The application of polypropylene mesh for testicular prosthesis in surgical castration for patients with prostate cancer.

BACKGROUND: To explore whether a polypropylene mesh is suitable for application as a new material for testicular prostheses. METHODS: The data of 65 patients with advanced prostate cancer who underwent surgical castration in hospital were collected and analyzed. Patients who preferred to undergo traditional orchidectomy (n = 16) were assigned to the control group, and patients who underwent subcapsular orchiectomy plus implantation of a polypropylene mesh testicular prosthesis (n = 49) were assigned to the experimental group. The presence of hematoma, infection, and other complications in patients in these two groups were investigated at 3 and 12 months following the surgery. The patients were also followed up using a self-designed testicular castration satisfaction questionnaire. RESULTS: A higher score indicated greater satisfaction. The mean score was 15.33 ± 2.85 in the experimental group and 4.63 ± 1.45 in the control group at 3 months after the surgery. The mean score was 14.92 ± 1.74 in the experimental group and 4.25 ± 1.61 in the control group at 12 months after the surgery. The difference between the two groups was statistically significant at the two time points (P < 0.01). CONCLUSIONS: Compared with orchidectomy alone, patients were more satisfied with subcapsular orchiectomy plus the implantation of a polypropylene mesh testicular prosthesis for the treatment of advanced prostate cancer. Furthermore, the polypropylene mesh testicular prosthesis maintained its original character over the duration of the study, with a good long-term effect. Thus, implantation of a polypropylene mesh testicular prosthesis is indicated to be safe and effective, and polypropylene mesh is potentially useful as a new material for testicular prostheses.

Transient receptor potential melastatin 4 contributes to early-stage endothelial injury induced by arsenic trioxide.

BACKGROUND/AIMS: To investigate the effect of Arsenic Trioxide (ATO) on endothelial cells injury and explore the role of transient receptor potential melastatin 4 channel (TRPM4) in ATO-induced endothelial injury. METHODS: qRT-PCR was used to examine the mRNA expression of TRPM4 in human umbilical vein endothelial cells (HUVECs). The protein levels were measured by Western blot and immunostaining. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, apoptosis, and migration, respectively. The ultrastructural changes were observed by scanning electron microscopy. The membrane potential, cytosolic [Na+]i, cytosolic [Ca2+]i and reactive oxygen species (ROS) levels were detected by fluorescent probes. Isometric tension of mesenteric artery was recorded by using a multiwire myograph system. RESULTS: ATO induced HUVEC cells injury, the significant upregulation of TRPM4 in this process was inhibited by 9-phenanthrol or siRNA. ATO-induced apoptosis and decrease in the cell viability/ migration were all partially reversed upon the treatment with 9-phenanthrol. Whereas, ATO-mediated increase in membrane potential, cytosolic [Na+]i, cytosolic [Ca2+]i and the ROS levels were also abolished by 9-phenanthrol or siRNA, suggesting that oxidative stress may be the potential mechanisms underlying ATO-induced endothelial injury. Additionally, 9-phenanthrol treatment prevented ATO-mediated impairment of acetylcholine-induced endothelium-dependent relaxations. CONCLUSION: TRPM4 is involved in endothelial injury induced by ATO and may be a promising therapeutic target for endothelial injury.

Association Between Thyroid Nodules and Volume and Metabolic Syndrome in an Iodine-Adequate Area: A Large Community-Based Population Study.

