Improved urinary melatonin level as the perspective indicator that leads to better sleeping quality in bladder cancer patients.

BACKGROUND: Individuals with higher-than-average melatonin concentrations are less likely to develop cancer. In cancer patients, psychosomatic coping patterns and treatment side effects are important indicators of cancer prevention and immune system deterioration. This study focused on changes in the urinary melatonin concentration, life resilience, and sleep quality in bladder cancer patients before, and 3 months after, treatment. METHODS: A controlled before-and-after study was performed. The subjects were patients who were previously diagnosed with bladder cancer and had received treatment (transurethral resection of bladder tumor + intravesical chemotherapy). Data from 23 subjects were analyzed. RESULTS: The results showed a significant difference in the melatonin concentration before and after treatment (Wilcoxon signed-rank test, Z = -2.220, p = 0.026). The melatonin concentration in 16 patients (70%) increased after treatment. The mean Pittsburgh Sleep Quality Index (PSQI) score before treatment was 7.348 (SD = 4.030), which was associated with poor sleep quality. The mean PSQI score after treatment was 6.435 (SD = 3.300; Z = -2.071; p = 0.038). These results represent the improved sleep quality in patients post-treatment. CONCLUSIONS: After treatment, the urinary melatonin concentration and sleep quality (PSQI) improved, both of which were statistically significant in bladder cancer patients. Consequently, bladder cancer treatment should be initiated as soon as possible. There was no significant difference in overall life resilience before and after treatment, possibly because elderly individuals have strong personality traits and emotional stability and are not easily affected by life events or stress.

The Health Promoting Mindfulness or Qigong Educational Programs for Beneficial Lifestyle Changes of Cancer Survivors.

This study used heart rate variability (HRV) to monitor levels of cancer-related fatigue (CRF) and quality of life (QOL) of cancer survivors subjected to program measures at different psychosomatic or functional levels. A longitudinal study was conducted at a cancer center in Taiwan. Fifty-two cancer survivals were randomly assigned to either the mindfulness group (n = 25) or the Qigong group (n = 27). Both groups received a 12-week mindfulness and Qigong programs, respectively. Improvements in CRF, QOL, and HRV after a 12-week program and at the 3-month follow-up point. For the long-term effects in both mindfulness and Qigong groups, CRF showed a significant downward trend (p < 0.05), but a significant upward trend was observed in HRV (p < 0.001). Mindfulness and Qigong exhibited different effectiveness in individuals, indicating that the mental and physical aspects of health are equally essential and should be addressed in a complementary combination. These findings are worthy of being shared with cancer survivors to benefit their physical and mental well-being. We suggest that healthcare professionals incorporate mindfulness and Qigong in cancer survivors' daily life as means to encourage lifestyle changes for improving their health.

Predictors for lower urinary tract symptoms and the urinary specific quality of life in prostate cancer patients: One-year follow-up.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer and is becoming a growing concern in global epidemiology. Quality of life of patients has become a major outcome for cancer care but limited study investigated quality of life of PCa patients. Our study is to investigate predictors for treatment outcomes of lower urinary tract symptoms (LUTS), nocturia, and the urinary specific quality of life (uQoL) in PCa patients one year following treatment. METHODS: A prospective study of 131 consecutive patients was conducted with outcome measurements before treatment, at 3 months, 6 months, and one year following therapy. We utilized the International Prostate Symptom Score questionnaire to collect data. Generalized estimating equations were performed to identify predictors for major outcomes of LUTS, nocturia, and uQoL. RESULTS: LUTS increased slightly over time, but nocturia and uQoL were improved from baseline to 12 months. Results of the interaction analysis indicated that patients with TNM stage 3 compared with those with stage 2 had a reduction in LUTS from diagnosis to 6 months. Patients who received surgery or radiation compared to hormone therapy had worse nocturia from diagnosis to 6 months compared to those of patients who received hormone therapy. Higher body mass index (BMI) decreased the uQoL from diagnosis to 3 months, and higher prostate-specific antigen (PSA) level deteriorated the uQoL from diagnosis to 12 months. CONCLUSION: TNM stage and BMI affected the LUTS. Patients undergone a prostatectomy or radiation therapy showed more frequency of nocturia, BMI and PSA were also risk factors for nocturia. Moreover, patients' age, BMI, and PSA affected uQoL. In such patients, we recommend close monitoring of patients' specific characteristics such as TNM stage, BMI, and PSA for a better quality of life.

Nephroprotective effect of electrolyzed reduced water against cisplatin-induced kidney toxicity and oxidative damage in mice.

