Search

Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with the recurrence of bladder cancer. Previous studies have shown that activation of FGFR and HER2 signaling are involved in bladder cancer cell proliferation and drug resistance. Smoking is the most common etiologic risk factor for bladder cancer, and there is emerging evidence that smoking is associated with cisplatin resistance. However, the underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes. Our previous studies have shown that acrolein contributes to bladder carcinogenesis through the induction of DNA damage and inhibition of DNA repair. In this study, we found that acrolein induced cisplatin resistance and tumor progression in both non–muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) cell lines RT4 and T24, respectively. Activation of HER2 and FGFR3 signaling contributes to acrolein-induced cisplatin resistance in RT4 and T24 cells, respectively. Furthermore, trastuzumab, an anti-HER2 antibody, and PD173074, an FGFR inhibitor, reversed cisplatin resistance in RT4 and T24 cells, respectively. Using a xenograft mouse model with acrolein-induced cisplatin-resistant T24 clones, we found that cisplatin combined with PD173074 significantly reduced tumor size compared with cisplatin alone. These results indicate that differential molecular alterations behind cisplatin resistance in NMIBC and MIBC significantly alter the effectiveness of targeted therapy combined with chemotherapy. This study provides valuable insights into therapeutic strategies for cisplatin-resistant bladder cancer.

Supplementary Figure from Cigarette Smoke Containing Acrolein Contributes to Cisplatin Resistance in Human Bladder Cancers through the Regulation of HER2 Pathway or FGFR3 Pathway

In recent years, wind power generation has been widely promoting by government policy. If the structural health of wind turbines can be screened effectively and quickly, the cost for operation and maintenance will be reduced. Such techniques are desirable since a vast number of wind turbines are scheduled to be operational in the next decade in Taiwan. This certainly sets the stage for research on developing the vibration analysis and monitoring techniques for the supporting structure of wind turbine (WT) systems. The authors demonstrated in a previous study that the defect location can be discovered using the frequency displacement mode output of the numerical model. In the current study, a PVC pipe with a mass attached at the top has been applied to validate the results of the numerical simulation. The displacement in three axes of each target of equal spacing on the PVC pipe is determined by using a technique based on digital image correlation. The resulted first modal vibration pattern in the frequency domain can be linked to the dynamic behaviour of this sized-reduced model of the wind turbine tower. The experimental data show that the proposed method has a good potential for damage assessment.

Large structures such as wind turbines are subject to environmental factors and varying operational loads which may result in structural damage, making components of these large structures prone to performance and mechanical degradation. The use of high-definition optical vision sensors in digital image correlation (DIC) allow for the application of a non-destructive image registration technique in which it measures finite three-dimensional deformations on surfaces through correlations of a unique pattern or set of unique localized patterns. However, the physical placement of an artificial marker such as a unique speckled pattern on the surface of the structure is time-consuming and often impractical for large structures. Therefore, we propose a novel auto-mated methodology that searches and segments salient and unique regions of an image as well as for all subsequent images to assist in performing efficient displacement measurements for vibrational study and structural health monitoring purposes. Our algorithm is validated on a con-trolled set of images, as well as on a small structure and large real-world wind turbine, which suggests the algorithm’s efficacy without the use of artificial markers for large structural health monitoring.

Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD.A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients.Acr-dG levels were statistically correlated with CKD stages in UC patients (P0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P0.005).These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

The amount of built wind resource has greatly increased since wind turbines have started to get installed offshore in order to power much of the world. Topics relating to wind turbine have encourag...

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

INTRODUCTION AND OBJECTIVE:To investigate the additional value of phi in predicting csPCa in Asian men with elevated PSA and MRI prostate performed.METHODS:This is a multicentre evaluation of prosp...

Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with the recurrence of bladder cancer. Previous studies have shown that activation of FGFR and HER2 signaling are involved in bladder cancer cell proliferation and drug resistance. Smoking is the most common etiologic risk factor for bladder cancer, and there is emerging evidence that smoking is associated with cisplatin resistance. However, the underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes. Our previous studies have shown that acrolein contributes to bladder carcinogenesis through the induction of DNA damage and inhibition of DNA repair. In this study, we found that acrolein induced cisplatin resistance and tumor progression in both non–muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) cell lines RT4 and T24, respectively. Activation of HER2 and FGFR3 signaling contributes to acrolein-induced cisplatin resistance in RT4 and T24 cells, respectively. Furthermore, trastuzumab, an anti-HER2 antibody, and PD173074, an FGFR inhibitor, reversed cisplatin resistance in RT4 and T24 cells, respectively. Using a xenograft mouse model with acrolein-induced cisplatin-resistant T24 clones, we found that cisplatin combined with PD173074 significantly reduced tumor size compared with cisplatin alone. These results indicate that differential molecular alterations behind cisplatin resistance in NMIBC and MIBC significantly alter the effectiveness of targeted therapy combined with chemotherapy. This study provides valuable insights into therapeutic strategies for cisplatin-resistant bladder cancer.