Background: Given its high incidence, thyroid nodule (TN) warrants public attention. Thyroid volume (TV) has also been associated with multiple factors, such as iodine deficiency and supply and body mass index. It is well known that metabolic syndrome (MetS) comprises many metabolic disturbances, with insulin resistance being its major component. Materials and Methods: The aim of this study was to investigate the relationship between TN and TV and MetS and its components in an iodine-adequate area in Asia. All participants were asked to complete a questionnaire. After excluding 938 individuals based on the exclusion criteria, we reviewed data from 927 of 1865 participants. Adopting MetS diagnostic criteria, we found 437 subjects to be MetS positive [MetS(+)] and 490 subjects to be MetS negative [MetS(-)], respectively. Multivariate linear regression was used to assess the relationship between TNs and MetS. Moreover, univariate binary logistic regression analyses were used to calculate odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the associations between different variables and TNs. Results: A total of 232 females and 205 males were MetS(+), as diagnosed using the International Diabetes Federation criteria. However, there were 330 females and 160 males in the group of MetS(-) individuals. The prevalence of TNs was 38.29% in the MetS(+) group and 17.79% in the MetS(-) group. After adjusting for systolic blood pressure, diastolic blood pressure, and gender, only high-density lipoprotein, waist circumference (WC), and age were related to TNs (OR = 0.45, 95% CI 0.27-0.75, P = 0.0023; OR = 1.04, 95% CI 1.02-1.06, P = 0.0036). The TV of all participants was 13.98 (11.24, 17.01) mL; 13.26 (10.62, 16.17) mL for females and 14.96 (11.83, 18.01) mL for males. It was found that only WC was related to TV, after controlling for sex and age (P = 0.02). Conclusions: The morbidity among TN patients in the MetS(+) group was higher than that among the MetS(-) group. High-density lipoprotein cholesterol emerged as a protective factor, and WC was a risk factor for TN. Moreover, TV was related to MetS, and WC was an independent risk factor for TV.

The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS. MATERIAL AND METHODS Databases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results. RESULTS Meta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, -0.43; 95% CI, -0.81-0.06; p=0.02; I²=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, -0.63; 95% CI, -1.20 - -0.05; p=0.03; I²=38%) but simvastatin did not significantly reduce DHEA levels (SMD: -0.14; 95% CI, -0.49-0.28; p=0.43; I²=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, -0.61; 95% CI, -1.23-0.02; p=0.06; I²=85%) and 24 weeks (SMD, -0.34; 95% CI -0.95-0.28; p=0.29; I²=83%). CONCLUSIONS Meta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.

PMLIV overexpression promotes TGF-ß-associated epithelial-mesenchymal transition and migration in MCF-7 cancer cells.

The epithelial-mesenchymal transition (EMT) is a key event associated with metastasis and dissemination in breast tumor pathogenesis. Promyelocytic leukemia (PML) gene produces several isoforms due to alternative splicing; however, the biological function of each specific isoform has yet to be identified. In this study, we report a previously unknown role for PMLIV, the most intensely studied nuclear isoform, in transforming growth factor-ß (TGF-ß) signaling-associated EMT and migration in breast cancer. This study demonstrates that PMLIV overexpression promotes a more aggressive mesenchymal phenotype and increases the migration of MCF-7 cancer cells. This event is associated with activation of the TGF-ß canonical signaling pathway through the induction of Smad2/3 phosphorylation and the translocation of phospho-Smad2/3 to the nucleus. In this study, we report a previously unknown role for PMLIV in TGF-ß signaling-induced regulation of breast cancer-associated EMT and migration. Targeting this pathway may be therapeutically beneficial.

[Polypropylene mesh for testicular prothesis implantation: A report of 57 cases].

OBJECTIVE: To search for an optimum method for testicular prothesis implantation in the treatment of testis loss. METHODS: We retrospectively analyzed the surgical methods and outcomes of 53 cases of terminal prostate cancer and 4 cases of unilateral testicular torsion treated by implantation of testicular prothesis with the polypropylene mesh. RESULTS: The 57 male patients all received testicular prothesis with the polypropylene mesh. All the patients were satisfied with the appearance and size of the scrotum after surgery. No scrotal hematoma, prosthesis infection, or autoimmune disease occurred postoperatively. CONCLUSION: Testis loss is not a rare condition clinically, for the treatment of which surgical implantation of testicular prothesis with the polypropylene mesh can achieve both a fine tissue compatibility and a desirable scrotal appearance.

Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease.

