PSA at diagnosis was 99 ng/ml. In the study group, 96 patients underwent RLT (85 RP and 11 RT). In the control group, 17 patients eventually received RLT (15 RP and two RT). All patients were included for an intention-to-treat analysis. After a median follow-up of -48 mo, the median rPFS was not reached in the study group and was 40 mo in the control group (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.27-0.70; p = 0.001). The 3-yr OS rate was 88% for the study group and 70% for the control group (HR 0.44, 95% CI 0.24-0.81; p = 0.008). CONCLUSIONS: Men with newly diagnosed OMPCa who received ADT plus RLT (mainly prostatectomy) had significantly higher rates of rPFS and OS than those who received ADT alone. PATIENT SUMMARY: This study investigated the effect of radical local therapy (RLT) of the primary tumor on survival in patents with oligometastatic prostate cancer. In our group, RLT improved radiographic progression-free and overall survival.

[Changes in the penis size of prostate cancer patients after radical prostatectomy and its influencing factors].

OBJECTIVE: To investigate the changes in the size of the penis after radical prostatectomy (RP) and the possible influencing factors. METHODS: This study included 45 cases of RP for PCa performed by the same surgeon from January to June 2019. Before and at 2 weeks after surgery, we measured the stretched penile length (SPL), flaccid penile length (FPL) and penile circumference of the patients. We conducted an IIEF-5 questionnaire investigation on the preoperative characteristics of the patients and their attitudes towards postoperative penile rehabilitation. We also analyzed the factors associated with the postoperative changes in the size of the penis. RESULTS: Compared with the baseline, the postoperative SPL (ï¼»9.72 ± 1.87ï¼½ vs ï¼»7.80 ± 1.57ï¼½ cm, P = 0), FPL (ï¼»6.26 ± 1.14ï¼½ vs ï¼»5.13 ± 1.10ï¼½ cm, P = 0) and penile circumference (ï¼»7.69 ± 0.83ï¼½ vs ï¼»7.26 ± 0.78ï¼½ cm, P = 0.012) were decreased significantly, by (1.92 ± 0.12) cm, (1.13 ± 0.09) cm and (0.43 ± 0.08) cm, respectively. The age of the patients was significantly correlated with the change of the FPL (P = 0.042), but not the other factors with the change of the penile size. Twenty-six (57.7%) cases of severe and moderate ED were observed in the patients postoperatively. Those with better preoperative sexual function took a more positive attitude towards penile rehabilitation and treatment postoperatively (n = 3, 75.0%). CONCLUSIONS: The penile size of the PCa patient is decreased markedly after radical prostatectomy, with a significant correlation between the patient's age and the postoperative change of the flaccid penile length. The patients with better preoperative sexual function are more likely to seek penile rehabilitation and treatment postoperatively.

Genetic variants in RTEL1 influencing telomere length are associated with prostate cancer risk.

Telomere length measured in lymphocytes has been evaluated as a potential biomarker for prostate cancer (PCa) risk. Identifying genetic variants that affect telomere length and testing their association with disease could clarify any causal role. We therefore investigated associations between genetic variants in three telomere length-related genes and PCa risk in a case-control study. The influence of these variants on the leukocyte telomere lengths was then appraised by real-time PCR. RTEL1 rs2297441 [odds ratio (OR): 1.23; 95% confidence interval (CI): 1.03-1.46, P = 0.021] and rs3208008 (OR: 1.23; 95% CI: 1.03-1.46) were associated with PCa risk. These two risk single nucleotide polymorphisms (SNPs) (OR: 0.59; 95% CI: 0.39-0.89, P = 0.012 and OR: 0.58; 95% CI: 0.38-0.87, P = 0.009, respectively) and another SNP PARP1 rs1136410 (OR: 1.53; 95% CI: 1.01-2.31, P = 0.043) were also associated with leukocyte telomere length. These findings support that genetic determinants of telomere length may influence PCa risk.

Elevated MRE11 expression associated with progression and poor outcome in prostate cancer.

