Selective estrogen receptor modulator is a proven agent for chemoprevention and chemotherapy of cancer. Raloxifene, a mixed estrogen agonist/antagonist, was developed to prevent osteoporosis and potentially reduce the risk of breast cancer. In this study, we examined the effect of raloxifene on the TSU-PR1 cell line. This cell line was originally reported to be a prostate cancer cell line, but recently it has been shown to be a human bladder transitional cell carcinoma cell line. The TSU-PR1 cell line contains high levels of estrogen receptor ␤. Following treatment with raloxifene, evidence of apoptosis, including change in nuclear morphology, DNA fragmentation, and cytochrome c release, was observed in a dose-dependent manner in the TSU-PR1 cells (10 ؊9 to 10 ؊6 M range). We observed no detectable change in the steady-state levels of Bax, Bcl-2, and Bcl-X L following raloxifene treatment. However, raloxifene induced caspase-dependent cleavage of BAD to generate a 15-kDa truncated protein. Overexpression of a double mutant BAD resistant to caspase 3 cleavage blocked raloxifene-induced apoptosis. These results demonstrate that raloxifene induces apoptosis through the cleavage of BAD in TSU-PR1 cells. This molecular mechanism of apoptosis suggests that raloxifene may be a therapeutic agent for human bladder cancer.

A triboelectric-based artificial basilar membrane (TEABM) can mimic cochlear tonotopy by triboelectrification between Kapton film and aluminum foil. The two films are stacked and clamped to form a beam structure. The TEABM tonotopy is tested using an animal model to verify the feasibility of a self-powered acoustic sensor for a prototype cochlear implant.

We proposed a piezoelectric artificial basilar membrane (ABM) composed of a microelectromechanical system cantilever array. The ABM mimics the tonotopy of the cochlea: frequency selectivity and mechanoelectric transduction. The fabricated ABM exhibits a clear tonotopy in an audible frequency range (2.92–12.6 kHz). Also, an animal model was used to verify the characteristics of the ABM as a front end for potential cochlear implant applications. For this, a signal processor was used to convert the piezoelectric output from the ABM to an electrical stimulus for auditory neurons. The electrical stimulus for auditory neurons was delivered through an implanted intra-cochlear electrode array. The amplitude of the electrical stimulus was modulated in the range of 0.15 to 3.5 V with incoming sound pressure levels (SPL) of 70.1 to 94.8 dB SPL. The electrical stimulus was used to elicit an electrically evoked auditory brainstem response (EABR) from deafened guinea pigs. EABRs were successfully measured and their magnitude increased upon application of acoustic stimuli from 75 to 95 dB SPL. The frequency selectivity of the ABM was estimated by measuring the magnitude of EABRs while applying sound pressure at the resonance and off-resonance frequencies of the corresponding cantilever of the selected channel. In this study, we demonstrated a novel piezoelectric ABM and verified its characteristics by measuring EABRs.

529sis determines patient eligibility for and the potential success of curative treatments. Therefore, CT and MRI aided by technologic advances that afford improved spatial, temporal, and contrast resolution are regarded as promising alternative surveillance tools for detecting HCC [4,5]. Contrast-enhanced dynamic multiphasic imaging has substantial performance benefits because most HCCs are hypervascular lesions that typically become enhanced during the hepatic arterydominant phase of imaging [6]. OBJECTIVE. The purpose of this study was to retrospectively evaluate the diagnostic performance of dynamic gadobenate dimeglumine-enhanced MRI with explant pathologic correlation in the detection of hepatocellular carcinoma (HCC) in patients undergoing liver transplantation. Hepatocellular Carcinoma in H e p a t o b i l i a r y I m ag i ng • O r ig i n a l R e s e a rc hMATERIALS AND METHODS. Forty-seven patients (28 men, 19 women; mean age, 49 years) underwent dynamic gadobenate dimeglumine-enhanced MRI within 3 months before primary liver transplantation. Dynamic imaging was performed before (unenhanced) and after (hepatic arterial, portal venous, equilibrium, and 1-hour delayed phases) IV bolus administration of gadobenate dimeglumine at 0.1 mmol/kg body weight. Retrospective image analysis to detect HCC nodules was performed independently by two abdominal radiologists who had no pathologic information. On a per-nodule basis, the sensitivity and positive predictive value were calculated for the two observers. Sensitivity and specificity in the diagnosis of HCC also were evaluated. Fisher's exact test was performed to determine whether there was a detection difference between HCC nodules 1 cm in diameter or larger and nodules smaller than 1 cm and to evaluate the differences in causes of false-positive MRI findings based on lesion size (≥ 1 cm vs < 1 cm).RESULTS. Twenty-seven patients had 41 HCCs. In HCC detection, gadobenate dimeglumine-enhanced MRI had a sensitivity of 85% (35 of 41 HCCs) and a positive predictive value of 66% (35 of 53 readings) for observer 1 and a sensitivity of 80% (33 of 41 HCCs) and a positive predictive value of 65% (34 of 52 readings) for observer 2. For both observers, sensitivity in the detection of HCCs 1 cm in diameter and larger (91-94%) was significantly different (p < 0.05) from that in detection of HCCs smaller than 1 cm (29-43%). Nonneoplastic arterial hypervascular lesions more often caused false-positive diagnoses of lesions smaller than 1 cm in diameter (80-86%) on MR images than of those 1 cm in diameter and larger (0-25%). The difference was statistically significant (p < 0.05) for both observers. In diagnosis, gadobenate dimeglumine-enhanced MRI had a sensitivity of 87% (20 of 23 patients) and a specificity of 79% (19 of 24 patients) for both observers.CONCLUSION. Dynamic gadobenate dimeglumine-enhanced MRI has a sensitivity of 80-85% and a positive predictive value of 65-66% in the detection of HCC. The technique, however, is of limited value for detecting and characterizi...