Development and validation of a nomogram for predicting prostate cancer in patients with PSA ≤ 20 ng/mL at initial biopsy.

ABSTRACT: The aim of this study was to construct a nomogram for predicting prostate cancer (PCa) in patients with PSA ≤ 20 ng/mL at initial biopsy.The patients with PSA ≤ 20 ng/mL who underwent prostate biopsy were retrospectively included in this study. The nomogram was developed based on predictors for PCa, which were assessed by multivariable logistic regression analysis. The receiver operating characteristic curve, calibration plots and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.This retrospective study included 691 patients, who were divided into training set (505 patients) and validation set (186 patients). The nomogram was developed based on the multivariable logistic regression model, including age, total PSA, free PSA, and prostate volume. It had a high area under the curve of 0.857, and was well verified in validation set. Calibration plots and DCA further validated its discrimination and potential clinical benefits. Applying the cut-off value of 15%, our nomogram would avoid 42.5% of unnecessary biopsies while miss only 4.4% of PCa patients.The nomogram provided high predictive accuracy for PCa in patients with PSA ≤ 20 ng/mL at initial biopsy, which could be used to avoid the unnecessary biopsies in clinical practice.

Autophagy-regulating N-heterocycles derivatives as potential anticancer agents.

As a double-edged sword, autophagy in cancer cells could either suppress or promote tumorigenesis. Nowadays, more and more natural compounds with autophagy-regulating activities exhibit therapeutic effects against various cancers. N-Heterocycle derivatives plays an important role for discovery new drugs. In this review, we summarize and classify 116 N-heterocycle derivatives with autophagy-regulating activities in the past decade into 12 classes according to structure characteristics. The structural features, bioactivities, mechanism and problems faced in this field are discussed and reported for the first time. Some of these even exhibited outstanding in vivo antitumor activities, including bisaminoquinoline (3), pancratistatin (8), 10-hydroxyevodiamine (18), lycorine (28), piperine (31) and iridium (III) complex (57), which are potential drug candidates for antitumor therapy.

Efficient racemization of N-phenylacetyl-D-glufosinate for L-glufosinate production.

Most amino acids contain chiral centres and exist as both D-enantiomer and L-enantiomer. The optically pure enantiomer is often more valuable than the racemate. Enzymatic resolution provides an effective strategy to obtain optically pure amino acids but often results in large amounts of unwanted isomer. In this study, optically pure L-glufosinate (L-PPT) was obtained by coupling amidase-mediated hydrolysis of N-phenylacetyl-D,L-glufosinate with racemization of N-phenylacetyl-D-glufosinate (NPDG), which exclusively exhibits effective herbicidal properties compared with its D-enantiomer. To improve the yield of L-PPT, the racemization reaction conditions were optimized, and through single-factor experiments, the optimal reaction temperature, reaction time, and mole ratio of phenylacetic acid to NPDG were determined to be 150°C, 30 minutes, and 1.5, respectively. The response surface methodology was applied to further optimize the racemization conditions, and the final yield of L-PPT reached 96.13% with optimum reaction temperature of 154°C, reaction time of 23 minutes, and phenylacetic acid/NPDG mole ratio of 1.7, respectively. Moreover, adding a small amount of acetic anhydride further raised the yield of L-PPT to 97.02%.

[Establishment of a human bladder cancer cell line stably co-expressing hSPRY2 and luciferase genes and its subcutaneous tumor xenograft model in nude mice].

Objective To establish a human bladder cancer cell line stably co-expressing human sprouty2 (hSPRY2) and luciferase (Luc) genes simultaneously, and develop its subcutaneous tumor xenograft model in nude mice. Methods The hSPRY2 and Luc gene segments were amplified by PCR, and were cloned into lentiviral vector pCDH and pLVX respectively to produce corresponding lentivirus particles. The J82 human bladder cancer cells were infected with these two kinds of lentivirus particles, and then further screened by puromycin and G418. The expressions of hSPRY2 and Luc genes were detected by bioluminescence, immunofluorescence and Western blot analysis. The screened J82-hSPRY2/Luc cells were injected subcutaneously into BALB/c nude mice, and the growth of tumor was monitored dynamically using in vivo fluorescence imaging system. Results J82-hSPRY2/Luc cell line stably expressing hSPRY2 and Luc genes was established successfully. Bioluminescence, immunofluorescence and Western blot analysis validated the expressions of hSPRY2 and Luc genes. The in vivo fluorescence imaging system showed obvious fluorescence in subcutaneous tumor xenograft in nude mice. Conclusion The J82-hSPRY2/Luc bladder cancer cell line and its subcutaneous tumor xenograft model in nude mice have been established successfully.

MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration.

BACKGROUND: Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. METHODS: MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1. RESULTS: MEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells. CONCLUSIONS: By investigating the role of MEIS1 in ccRCC cells' survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (ccRCC) development.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Prostate Cancer: A Systematic Review and Meta-analysis.

Inflammation is increasingly reported to be associated with the prognosis of patients with cancers. And the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in patients with prostate cancer (PCa) remains inconsistent. Therefore, we conducted this systematic review and meta-analysis to obtain a more reliable assessment of prognostic significance of NLR in PCa.A comprehensive literature research regarding the association of NLR and prognosis of PCa was performed through PubMed, Embase, Cochrane Central, and Web of Science. The hazard ratios (HRs) and its 95% confidence intervals (CIs) for overall survival (OS), progression-free survival, or recurrence-free survival were extracted and pooled using fix-effects model or random-effects model.A total of 14 studies that met our criterion were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was not significantly associated with the poor OS (HR = 1.45; 95% CI 0.77-2.71; P = 0.248) or recurrence-free survival (HR = 1.34; 95% CI 0.89-2.02; P = 0.155) of patients with localized PCa. Although elevated NLR predicted poorer OS (HR = 1.57; 95% CI 1.41-1.74; P < 0.001) and progression-free survival (HR = 1.97; 95% CI 1.28-3.04; P = 0.002) of patients with metastatic castration resistant prostate cancer (mCRPC).Elevated NLR is a strong indicator of poorer prognosis of patients with mCRPC, whereas the NLR is not significantly associated with prognosis of patients with localized PCa. Therefore, NLR could be used in patients with mCRPC for risk stratification and decision making of individual treatment.

Lateroconal fascia suspension for management of peritoneal tear and "curtain" effect during retroperitoneal laparoscopic operations.

PURPOSE: To describe the method of lateroconal fascia suspension for the management of peritoneal tear and curtain effect during retroperitoneal laparoscopic operations. MATERIALS AND METHODS: Between May 2013 and October 2014, we performed lateroconal fascia suspension in 30 cases of retroperitoneal laparoscopic operations. Peritoneal tear occurred and retroperitoneal space collapsed in 18 cases of them during the operation, and free edge of the lateroconal fascia caused curtain effect and sheltered the field of view in another 12 cases after the lateroconal fascia was incised longitudinally. RESULTS: The curtain effect of lateroconal fascia was eliminated successfully, and the sheltered field of view got normal in all the 12 cases. The collapsed retroperitoneal space due to peritoneal tear got enlarged effectively and was sufficient for the following operations in 15 patients of the overall 18 cases, while the collapsed retroperitoneal space did not get enlarged significantly in the other three cases. After the insertion of an extra 5-mm trocar into peritoneal space, the collapsed retroperitoneal space got enlarged eventually. Finally, retroperitoneal laparoscopic operations were continued and completed successfully in all these 30 patients. It took 4 min to complete the suspension procedure, and no related complications occurred during the whole suspension process. CONCLUSION: Lateroconal fascia suspension method could manage most peritoneal tears and curtain effect effectively during retroperitoneal laparoscopic operations.

Radiofrequency Ablation Versus Partial Nephrectomy in Treating Small Renal Tumors: A Systematic Review and Meta-Analysis.

Radiofrequency ablation (RFA) has emerged as an alternative treatment to surgical partial nephrectomy (PN) in the treatment of small renal tumors (SRTs). But its safety and oncological efficacy are still controversial. We conducted this systematic review and meta-analysis to compare the peritoperative and oncological outcomes of RFA and PN in the treatment of SRTs. Pubmed, EMBASE, Cochrane CENTRAL, and Web of Science were searched to identify eligible studies that compared the RFA and PN in the treatment of SRTs. Twelve retrospective studies that compared RFA with PN in the treatment of SRTs met our selection criterion and were included in this meta-analysis. The pooled results indicated that the local recurrence rate (4.14% vs 4.10%, RR: 1.18, 95% CI: 0.68, 2.07, P = 0.550) and distant metastases rate (2.76% vs 1.89%, RR: 1.31, 95% CI: 0.70, 2.46, P = 0.686) were not significantly different between the RFA group and the PN group. In terms of perioperative outcomes, RFA was associated with shorter length of stay (LOS) (WMD: -2.02 days, 95% CI: -2.77, -1.27, P < 0.001), lower eGFR decline after treatment (WMD: -3.90, 95% CI: -6.660, -1.140, P = 0.006). However, the overall perioperative complication rate (7.5% vs 6.2%, RR:1.10, 95% CI: 0.64, 1.87, P = 0.740) and the major complication rate (3.7% vs 4.4%, RR: 0.83, 95% CI: 0.43, 1.60, P = 0.579) were both similar between RFA and PN groups. Compared with PN, RFA achieves an equal oncological outcome for SRTs with similar local recurrence rate and distant metastases rate. Additionally, RFA is associated with a similar perioperative complication rate, lower decline of eGFR, and shorter LOS. Therefore, RFA is an effective option in the treatment of SRTs for selected patients.

