Renal Transplant Recipients: The Factors Related to Immunosuppressive Medication Adherence Based on the Health Belief Model.

BACKGROUND: Kidney transplant failures are caused primarily by lack of adherence to immunosuppressive medication regimens by patients after transplantation. A number of studies have indicated that health-related beliefs are an effective predictor of health-related behavior. PURPOSE: The aim of this study is to understand the influence of the personal characteristics and health-related beliefs of patients on adherence to treatment with immunosuppressive medication based on the Health Belief Model. METHODS: This cross-sectional study distributed questionnaires to patients who had been recruited via purposive sampling at one medical center in Taipei. All of the potential participants had undergone kidney transplantation at least 6 months previously. The self-developed questionnaire collected data in three areas: personal characteristics, health-related beliefs regarding transplant rejection, and adherence to the immunosuppressive medication regimen. One hundred twenty-two valid questionnaires were received. The collected data were analyzed using descriptive statistics, independent t test, one-way analysis of variance, Pearson's correlation, and multiple regression. RESULTS: Participants who had received dialysis treatment or had experienced rejection perceived susceptibility to rejection more strongly than those who had not. Participants who had undergone transplantation in Taiwan, had experienced more drug-related symptoms, or had contracted severe to extremely severe infections in the past showed lower rates of adherence to treatment with immunosuppressive medication. Adherence to medication regimens correlated negatively with length of time since transplantation. Length of time since transplantation, drug-related symptoms, perceived susceptibility to rejection, and perceived benefits of treatment were identified as major predictors of adherence to immunosuppressive medication regimens. CONCLUSIONS: The results partially conformed to the concepts of the Health Belief Model. Perceived susceptibility to rejection and perceived benefits of adherence to treatment were found to predict adherence rates. Patient education should be enhanced to reduce the risks of rejection and increase adherence rates to improve outcomes.

Impact of androgen-deprivation therapy on the outcome of dose-escalation prostate cancer radiotherapy without elective pelvic irradiation.

The benefit of androgen-deprivation therapy (ADT) in combination with dose-escalated radiotherapy (DERT) for localized prostate cancer has not been determined in randomized studies. In this study, the benefit of ADT was assessed in patients uniformly treated with dose-escalated intensity-modulated radiation therapy (IMRT) to the prostate and seminal vesicles but not pelvis. In all, 419 patients with localized prostate adenocarcinoma underwent definitive IMRT (cumulative dose 78 Gy), with 32.6%, 33.1%, 32.1%, and 2.1% having T1 through T4 disease, respectively, and 51.2% having high-risk disease. ADT was given to 76.1% of patients. With a median follow-up of 60 months, 5-year biochemical failure-free, disease-free, and overall survival rates were 87%, 86%, and 87%, respectively. T stage was an independent predictor of all three rates. Five-year pelvic nodal recurrence rate was 2.9%. ADT improved biochemical failure-free and disease-free survival but not overall survival. ADT showed benefit in high-risk disease but not intermediate-risk disease. Late gastrointestinal and genitourinary toxicities ≥ grade 2 occurred in 11.0% and 6.7%, respectively. In conclusion, DERT with 78 Gy yields good disease control and low rate of pelvic nodal recurrence. ADT improves disease-free survival in patients with high-risk but not intermediate-risk disease.

Dual-timing PSA as a biomarker for patients with salvage intensity modulated radiation therapy for biochemical failure after radical prostatectomy.

We investigated the outcomes and the associated clinical-pathological factors in patients with prostate cancer (PCa) undergoing salvage intensity modulated radiation therapy (IMRT) for post-radical-prostatectomy (RP) biochemical failure. We report clinical outcomes of post-RP salvage IMRT, and describe chronic toxicity in these patients.Fifty patients with PCa underwent post-RP salvage IMRT. The median dose of IMRT was 70 Gy to the prostatic and seminal vesicle bed. Clinical-pathological and toxicity information were collected. The prostate cancer-specific survival (PCSS), disease-free survival (DFS), and biochemical-failure-free survival (BFFS) were calculated. Prognostic factors were analyzed for their association with disease control.The median follow-up time was 74 months. The 5-year PCSS, DFS, and BFFS after salvage IMRT were 95%, 88%, and 60%, respectively. Two patients (4%) experienced late gastrointestinal toxicity ≥ grade 3, and 5 patients (10%) had late genitourinary toxicity ≥ grade 3. On multivariate analysis, post-RP prostate-specific antigen (PSA) nadir ≤0.1 ng/ml (P=0.018) and PSA ≤0.5 ng/ml at salvage IMRT (P=0.016) were independent factors predicting better BFFS. Patients with both post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT had a 5-year BFFS of 83% as compared with 43% in other patients (P=0.001).In conclusion, with hormonal therapy in most PCa patients, the addition of salvage IMRT for post-RP biochemical failure can achieve a good outcome with low toxicity. Patients with a post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT could benefit the most from salvage IMRT.

