Ketamine Promoted Breast Cancer Invasion and Metastasis Through Up-regulating Wnt, BMP, and EGFR Signaling.

BACKGROUND/AIM: In this study, we used an orthotropic breast cancer model combined with ketamine addiction and next-generation sequencing (NGS) to comprehensively investigate molecular alterations in ketamine-mediated metastasis. Ketamine is widely used in anesthesia and drug abuse. Our previous study revealed that ketamine promotes the growth of breast cancer cells; however, the detailed molecular mechanism remains unknown. MATERIALS AND METHODS: An orthotropic breast cancer model was established by injecting EO771 breast cancer cells into the mammary fat pad of mice intraperitoneally administered ketamine (30 mg/kg, daily) for 68 days. Tumors collected at day 38 were frozen for future analysis, and their metastasis state was checked at day 68. RESULTS: Tumors were grouped and subjected to NGS analysis, followed by differential gene expression analysis (DEseq) and pathway identification. DEseq analysis showed that ketamine up-regulated metastasis-related signaling, and the key genes were BMP5, FZD6, MMP1B, EGFR, WNT5A, BMP7, and DCN. CONCLUSION: Ketamine addiction up-regulates the expression of genes involved in the Wnt, EGFR, and BMP signaling cascades, which may be associated with breast cancer progression and metastasis.

Asiatic acid exhibits antimetastatic activity in human prostate cancer cells by modulating the MZF-1/Elk-1/Snail signaling axis.

Prostate cancer metastasis is associated with poor prognosis and is difficult to treat clinically. Numerous studies have shown that Asiatic Acid (AA) has antibacterial, anti-inflammatory, and antioxidant effects. However, the effect of AA on prostate cancer metastasis is still unclear. This purpose of this study is to investigate the effect of AA on prostate cancer metastasis and to better understand its molecular mechanisms of action. Our results indicate that AA ≤ 30 µM did not influence cell viability and cell cycle distribution in PC3, 22Rv1 and DU145 cells. AA inhibited the migratory and invasive capabilities of three prostate cancer cells to be due to its effects on Snail, but did not have activity on Slug. We observed that AA inhibited the Myeloid zinc finger 1 (MZF-1) and ETS Like-1 (Elk-1) protein interaction and affected the complex's binding capacity to the Snail promoter region, ultimately blocking Snail transcription activity. Kinase cascade analysis revealed that phosphorylation of MEK3/6 and p38MAPK was inhibited by AA treatment. Moreover, knockdown of p38MAPK enhanced AA-suppressed protein levels of MZF-1, Elk-1, and Snail, suggesting that p38MAPK influences prostate cancer cell metastasis. These results provide promise for AA as a future candidate in the development of drug therapies to prevent or treat prostate cancer metastasis.

Ketamine promotes breast tumor growth in a mouse breast tumor model involving with high expression of miR-27b-3p and EGFR.

Non-medical use of ketamine as an adulterant to ecstasy is more prevalent than amphetamine in Taiwan. Ketamine's effect on immunosuppression might play some functional role in tumor growth, while it is still controversial whether ketamine abuse could increase tumor growth or not. This study aimed to investigate the influence of ketamine addiction in breast tumors and related gene expressions. The effect of ketamine treatment on proliferation, colony formation, migration, and invasion of triple-negative breast cancer cell line EO771 was examined. In addition, a ketamine addiction mice model was established by intraperitoneal injection (IP) of ketamine in mice and used to investigate the effects of ketamine addiction on tumor growth and the possible mechanisms. In the in vitro studies, ketamine treatment at different concentrations did not affect EO771 cell proliferation and colony formation. But ketamine did enhance migration and invasion of EO771 cells. The in vivo experiments showed significantly increased breast tumor volume and weight in ketamine-addicted mice than in normal saline groups. miR-27b-3p level, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) significantly increased in tumors of ketamine addiction mice compared to control mice. In vivo evidence showed that Ketamine might increase tumor growth on the tumor microenvironment, and miR-27b-3p, HER2, and EGFR might play a role in the process.

Ten-years outcome analysis in patients with clinically localized prostate cancer treated by radical prostatectomy or external beam radiation therapy.

