Reserpine treatment activates AMP activated protein kinase (AMPK)

Reserpine is a well-known medicine for the treatment of hypertension, however the role of reserpine in cell signaling is not fully understood. Here, we report that reserpine treatment induces the phosphorylation of AMP activated protein kinase (AMPK) at threonine 172 (T172) in PC12 cells. Phosphorylation of AMPK T172 is regulated by upstream signaling molecules, and the increase of phospho-T172 indicates that AMPK is activated. When we examined the FOXO3a dependent transcription by using the FHRE-Luc reporter assay, reserpine treatment repressed the FHRE-Luc reporter activity in a dose dependent manner. Finally, we showed that reserpine treatment induced the phosphorylation of AMPK as well as cell death in MCF-7 cells. These results suggest that AMPK is a potential cellular target of reserpine.

Validation of the 2009 TNM Classification for Renal Cell Carcinoma: Comparison with the 2002 TNM Classification by Concordance Index

PURPOSE: To assess the validity of the 2009 TNM classification for renal cell carcinoma (RCC) and compare its ability to predict survival relative to the 2002 classification. MATERIALS AND METHODS: We identified 1,691 patients who underwent radical nephrectomy or partial nephrectomy for unilateral, sporadic RCC between 1989 and 2007. Cancer-specific survival was estimated by the Kaplan-Meier method and was compared among groups by the log-rank test. Associations of the 2002 and 2009 TNM classifications with death from RCC were evaluated by Cox proportional hazards regression models. The predictive abilities of the two classifications were compared by using Harrell's concordance (c) index. RESULTS: There were 234 deaths from RCC a mean of 38 months after nephrectomy. According to the 2002 primary tumor classification, 5-year cancer-specific survival was 97.6% in T1a, 92.0% in T1b, 83.3% in T2, 61.9% in T3a, 51.1% in T3b, 40.0% in T3c, and 33.6% in T4 (p for trend<0.001). According to the 2009 classification, 5-year cancer-specific survival was 83.2% in T2a, 83.8% in T2b, 62.6% in T3a, 41.1% in T3b, 50.0% in T3c, and 26.1% in T4 (p for trend<0.001). The c index for the 2002 primary tumor classification was 0.810 in the univariate analysis and increased to 0.906 in the multivariate analysis. The c index for the 2009 primary tumor classification was 0.808 in the univariate analysis and increased to 0.904 in the multivariate analysis. CONCLUSIONS: Our data suggest that the predictive ability the 2009 TNM classification is not superior to that of the 2002 classification.

Erratum: Validation of the 2009 TNM Classification for Renal Cell Carcinoma: Comparison with the 2002 TNM Classification by Concordance Index

No abstract available.

Predictive Characteristics of Malignant Pheochromocytoma

PURPOSE: The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery. RESULTS: Malignant tumors were significantly larger than benign tumors (11.1+/-4.0 cm vs. 6.2+/-3.4 cm, p5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (>2.1 vs. 5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (< or =2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.

AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration

Ovarian cancer is a leading cause of death in women. Early detection of ovarian cancer is essential to decrease mortality. However, the early diagnosis of ovarian cancer is difficult due to a lack of clinical symptoms and suitable molecular diagnostic markers. Thus, identification of meaningful tumor biomarkers with potential clinical application is clearly needed. To search for a biomarker for the early detection of ovarian cancer, we identified human anterior gradient 2 (AGR2) from our systematic analysis of paired normal and ovarian tumor tissue cDNA microarray. We noted a marked overexpression of AGR2 mRNA and protein in early stage mucinous ovarian tumors compared to normal ovarian tissues and serous type ovarian tumors by Western blot analysis and immunohistochemistry. To further elucidate the role of AGR2 in ovarian tumorigenesis, stable 2774 human ovarian cancer cell lines overexpressing AGR2 were established. Forced expression of AGR2 in 2774 cells enhanced the growth and migration of ovarian cancer cells. AGR2 protein was detected in the serum of mucinous ovarian cancer patients by Western blot and ELISA analysis. Thus, AGR2 is a potential biomarker for the diagnosis of mucinous ovarian cancer and an ELISA assay may facilitate the early detection of mucinous ovarian cancer using patient serum.