The outcome and prognostic factors for lymph node recurrence after node-sparing definitive external beam radiotherapy for localized prostate cancer.

BACKGROUND: The prognostic factors for the recurrence of lymph node (LN) metastasis after dose-escalated radiotherapy (RT) in prostate cancer patients have not been well investigated. We report the prognostic factors and outcomes in patients receiving salvage treatment for LN recurrence after high-dose intensity-modulated RT (IMRT). METHODS: We studied a cohort of 419 patients with localized prostate adenocarcinoma undergoing definitive IMRT (78 Gy). LN recurrence was diagnosed by size criteria using computed tomography (CT) or magnetic resonance imaging, or abnormal uptake of (18)F-fluorocholine by LNs on positron emission tomography/CT. Overall survival and LN recurrence-free survival (LNRFS) were calculated, and prognostic factors were evaluated. RESULTS: With a median follow-up of 60 months, 18 patients (4.3 %) had LN recurrence and a significantly lower 5-year overall survival rate (60 vs. 90 %, p = 0.003). Univariate analysis showed that T3/T4 stage (p = 0.003), Gleason score >7 (p < 0.001), and estimated risk of pelvic LN involvement of >30 % by the Roach formula (p = 0.029) were associated with significantly lower LNRFS. On multivariate analysis, high Gleason score (hazard ratio = 5.99, p = 0.007) was the only independent factor. The 1/2-year overall survivals after LN recurrence were 67/54 %. Patients with isolated LN recurrence (p = 0.003), prostate-specific antigen (PSA) doubling time >5 months (p = 0.009), interval between PSA nadir and biochemical failure >12 months (p = 0.035), and PSA <10 ng/ml at LN recurrence (p = 0.003) had significantly better survival. Patients with isolated LN recurrence had significantly better survival when treated with combined RT and hormones than when treated with hormones alone (p = 0.011). CONCLUSIONS: Gleason score of >7 may predict LN recurrence in prostate cancer patients treated with definitive IMRT. Small number of patients limits the extrapolation of this risk with the primary treatment strategy. Combined RT and hormones may prolong survival in patients with isolated LN recurrence.

The impact of pain control on physical and psychiatric functions of cancer patients: a nation-wide survey in Taiwan.

OBJECTIVE: To investigate the prevalence of pain in cancer patients at different disease statuses, the impact of pain on physical and psychiatric functions of patients and the satisfaction of pain control of patients at outpatient clinic department in Taiwan. METHODS: Short form of the Brief Pain Inventory was used as the outcome questionnaire. Unselected patients of different cancers and different disease statuses at outpatient clinic department were included. The impacts of their current pain control on physical function, psychiatric function and the satisfaction of doctors were evaluated. Logistic regression analyses were performed to evaluate whether the interference scale performed identically in the different analgesic ladders. The dependent variables were satisfaction toward physician and treatment. RESULTS: A total of 14 sites enrolled 2075 patients in the study. One thousand and fifty-one patients reported pain within the last 1 week. In patients whose diseases deteriorated, >60% of them need analgesics for pain control. Pain influenced physical and psychiatric functions of patients, especially in the deteriorated status. More than 80% of patients were satisfied about current pain control, satisfaction rate related to disease status, pain intensities and treatments for pain. CONCLUSION: Our study found that different cancers at different statuses had pain at variable severity. Pain can influence physical and psychological functions significantly. More than 75% of subjects reported satisfaction over physician and pain management in outpatient clinic department patients with cancer pain in Taiwan.

Does varicocele grade predict the postoperative changes of semen parameters following left inguinal micro-varicocelectomy?