BACKGROUND: Cisplatin is a potent chemotherapeutic drug for cancer therapy, but it has serious side effects in clinical treatment, particularly nephrotoxicity. The purpose of this study was to evaluate the protective effect of electrolyzed reduced water (ERW) on renal injury caused by cisplatin. METHODS: Animals were divided into four groups as follows: normal control group, cisplatin control group, ERW control group and ERW + cisplatin group. Each group comprised 10 animals, which were orally treated with normal saline or ERW daily companion by administration of one dose of cisplatin for 28 days. Animals in the cisplatin group received an intraperitoneal single-dose injection of cisplatin (20 mg/kg body weight) as a single i.p. dose on the 25th day of the experiment. We determined the hydration state in urine and the level of serum markers of kidney function, the levels of glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) levels and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxidase dismutase (SOD) in kidney and histopathological changes. RESULTS: After administration of ERW, the reduced urinary osmolality was increased and elevated Na+, K+, Mg2+ and Ca2+ levels in urine were significantly decreased in cisplatin-induced renal injury mice. Besides, the results demonstrated that significantly decreased elevated serum levels of creatinine and blood urea nitrogen (BUN) and the levels of TBARS in the kidneys that were induced by cisplatin. Moreover, ERW treatment was also found to markedly increase (p < 0.05) the activities of GPx, GR, CAT and SOD, and to increase GSH content in the kidneys. Histopathology showed that ERW protects against cisplatin-induced renal injury to both the proximal and distal tubules. CONCLUSION: ERW exhibits potent nephroprotective effects on cisplatin-induced kidney damage in mice, likely due to both the increase in antioxidant-defense system activity and the inhibition of lipid peroxidation.

Associations between interventions for urolithiasis and urinary tract cancer among patients in Taiwan: The effect of early intervention.

The aim of this study was to investigate cancer risk in patients with a history of urolithiasis and to determine whether intervention for calculi attenuated the risk of subsequent urinary tract cancer (UTC).Using data from the National Health Insurance Research Database in Taiwan, we performed a nationwide cohort study enrolling participants (n = 42,732) aged > 30 years who were diagnosed with urinary tract calculi between 2000 and 2009. Age- and gender-matched insured individuals (n = 213,660) found in the health service records over the same period were recruited as the control group. The Cox proportional hazards model and competing risks regression model were used to examine the relationship between urolithiasis and UTC, as well as whether early intervention for urolithiasis decreased the subsequent cancer risk relative to late intervention.Participants with a previous diagnosis of urolithiasis (n = 695) had a 1.82-fold (95% CI: 1.66-1.99, P < 0.001) increased risk of developing UTC. Furthermore, the risk of UTC associated with urolithiasis was higher in women (adjusted HR: 2.43, 95% CI: 1.94-3.05) than in men (adjusted HR: 1.72, 95% CI: 1.55-1.90). When stratified by cancer site, the adjusted HR for bladder, renal pelvis/ureter, renal, and prostate cancers were 1.94 (95% CI: 1.62-2.33), 2.94 (95% CI: 2.24-3.87), 2.94 (95% CI: 2.29-3.77), and 1.45 (95% CI: 1.27-1.65), respectively. Patients who received interventions for urolithiasis within 3 months of detection had a decreased risk of subsequent UTC (adjusted HR: 0.53, 95% CI: 0.40-0.71, P < 0.001).The present study demonstrated that urolithiasis increased the risk of subsequent UTC, especially upper UTC. Hence, it is recommended that physicians administer the appropriate interventions as early as possible upon diagnosis of urolithiasis.

Antiproliferation effect and apoptosis mechanism of prostate cancer cell PC-3 by flavonoids and saponins prepared from Gynostemma pentaphyllum.

The objectives of this study were to investigate the antiproliferation and apoptosis mechanism of saponin and flavonoid fractions from Gynostemma pentaphyllum (Thunb.) Makino on prostate cancer cell PC-3. Both flavonoid and saponin fractions were isolated by a column chromatographic method with Cosmosil 75C(18)-OPN as adsorbent and elution solvents of ethanol-water (30:70, v/v) for the former and 100% ethanol for the latter, followed by high-performance liquid chromatography-tandem mass spectrometry analysis. On the basis of the MTT assay, the saponin and flavonoid fraction were comparably effective in inhibiting the growth of PC-3 cells, with the IC(50) being 39.3 and 33.3 µg/mL, respectively. Additionally, both fractions induced an arrest of PC-3 cell cycle at both S and G2/M phases, with both early and late apoptotic cell populations showing a dose-dependent rise. The Western blot assay indicated that the incorporation of flavonoid or saponin fraction could modulate the expression of G2 and M checkpoint regulators, cyclins A and B, and the antiapoptotic proteins Bcl-2 and Bcl-xl and pro-apoptotic proteins Bad and Bax. The expression of the caspase-3 and its activated downstream substrate effectors, DFF45 and poly (ADP-ribose) polymerase-1 (PARP-1), was also increased and followed a dose-dependent manner. All of these findings suggest that the apoptosis of PC-3 cells may proceed through the intrinsic mitochondria pathway.

Activation of muscarinic M-1 cholinoceptors by curcumin to increase contractility in urinary bladder isolated from Wistar rats.