AIM: To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS: Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg·kg(-1)·d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-κB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR. RESULTS: The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-κB, cyclin D1, and PCNA in thyroids of the GD mice. CONCLUSION: Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-κB, cyclin D1, and PCNA expression.

Identification of epidermal growth factor receptor (EGFR) exon 20 single nucleotide polymorphism in Chinese squamous cell carcinoma of head and neck (SCCHN).

CONCLUSION: The 78th single nucleotide polymorphism (SNP) in exon 20 of epidermal growth factor receptor (EGFR) might be a predictor of the clinical course of squamous cell carcinoma of the head and neck (SCCHN), and genetic predisposition could influence the progression of SCCHN in Chinese subjects. OBJECTIVE: To analyze the clinical significance of EGFR SNP in Chinese SCCHN patients. MATERIALS AND METHODS: Direct sequencing of exons 18-21 was used to analyze somatic mutations of EGFR. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the expression level of EGFR. The chi-square test and Kaplan-Meier method were the main statistical methods used to analyze the correlation of the investigated variables and prognostic significance. RESULTS: In analyzing exons 18-21 of EGFR in 96 patients with SCCHN, only one SNP was found in the 78th site of exon 20 and it mostly existed in specimens coming from the hypopharynx. Further statistical analysis showed that among the clinical or histopathologic parameters, the 78th SNP had a close relationship with earlier stage and more localized primary carcinoma, while at present the analysis did not support the proposition that the SNP was an independent prognostic factor.

Identification of Sp1-elements in the promoter region of human homeobox gene NKX3.1.

NKX3.1 is a prostate-specific homeobox gene related strongly to prostate development and prostate cancer. However, little is known about the mechanism for regulation of NKX3.1 in prostate cancer. With RT-PCR and western blot, we found that NKX3.1 expression was enhanced by over-expression of Sp1 at both the mRNA and protein levels in prostate cancer LNCaP cells. To identify the Sp1-elements in the promoter region of NKX3.1, a 521 bp-promoter of human NKX3.1 gene containing three possible Sp1-elements was cloned into the upstream of the luciferase reporter gene in pGL(3)-basic plasmid. With deletion mutation analysis, plasmid construction, EMSA and oligonucleotide decoy technique, two Sp1-elements which located between ?29 to ?43 and -60 to -46 of NKX3.1 gene were identified and proven to be functional elements. It will be important to further study on the functions and the regulatory mechanisms of Sp1 element in NKX3.1 gene expression.

Emodin induces apoptosis in human prostate cancer cell LNCaP.

AIM: To elucidate effects and mechanisms of emodin in prostate cancer cells. METHODS: Viability of emodin-treated LNCaP cells and PC-3 cells was measured by MTT assay. Following emodin treatments, DNA fragmentation was assayed by agarose gel electrophoresis. Apoptosis rate and the expression of Fas and FasL were assayed by flow cytometric analysis. The mRNA expression levels of androgen receptor (AR), prostate-specific antigen (PSA), p53, p21, Bcl-2, Bax, caspase-3, -8, -9 and Fas were detected by RT-PCR, and the protein expression levels of AR, p53 and p21 were detected by Western blot analysis. RESULTS: In contrast to PC-3, emodin caused a marked increase in apoptosis and a decrease in cell proliferation in LNCaP cells. The expression of AR and PSA was decreased and the expression of p53 and p21 was increased as the emodin concentrations were increased. In the same time, emodin induced apoptosis of LNCaP cells through the upregulation of caspase-3 and -9, as well as the increase of Bax /Bcl-2 ratio. However, it did not involve modulation of Fas or caspase-8 protein expression. CONCLUSION: In prostate cancer cell line, LNCaP, emodin inhibites the proliferation by AR and p53-p21 pathways, and induces apoptosis via the mitochondrial pathway.

Curcumin downregulates homeobox gene NKX3.1 in prostate cancer cell LNCaP.