OBJECTIVE: To evaluate the relationship between preoperative grade and postoperative changes of semen parameters following left inguinal varicocelectomy. METHODS: This study included 44 patients undergoing left microsurgical inguinal varicocelectomy. Internal spermatic veins were classified as large (4 mm or more in diameter), medium (2-4 mm), or small (2 mm or less). Changes in sperm activity, morphology and count were estimated perioperatively. The introperative findings and semen parameters were compared between varicocele groups of grades 2 and 3. RESULTS: Both sperm motility and count improved significantly postoperatively (from (31.9 ± 16.3)% to (47.3  ± 15.5)%, from (28.1 ± 28.1) × 106/mL to (52.1 ± 74.2) × 106/mL). In varicoceles with grade 2 and 3, significant differences were found in the number of large veins (0.4 ± 0.6 vs. 1.2 ± 0.7, p < 0.001) and ultrasonographic maximum diameters of spermatic vein in supine and standing positions (2.3 ± 0.4 cm vs. 2.8 ± 0.6 cm, 3.1 ± 0.7 cm vs. 3.9 ± 0.7 cm, p = 0.001 and 0.001 respectively). However no difference of changes in sperm motility and count was detected ((16.3  ±  13.5)% vs. (14.4  ±  12.6)%, (30.5 ± 84.4) × 106/mL vs. (12.9 ± 20.6) × 106/mL respectively, p = 0.65 and 0.40 respectively). CONCLUSION: Preoperative varicocele grade might not predict postoperative semen changes regardless of possible existence of anatomic and ultrasonographic associations.

Increased upper and lower tract urothelial carcinoma in patients with end-stage renal disease: a nationwide cohort study in Taiwan during 1997-2008.

BACKGROUND: Urothelial cancer (UC) is the leading cancer of patients with end-stage renal disease (ESRD) in Taiwan. The aims of this study were to explore the time trends of UC incidences and propose possible etiologic factors. METHODS: Abstracting from the National Health Insurance Research Database (NHIRD), there were 90,477 newly diagnosed cases of ESRD between 1997 and 2008 covering the patients aged 40-85. Among them, 2,708 had developed UC after diagnosis of ESRD. The CIR40-85 (cumulative incidence rate) of upper tract UC (UTUC) and lower tract UC (LTUC) were calculated for ESRD patients and general population, as well as SIR40-85 (standardized incidence ratio) for comparison. RESULTS: Female ESRD patients were found to have 9-18 times of elevated risks of UC, while those of males were increased up to 4-14 times. The time trends of CIR40-84 and SIR40-84 of UTUC in females appear to decline after calendar year 2000. These trends may be related to AA associated herbal products after 1998. CONCLUSIONS: Patients with ESRD are at increased risks for both LTUC and UTUC in Taiwan. We hypothesize that the time trends associate with the consumption of aristolochic acid in Chinese herbal products (female predominant).

Laparoscopic radical prostatectomy monotherapy, a more aggressive yet less invasive option, is oncologically effective in selected men with high-risk prostate cancer having only one D'Amico risk factor: experience from an Asian tertiary referral center.

PURPOSE: To present oncologic results of laparoscopic radical prostatectomy (LRP) monotherapy for men with high-risk, localized prostate cancer, and to find factors associated with a good prognosis via surgery alone. PATIENTS AND METHODS: Between 2002 and 2009, 241 men underwent LRP at an Asian tertiary referral center. Among them, we retrospectively identified 85 (35.3%) men who met the D'Amico's high-risk criteria: Prostate-specific antigen level >20 ng/mL, Gleason score of 8 to 10, or clinical stage ≥T2c. Perioperative parameters were analyzed against biochemical recurrence (BCR)-free survival. RESULTS: At a median follow-up of 54 months, BCR developed in 28 (34.1%), with an actuarial BCR-free survival rate of 63.3% at 5 years. Pathologically, 37.6% of the men had organ-confined (OC) disease. Positive surgical margins (PSM) were identified in 49.4% of the patients. A favorable pathologic outcome, defined as OC(+)PSM(-), was observed in 24 patients and associated with a 5-year BCR-free survival rate of 87.0%, compared with 100%, 54.0%, and 46.4% in men with OC(+)PSM(+), OC(-)PSM(-) and OC(-)PSM(+) disease (log-rank, P=0.008). The overall positive lymph node rate was 14.1%. Men (65.9%) with only one D'Amico risk factor had a 5-year BCR-free survival rate of 76.9%, compared with 34.6% in men (34.1%) with ≥2 risk factors (log-rank, P<0.001). CONCLUSIONS: Radical prostatectomy monotherapy performed laparoscopically or robotically appears to be an option for high-risk prostate cancer, especially in men with a single D'Amico risk factor. Men with ≥2 risk factors are more prone for BCR to develop after surgery and may need second-line therapy.

ΑB-crystallin in clear cell renal cell carcinoma: tumor progression and prognostic significance.