Objective: Growing evidence has proved that MRE11, a protein underpinned to be involved in DNA double-strand break (DSB) repair process, is correlated with cancer outcomes. However, its role in prostate cancer (PCa) remains unclear. This study aimed to investigate the expression of MRE11 in tumor tissue and defining its value in predicting prognosis of PCa patients. Methods: A total of 578 patients from two cohorts were enrolled in this study. Distribution of categorical clinical-pathological data together with levels of MRE11 expression was compared with χ2-test in a contingency table. Immunohistochemical (IHC) staining and evaluation was detected from 78 paired PCa and adjacent normal tissues. Partial likelihood test from univariate and multivariate Cox regression analysis was developed to address the influence of independent factors on disease-free survival (DFS) and overall survival (OS) in two cohorts. The Kaplan-Meier method and log-rank test were performed to assess the survival benefits between discrete levels. Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from The Cancer Genome Atlas (TCGA) database. Results: In the current study, we demonstrated that MRE11 was highly expressed in PCa compared with normal tissues (P=0.011). In addition, in the TCGA cohort, the median DFS in patients with IHC positive and negative MRE11 expression levels was 24.5 and 30.6 months, and median OS was 28.7 and 33.0 months, respectively. In FUSCC cohort, median DFS in patients with IHC positive and negative MRE11 expression was 28.0 and 35.6 months. Furthermore, survival curves suggested that PCa patients with elevated MRE11 expression levels showed poorer OS (P=0.019) in TCGA cohort and poor DFS (P=0.047) in FUSCC cohort. Conclusion: In conclusion, our study reveals that elevated MRE11 expression is significantly correlated with cancer progression and poor survival in PCa patients. These data suggest that MRE11 may act as an oncoprotein and a promising prognostic marker for PCa patients.

Clinical significance of urine prostatic exosomal protein in the diagnosis of prostate cancer.

PSA may be elevated in non-malignant conditions such as prostatitis and leads to unnecessary prostate needle biopsy. Urine prostatic exosomal protein (PSEP) has been proved to be a promising biomarker of prostatic inflammation. The aim of this study is to determine the relationships between PSEP and the diagnosis of prostate cancer (PCa), and their association with histologic prostatic inflammation. Prostate needle biopsies from 674 patients were evaluated for the presence of histological inflammation and PCa. The urine PSEP levels were measured using an enzyme-linked immunosorbent assay kit. 286 cases were diagnosed as PCa and prostatic inflammation was observed in 33.7% of the biopsies. The presence of histological inflammation was significantly associated with a lower PCa risk (P < 0.001). The urine PSEP levels was significantly lower in PCa patients compared to the controls (P = 0.003). When subanalyzed by PSA levels, the difference was more evident in cases with PSA 4-10 ng/ml (P = 0.039). The urine PSEP levels was correlated with histological inflammation on prostate needle biopsy (P = 0.018, r = 0.12). Urine PSEP examination may be helpful to eliminate false positive PSA levels due to prostatic inflammation and reduce unnecessary prostate needle biopsy in cases with PSA grey zone.

[Attitudes of prostate cancer patients towards postoperative penile rehabilitation and their influencing factors].

OBJECTIVE: To investigate the attitudes of prostate cancer (PCa) patients towards postoperative penile rehabilitation and their influencing factors. METHODS: Seventy-nine PCa patients underwent radical prostatectomy from January through June 2017 and all received a questionnaire investigation before surgery on IIEF-5 and their attitudes towards postoperative penile rehabilitation. We analyzed the reasons for the patients' rejection of postoperative penile rehabilitation. RESULTS: Totally 56 (71%) of the patients accepted and the other 23 (29%) refused postoperative penile rehabilitation. The factors influencing their attitudes towards penile rehabilitation mainly included age (P = 0.023), income (P = 0.040), tumor stage (P = 0.044), and preoperative sexual activity (P = 0.004). The patients who accepted penile rehabilitation had significantly higher IIEF-5 scores than those who refused it (14.75 ± 0.88 vs 8.48 ± 1.16, P = 0.000 2). During the follow-up period, only 29 (36.7%) of the patients bought the vacuum erection device but not the other 50 (63.3%). The tumor stage (P = 0.004), income (P < 0.01) and preoperative androgen-deprivation therapy (P = 0.039) significantly influenced the patients' decision on the purchase of the device. Relevant admission education achieved a 45% decrease in the number of the patients unwilling to accept penile rehabilitation for worrying about its negative effect on cancer treatment, a 25% decrease in those rejecting penile rehabilitation because of age, and a 20% decrease in those refusing it due to the tumor stage. The cost of treatment was an important reason for the patients' rejection of postoperative penile rehabilitation. CONCLUSIONS: The tumor stage and income are the main factors influencing PCa patients' decision on postoperative penile rehabilitation. Relevant admission education and reduced cost of rehabilitation are important for popularization of postoperative penile rehabilitation in PCa patients.

A single nucleotide polymorphism in CYP1B1 leads to differential prostate cancer risk and telomere length.

