Here we evaluated the potential anti-pancreatic cancer activity by TIC10/ONC201, a first-in-class small-molecule inducer of tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL). The ...in vitro results showed that TIC10 induced potent cytotoxic and cytostatic activities in several human pancreatic cancer cell lines (Panc-1, Mia-PaCa2, AsPC-1 or L3.6). TIC10 activated both extrinsic (TRAIL-caspase-8-dependent) and endogenous/mitochondrial (caspase-9-dependent) apoptosis pathways in the pancreatic cancer cells. Molecularly, we showed that TIC10 inhibited Akt-Erk activation, yet induced TRAIL expression in pancreatic cancer cells. Significantly, TIC10, at a relatively low concentration, sensitized gemcitabine-induced growth inhibition and apoptosis against pancreatic cancer cells. Further, TIC10 and gemcitabine synergistically inhibited Panc-1 xenograft growth in SCID mice. The combination treatment also significantly improved mice survival. In addition, Akt-Erk in-activation and TRAIL/cleaved-caspase-8 induction were observed in TIC10-treated Panc-1 xenografts. Together, the preclinical results of the study demonstrate the potent anti-pancreatic cancer activity by TIC10, or with gemcitabine.
•TIC10/ONC201 is cytotoxic and cytostatic against pancreatic cancer cells.•TIC10 activates extrinsic and endogenous apoptotic pathways in pancreatic cancer cells.•TIC10 inhibits Akt-Erk activation, and induces TRAIL expression.•TIC10 oral administration inhibits Panc-1 xenografts, improving SCID mice survival.•TIC10 sensitizes gemcitabine-induced anti-pancreatic cancer activity in vitro and in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Pancreatic cancer is a leading cause of cancer death, and boron neutron capture therapy (BNCT) is one of the promising radiotherapy techniques for patients with pancreatic cancer. In this study, we ...evaluated the biological effectiveness of BNCT at multicellular levels using in vitro and in silico models. To recapture the phenotypic characteristic of pancreatic tumors, we developed a cell self-assembly approach with human pancreatic cancer cells Panc-1 and BxPC-3 cocultured with MRC-5 fibroblasts. On substrate with physiological stiffness, tumor cells self-assembled into 3D spheroids, and the cocultured fibroblasts further facilitated the assembly process, which recapture the influence of tumor stroma. Interestingly, after 1.2 MW neutron irradiation, lower survival rates and higher apoptosis (increasing by 4-fold for Panc-1 and 1.5-fold for BxPC-3) were observed in 3D spheroids, instead of in 2D monolayers. The unexpected low tolerance of 3D spheroids to BNCT highlights the unique characteristics of BNCT over conventional radiotherapy. The uptake of boron-containing compound boronophenylalanine (BPA) and the alteration of E-cadherin can partially contribute to the observed susceptibility. In addition to biological effects, the probability of induced α-particle exposure correlated to the multicellular organization was speculated to affect the cellular responses to BNCT. A Monte Carlo (MC) simulation was also established to further interpret the observed survival. Intracellular boron distribution in the multicellular structure and related treatment resistance were reconstructed in silico. Simulation results demonstrated that the physical architecture is one of the essential factors for biological effectiveness in BNCT, which supports our in vitro findings. In summary, we developed in vitro and in silico self-assembly 3D models to evaluate the effectiveness of BNCT on pancreatic tumors. Considering the easy-access of this 3D cell-assembly platform, this study may not only contribute to the current understanding of BNCT but is also expected to be applied to evaluate the BNCT efficacy for individualized treatment plans in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•An automated bearing remaining useful life (RUL) prediction technique is developed in this study.•Both spatial and temporal information contained in bearing data are utilized to render an accurate ...RUL prediction.•A smoothing technique is employed in the approach to reduce the fluctuation in the RUL prediction.
An automated remaining useful life (RUL) prediction technique based on a deep learning network is proposed in this study for an end-to-end RUL prediction of rolling element bearings. The technique utilizes a Convolutional Neural Network (CNN) to learn the spatial features from the bearing condition monitoring data, and then employs a stack of Bidirectional Gate Recurrent Units (BGRU) to extract the temporal degrading trend from the data for a more accurate RUL prediction. A weighted average method is employed to smooth out the trend of the RUL prediction. The effectiveness of the proposed technique is validated using two bearing degradation datasets, and the advantage of the proposed technique is examined by comparing the predicted RUL with those predicted using other commonly employed deep learning techniques. It is shown that the proposed technique can yield a much more accurate result for the bearing RUL prediction than other commonly employed deep learning techniques.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tenascin-C (TNC), a very large multimeric glycoprotein, is overexpressed in human glioblastomas, leading to a highly motile and invasive phenotype of glioma cells. However, the regulation of TNC ...expression in glioma has remained unclear until now. Our data suggest that interleukin-33 (IL-33) may promote the accumulation of TNC protein by autocrine or paracrine modes of action in glioma. In the present study, the expression levels of TNC, IL-33, and ST2 were measured in glioma tissue specimens, and the impact of altered IL-33 expression on TNC was investigated in vitro and in vivo. In contrast with control treatment, IL-33 treatment increased TNC expression, and knockdown of IL-33 attenuated TNC expression in glioma cells. Furthermore, IL-33 induced the activation of nuclear factor κB (NF-κB) and increased the expression of TNC in U251 cells. In addition, blockage of the IL-33-ST2-NFκB pathway resulted in downregulation of TNC production. IL-33 promoted glioma cell invasion by stimulating the secretion of TNC. Similarly, knockdown of TNC inhibited the invasiveness of glioma cells. These findings provide a novel perspective on the role of the IL-33/NF-κB/TNC signalling pathway in supporting cancer progression. Thus, targeting the IL-33/NF-κB/TNC signalling pathway may be a useful therapeutic approach in glioma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The benefit of direct-acting antiviral therapy (DAA) in chronic hepatitis C (CHC) infected patients who received curative treatment for early-stage hepatocellular carcinoma (HCC) is well known, but ...is unclear for intermediate stage HCC.