OBJECTIVES: AlphaB-crystallin (αB-crystallin), a small heat shock protein, has been reported to be involved in the growth, antiapoptosis, migration, and chemoresistance of human malignancies. MATERIALS AND METHODS: αB-crystallin expression in normal renal and clear cell renal cell carcinoma (ccRCC) tissues was examined with two-dimensional (2D) gel electrophoresis assays. Immunohistochemistry was conducted to determine the presence of αB-crystallin-positive tumor cells and staining intensity in 50 cases of ccRCC tissue samples. The association of αB-crystallin protein expression, clinicopathogic parameters and prognosis of ccRCC patients was also analyzed with Student's t-test and Kaplan-Meier analysis. Moreover, Western blot assays were performed to detect the protein expression of αB-crystallin in normal and tumor tissues and the alteration of cell cycle regulators in αB-crystallin-overexpressing cells. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide), BrdU, and transwell assays were performed to demonstrate the effects of αB-crystallin overexpression on cell growth, DNA synthesis and cell migration of ccRCC cells, respectively. RESULTS: The results showed the up-regulation of αB-crystallin expression in ccRCC tissues. Overall survival of ccRCC patients was significantly correlated with αB-crystallin expression in tumor tissues. We found that αB-crystallin overexpression increased the expression of cyclin A and the incorporation of BrdU, which may be related to the enhancement of cell growth. Transwell analyses demonstrated that presence of αB-crystallin overexpression enhanced cell migration in ccRCC cells. Furthermore, rapamycin-resistance of tumor cells was induced when αB-crystallin was overexpressed. CONCLUSIONS: Our experimental findings highlight the importance of αB-crystallin in the tumor growth, migration, and target therapy-resistance of ccRCC cells.

Microanatomy of the spermatic cords during microsurgical inguinal varicocelectomy: initial experience in Asian men.

The microanatomy of the inguinal spermatic cords has never been reported in Asia. The purpose of this study was to describe the number and relationship of the veins, arteries and lymphatics in the spermatic cord and to clarify the location of the vas deferens in Asian men. Fifty-one patients receiving 79 primary microsurgical varicocelectomies performed by a single surgeon from April 2011 to July 2012 were studied. The number of internal and external spermatic veins, testicular arteries and lymphatic channels preserved during the inguinal microsurgical varicocelectomy were recorded. The relationship between the right and left vascular anatomy during bilateral varicocelectomies was evaluated. The data showed that mean numbers of 1.5±0.9 arteries, 5.6±2.2 spermatic veins and 3.6±1.9 lymphatics were identified during the repairs. The internal spermatic arteries were surrounded by a dense complex of adherent veins in 81.2% of the cases. The external spermatic vein or veins were found in 60.8% of the cases. The vas deferens may be contained within the internal spermatic fascia. The results suggest that the number of veins may be highly variable and less than those reported in the English literature, but there is some similarity in the inguinal microanatomy of the right and left spermatic cords. Further research is warranted to clarify our results.

Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications.

BACKGROUND: Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCζ is an important regulator of tumorigenesis. However, the correlation between PKCζ expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC. METHODS: PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT. RESULTS: PKCζ expression was significantly higher in normal than in cancerous tissues (P<0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P=0.04), but no such association was found in TNM stage (P=0.13). Tumors with higher PKCζ expression were associated with tumor size (P=0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCζ siRNA and inhibitor. CONCLUSIONS: PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.

Long-term oncologic outcomes of hand-assisted retroperitoneoscopic radical nephrectomy to treat clinically localized renal cell carcinoma.

BACKGROUND/PURPOSE: To evaluate the long-term oncological outcomes of hand-assisted retroperitoneoscopic radical nephrectomy (HARRN) for treating clinically localized renal cell carcinoma. METHODS: We retrospectively collected and analyzed the data and clinical outcomes of 46 patients who underwent HARRN and 50 patients who underwent conventional open radical nephrectomy (ORN) at our institution for clinical localized renal cell carcinoma (RCC). RESULTS: The median follow-up period of the HARRN group was 56.5 months (range: 14.6-78.7 months); for the ORN group, the median follow-up period was 110.8 months (range: 15.5-123 months). Patient age, sex, body mass index, pathologic parameters, and classification based on the guidelines of the American Society of Anesthesiologists were not significantly different between the two groups. The HARRN group had a significantly longer operative time (218 minutes vs. 178 minutes, p = 0.003) and less blood loss (203 mL vs. 670 mL, p < 0.001). The complication rates of the ORN and HARRN groups were similar (8% and 4.3%, respectively, p = 0.46). No conversions to an open procedure or intraoperative mortality occurred in the HARRN group. The disease-free and disease-specific survival rates were comparable between the two groups. CONCLUSION: The results of our study indicate that HARRN is a feasible, minimally invasive treatment for managing clinically organ-confined RCC with a good long-term oncological outcome.