The aim of the present study is to investigate anticancer effect and mechanism of regorafenib in bladder cancer in vitro and in vivo. Human bladder cancer TSGH 8301 cells were treated with regorafenib, NF‐κB, AKT, or mitogen‐activated protein kinase (MAPK) inhibitors for different time. The changes of cell viability, NF‐κB activation, apoptotic signaling transduction, and expression of tumor progression‐associated proteins were evaluated with MTT, NF‐κB reporter gene assay, flow cytometry, and Western blotting assay. TSGH 8301 tumor bearing mice were established and treated with vehicle (140 μL of 0.1% DMSO) or regorafenib (10 mg/kg/day by gavage) for 15 days. The changes of tumor volume, body weight, NF‐κB activation, MAPK activation, and tumor progression‐associated proteins (MMP‐9, XIAP, VEGF, and Cyclin‐D1) after regorafenib treatment were evaluated with digital caliper, digital weight, and ex vivo Western blotting assay. Our results demonstrated NF‐κB activation and protein levels of MMP‐9, XIAP, VEGF, and Cyclin‐D1 were significantly reduced by NF‐κB (QNZ), ERK (PD98059), and P38 (SB203580) inhibitors. Regorafenib also significantly induced extrinsic and intrinsic apoptotic signaling transduction in bladder cancer in vitro. In addition, regorafenib significantly inhibited tumor growth, NF‐κB, p38, ERK activation and expression of tumor progression‐associated proteins in bladder cancer in vitro and in vivo. Taken together, these results proved that regorafenib not only induced apoptosis through extrinsic and intrinsic pathways and but suppressed MAPK/ NF‐κB‐modulated tumor progression in bladder cancer.

Background/aim Muscle-invasive bladder cancer (MIBC) has long been recognized as a difficult to treat cancer type, thus a new treatment strategy is needed. The major purpose of the present study was to verify the anticancer effect of hyperforin and the mechanism through which it affects tumor cell growth and invasion in bladder cancer in vitro. Materials and methods Bladder cancer TSGH-8301 cells were treated with different concentrations of hyperforin for different durations of time. The changes in cell viability, production of calcium and reactive oxygen species (ROS), and anti-apoptotic signaling were evaluated using MTT assay, flow cytometry, and western blot analysis. The effect of hyperforin on the expression of nuclear factor-kappaB (NF-ĸB) p65 (Ser276), tumor progression-associated proteins, as well as on cell invasion was investigated using western blotting and cell invasion assay, respectively. Results Hyperforin significantly induces apoptosis, extrinsic/intrinsic apoptotic signaling, accumulation of cytosol ROS, and calcium signalling. Hyperforin also significantly diminishes the expression of NF-ĸB p65 (Ser276), anti-apoptotic and tumor progression-associated proteins, as well as the cell invasion ability of TSGH-8301 cells. Conclusion Our findings demonstrate that hyperforin triggers apoptosis depending on extrinsic/intrinsic pathways and suppresses NF-ĸB-mediated cell survival as well as the invasive properties of bladder cancer in vitro.

In this research, the incineration slag is treated with high temperature by the plasma melting treatment technology to effectively solve the resource recovery and reuse of the incineration slag. After the thermal plasma melting, the molten slag is vitrified into microcrystalline materials by cooling with water. It is called water quenched slag (WQS). Based on the characteristics of molten slag, the feasibility of reusing artificial stone resources is an importance issue. The objective of this study is to investigate mechanical properties of artificial stone made by WQS from the incinerator ash. The WQS is utilized for replacing stone powder and make artificial stone in this study. The research scope is to assess the proper ratio of coarse and fine WQS particles to produce the artificial stone. The experimental testing program includes hardness, specific gravity, water absorption, compressive strength, tensile strength, heat resistance, and toxic dissolution tests. The testing results show when the ratio of coarse and fine particles of WQS is 1:1 blended, the physical properties of the specimens are closer to those of general artificial stone; the tensile strength decrease but the compressive strength increase when more the amount of resin or WQS are mixed; in the heat resistance test, its softening point and failure point are similar to those of artificial stone. In summary, the comprehensive test results show that WQS demonstrate great potential to largely replace the stone powder component of artificial stone as an ecological and environmentally friendly material.