Long-Term Study of the Effects of the Tension-Free Vaginal Tape Procedure for Female Stress Urinary Incontinence on Voiding, Storage, and Patient Satisfaction: A Post-Hoc Analysis

PURPOSE: We assessed the long-term effects of the tension-free vaginal tape (TVT) procedure for stress urinary incontinence (SUI) on voiding, storage, and patient satisfaction. MATERIALS AND METHODS: This retrospective study examined the records of 134 patients who had undergone the TVT procedure for SUI and were followed up for more than 5 years. Voiding function was evaluated by measuring maximum urinary flow rate (MFR), post-void residual urine volume (PVR), and storage function by using a voiding diary. Patients were asked to describe their satisfaction with the operation. RESULTS: MFR was lower at 1 month compared with the preoperative level, but had recovered to preoperative levels by 5 years postoperatively. However, some patients with >50%, 25-50%, and 50% at 5 years. PVR increased over the 5 postoperative years. Of the patients with urgency and urgency incontinence, 43.8% and 48.1% showed improvement, respectively, whereas new patients developed postoperatively. Thus, the total number of patients with urgency or urgency incontinence remained similar over the 5 years. In those with a changed voiding pattern, patient satisfaction was negatively affected by de novo urgency and urgency incontinence and decreased MFR. CONCLUSIONS: Any obstructive effect of the TVT procedure diminished over time in most patients, although a decrease in the MFR was sustained in some patients. With regard to overactive bladder symptoms, some patients were cured and some patients complained of de novo symptoms. The most major factor affecting patient satisfaction was de novo urgency.

Preoperative Clinical and Pathological Characteristics of pT0 Prostate Cancer in Radical Prostatectomy

PURPOSE: To analyze the preoperative clinical and pathological characteristics of patients with pT0 prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of 702 patients who underwent radical prostatectomy (RP) at our institution between January 2004 and July 2008 for clinically localized prostate cancer. If there was no evidence of residual tumor in the pathological specimen of the prostate, a patient was staged as pT0. Patients with pT0 disease were compared with a control group of patients who were operated on during the same period. RESULTS: Overall, 9 (1.3%) patients were staged as pT0 on the pathologic examination. Significant differences were observed between the pT0 group and the control patients in the biopsy Gleason score (p=0.004), the number of positive cores on biopsy (p=0.018), the tumor length of positive cores (p30 cm3. Whereas 8 of the 9 (88.9%) pT0 patients showed all of these characteristics, only 55 of the 693 (7.9%) control patients fulfilled the criteria. The combination suggested above afforded a sensitivity of 88.8% and a specificity of 92.1% for the prediction of pT0 status. CONCLUSIONS: The frequency of pT0 prostate cancer seen on RP was 1.3%. A combination of clinicopathological features, incorporating a biopsy Gleason score, the number of positive biopsy cores, tumor length on biopsy, and prostate volume, was useful to predict pT0 stage on RP.

Risk Factors for Upper Urinary Tract Deterioration in Children with Neurogenic Bladder

PURPOSE: We evaluated the risk factors for upper urinary tract deterioration in children with neurogenic bladder. MATERIALS AND METHODS: The study population consisted of 60 children (36 boys, 24 girls) with neurogenic bladder confirmed by urodynamic study between January 1994 and June 2007. The average follow-up period was 48 months. The patients' medical records were assessed concerning gender, presence of vesicoureteral reflux (VUR), hydronephrosis, type of spinal dysraphism, level of spinal dysraphism, practice of clean intermittent catheterization (CIC), type of neurogenic bladder, bladder capacity, compliance, detrusor sphincter dyssynergia, recurrent urinary tract infection (UTI), and timing of primary neurosurgical repair. Upper urinary tract deterioration was diagnosed by 99m technetium-dimercaptosuccinic acid renal scan (DMSA) and aggravation of hydronephrosis and VUR. RESULTS: Upper urinary tract deterioration was detected in 15 patients (25%). Hydronephrosis, VUR, and UTI were associated with upper urinary tract deterioration in the univariate analyses. In the multivariate analyses, hydronephrosis [odds ratio (OR)=2.181, 95% confidence interval (CI)=1.191-11.941, p=0.036] and recurrent UTI [OR=5.810, 95% CI=1.200-28.192, p=0.029] were independent risk factors for upper urinary tract deterioration. CONCLUSIONS: Hydronephrosis and recurrent UTI increase the risk of upper urinary tract deterioration in children and adolescents with neurogenic bladder. Therefore, intensive observation and prompt intervention may be recommended for such cases.