Oncologic outcomes of asian men with clinically localized prostate cancer after extraperitoneal laparoscopic radical prostatectomy: a single-institution experience.

Purpose. To evaluate the midterm oncologic results of extraperitoneal laparoscopic radical prostatectomy (EPLRP) for Asian men with localized prostate cancer. Methods. Between 2004 and 2009, 218 men underwent EPLRP at an Asian tertiary hospital. The mean preoperative prostate-specific antigen (PSA) was 15.5 ng/ml and mean Gleason score was 6.6. Stage distributions were cT1a-b in 21 cases, cT1c in 139, cT2 in 48 and cT3 in 10. Disease recurrence was defined as PSA ≥ 0.2 ng/mL in 2 consecutive measurements or initiation of secondary therapy. Results. Postoperative pathological stage was pT2a-b in 33 patients, pT2cN0 in 10, pT3a in 27, pT3b in 36, pT4 in 9 and pN1 in 10. Positive surgical margins occurred in 14.6% and 48.6% for pT2 and pT3 diseases, respectively (P < .001). The overall PSA recurrence-free survival at 3 and 5 years was 82.1% and 74.5%. By the pathological stages, 3-year recurrence-free survival was 92.4% (pT2), 81.1% (pT3a), 62.6% (pT3b-4) and 55.6% (pN1), respectively (P < .001). Conclusions. EPLRP is curative even for some locally advanced prostate cancers in a midterm follow-up. Even at an Asian center of low volume of radical prostatectomy EPLRP still provides oncologic outcomes similar to that of high volume centers.

Bladder migration of Hem-o-Lok clips after laparoscopic radical nephroureterectomy and bladder cuff excision.

The Hem-o-Lok clips are widely used in various laparoscopic operations because of its easy application and secure clamping. The Hem-o-Lok clips were adopted to ligate bladder cuff during bladder cuff excision because of its advantages. We report 2 cases of bladder migration of Hem-o-Lok clips after laparoscopic nephroureterectomy and bladder cuff excision. The clips were found during routine follow-up cystoscopy and were removed by cystoscopic procedure. We described the case presentation, treatment, and the alternative method to avoid such shortcomings.

Nicotinamide N-methyltransferase induces cellular invasion through activating matrix metalloproteinase-2 expression in clear cell renal cell carcinoma cells.

Nicotinamide N-methyltransferase (NNMT) was recently identified as one clear cell renal cell carcinoma (ccRCC)-associated gene by analyzing full-length complementary DNA-enriched libraries of ccRCC tissues. The aim of this study is to investigate the potential role of NNMT in cellular invasion. A strong NNMT expression is accompanied with a high invasive activity in ccRCC cell lines, and small interfering RNA-mediated NNMT knockdown effectively suppressed the invasive capacity of ccRCC cells, whereas NNMT overexpression markedly enhanced that of human embryonic kidney 293 (HEK293) cells. A positive correlation between the expression of NNMT and matrix metallopeptidase (MMP)-2 was found in ccRCC cell lines and clinical tissues. The treatment of blocking antibody or inhibitor specific to MMP-2 significantly suppressed NNMT-dependent cellular invasion in HEK293 cells. Furthermore, SP-1-binding region of MMP-2 promoter was found to be essential in NNMT-induced MMP-2 expression. The specific inhibitors of PI3K/Akt signaling markedly decreased the binding of SP1 to MMP-2 promoter as shown by chromatin immunoprecipitation assay. We also demonstrated that PI3K/Akt pathway plays a role in NNMT-dependent cellular invasion and MMP-2 activation. Moreover, short hairpin RNA-mediated knockdown of NNMT expression efficiently inhibited the growth and metastasis of ccRCC cells in non-obese diabetic severe combined immunodeficiency mice. Taken together, the present study suggests that NNMT has a crucial role in cellular invasion via activating PI3K/Akt/SP1/MMP-2 pathway in ccRCC.

Novel inanimate training model for urethrovesical anastomosis in laparoscopic radical prostatectomy.