CHC patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC receiving chemoembolization were identified. Univariate, multivariate analyses, and Kaplan-Meier curve were used to identify factors associated with survival outcomes.
Among 113 included patients, the median survival of DAA treated group (n=14) and non-treated group (n=99) were 40.1 months and 22.9 months, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score, DAA, and serum albumin were key independent factors associated with overall survival. Moreover, the time-to-complete remission (TTCR) was improved in the DAA treated group.
ECOG, DAA, and serum albumin were prognostic factors for CHC/intermediate-stage HCC patients. DAA was also a beneficial factor for TTCR.
There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple ...therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin.
After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion.
A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure.
Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hepatocytes come out of left field Alison, Malcolm R.; Lin, Wey‐Ran
Hepatology (Baltimore, Md.),
March 2016, 2016-Mar, 2016-03-00, 20160301, Volume:
63, Issue:
3
Journal Article
Peer reviewed
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
An accurate intraoperative prediction of lymph node metastatic risk can help surgeons in choosing precise surgical procedures. We aimed to develop and validate nomograms to intraoperatively predict ...patterns of regional lymph node (LN) metastasis in patients with esophageal cancer.
The prediction model was developed in a training cohort consisting of 487 patients diagnosed with esophageal cancer who underwent esophagectomy with complete LN dissection from January 2016 to December 2016. Univariate and multivariable logistic regression were used to identify independent risk factors that were incorporated into a prediction model and used to construct a nomogram. Contrast-enhanced computed tomography reported LN status and was an important comparative factor of clinical usefulness in a validation cohort. Nomogram performance was assessed in terms of calibration, discrimination, and clinical usefulness. An independent validation cohort comprised 206 consecutive patients from January 2017 to December 2017.
Univariate analysis and multivariable logistic regression revealed three independent predictors of metastatic regional LNs, three independent predictors of continuous regional LNs, and two independent predictors of skipping regional LNs. Independent predictors were used to build three individualized prediction nomograms. The models showed good calibration and discrimination, with area under the curve (AUC) values of 0.737, 0.738, and 0.707. Application of the nomogram in the validation cohort yielded good calibration and discrimination, with AUC values of 0.728, 0.668, and 0.657. Decision curve analysis demonstrated that the three nomograms were clinically useful in the validation cohort.
This study presents three nomograms that incorporate clinicopathologic factors, which can be used to facilitate the intraoperative prediction of metastatic regional LN patterns in patients with esophageal cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Digital images captured from CMOS/CCD image sensors are prone to noise due to inherent electronic fluctuations and low photon count. To efficiently reduce the noise in the image, a novel image ...denoising strategy is proposed, which exploits both nonlocal self-similarity and local shape adaptation. With wavelet thresholding, the residual image in method noise, derived from the initial estimate using nonlocal means (NLM), is exploited further. By incorporating the role of both the initial estimate and the residual image, spatially adaptive patch shapes are defined, and new weights are calculated, which thus results in better denoising performance for NLM. Experimental results demonstrate that our proposed method significantly outperforms original NLM and achieves competitive denoising performance compared with state-of-the-art denoising methods.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
This study aims to solve the problem of limited learning efficiency caused by information overload and resource diversity in online course learning. We adopt a recommendation algorithm that combines ...knowledge graph and collaborative filtering, aiming to provide an application that can meet users’ personalized learning needs and consider the semantic information of learning resources. In addition, this article collects and models implicit data in online courses and compares the impact of video and text learning resources on user learning needs under different weights in order to deeply understand the different contributions of video and text learning resources to meeting learning needs. The experimental results show that the video high-weight experimental group performs better than the text high-weight experimental group; students tend to prefer video resources. This experiment can help students cope with the challenges brought by numerous types of learning resources and provide personalized and high-quality learning experiences for learners. At the same time, adjusting and innovating teaching models for teachers has great reference value.
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