Ovatodiolide Targets<b><i>β</i></b>-Catenin Signaling in Suppressing Tumorigenesis and Overcoming Drug Resistance in Renal Cell Carcinoma

Dysregulatedβ-catenin signaling is intricately involved in renal cell carcinoma (RCC) carcinogenesis and progression. Determining potentialβ-catenin signaling inhibitors would be helpful in ameliorating drug resistance in advanced or metastatic RCC. Screening forβ-catenin signaling inhibitors involvedin silicoinquiry of the PubChem Bioactivity database followed by TCF/LEF reporter assay. The biological effects of ovatodiolide were evaluated in 4 RCC cell linesin vitroand 2 RCC cell lines in a mouse xenograft model. The synergistic effects of ovatodiolide and sorafenib or sunitinib were examined in 2 TKI-resistant RCC cell lines. Ovatodiolide, a pure compound ofAnisomeles indica, inhibitedβ-catenin signaling and reduced RCC cell viability, survival, migration/invasion, andin vitrocell orin vivomouse tumorigenicity. Cytotoxicity was significantly reduced in a normal kidney epithelial cell line with the treatment. Ovatodiolide reduced phosphorylatedβ-catenin (S552) that inhibitedβ-catenin nuclear translocation. Moreover, ovatodiolide decreasedβ-catenin stability and impaired the association ofβ-catenin and transcription factor 4. Ovatodiolide combined with sorafenib or sunitinib overcame drug resistance in TKI-resistant RCC cells. Ovatodiolide may be a potentβ-catenin signaling inhibitor, with synergistic effects with sorafenib or sunitinib, and therefore, a useful candidate for improving RCC therapy.</jats:p

Combining prostrate-specific antigen and Gleason score increases the diagnostic power of endorectal coil magnetic resonance imaging in prostate cancer pathological stage

Abstract Background: The proper use of endorectal coil MRI (eMRI) images provide detailed information for the real extent of locally prostate cancer invasion and involvement of pelvic lymph nodes. This study evaluated the accuracy of endorectal coil magnetic resonance imaging (eMRI) results, combining the preoperative prostate-specific antigen (PSA), and the biopsy Gleason score to improve the diagnostic accuracy of prostate cancer (PCa) with organ-confined disease (OCD) or extracapsular extension (ECE)/seminal vesicle invasion (SVI). Methods: Between 2001 and 2007, 94 PCa patients received eMRI testing during presurgical evaluation and underwent radical prostatectomy. As a part of routine patient workup, serum PSA level and Gleason score after pathology examination were recorded. The eMRI images were used to help assess patient PCa staging status regarding OCD or ECE/SVI. These stage assessments as evaluated through the use of MRI were compared with the final specimen pathological stage after the patients underwent radical prostatectomy. Results: Of the total 94 patients in our study, 65 had stage pT2, 12 had stage pT3a, and 17 had stage pT3b PCa. In patients with clinical stage T2 PCa, the Gleason score significantly improved the discriminative ability of eMRI to successfully predict PCa at the OCD stage. Otherwise, in cases of clinical stage T3 PCa, accurate determination of PSA levels significantly improved eMRI predictive ability to assess ECE or SVI staging. Conclusion: In clinical stage T2 PCa patients, integrating the biopsy Gleason score improved the discriminative ability to assess OCD PCa staging. Additionally, combining the preoperative PSA levels of clinical T3 prostate cancer cases with Gleason scores significantly improved the sensitivity and accuracy of eMRI diagnosis to distinguish ECE from SVI

Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005

We report 5 years’ surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%)

Gelatin Packing of Intracortical Tract After Percutaneous Nephrostomy Lithotripsy for Decreasing Bleeding and Urine Leakage

BackgroundPercutaneous nephrostomy is almost a daily routine procedure in clinical urologic practice. Tract bleeding and urine leakage along the percutaneous tract is a common event and bothersome to both patients and the surgeon. Herein we introduce a simple technique of gelatin packing for stopping subsequent bleeding and urine leakage immediately after a percutaneous nephrostomy lithotripsy (PCNL) procedure.MethodsPCNL, using a tubeless technique, was performed in 15 patients with renal calculi. In all cases, stones were removed using grasping forceps after the stones were disintegrated with a lithoclast. In all patients, a retrograde internal ureteral stent was put in place before the PCNL procedure, as was a Foley catheter for bladder drainage. A gelatin patch sealant was placed in the nephrostomy cortical tract under nephroscopic vision, immediately after the PCNL procedure. Another 15 patients, treated using a standard PCNL with tube drainage post-PCNL, were enrolled as a control group.ResultsThe stone burden, mean operative time, and stone-free rate (67% versus 73%, p = 0.33) were not statistically different between the 2 groups. In the 15 patients who received tubeless PCNL treatment, there were no severe complications related to the gelatin packing in the nephrostomy tract, and no significant bleeding or urine leakage occurred after the packing. The necessity for blood transfusion was much lower in the tubeless group as compared with the tube-drainage group (6.6% versus 26.7%; 0.2 ± 0.1 units versus 0.9 ± 0.5 units, p = 0.013). Tubeless patients began ambulation and were discharged from the hospital earlier (3.4 days versus 5.1 days, p = 0.035) than those in the tube-drainage group. Analgesic requirement was significantly less with the gelatin sealant technique when compared with the tube drainage group (85 ± 20 mg versus 185 ± 25 mg, p = 0.008).ConclusionGelatin sealant packing is an alternative, available, and feasible method for preventing bleeding and urine leakage postoperatively in selected patients receiving tubeless PCNL