OBJECTIVE: We developed a novel ex vivo training model for advanced laparoscopic suturing techniques necessary in laparoscopic radical prostatectomy (LRP). METHODS: An inanimate model was developed to approximate real-life conditions in laparoscopic urethrovesical anastomosis. A segment of porcine ovarian tube inserted through a hard piece of cardboard (urethral stump) in a small open box and a part of pig stomach with a 2-cm hole (bladder neck) were placed in a specially designed setup in a traditional pelvic trainer, while the trocars were arranged in the usual five-port style during an LRP. The trainees practised suturing the "bladder neck" to the "urethral stump" with intermittent or continuous sutures according to their preferences. RESULTS: The setup successfully mimicked the spatial relationships of the organs to be anastomosed during live surgery. The directions of the trocars and the angles of the instrumentations in the training model also imitated those during LRP. After practising on our models, the surgeons spent significantly less time (65 ± 24 min vs. 36 ± 12 min, p = 0.035) performing actual urethrovesical anastomosis. CONCLUSION: This inanimate laparoscopic suturing training model for urethrovesical anastomosis is a novel, effective, convenient and economic training tool, especially for beginners of LRP.

Cadmium burden and the risk and phenotype of prostate cancer.

BACKGROUND: Studies on the association between prostate cancer and cadmium exposure have yielded conflicting results. This study explored cadmium burden on the risk and phenotype of prostate cancer in men with no evident environmental exposure. METHODS: Hospital-based 261 prostate cancer cases and 267 controls with benign diseases were recruited from four hospitals in Taiwan. Demographic, dietary and lifestyle data were collected by standardized questionnaires. Blood cadmium (BCd) and creatinine-adjusted urine cadmium (CAUCd) levels were measured for each participant. Statistical analyses measured the prostate cancer risk associated with BCd and CAUCd separately, controlling for age, smoking and institution. BCd and CAUCd levels within cases were compared in relation to the disease stage and the Gleason score. RESULTS: High family income, low beef intake, low dairy product consumption and positive family history were independently associated with the prostate carcinogenesis. There was no difference in BCd levels between cases and controls (median, 0.88 versus 0.87 microg/l, p = 0.45). Cases had lower CAUCd levels than controls (median, 0.94 versus 1.40 microg/g creatinine, p = 0.001). However, cases with higher BCd and CAUCd levels tended to be at more advanced stages and to have higher Gleason scores. The prostate cancer cases with Gleason scores of > or = 8 had an odds ratio of 2.89 (95% confidence interval 1.25-6.70), compared with patients with scores of 2-6. CONCLUSION: Higher CAUCd and BCd levels may be associated with advanced cancer phenotypes, but there was only a tenuous association between cadmium and prostate cancer.

Repetitive hypoxic preconditioning attenuates renal ischemia/reperfusion induced oxidative injury via upregulating HIF-1 alpha-dependent bcl-2 signaling.

BACKGROUND: In response to ischemic/hypoxic preconditioning, tissues/organs exhibit protective responses to subsequent and severe ischemic stress. We hypothesized that repetitive hypoxic preconditioning (RHP) may provide long-lasting protection than single preconditioning against ischemia/reperfusion injury in rat kidneys through hypoxia-induced factor (HIF)-1-dependent pathway. METHODS: For RHP induction, female Wistar rats were subjected to intermittent hypoxic exposure (380 Torr) 15 hr/day for 28 days. RESULTS: RHP increased renal HIF-1 alpha mRNA and protein expression and triggered HIF-1 alpha-dependent renal Bcl-2 protein expression in a time-dependent manner. When returning to normoxia, increased RHP exposure prolonged renal Bcl-2 expression. Forty-five minutes of renal ischemia with 4 hr of reperfusion enhanced O2- levels and proapoptotic mechanisms, including enhanced cytosolic Bax translocation to mitochondria, release of cytochrome c to cytosol, activation of caspase 3, poly-(ADP-ribose)-polymerase fragments, tubular apoptosis, blood urea nitrogen, and creatinine level. RHP treatment depressed renal O2- production, mitochondrial Bax translocation and cytochrome c release, and tubular apoptosis. In the primary tubular cultures from RHP-treated kidneys, antisense oligodeoxyribonucleotides of bcl-2 abrogated this protection. CONCLUSIONS: RHP activates an HIF-1 alpha-dependent signaling cascade leading to an increase in Bcl-2 protein expression, an inhibition in cytosolic Bax and mitochondrial cytochrome c translocation, and a hypoxic/ischemia tolerance against renal ischemia/reperfusion injury.