Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.

The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/β-catenin signaling in a casein kinase 1 (CK1) ε/δ-dependent manner. TPA stabilized CK1ε and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1ε-LRP6-axin1 complex, leading to an increase in cytosolic β-catenin. Moreover, TPA increased the association of β-catenin with TCF4E in a CK1ε/δ-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1ε/δ inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/β-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/β-catenin signaling

Multi-omics analyses of glucose metabolic reprogramming in colorectal cancer

BackgroundGlucose metabolic reprogramming (GMR) is a cardinal feature of carcinogenesis and metastasis. However, the underlying mechanisms have not been fully elucidated. The aim of this study was to profile the metabolic signature of primary tumor and circulating tumor cells from metastatic colorectal cancer (mCRC) patients using integrated omics analysis.MethodsPET-CT imaging, serum metabolomics, genomics and proteomics data of 325 high 18F-fluorinated deoxyglucose (FDGhigh) mCRC patients were analyzed. The para-tumor, primary tumor and liver metastatic tissues of mCRC patients were used for proteomics analysis.ResultsThe glucose uptake in tumor tissues as per the PET/CT images was correlated to serum levels of glutamic-pyruvic transaminase (ALT), total bilirubin (TBIL), creatinine (CRE). Proteomics analysis indicated that several differentially expressed proteins were enriched in both GMR and epithelial-mesenchymal transition (EMT)-related pathways. Using a tissue-optimized proteomic workflow, we identified novel proteomic markers (e.g. CCND1, EPCAM, RPS6), a novel PCK1-CDK6-INSR protein axis, and a potential role for FOLR (FR) in GMR/EMT of CRC cells. Finally, CEA/blood glucose (CSR) was defined as a new index, which can be used to jointly diagnose liver metastasis of colorectal cancer.ConclusionsGMR in CRC cells is closely associated with the EMT pathway, and this network is a promising source of potential therapeutic targets

Identification of hub genes and construction of prognostic nomogram for patients with Wilms tumors

BackgroundIn children, Wilms’ tumors are the most common urological cancer with unsatisfactory prognosis, but few molecular prognostic markers have been discovered for it. With the rapid development of high-throughput quantitative proteomic and transcriptomic approaches, the molecular mechanisms of various cancers have been comprehensively explored. This study aimed to uncover the molecular mechanisms underlying Wilms tumor and build predictive models by use of microarray and RNA-seq data.MethodsGene expression datasets were downloaded from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. Bioinformatics methods wereutilized to identified hub genes, and these hub genes were validated by experiment. Nomogram predicting OS was developed using genetic risk score model and clinicopathological variables.ResultsCDC20, BUB1 and CCNB2 were highly expressed in tumor tissues and able to affect cell proliferation and the cell cycle of SK-NEP-1 cells. This may reveal molecular biology features and a new therapeutic target of Wilms tumour.7 genes were selected as prognostic genes after univariate, Lasso, and multivariate Cox regression analyses and had good accuracy, a prognostic nomogram combined gene model with clinical factors was completed with high accuracy.ConclusionsThe current study discovered CDC20,BUB1 and CCNB2 as hub-genes associated with Wilms tumor, providing references to understand the pathogenesis and be considered a novel candidate to target therapy and construct novel nomogram, incorporating both clinical risk factors and gene model, could be appropriately applied in preoperative individualized prediction of malignancy in patients with Wilms tumor

Development of a CT image analysis-based scoring system to differentiate gastric schwannomas from gastrointestinal stromal tumors