The present study is based on developing a novel in-house BRISK-DIC methodology to identify and correlate natural patterns to perform 3D vibration studies of large structures such as wind turbines. The method includes identifying natural patterns using the BRISK (Binary Robust Invariant Scalable Keypoints) algorithm and its integration with an in-house 3D-DIC method for the measurement of in-plane and out-of-plane displacements. The stereo-calibration is performed using a novel calibration technique that uses an IMU sensor and Laser Measure for extrinsic parameters and a representative computational stereovision system for intrinsic parameters. In a preliminary field experiment, the developed technique is used to study the vibrations of a light tower of 10m height. The BRISK algorithm is applied to the selected reference images from both of the cameras to detect natural patterns. The in-house 3D-DIC program uses the identified natural patterns as well as calibration parameters for correlation and reconstruction purposes. The developed BRISK-DIC method is able to measure 3D displacements as well as accurately obtain the natural frequencies of the light tower. The vibration results are validated using an accelerometer. Finally, in another field experiment, the technique is successfully implemented for 3D vibration study of a utility-scale wind turbine. Natural patterns are identified at the nacelle and correlated to obtain the vibrational parameters of the wind turbine tower. The measured natural frequencies are validated with the measurement carried out in the past using a ground-based microwave interferometer.

Digital image correlation (DIC) is an image registration technique to measure finite three-dimensional shape and deformations of planar and curved surfaces. This technique requires an optimal unique pattern or set of unique localized patterns as a carrier of deformation information in order to accurately measure correlations in temporal images. Recent advances in obtaining an optimal pattern in terms of saliency and uniqueness require operators’ experience and/or prior metrics. In our study, we propose a preprocessing methodology to automatically classify the saliency and uniqueness of a localized pattern for DIC processing of a large structure for structural health monitoring. In order to ensure pattern saliency, we develop a localized multi-scale CNN classifier using an in-house dataset containing 20k unique coarse and fine patterns. This classifier ensures that the projected pattern is salient within a real world image. For ensuring uniqueness within an image and a set of images, we develop a novel uniqueness algorithm that ensures the structural similarity (SSIM) index of the pattern is above a similarity threshold in every part of an image as well as for all subsequent images. We integrate these algorithms as a preprocessing step to our in-house 3D-DIC program for an efficient study of 3D vibrations of large-sized structures. Initial experiments are performed on a large-sized (10m height) light tower, and it is observed that our methodology is capable of optimizing the size, saliency, and uniqueness of a pattern in order to perform efficient displacement measurements for vibrational study and health monitoring purposes.

Background Although both chemotherapy and radiotherapy (RT) can sufficiently maintain tumor suppression of colorectal cancer (CRC), these treatments may trigger the expression of nuclear factor kappa B (NF-κB) and compromise patients' survival. Regorafenib suppresses NF-κB activity in various tumor types. However, whether regorafenib may act as a suitable radiosensitizer to enhance therapeutic efficacy of RT remains unknown. Materials and methods Here, we established a CRC-bearing animal model to investigate the therapeutic efficacy of regorafenib in combination with RT, through measurement of tumor growth, body weight, whole-body computed tomography (CT) scan and immunohisto-chemistry staining. Results Smallest tumor size and weight were found in the combination treatment group. In addition, RT-induced up-regulation of NF-κB and downstream proteins were diminished by regorafenib. Moreover, the body weight and liver pathology in the treated group were similar to those of the non-treated control group. Conclusion Regorafenib may enhance the anti-CRC efficacy of RT.

The biomimicking and understanding of the dynamics of insect flyers is important in developing agile and efficient MAVs. The present study is based on the development of dragonfly inspired MAV and investigation of its motion characteristics. Initially, a tethered two-winged MAV model is constructed, composing of two flapping wings, a flapping mechanism, a chassis, and an external power supply with a function generator. The wings are fabricated with composite stiffeners and membrane. The material of the wings consists of carbon nanotubes (CNTs)/polypropylene (PP) nanocomposite and low density polyethylene (LDPE). The wings are thus lightweight, thin, flexible, and can generate large amplitude bending-twisting motion. The flapping mechanism is constructed with a cantilever type piezoelectric actuator, a mediator mechanism having CNTs/PP nanocomposite flexure joints, and carbon fiber/epoxy composite linkages. The assembled two-winged MAV model has a total mass, body length, wingspan, and aspect ratio of 0.61g, 60.46mm, 90.14mm, and 10.06, respectively. The characteristic flapping frequency of the model is 20Hz, as compared to the wingbeats (or characteristic frequency) of 27.53Hz of an actual dragonfly species, i.e., the Anax Parthenope Julius. Measured via digital image correlation (DIC) technique, the fabricated wings exhibit a bending dominated motion during downstroke as well as upstroke. The combined design of flapping wings and flexure joint mechanism is also computationally studied for their structural dynamic characteristics (performed using ANSYS). The first resonance mode or the characteristic frequency, at which the wings have highest deflections, is 17.25Hz. The flexure mechanism is able to generate very large wing deflections (maximum deflection 22.7mm at wing tip) with a sinusoidal heaving input excitation of very small amplitude (0.1mm given at the actuator attachment location). This is useful to generate higher aerodynamic forces and improve efficiency. The maximum stresses and strains are found at flexure-rigid link and wing stiffener attachment, respectively. Finally, a dragonfly-inspired four-winged MAV is developed. It consists of two pairs of nanocomposite wings with independently actuated flapping mechanisms. Like a natural dragonfly, the forewing and hindwing pairs can be controlled independently and operated at different characteristic frequencies as well as relative phase angles.