A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

AbstractObjectiveTo determine if tyrosine kinase receptor inhibitor, sunitinib malate, combined with chemotherapeutic drugs may present synergistic enhancement of cytotoxicity to transitional cell carcinoma cells (TCC).MethodsThe mRNA and protein contents of vascular endothelial growth factor-α (VEGFα) in various TCC cell lines were detected individually by quantitative-polymerase chain reaction and Western blot. The inhibitory concentrations of various chemotherapeutic drugs, including gemcitabine, doxorubicin, and cisplatin, and their combination with sunitinib to TCC cancer cells were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The synergist efficacy was measured using the observed/expected ratio calculation method. Finally, the synergistic effect of sunitinib and selected anticancer drug gemcitabine was elucidated in C3H/MBT-2 animal tumor model with monitoring tumor growth volume and survival rate.ResultsThe mRNA of VEGFα had high expression in high-grade TCC cell lines (T24, TCC 8701, and TCC 8702) when compared with low-grade TCC cell lines (TCC 8301 and TSGH 9201). The expression of VEGFα protein level was closely correlated with the mRNA content in each individual cell line. Sunitinib, combined with gemcitabine, has shown the highest synergistic cytotoxic effect to TCC cells in an MTT assay. In the xenografted tumor model, MBT-2 bearing mice treated by sunitinib and gemcitabine combination had the lower mean tumor volume (265 ± 95 mm3 vs. 2605 ± 320 mm3) and higher survival rate (100% vs. 56%) at 30 days follow-up when compared with control mice.ConclusionCombination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer

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Background: Percutaneous nephrostomy is almost a daily routine procedure in clinical urologic practice. Tract bleeding and urine leakage along the percutaneous tract is a common event and bothersome to both patients and the surgeon. Herein we introduce a simple technique of gelatin packing for stopping subsequent bleeding and urine leakage immediately after a percutaneous nephrostomy lithotripsy (PCNL) procedure. Methods: PCNL, using a tubeless technique, was performed in 15 patients with renal calculi. In all cases, stones were removed using grasping forceps after the stones were disintegrated with a lithoclast. In all patients, a retrograde internal ureteral stent was put in place before the PCNL procedure, as was a Foley catheter for bladder drainage. A gelatin patch sealant was placed in the nephrostomy cortical tract under nephroscopic vision, immediately after the PCNL procedure. Another 15 patients, treated using a standard PCNL with tube drainage post-PCNL, were enrolled as a control group. Results: The stone burden, mean operative time, and stone-free rate (67% versus 73%, p = 0.33) were not statistically different between the 2 groups. In the 15 patients who received tubeless PCNL treatment, there were no severe complications related to the gelatin packing in the nephrostomy tract, and no significant bleeding or urine leakage occurred after the packing. The necessity for blood transfusion was much lower in the tubeless group as compared with the tube-drainage group (6.6% versus 26.7%; 0.2 ± 0.1 units versus 0.9 ± 0.5 units, p = 0.013). Tubeless patients began ambulation and were discharged from the hospital earlier (3.4 days versus 5.1 days, p = 0.035) than those in the tube-drainage group. Analgesic requirement was significantly less with the gelatin sealant technique when compared with the tube drainage group (85 ± 20 mg versus 185 ± 25 mg, p = 0.008). Conclusion: Gelatin sealant packing is an alternative, available, and feasible method for preventing bleeding and urine leakage postoperatively in selected patients receiving tubeless PCNL. [J Chin Med Assoc 2006;69(4):162-165

Folate receptor expression in bladder cancer and its correlation with tumor behaviors and clinical outcome

Background: Folate receptor (FR) has been recognized as having the capacity to become a biological marker for early diagnosis or prognostication of bladder cancer in previous studies. The aim of this study was to evaluate the expression of FR in bladder cancer, and its potential relevance to clinicopathological characteristics and patient survival. Materials and methods: Surgical specimens of cancer tissue were obtained from 78 patients with bladder cancer. The relative expression levels of FR in the bladder cancer tissue were measured by immunohistochemistry stain and graded according to stain intensity. Thereafter, the correlation with clinicopathological parameters and patient survival was analyzed. Results: The staining intensity and positivity rate of FR were significantly higher in low grade tumor tissues than in high grade tissues (P = 0.0035 and 0.003). Nevertheless, in the univariate Cox proportional hval. There was no correlation of FR expression or intensity with patient survival was seen (P > 0.01). Conclusion: In addition to tumor grade and stage, the expression of FR in bladder cancer is related to cellular differentiation. However, no correlation with patient survival was seen in this limited study