Purpose: Since there was no consensus on treatment options for localized prostate cancer, we performed a retrospective study to compare the long-term survival benefit of radiotherapy (RT) versus laparoscopic radical prostatectomy (LRP) in Taiwan. Methods: 218 patients with clinically localized prostate cancer treated between 2008 and 2017 (64 with LRP and 154 with RT) were enrolled in this study. The outcomes of RT and LRP were assessed after patients were stratified according to Gleason score, stage, and risk group. Crude survival, prostate cancer-specific survival, and metastasis-free survival were evaluated using the log-rank test. Results: The 5-year crude survival rate was 93.3% in the LRP group and 59.3% in the RT group. A significant survival benefit was found in the LRP group compared with the RT group (p = 0.004). Furthermore, significant differences were found in disease-specific survival (93.3% vs. 64.7%, p = 0.022) and metastasis-free survival (48% vs. 40.2%, p = 0.045) between the LRP and RT groups. Conclusions: Men with localized prostate cancer treated initially with LRP had a lower risk of prostate cancer-specific death and metastases compared with those treated with RT.

Effect of phenylurea hydroxamic acids on histone deacetylase and VEGFR-2.

A series of phenylurea hydroxamic acids incorporating pharmacophores of inhibitors of HDAC inhibitors and VEGFR-2 has been designed. Most of the compounds show antiproliferative activity comparable to that of Vorinostat and Sorafenib, and better EPC inhibitory activity. Enzymatic assays and Western blotting results indicated that compound 14 not only inhibits HDAC but also has slight VEGFR-2 inhibitory activity. A docking study revealed that the polar hydroxamic acid retains the interaction with HDAC through a zinc ion and also interacts with some residues of the active site of VEGFR-2. Despite 14 displaying a weaker VEGFR-2 activity, a possible route to develop potent HDAC/VEGFR-2 inhibitors is suggested.

Melatonin impedes prostate cancer metastasis by suppressing MMP-13 expression.

Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP-13) expression are higher in prostate cancer patients than in healthy cancer-free individuals. Mechanistic investigations revealed that melatonin inhibits MMP-13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c-Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP-13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.

Synthesis and biological evaluation of 2-quinolineacrylamides.

A series of C6-substituted N-hydroxy-2-quinolineacrylamides (3-15), with four types of bridging groups have been synthesized. Most of these compounds exhibit antiproliferative activity against A549 and HCT116 cells and Western blot analysis revealed that they are able to inhibit HDAC. Measurement of the HDAC isoform activity of ether-containing compounds showed that compound 9 has distinct HDAC6 selectivity, more than 300-fold over other isoforms. This paper describes the development of 6-aryloxy-N-hydroxy-2-quinolineacrylamides as potential HDAC6 inhibitors.

Phomaketide A Inhibits Lymphangiogenesis in Human Lymphatic Endothelial Cells.

Lymphangiogenesis is an important biological process associated with cancer metastasis. The development of new drugs that block lymphangiogenesis represents a promising therapeutic strategy. Marine fungus-derived compound phomaketide A, isolated from the fermented broth of Phoma sp. NTOU4195, has been reported to exhibit anti-angiogenic and anti-inflammatory effects. However, its anti-lymphangiogenic activity has not been clarified to date. In this study, we showed that phomaketide A inhibited cell growth, migration, and tube formation of lymphatic endothelial cells (LECs) without an evidence of cytotoxicity. Mechanistic investigations revealed that phomaketide A reduced LECs-induced lymphangiogenesis via vascular endothelial growth factor receptor-3 (VEGFR-3), protein kinase Cδ (PKCδ), and endothelial nitric oxide synthase (eNOS) signalings. Furthermore, human proteome array analysis indicated that phomaketide A significantly enhanced the protein levels of various protease inhibitors, including cystatin A, serpin B6, tissue factor pathway inhibitor (TFPI), and tissue inhibitor matrix metalloproteinase 1 (TIMP-1). Importantly, phomaketide A impeded tumor growth and lymphangiogenesis by decreasing the expression of LYVE-1, a specific marker for lymphatic vessels, in tumor xenograft animal model. These results suggest that phomaketide A may impair lymphangiogenesis by suppressing VEGFR-3, PKCδ, and eNOS signaling cascades, while simultaneously activating protease inhibitors in human LECs. We document for the first time that phomaketide A inhibits lymphangiogenesis both in vitro and in vivo, which suggests that this natural product could potentially treat cancer metastasis.

