Possible Role of Sonic Hedgehog and Epithelial-Mesenchymal Transition in Renal Cell Cancer Progression

PURPOSE: Sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) are both known to relate to cancer progression. The purpose of this study was to investigate the role of Shh signaling and EMT in renal cell carcinoma (RCC). MATERIALS AND METHODS: Cell proliferation was assayed in RCC cell lines in the presence or absence of a Shh signaling stimulator, recombinant Shh (r-Shh) protein, or a Shh signaling inhibitor, cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the expression of EMT markers (E-cadherin, N-cadherin, and vimentin) and osteonectin. The expression of Ki-67, Gli-1, osteonectin, and EMT markers in nephrectomy specimens from RCC patients was also measured by immunohistochemical (IHC) staining. RESULTS: RCC cells showed enhanced cell proliferation by r-Shh protein, whereas cell proliferation was suppressed by the addition of cyclopamine in RenCa cells. Real-time RT-PCR showed that r-Shh suppressed the expression of E-cadherin and that this suppression was partly blocked by cyclopamine alone in RenCa cells. In the IHC results, osteonectin significantly correlated with vein sinus invasion (p=0.0218), and the expression of vimentin significantly correlated with lymphatic invasion (p=0.0392). CONCLUSIONS: Shh signaling and EMT play roles in RCC progression, and the Shh signaling inhibitor cyclopamine might be a possible molecular targeted therapeutic strategy for RCC.

Can Diffusion-Weighted Magnetic Resonance Imaging Predict a High Gleason Score of Prostate Cancer?

PURPOSE: To determine the relationship between cancer-positive findings on diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) and the Gleason score (GS) of radical prostatectomy specimens in prostate cancer (PC). MATERIALS AND METHODS: We performed a retrospective study of 105 consecutive patients with PC who underwent radical prostatectomy between January 2009 and October 2011 with DWI MRI and full data available for analyses. Prostatectomy specimen pathology included GS, margin status, and capsule invasion, and the clinical factors investigated included age and serum prostate-specific antigen. We investigated the relationship between positive DWI MRI results and these pathological and clinical factors. RESULTS: PC was diagnosed in 62 of 105 patients on DWI MRI. The prostatectomy specimens revealed that the number of cases with GS >4+3 was significantly greater in patients with PC-positive DWI MRI results (34/62, 54.80%) than in those with PC-negative results (2/43, 2.33%; p<0.0001). Positive surgical margins occurred significantly more often in cases with PC-positive DWI MRI results (31/62, 50.0%, compared with 9/43, 21.4%; p=0.0253), and patients with a single tumor lesion in DWI MRI had significantly higher GSs than did those with multiple tumor lesions (p=0.0301). Our statistical results with multiple regression analysis showed that PC-positive DWI MRI results are significantly associated with high GSs. CONCLUSIONS: DWI MRI may help to predict high GSs in prostatectomy specimens. Further studies assessing a greater number of patients will be necessary for a definitive evaluation of DWI MRI as a diagnostic tool for determining PC malignancy.

Efficacy of Combination Use of Beta-Lactamase Inhibitor with Penicillin and Fluoroquinolones for Antibiotic Prophylaxis in Transrectal Prostate Biopsy

PURPOSE: To investigate the efficacy of tazobactam/piperacillin (TAZ/PIPC) plus levofloxacin (LVFX) as a prophylactic administration in transrectal prostate biopsy (TPBX). MATERIALS AND METHODS: We investigated 201 consecutive patients who underwent TPBX in one Japanese hospital during the period of 2009-2010. The patients received TAZ/PIPC 4.5 g i.v. once just before and 3 hours after TPBX, plus oral LVFX 300 mg or 500 mg daily for 3 days. We examined the infectious adverse events and laboratory data (serum white blood cell [WBC] count and C-reactive protein [CRP]) before and 1 day after TPBX. RESULTS: Only one patient (0.50%) in 201 cases had febrile complications after TPBX. Serum WBC and CRP did not rise significantly on the day after TPBX compared with before TPBX (p>0.05). There was no significant difference in the rise of serum WBC and CRP before and after TPBX in the comparison of LVFX 500 mg with LVFX 300 mg in the TAZ/PIPC plus LVFX regimen. CONCLUSIONS: TAZ/PIPC plus LVFX can be considered as a prophylactic regimen for preventing infectious complications in TPBX.