Cracks do exist in a concrete building, and the reasons for cracks can be attributed to grouting, force actions, and concrete properties. Detecting existing cracks and monitoring their growth conditions is an important issue in structure health monitoring. This study proposed an integrated approach to fuse the thermal infrared images, high-resolution image, and acoustic tracking. Thermal infrared images can be used to record the surface temperatures. Those defect areas usually have their surface temperatures different from their neighborhoods. Those surface temperature differences can be an important clue to identify the defects. From the high-resolution images, cracks do occur at those discontinuities, and those discontinuities can be treated as the boundaries of the segmented regions. In this study, an approach based on considering the distributions of the segmented regions to segment the given high-resolution images to locate the boundaries of the segmented regions. Then, the defect map is generated by overlaying the thermal infrared image on the segmented regions such that the map can reveal the defect locations, and the surface temperatures can be another evidence to show the defects. Acoustic tracking is introduced to verify the results. All the defect information is stored in a 3D model such that a defect model can be established.

Background: Induced pluripotent stem cells (iPSCs) have a great potential for application in patient-specific therapy. The reprogramming method that does not involve c-Myc reduces tumorigenic risk, but also largely reduces the efficiency of generation of iPSCs, especially for those reprogrammed from damaged cells. Poly(ADP-ribose) polymerase 1 (Parp1) catalyzes a reaction of poly(ADP-ribosylation) and has been reported to enhance cell reprogramming. Methods: Using Oct-4/Sox2/Klf4/Parp1 (OSKP) reprogramming method, reprogramming factors plus Parp1 were capable of generation of iPSCs from adult fibroblasts and further toward to differentiate from iPSCs status into hepatocyte-like cells. Results: Our results showed that Oct-4/Sox2/Klf4/Parp1 (OSKP)-derived iPSC exhibited regular pluripotent properties, long-term passages and more stable cellular-divided period. These OSKP-derived iPSCs can effectively differentiate into hepatocyte-like cells (OSKP-iPSC-Heps), and present high mRNA levels of Sox17, HNF3b, and HNF4a in OSKP-iPSC-Heps. The mature hepatic functions, including CYP3A4, LDL uptake, glycogen synthesis and urea secretion were analyzed and well detected in OSKP-iPSC-Heps on day 14 post-differentiation. Conclusion: In conclusion, we demonstrated that Parp1 promoted reprogramming process to generate the high quality of iPSCs, which could be used as a high quality source of hepatocytes. Keywords: Hepatocyte, Induced pluripotent stem cells, Poly(ADP-ribose) polymerase 1

Background/aim Amentoflavone has been shown to be effective against a variety of cancer cells, but its role in bladder cancer remains unclear. Thus, the aim of this study is to evaluate whether amentoflavone may induce toxicity effect of bladder cancer. Materials and methods Herein, we evaluated amentoflavone effects in a human bladder cancer cell line TSGH8301 in vitro. Results Amentoflavone caused significant cytotoxicity in TSGH8301 cells at a concentration as low as 200 μM. FAS/FASL-dependent extrinsic apoptosis and mitochondria-dependent intrinsic apoptosis were observed in amentoflavone-treated cells in a dose-dependent manner. Levels of several proapoptotic proteins, such as FAS, FAS-ligand and BAX (B-cell lymphoma 2 associated X) were increased following amentoflavone treatment. Meanwhile, anti-apoptotic MCL-1 (myeloid cell leukemia sequence 1) and cellular FLICE-inhibitory protein (C-FLIP) protein levels were reduced. Additionally, angiogenesis and proliferation-related proteins, including matrix metalloproteinase (MMP)-2, -9, vascular endothelial growth factor (VEGF), urokinase-type plasminogen actvator (uPA) and cyclin D1 were diminished by amentoflavone. Conclusion Amentoflavone induced toxicity of bladder cancer by inhibiting tumor progression and inducing apoptosis signaling transduction.

INTRODUCTION AND OBJECTIVES:Prostate health index (PHI) is a promising biomarker in the prediction of aggressive prostate cancer. Since prostate volume has been regarded as an important factor cont...