Resistin facilitates VEGF-A-dependent angiogenesis by inhibiting miR-16-5p in human chondrosarcoma cells.

Resistin is an adipokine that is associated with obesity, inflammation, and various cancers. Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. VEGF-A is a critical angiogenic factor that is known to promote angiogenesis and metastasis in chondrosarcoma. It is unknown as to whether resistin affects human chondrosarcoma angiogenesis. In this study, we show how resistin promotes VEGF-A expression and subsequently induces angiogenesis of endothelial progenitor cells (EPCs). Resistin treatment activated the phosphatidylinositol-3-kinase (PI3K) and Akt signaling pathways, while PI3K and Akt inhibitors or siRNA diminished resistin-induced VEGF-A expression. In vitro and in vivo studies revealed the downregulation of micro RNA (miR)-16-5p in resistin-induced VEGF-A expression and EPCs angiogenesis. We also found a positive correlation between resistin and VEGF-A expression, and a negative correlation between resistin and VEGF-A with miR-16-5p in chondrosarcoma patients. These findings reveal that resistin facilitates VEGF-A expression and angiogenesis through the inhibition of miR-16-5p expression via PI3K/Akt signaling cascades. Resistin may be a promising target in chondrosarcoma angiogenesis.

Prospective observational pharmacogenetic study of side effects induced by intravenous morphine for postoperative analgesia.

Nausea and vomiting are probably the most unpleasant side effects that occur when morphine used. A number of studies have investigated the effect on pain relief of single nucleotide polymorphisms (SNPs) in genes involved in morphine's metabolism, distribution, binding, and cellular action. The mechanism through which morphine causes nausea and vomiting has not been elucidated clearly. We examined all the reported SNPs which are associated with the complications of morphine, including SNPs in genes for phase I and phase II metabolic enzymes, ABC binding cassette drug transporters, κ and δ opioid receptors, and ion channels implicated in the postreceptor action of morphine.A prospective, observational study in 129 female patients was conducted to investigate the effect of 14 SNPs on nausea or vomiting induced by intravenous patient-controlled analgesia (IVPCA) with morphine after gynecology surgery. Clinical phenotype, subjective complaints, and objective observations were recorded. DNA from blood samples was used to record the SNPs. Eleven SNPs were then analyzed further.No significant association with the presence of phenotype (nausea or vomiting) versus genotype was observed (all P > .05). No significant association with severity of phenotype versus genotype of the 11 SNPs was observed except for unadjusted data for rs2737703.There was no significant difference between severity or incidence of IVPCA morphine-induced nausea and vomiting and genotype (11 SNPs). Further study should perhaps be focused on mRNA and proteinomics rather than SNPs.

CCL5 promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-507 in human chondrosarcoma cells.

Chondrosarcoma is the second most frequently occurring type of bone malignancy that is characterized by the distant metastasis propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumor lymphangiogenesis and lymphatic metastasis. Chemokine CCL5 has been reported to facilitate angiogenesis and metastasis in chondrosarcoma. However, the effect of chemokine CCL5 on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has largely remained a mystery. In this study, we showed a clinical correlation between CCL5 and VEGF-C as well as tumor stage in human chondrosarcoma tissues. We further demonstrated that CCL5 promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium (CM) from CCL5-overexpressed cells significantly induced tube formation of human lymphatic endothelial cells (LECs). Mechanistic investigations showed that CCL5 activated VEGF-C-dependent lymphangiogenesis by down-regulating miR-507. Moreover, inhibiting CCL5 dramatically reduced VEGF-C and lymphangiogenesis in the chondrosarcoma xenograft animal model. Collectively, we document for the first time that CCL5 induces tumor lymphangiogenesis by the induction of VEGF-C in human cancer cells. Our present study reveals miR-507/VEGF-C signaling as a novel mechanism in CCL5-mediated tumor lymphangiogenesis. Targeting both CCL5 and VEGF-C pathways might serve as the potential therapeutic strategy to block cancer progression and metastasis in chondrosarcoma.