BACKGROUND: Cytochrome P450 1B1 (CYP1B1) is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Functionally relevant genetic variants within CYP1B1 may affect the telomere length and subsequently lead to prostate carcinogenesis. METHODS: We evaluated 8 CYP1B1 tag single nucleotide polymorphisms (SNPs) in 1015 men with prostate cancer (PCa) and 1052 cancer-free controls, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate their association with risk of PCa. The influence of CYP1B1 SNPs on the relative telomere lengths was then appraised in peripheral blood leukocytes using real-time PCR. RESULTS:CYP1B1 rs1056836 variant was associated with decreased risk of PCa [odds ratio (OR): 0.80; 95% confidence interval (CI): 0.68-0.99, P = 0.041]. Longer telomere length showed a significantly higher proportion of the CYP1B1 rs1056836 CG/GG genotypes, compared with that of the CC genotype (OR: 1.60, 95% CI: 1.04-2.45). CONCLUSION: Our findings suggest that genetic variants within CYP1B1 may confer genetic susceptibility to PCa by altering telomere length.

Genetic variants of the CYP1B1 gene as predictors of biochemical recurrence after radical prostatectomy in localized prostate cancer patients.

Clinically localized prostate cancer is curative. Nevertheless many patients suffered from biochemical recurrence (BCR) after radical prostatectomy (RP). Mounting evidence suggest that estrogen and xenobiotic carcinogens play an essential role in progression of prostate cancervia oxidative estrogen metabolism. CYP1B1 is an enzyme involved in the hydroxylation of estrogens, a reaction of key relevance in estrogen metabolism. Given the role of CYP1B1 in the oxidative metabolism of endogenous/exogenous estrogen and compounds, CYP1B1 polymorphisms have the potential to modify its expression and subsequently lead to progression. We hypothesize that genetic variants of the CYP1B1 gene may influence clinical outcome in clinically localized prostate cancer patients. In this cohort study, we genotyped 9 tagging single nucleotide polymorphisms (SNPs) from the CYP1B1 gene in 312 patients treated with RP. For replication, these SNPs were genotyped in an independent cohort of 426 patients. The expression level of CYP1B1 in the adjacent normal prostate tissues was quantified by reverse transcription and real-time polymerase chain reaction. Kaplan-Meier analysis and Cox proportional hazard models were utilized to identify SNPs that correlated with BCR. CYP1B1 rs1056836 was significantly associated with BCR (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.40-0.89, P = 0.002) and relative CYP1B1 mRNA expression. Our findings suggest inherited genetic variation in the CYP1B1 gene may contribute to variable clinical outcomes for patients with clinically localized prostate cancer.

Nephrometry score-guided off-clamp laparoscopic partial nephrectomy: patient selection and short-time functional results.

BACKGROUND: Laparoscopic partial nephrectomy (LPN) is not a novel but a relatively technically challenging surgical procedure. Off-clamp LPN with zero ischemia can completely eliminate ischemic reperfusion injury to the kidney. The purpose of this study was to evaluate the safety and functional outcome of nephrometry score-guided off-clamp technique in LPN. METHODS: A total of 44 patients underwent LPN between January 2015 and July 2015 for renal mass with radius, exophytic/endophytic, nearness to sinus, anterior/posterior location (RENAL) score 4 were enrolled. Twenty-two of them underwent off-clamp LPN with zero ischemia, and the other 22 received standard LPN with common renal artery clamp. Estimate blood loss (EBL), total operation time, resection time, renorrhaphy time, preoperative estimated glomerular filtration rate (eGFR), postoperative eGFR, eGFR change, and drainage after surgery were compared between these two groups using t test. RESULTS: Patients' characteristics including gender, age, BMI, tumor size, and RENAL score were balanced between the two groups. Average EBL was more in the off-clamp group than in the on-clamp group (134.32 versus 70.23 ml, p = 0.001). Average eGFR change was less in the off-clamp group than in the on-clamp group (-1.56 versus -6.45, p < 0.001). Average drainage after surgery was 203.41 ml for the off-clamp group and 145.46 ml for the on-clamp group, p = 0.062. No urinary leakage and hematuria occurred in both groups. There were no statistical difference in total operation time, resection time, renorrhaphy time, preoperative eGFR, and postoperative eGFR between the two groups. CONCLUSIONS: Off-clamp LPN is a safe and feasible approach to excise certain kidney tumors with RENAL score 4. This technique can better preserve kidney function without ischemic reperfusion injury.

Predicting the failure of retrograde ureteral stent insertion for managing malignant ureteral obstruction in outpatients.