[Association between obesity-related plasma hemodilution and the concentration of prostate specific antigen].

OBJECTIVE: To determine the effect of obesity on prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH) and develop a PSA-related parameter that can eliminate the effect of obesity. METHODS: We reviewed the clinical data of 706 patients with BPH. Two PSA-related parameters, namely PSA mass (total circulating PSA protein) and PSA mass ratio (total circulation PSA protein per prostate volume), were calculated for all the patients and the association of BMI with PSA, PSA mass, and PSA mass ratio was assessed. RESULTS: A higher BMI was significantly associated with a greater plasma volume and prostate volume (P<0.05). Linear regression analysis revealed a greater adjusted R2 of BMI versus plasma volume than of BMI PSA (0.569 vs 0.027). PSA was positively associated with the prostate volume and negatively with BMI and plasma volume (P<0.05). PSA mass was positively associated with prostate volume (P<0.05) but was not associated with BMI or plasma volume (P>0.05). PSA mass ratio was not associated with prostate volume (P>0.05) but negatively associated with BMI and plasma volume. Plasma volume and prostate volume, PSA, and PSA mass ratio (P<0.05), but not PSA mass (P>0.05), differed significantly among normal-weight, overweight, and obese patients. CONCLUSION: A higher BMI is associated with a greater plasma volume in BPH patients. In obese patients with BPH, a lower PSA concentration may result from hemodilution caused by a greater plasma volume, and PSA mass can eliminate the effect of obesity on PSA.

[Effect of p53-regulated apoptosis-inducing protein 1 transfection on the biological characteristics of PC-3M human prostate cancer cells].

OBJECTIVE: To investigate the effect of p53-regulated apoptosis-inducing protein 1 (p53AIP1) gene on the proliferation, cell cycle, apoptosis, invasion and migration of PC-3M human prostate cancer cells in vitro. METHODS: The eukaryotic expression vector pDC316-p53AIP1 was constructed and confirmed by double enzyme digestion and PCR analysis. Then it was transfected into PC-3M human prostate cancer cells by Lipofectamine (TM) 2000. The expression of p53AIP1 protein was detected by Western blotting. The proliferation of PC-3M cells was tested by CCK-8 assay; the cell cycle and apoptosis rate were analyzed by flow cytometry combined with annexin V-FITC/PI staining; the effect of p53AIP1 on the cell invasion and migration was detected by Transwell(TM) assay. RESULTS The eukaryotic expression vector pDC316-p53AIP1 was constructed successfully. After transfected into PC-3M cells, Western blotting demonstrated that the protein p53AIP1 was effectively expressed. CCK-8 assay revealed that the proliferation of PC-3M cells was significantly inhibited by p53AIP1 (P<0.05). Flow cytometry indicated that the cells were arrested at S/G2-M phase (P<0.05) and cell apoptosis was evidently promoted (P<0.05). Transwell(TM) chamber experiments showed that p53AIP1 decreased the abilities of both invasion and migration of the cells (P<0.05). CONCLUSION: The p53AIP1 inhibits the proliferation of PC-3M cells, arrests cell cycle at S/G2-M phase, decreases the abilities of invasion and migration and promotes cell apoptosis.

An in-source stretched membrane inlet for on-line analysis of VOCs in water with single photon ionization TOFMS.