Butein inhibits metastatic behavior in mouse melanoma cells through VEGF expression and translation-dependent signaling pathway regulation.

BACKGROUND: Melanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated. METHODS: MTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL/6 mice. RESULTS: We first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations (1, 3, and 10 µM). In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR/p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model. CONCLUSION: The results of the present study indicate the potential utility of butein in the treatment of melanoma.

Associations of VEGF-C genetic polymorphisms with urothelial cell carcinoma susceptibility differ between smokers and non-smokers in Taiwan.

BACKGROUND: Vascular endothelial growth factor (VEGF)-C is associated with lymphangiogenesis, pelvic regional lymph node metastasis, and an antiapoptotic phenotype in urothelial cell carcinoma (UCC). Knowledge of potential roles of VEGF-C genetic polymorphisms in susceptibility to UCC is lacking. This study was designed to examine associations between VEGF-C gene variants and UCC susceptibility and evaluate whether they are modified by smoking. METHODOLOGY/PRINCIPAL FINDINGS: Five single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a TaqMan-based real-time polymerase chain reaction (PCR) in 233 patients with UCC and 520 cancer-free controls. A multivariate logistic regression was applied to model associations between genetic polymorphisms and UCC susceptibility, and to determine if the effect was modified by smoking. We found that after adjusting for other covariates, individuals within the entire population and the 476 non-smokers carrying at least one A allele at VEGF-C rs1485766 respectively had 1.742- and 1.834-fold risks of developing UCC than did wild-type (CC) carriers. Among the 277 smokers, we found that VEGF-C rs7664413 T (CT+TT) and rs2046463 G (AG+GG) allelic carriers were more prevalent in UCC patients than in non-cancer participants. Moreover, UCC patients with the smoking habit who had at least one T allele of VEGF-C rs7664413 were at higher risk of developing larger tumor sizes (p = 0.021), compared to those patients with CC homozygotes. CONCLUSIONS: Our results suggest that the involvement of VEGF-C genotypes in UCC risk differs among smokers compared to non-smokers among Taiwanese. The genetic polymorphism of VEGF-C rs7664413 might be a predictive factor for the tumor size of UCC patients who have a smoking habit.

Butein Inhibits Angiogenesis of Human Endothelial Progenitor Cells via the Translation Dependent Signaling Pathway.

Compelling evidence indicates that bone marrow-derived endothelial progenitor cells (EPCs) can contribute to postnatal neovascularization and tumor angiogenesis. EPCs have been shown to play a "catalytic" role in metastatic progression by mediating the angiogenic switch. Understanding the pharmacological functions and molecular targets of natural products is critical for drug development. Butein, a natural chalcone derivative, has been reported to exert potent anticancer activity. However, the antiangiogenic activity of butein has not been addressed. In this study, we found that butein inhibited serum- and vascular endothelial growth factor- (VEGF-) induced cell proliferation, migration, and tube formation of human EPCs in a concentration dependent manner without cytotoxic effect. Furthermore, butein markedly abrogated VEGF-induced vessels sprouting from aortic rings and suppressed microvessel formation in the Matrigel implant assay in vivo. In addition, butein concentration-dependently repressed the phosphorylation of Akt, mTOR, and the major downstream effectors, p70S6K, 4E-BP1, and eIF4E in EPCs. Taken together, our results demonstrate for the first time that butein exhibits the antiangiogenic effect both in vitro and in vivo by targeting the translational machinery. Butein is a promising angiogenesis inhibitor with the potential for treatment of cancer and other angiogenesis-related diseases.

Polymorphism of µ-Opioid Receptor Gene (OPRM1:c.118A>G) Might Not Protect against or Enhance Morphine-Induced Nausea or Vomiting.