Malignant ureteral obstruction (MUO) is an unpropitious sign that is commonly observed in patients with advanced incurable cancer. The present study aimed to evaluate predictive factors for the failure of retrograde ureteral stent insertion in the management of MUO in outpatients. A total of 164 patients with MUO were retrospectively assessed in this study. Clinical factors, including age, gender, type of malignancy, level of obstruction, cause of obstruction, pre-operative creatinine level, degree of hydronephrosis, condition of the contralateral ureter, prior radiotherapy, Eastern Cooperative Oncology Group performance status (ECOG PS), bladder wall invasion and technical failure, were recorded for each case. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for predicting the failure of retrograde ureteral stent insertion. In total, 38 out of 164 patients experienced bilateral obstruction, therefore, a total of 202 ureteral units were available for data analysis. The rate of insertion failure in MUO was 34.65%. Multivariate analyses identified ECOG PS, degree of hydronephrosis and bladder wall invasion as independent predictors for insertion failure. Overall, the present study found that rate of retrograde ureteral stent insertion failure is high in outpatients with MUO, and that ECOG PS, degree of hydronephrosis and bladder invasion are potential independent predictors of insertion failure.

Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005.

The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

Clinicopathological and prognostic factors for long-term survival in Chinese patients with metastatic renal cell carcinoma treated with sorafenib: a single-center retrospective study.

Data on long-term survival and prognostic significance of demographic factors and adverse events (AEs) associated with sorafenib, an orally administered multikinase inhibitor in Chinese population with advanced renal cell carcinoma (RCC) are limited. Outcome data from adult patients (n = 256) with advanced RCC who received sorafenib (400 mg twice daily) either as first-line or second-line therapy between April 2006 and May 2013 were analyzed retrospectively. The primary endpoint was median overall survival (OS), determined to be 22.2 (95% CI: 17.1-27.4) months, and the secondary endpoint was overall median progression-free survival (PFS), determined to be 13.6 (95% CI: 10.7-16.4) months at a median follow-up time of 61.8 (95% CI: 16.2-97.4) months. Analysis of the incidence of AEs revealed the most common side effect as hand-foot skin reactions (60.5%) followed by diarrhea (38.7%), fatigue (35.5%), alopecia (34.0%), rash (24.6%), hypertension (21.5%) and gingival hemorrhage (21.1%). Multivariate regression analysis revealed older age (≥ 58 years), lower Memorial Sloan-Kettering Cancer Center score, time from nephrectomy to sorafenib treatment, number of metastatic tumors and best response as significant and independent demographic predictors for improved PFS and/or OS (p ≤ 0.05). Alopecia was identified as a significant and independent predictor of increased OS, whereas vomiting and weight loss were identified as significant predictors of decreased OS (p ≤ 0.05). Sorafenib significantly improved OS and PFS in Chinese patients with advanced RCC. Considering the identified significant prognostic demographic factors along with the advocated prognostic manageable AEs while identifying treatment strategy may help clinicians select the best treatment modality and better predict survival in these patients.

Pretreatment Neutrophil-to-Lymphocyte Ratio: A Predictor of Advanced Prostate Cancer and Biochemical Recurrence in Patients Receiving Radical Prostatectomy.

The pretreatment neutrophil-to-lymphocyte ratio (NLR) is reportedly associated with the clinical outcomes of many cancers. However, it has not been widely investigated whether the pretreatment NLR is associated with the pathological characteristics of prostate cancer (PCa) and biochemical recurrence in PCa patients receiving radical prostatectomy (RP).In this cohort study, a total of 1688 PCa patients who had undergone RP were analyzed retrospectively, and a subset of 237 of these patients were evaluated to determine the relationship between pretreatment NLR and biochemical recurrence. Patients were divided into a high-NLR group (NLR ≥2.36) and a low-NLR group (NLR < 2.36) according to the pretreatment NLR. The association between the pretreatment NLR and pathological stage and lymph node involvement was evaluated using logistic regression analysis. Time of biochemical recurrence was determined using the Kaplan-Meier method. Cox's proportional hazard regression model was used to compare the time of biochemical recurrence between the groups.As compared with patients in the low-NLR group, those in the high-NLR group had an increased risk of pT3-4 disease (odds ratio (OR), 1.883; 95% confidence interval (CI), 1.419-2.500; P < 0.001), and a 1.7-fold increased risk of lymph node involvement (OR, 1.685; 95% CI, 1.101-2.579; P = 0.016). For the subset of 237 patients, those with a high NLR showed a significantly shorter median biochemical recurrence-free survival time (51.9 months) than those with a low NLR (76.5 months; log-rank test, P = 0.019). However, multivariate analysis indicated that the NLR was not an independent predictor of biochemical recurrence (hazard ratio, 1.388; 95% CI, 0.909-2.118; P = 0.129).Our findings suggest that the pretreatment NLR may be associated with pathological stage and lymph node involvement in PCa patients receiving RP, and that PCa patients with a high NLR may have a higher rate of biochemical recurrence following RP than those with a low NLR.