PurposeTo develop a point-based scoring system (PSS) based on contrast-enhanced computed tomography (CT) qualitative and quantitative features to differentiate gastric schwannomas (GSs) from gastrointestinal stromal tumors (GISTs).MethodsThis retrospective study included 51 consecutive GS patients and 147 GIST patients. Clinical and CT features of the tumors were collected and compared. Univariate and multivariate logistic regression analyses using the stepwise forward method were used to determine the risk factors for GSs and create a PSS. Area under the receiver operating characteristic curve (AUC) analysis was performed to evaluate the diagnostic efficiency of PSS.ResultsThe CT attenuation value of tumors in venous phase images, tumor-to-spleen ratio in venous phase images, tumor location, growth pattern, and tumor surface ulceration were identified as predictors for GSs and were assigned scores based on the PSS. Within the PSS, GS prediction probability ranged from 0.60% to 100% and increased as the total risk scores increased. The AUC of PSS in differentiating GSs from GISTs was 0.915 (95% CI: 0.874–0.957) with a total cutoff score of 3.0, accuracy of 0.848, sensitivity of 0.843, and specificity of 0.850.ConclusionsThe PSS of both qualitative and quantitative CT features can provide an easy tool for radiologists to successfully differentiate GS from GIST prior to surgery

Melt-based, solvent-free additive manufacturing of biodegradable polymeric scaffolds with designer microstructures for tailored mechanical/biological properties and clinical applications

Biodegradable scaffolds are considered as the key component of tissue engineering which serve as temporary structural supports for tissue regeneration. The mechanical/biological properties of artificial synthetic polymeric scaffolds are highly dependent on their structural organisations. Additive manufacturing (AM) techniques have provided unprecedented opportunities to customise patient-specific scaffolds with complex architectures in a reproducible manner. Here we provide a state-of-the-art review on the recent development and application of melt-based, solvent-free AM techniques to produce biodegradable polymeric scaffolds for better understanding their structure–property-function relationships for different tissue regeneration. Typical biodegradable polymers for melt-based AM are introduced, and key melt-based AM techniques including extrusion-based printing, selective laser sintering and high-resolution electrohydrodynamic bioprinting are highlighted. The critical strategies by structural design to regulate the mechanical/biological properties of as-fabricated biodegradable scaffolds in vitro and in vivo are summarised. The clinical trials as well as potential challenges of the resultant scaffolds were finally reviewed and discussed

Bilateral chylothorax after left neck lymphadenectomy for thyroid cancer: A case report

Introduction: Chylothorax is caused by lymphatic chyle fluid leaking back through the thoracic duct and accumulating in the pleural cavity. It is related to a thoracic duct injury or occlusion. It is rare to have bilateral chylothorax after cervical lymph node dissection for thyroid cancer diagnosis. Case report: A 28-year-old woman was admitted to our hospital with bilateral hypoechoic thyroid nodules and cervical lymph node abnormalities. She underwent thyroidectomy and lymphadenectomy but developed chylothorax 3 days after surgery. She was treated with bilateral thoracic drainage, electrolyte supplementation, and somatostatin, and was discharged 17 days post-treatment. Conclusion: Bilateral chylothorax is a rare complication of thyroid cancer surgery. Early diagnosis and treatment, especially the detection of dyspnea, are key. Also, unobstructed bilateral thoracic drainage, improved surgical skills, and reduced thoracic duct injuries can help reduce complications

Polymeric Ionic Liquid Grafted on Silica for Efficient Conversion of CO2 into Cyclic Carbonates

On the basis of efficient and recyclable criteria for catalytic conversion of CO2 into cyclic carbonates, functionalized polymeric ionic liquids grafted onto the silica (PIL@SiO2) are explored by the polymeric method herein. Among all the prepared PIL@SiO2, the PIL@SiO2 loaded with a high mass fraction (50%) of PIL is the best in catalytic activity, achieving 91% PO conversion, nearly 50% saved than the non-grafted PIL. In addition, the PIL@SiO2 exhibits higher performance than PILs under identical reaction conditions. Subsequent studies concerning recyclability confirm that the as-prepared catalyst is stable after 5 times recycle without obvious loss in activity. This grafting and polymerization process provides an efficient and sustainable way of CO2 conversion in the long term. [GRAPHICS]