A cohort, double blind, and randomized study was conducted to investigate the effect of a single nucleotide polymorphism of the µ-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) on the association with the most common side effects (nausea or vomiting) induced by intravenous patient control analgesia (IVPCA) with morphine, including incidence and severity analysis. A total of 129 Taiwanese women undergoing gynecology surgery received IVPCA with pure morphine for postoperative pain relief. Blood samples were collected and sequenced with high resolution melting analysis to detect three different genotypes of OPRM1 (AA, AG, and GG). All candidates 24 h postoperatively will be interviewed to record the clinical phenotype with subjective complaints and objective observations. The genotyping after laboratory analysis showed that 56 women (43.4%) were AA, 57 (44.2%) were AG, and 16 (12.4%) were GG. The distribution of genotype did not violate Hardy-Weinberg equilibrium test. There was no significant difference neither between the severity and incidence of IVPCA morphine-induced side effects and genotype nor between the association between morphine consumption versus genotype. However, there was significant difference of the relation between morphine consumption and the severity and incidence of IVPCA morphine-induced nausea and vomiting. The genetic analysis for the severity and incidence of IVPCA morphine-induced nausea or vomiting showed no association between phenotype and genotype. It might imply that OPRM1:c.118A>G does not protect against IVPCA morphine-induced nausea or vomiting.

Predictive factors of successful varicocelectomy in infertile patients.

AIM: To examine the predictive factors of successful varicocelectomy in infertile patients. METHODS: Thirty-five infertile male patients with varicocele and requiring varicocelectomy were recruited in this study. The patients were divided into 2 groups based on their recovery outcome after subinguinal microsurgical varicocelectomy. Patients who showed significant improvement on their sperm density, motility and morphology 6 months after varicocelectomy were designated as group 1, whereas those who showed no improvement 6 months after surgery were designated as group 2. The predictive factors that were examined included: age; preoperative semen quality (i.e. sperm density, motility and morphology); testicular volume; seminal volume; varicocele grade; the number of ligated veins; body mass index (BMI), and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, alkaline phosphatase (Alk-p), lactic dehydrogenase (LDH), cholesterol and triglyceride. RESULTS: Sperm density, motility and morphology improved significantly 6 months after varicocelectomy in group 1 patients (n = 35; 71.4%). Group 1 patients had significantly higher testicular volumes (mean ± SD: 29.6 ± 5.9 vs. 23.2 ± 6.1 ml), lower FSH (11.3 ± 2.9 vs. 16.1 ± 4.8 mIU/ml) and higher numbers of ligated veins (9.3 ± 0.8 vs. 7.9 ± 0.7) than group 2 patients. No significant association was observed between surgical outcome and age, preoperative sperm density, motility and morphology, seminal volume, varicocele grade, BMI and serum levels of LH, prolactin, testosterone, Alk-p, LDH, cholesterol and triglyceride. CONCLUSIONS: These findings suggest that the significant predictive factors of successful varicocelectomy in infertile patients were high testicular volume (>29.6 ml), low serum concentration of FSH (<11.3 mIU/ml) and high number of ligated veins (>9).

Comparison of transrectal ultrasound-guided biopsy of the prostate and transurethral resection of the prostate for detection of prostate cancer in patients with moderate lower urinary tract symptoms.

BACKGROUND: To compare transrectal ultrasound (TRUS)-guided biopsy of the prostate and transurethral resection of the prostate (TURP) for detection of prostate cancer (PCa) in patients with moderate lower urinary tract symptoms (LUTS) by retrospective chart review. METHODS: Between January 2004 and December 2008, a total of 520 patients, aged 50.3-81.5 years, with moderate LUTS (International Prostate Symptom Score, 8-19), and elevation of prostate-specific antigen (≥ 4 ng/mL), or abnormal findings by digital rectal examination, were enrolled for evaluation. All the patients were recommended to receive TRUS-guided biopsy of the prostate (TRUS biopsy group) or TURP (TURP group) due to the possibility of PCa, according to their choice after full explanation by the doctors. RESULTS: There were 379 patients in the TRUS biopsy group and 141 in the TURP group. PCa was detected in 80 patients (21.1%) in the TRUS group and in 27 (19.1%) in the TURP group. Clinically localized PCa (T1-2N0M0) was found in 46 patients (57.5%) in the TRUS biopsy group and in 16 (59.3%) in the TURP group. Bone metastasis was noticed in 22 (27.5%) patients in the TRUS biopsy group and in 7 (25.9%) in the TURP group. The percentage of low-grade tumor was significantly higher in the TURP group than in the TRUS biopsy group (11.1% vs. 5%). CONCLUSION: TURP was not superior to TRUS-guided biopsy of the prostate for detection of PCa in patients with moderate LUTS and prostate-specific antigen ≥ 4 ng/mL.