Association of glutathione S-transferase T1 and M1 polymorphisms with prostate cancer susceptibility in populations of Asian descent: a meta-analysis.

BACKGROUND: Genetic polymorphism was hypothesized to be reason of variation in prostate cancer incidence among different racial group. Based on that published data on the association of prostate cancer susceptibility with polymorphisms in genes encoding Glutathione S-transferases (GSTs) were inconclusive, the aim of this study was to more precisely address the role of GSTs polymorphisms (especially, GSTT1 and GSTM1 deletions) on prostate cancer risk in Asian descent. METHODS: A meta-analysis including 8 articles with 711 cases and 1122 controls for GSTT1 and 1098 cases and 1588 controls for GSTM1 was performed. RESULTS: Significantly increased prostate cancer risk was found among subjects carrying GSTM1 null genotype (odds ratio (OR) = 1.403; 95% confidence interval (CI) = 1.088 - 1.808) but not among subjects carrying GSTT1 deletion genotype (OR = 0.959; 95%CI = 0.709 - 1.297). When stratified by country, the null genotype of GSTT1 neither increased nor decreased prostate cancer risk significantly in China (OR = 1.355; 95%CI = 0.895 - 2.049), Japan (OR = 0.812; 95%CI = 0.545 - 1.211), and Korea (OR = 1.056; 95%CI = 0.727 - 1.534). While significant association of elevated prostate cancer risk with GSTM1 deletion were found in China (OR = 1.665; 95%CI = 1.324 - .094) and Korea (OR = 1.914; 95%CI = 1.311 - 2.793) but not in Japan (OR = 0.980; 95%CI = 0.726 - 1.321). CONCLUSIONS: In summary, this meta-analysis suggested that the null genotype of GSTM1 rather than GSTT1 may be involved in the etiology of prostate cancer in Asian population.

Prognostic significance of the TREK-1 K2P potassium channels in prostate cancer.

BACKGROUND: TREK-1 channels belong to the two-pore domain potassium channel superfamily and play an important role in central nervous system diseases. However, few studies have examined their role in carcinogenesis. METHODS: In this study, we assessed the expression of TREK-1 in 100 prostate cancer (PCa) tissues using immunohistochemistry and further analyzed its clinicopathological significance. Next, cell proliferation and cell cycle analysis were carried out on human PCa PC-3 cell lines where TREK-1 was stably knockdown. RESULTS: We found that compared with normal prostate tissues, PCa tissues showed overexpressed TREK-1 levels and TREK-1 levels were positively associated with Gleason score and T staging. High level of TREK-1 expression was related to shorter castration resistance free survival (CRFS). Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell cycle arrest. CONCLUSIONS: Our results suggest that TREK-1 might be a biomarker in CRFS judgment of PCa, as well as a potential therapeutic target.

MicroRNA-302a Suppresses Tumor Cell Proliferation by Inhibiting AKT in Prostate Cancer.

Micro (mi) RNAs are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in prostate cancer (PCa). MiRNA-302a expression was detected in 44 PCa tissues and 10 normal prostate tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal prostate tissues, miRNA-302a expression was downregulated in PCa tissues, and was even lower in PCa tissues with a Gleason score ≥8. Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3ß-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in PCa.

The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy.

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096-2.545, P= 0.017), and a 1.5-fold increased risk of pT3-4 disease (OR = 1.583, 95% CI 1.106-2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038-2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.

Serum lipid profiles: novel biomarkers predicting advanced prostate cancer in patients receiving radical prostatectomy.

This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer (PCa). We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy (RP) and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score (pGS), pathological stage and lymph node involvement (LNI) in RP specimens. Preoperative prostate-specific antigen (PSA) levels, biopsy GS (bGS), and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic (ROC) curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 (95% confidence interval [CI] 1.510-27.010), 3.270 (95% CI: 1.470-7.278) for high levels of TG for pT3-4 disease, and 2.670 (95% CI: 1.134-6.287) for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.