AIM: To elucidate the effect and the mechanisms of curcumin on the expression of the human homeobox gene NKX3.1 in the prostate cancer cell LNCaP. METHODS: The expression change of NKX3.1 in cells incubated with varying concentrations of curcumin was observed by Western blotting and RT-PCR. A dual luciferase reporter assay was used to test the effect of curcumin on the activity of the NKX3.1 1040 bp promoter. Curcumin-treated cells disposed to a designated amount of androgen analog R1881 and the androgen receptor (AR) antagonist flutamide, then the expression of NKX3.1 or the activity of the NKX3.1 promoter were investigated by Western blotting or reporter gene assay, respectively. Finally, Western blotting and electrophoretic mobility shift assay were performed to demonstrate the effect of curcumin on the expression of AR and its binding activity to the androgen response element (ARE). RESULTS: Curcumin downregulated the expression of NKX3.1 and the activity of the NKX3.1 1040 bp promoter in LNCaP cells. R1881 increased the expression of NKX3.1, and the AR antagonist flutamide decreased the expression of NKX3.1 in LNCaP cells, while curcumin could inhibit androgen-AR mediated induction of NKX3.1 expression. Curcumin decreased the expression of AR and the binding activity to ARE directly. CONCLUSION: Curcumin could downregulate NKX3.1 expression in LNCaP cells. It could also inhibit the androgen-AR mediated induction of NKX3.1 expression by downregulating AR expression and blocking its DNA binding activity.

Effects of 9-cis retinoic acid on human homeobox gene NKX3.1 expression in prostate cancer cell line LNCaP.

AIM: To study the regulatory effects of 9-cis retinoic acid (RA) on the expression of human homeobox gene NKX3.1 in prostate cancer cell line LNCaP. METHODS: Flow cytometry, reverse transcriptase polymerase chain reaction and Western blotting were performed to evaluate the effects of 9-cis RA on NKX3.1 expression and cell cycle of LNCaP cells. To identify a regulatory region within the NKX3.1 promoter contributing to the regulation induced by 9-cis RA, we have constructed an NKX3.1 promoter-reporter plasmid, pGL3-1040bp, and its 5'-deletion mutants, which were transfected into LNCaP cells with treatment of 9-cis RA in indicated concentrations. RESULTS: With the treatment of 9-cis RA, the NKX3.1 promoter activity was increased in reporter gene assay and NKX3.1 expression was enhanced at both mRNA and protein levels in LNCaP cells. We found that the region between -936 and -921 in the upstream of NKX3.1 gene involved the inducible regulation by 9-cis RA treatment. In flow cytometry, 9-cis RA treatment caused accumulation of cells in the G(1) phase of the cell cycle and a fewer cells pass through to G(2)/M. CONCLUSION: Our results demonstrated that 9-cis RA as a differentiating agent can arrest prostate cancer cells in G(1) phase and reduce cell mitosis, and upregulate the expression of human homeobox gene NKX3.1, which is thought to play an important role in prostate differentiation and to act as a tumor suppressor gene in the prostate.

[Up-regulates the expression of maspin gene in prostate cancer cell line LNCaP].

AIM: To study the effect of curcumin on the apoptosis of prostate cancer cell line LNCaP and regulation of expression of maspin gene. METHODS: MTT and DNA electrophoresis were used to examine the cell growth and apoptosis of prostate cancer cell line LNCaP after treated with different doses of curcumin. The expression of maspin gene at transcription level and translation level was also detected by RT-PCR and Western blotting. pGL3-maspin luciferase expression vector, containing 847 bp (- 764 -/+ 83) DNA of maspin gene 5' promoter region, was transient transfected into LNCaP cell. Through detecting the activity of luciferase, the effect of curcumin on the promoter of maspin was studied. RESULTS: Curcumin inhibited cell growth, induced the apoptosis and enhanced the expression of maspin gene in LNCaP cells. CONCLUSION: Curcumin up-regulated expression of maspin gene in LNCaP cells through enhancing the transcription activity of promoter of maspin gene.