Experience of varicocele management during ipsilateral inguinal herniorrhaphy: a prospective study.

BACKGROUND: This was a prospective study to evaluate the experience of varicocele management during ipsilateral herniorrhaphy in an inpatient urology setting. METHODS: A total of 65 patients with varicocele and inguinal hernia scheduled for herniorrhaphy were included for evaluation. They were categorized into 3 groups. Group 1 (n = 20) had painful varicocele and underwent simultaneous herniorrhaphy and varicocelectomy; group 2 (n = 20) had asymptomatic varicocele and received simultaneous herniorrhaphy and varicocelectomy; and group 3 (n = 25) had asymptomatic varicocele and underwent herniorrhaphy only. We used the Bassini method for herniorrhaphy and inguinal microsurgical varicocelectomy for varicocele. Varicocele was diagnosed by physical examination and further confirmed by Doppler ultrasonography. RESULTS: The mean follow-up was 30.2 months (range, 6-56 months). Of the 20 subjects in group 1, complete resolution of scrotal pain was noticed in 14 (70%), and 2 (10%) had hydrocele after varicocelectomy. Of the 20 patients in group 2, 1 (5%) had hydrocele after surgery, and no hydrocele was noticed in group 3 after surgery. Mean operation time was significantly longer in group 1 (70.5 + or - 15.2 minutes) and group 2 (69.8 + or - 14.5 minutes) than in group 3 (38.2 + or - 17.2 minutes). One case in group 1 had recurrent varicocele 6 months after surgery. Of the 25 subjects in group 3, 2 (8%) developed painful varicocele during the follow-up period, and both of them had indirect inguinal hernia and lower body mass index. CONCLUSION: Simultaneous herniorrhaphy and varicocelectomy are suggested for patients who have inguinal hernia and ipsilateral varicocele, but the average operation time is significantly longer and there is a higher rate of hydrocele than with herniorrhaphy only.

The difference in oxidative stress of the blood between using 5% glucose water and distilled water as the irrigant for BPH patients undergoing transurethral resection of the prostate.

INTRODUCTION: To evaluate the difference in oxidative stress in the blood between using 5% glucose water and using distilled water as the irrigant for BPH patients receiving transurethral resection of the prostate (TURP), we conducted this prospective study, on a total of 38 patients with symptomatic BPH. MATERIALS AND METHODS: All the patients were randomly divided into 2 groups. Distilled water in group A and 5% glucose water in group B were used as the irrigant. The oxidative stress and antioxidant capacity were evaluated by measuring malondialdehyde (MDA), mitochondrial DNA (mtDNA) copy number and total capacity of antioxidants (TOA) in the blood. The data were correlated with serum creatinine and sodium, which were measured before and immediately after TURP in all patients. RESULTS: Serum creatinine increased from 0.86 +/- 0.17 to 1.02 +/- 0.20 mg/dL while serum sodium decreased from 139.7 +/- 2.3 to 136.4 +/- 4.0 mEq/L immediately after surgery in patients of group A (p < 0.05). MDA was increased and TOA decreased in all the patients immediately after TURP. Patients in group A had significantly higher MDA, lower mtDNA copy number, higher degree of oxidative mtDNA damage and lower TOA than those in group B immediately after TURP. CONCLUSION: In conclusion, we observed an increase of MDA and decrease of TOA in blood in all the patients immediately after TURP, which might induce renal damage and decrease serum sodium. Moreover, the oxidative stress levels in blood of patients in group A were significantly higher than those in group B immediately after TURP.