An in-source, stretched, hollow fiber membrane (HFM) inlet has been developed to improve the sensitivity of on-line time-of-flight mass spectrometry (TOFMS) with a vacuum ultraviolet (VUV) lamp based single photon ionization (SPI) source for the direct analysis of liquid samples. A 2-cm HFM was stretched to 8 cm in length, and placed in the ion source and directly under the VUV lamp window with a distance of 15 mm. Compared with the conventional flow-through configuration under the same experimental conditions, the signal intensities of selected volatile organic compounds (VOCs) of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), benzene, toluene and p-xylene were increased over 5-fold in magnitude, and the response time was shortened to one-third. The limits of detection (LOD) of MTBE, ETBE, benzene, toluene and p-xylene ranged from 0.25 to 1.3 µg L(-1) with a measurement time of 60 s, and three orders of linear range were obtained with correlation coefficients of 0.9972-0.9992. The present results suggest that the in-source stretched HFM is a simple and effective way to increase the sensitivity and shorten response time of the membrane inlet, and we believe that it will also be beneficial to other types of on-line mass spectrometer for the on-line analysis of VOCs in water with a VUV lamp based SPI ion source.

[Real-time analysis of polyvinyl chloride thermal decomposition/combustion products with single photon ionization/photoelectron ionization online mass spectrometer].

With the features of a broad range of ionizable compounds, reduced fragments and simple mass spectrum, a homemade magnetic field enhanced photoelectron ionization (MEPEI) source combined with single photon ionization (SPI) for time-of-flight mass spectrometer was built and applied to analyze thermal decomposition/combustion products of polyvinyl chloride (PVC). The combined ion source can be switched very fast between SPI mode and SPI-MEPEI mode for detecting different targeted compounds, and only adjusting the voltage of the electrode in the ionization region to trigger the switch. Among the PVC thermal decomposition/combustion products, HCl and CO2, which ionization energies (12.74 eV, 13.77 eV respectively) were higher than the energy of photon (10.60 eV), were ionized by MEPEI, while alkenes, dichloroethylene, benzene and its homologs, monochlorobenzene, styrene, indane, naphthalene and its homologs were ionized by SPI and MEPEI simultaneously. Spectra of interested products as a function of temperatures indicated that products are formed via two main mechanisms: (1) dechlorination and intramolecular cyclization can lead to the formation of HCl, benzene and naphthalene at 250-370 degrees C; (2) intermolecular crosslinking leads to the formation of alkyl aromatics such as toluene and xylene/ethylbenzene at 380-510 degrees C. The experimental results show that the combined ion source of SPI/ SPI-MEPEI for TOF-MS has broad application prospects in the online analysis field.

Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin.

Biological therapies can be beneficial in cancer patients. The present study aims to examine the inhibitory mechanism of curcumin on cancer cells in patients with colorectal cancer. The results showed that curcumin administration increased body weight, decreased serum TNF-alpha levels, increased apoptotic tumor cells, enhanced expression of p53 molecule in tumor tissue, and modulated tumor cell apoptotic pathway. We conclude that the curcumin treatment improves the general health of patients with colorectal cancer via the mechanism of increased p53 molecule expression in tumor cells and consequently speeds up tumor cell apoptosis.

The potential of carcinoembryonic antigen, p53, Ki-67 and glutathion Stransferase-π as clinico-histopathological markers for colorectal cancer.

OBJECTIVE: Colorectal cancer is one of the major contributors to cancer death worldwide. Lack of reliable colorectal cancer markers has hampered the management of these cancer patients. Our main purpose was to study the correlation between histopathological variables of colorectal adenocarcinomas and identify histopathological markers that are of prognostic value in patients with colorectal cancer. METHODS: In the present study, we examined the expression of carcinoembryonic antigen (CEA), p53, Ki-67 and glutathion Stransferase (GST) -π by using immunohistochemical staining methods in 126 colorectal carcinoma patients and evaluated the lymph node metastasis status in these patients by histopathological examination. RESULTS: The positive rates of CEA, p53, Ki-67 and GST-π expression in the colorectal cancer tissue specimens examined were 95.23%, 55.56%, 53.38% and 82.30%, respectively. Expression of p53 and Ki-67 was significantly correlated with the Dukes stages of the tumor, with higher levels of these proteins in Dukes'C and D tumors than those in Dukes' A and B tumors. Furthermore, the expression of p53, GST-π and Ki-67 correlated with prognosis of patients with colorectal cancer. Additionally, the expression of p53 in colorectal cancer was closely related to the expression of Ki-67 and the expression of GST-π was directly correlated with that of p53. CONCLUSION: The expression of CEA, p53, Ki-67 and GST-π was correlated with various clinical features of patients with colorectal cancer. The combined use of these histopathological markers appeared to be a promising tool in predicting the prognosis of patients with this type of cancer.