Curcumin is an active principle contained in rhizome of Curcuma longa, and it has been recently mentioned to show affinity to muscarinic M-1 cholinoceptors (M(1)-mAChR). In the present study, we found that curcumin caused a concentration-dependent increase of muscle tone in urinary bladder isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block M(1)-mAChR. In radioligand-binding assay, specific binding of [(3)H]-oxotremorine (OXO-M) in the rat bladder homogenates was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PKC pathway, either U73122 (phospholipase C inhibitor) or chelerythrine (protein kinase C inhibitor), curcumin-stimulated contraction in urinary bladder was markedly reduced. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals to increase of muscle tone in urinary bladder through PLC-PKC pathway.

Expression of Epstein-Barr nuclear antigen 1 in gastric carcinoma cells is associated with enhanced tumorigenicity and reduced cisplatin sensitivity.

Epstein-Barr nuclear antigen 1 (EBNA-1) is consistently expressed in all EBV-associated gastric carcinomas. We explored its biological effects in gastric carcinoma cells by expressing the protein in two Epstein-Barr virus (EBV)-negative gastric carcinoma cell lines (SCM1 and TMC1). EBNA1-expressing SCM1 and TMC1 cells displayed no significant differences in growth rates, respectively, compared to those of vector-transfected SCM1 and TMC1 cells in vitro. However, EBNA1 was able to enhance tumorigenicity, the growth rate and the malignant histopathological grade in a xenograft nude mice test. We also evaluated whether EBNA1 caused EBNA1-expressing cells to have enhanced tumorigenicity in an immunocompetent host. We showed that EBNA1-expressing LL/2 cells (derived from lung carcinoma of a Swiss mouse) had enhanced tumorigenicity and growth ability in the immunocompetent allograft Balb/c mice test. These results support the expression of EBNA1 in EBV-associated gastric carcinoma being able to provide advantages of EBV-mediated cell growth and transformation, and to enhance the malignant potential in vivo. In a clonogenic assay, we showed that EBNA1 could reduce the sensitivity of gastric carcinoma cells (SCM1 cells) harboring wild-type p53 to cisplatin, but this was not found in mutant p53-bearing TMC1 cells. In addition, we demonstrated that EBNA1-expressing SCM1 cells, but not EBNA1-expressing TMC1 cells, were associated with reduced expression levels of p53. These findings are compatible with EBNA1 efficiently competing with p53 for binding to ubiquitin-specific protease 7, which causes p53 to degrade by the ubiquitin/proteasome system. These findings suggest that EBNA1 expression is able to reduce the p53 protein level, resulting in the inhibition of its functional activities. Finally, our results suggest that EBV infection with EBNA1 expression in gastric carcinomas provides advantages for host cell survival, growth ability and transformation potential involving escape from immunosurveillance and a reduction in the sensitivity to DNA damage or other apoptotic stress stimuli mediated by suppression of the wild-type p53 protein level; these are distinct from the pathogenesis of EBV-negative gastric carcinomas.

Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats.

Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway.

Dual degradation of aurora A and B kinases by the histone deacetylase inhibitor LBH589 induces G2-M arrest and apoptosis of renal cancer cells.

PURPOSE: This study is aimed at investigating antineoplastic efficacy of histone deacetylase inhibitor (HDACI) LBH589 on renal cell carcinoma (RCC) and elucidating the novel molecular mechanisms involved in growth arrest and apoptosis by targeting the important nonhistone molecules. EXPERIMENTAL DESIGN: We analyzed the growth-inhibitory effect of LBH589 on RCC by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in vitro and antitumor efficacy by xenograft experiments in vivo. To verify the associated molecular mechanisms involved in LBH589-mediated cell death and cell cycle progression by Western blotting and fluorescence-activated cell sorting analysis. RESULTS: HDACI LBH589 induced degradation of both Aurora A and B kinases through a proteasome-mediated pathway by targeting HDAC3 and HDAC6. The dual degradation of Aurora A and B kinases mediated by LBH589 resulted in inducing G2-M arrest and apoptosis of renal cancer cell lines and our results also showed that LBH589 potently inhibited renal cancer cell growth in vitro and suppressed tumor formation in vivo. The Aurora A and B kinases and HDAC3 are overexpressed in the human RCC tumor tissues examined, which make them perfect targets for HDACI LBH589 treatment. CONCLUSIONS: Our in vitro and in vivo data showed that LBH589 has potent anticancer effect of renal cancer cells. LBH589 and other HDACI treatment resulted in inducing G2-M arrest and apoptosis of renal cancer cells through degradation of Aurora A and B kinases by inhibition of HDAC3 and HDAC6. The clinical efficacy of LBH589 in the treatment of patients with metastatic RCC, especially those with high Aurora kinase and HDAC expression, is worthy of further investigation.

Ureteral injury due to blunt abdominal trauma.

Ureteral injury is usually due to abdominal penetrating trauma or surgical insult. It has seldom been reported in patients with blunt abdominal trauma. A 20-year-old man presented with left flank and inguinal area pain after blunt abdominal trauma sustained in a motor scooter accident. Acute hydronephrosis and hematuria were noted. Retrograde pyelography and ureteroscopic examination revealed left distal ureter edema with obstruction. The hydronephrosis resolved after temporary double-J-stenting.