Dual blockade of EGFR and PI3K signaling pathways offers a therapeutic strategy for glioblastoma.

Background: Glioblastoma multiforme (GBM) is a devastating disease that lacks effective drugs for targeted therapy. Previously, we found that the third-generation epidermal growth factor receptor (EGFR) inhibitor AZD-9291 persistently blocked the activation of the ERK pathway but had no inhibitory effect on the phosphoinositide 3-kinase (PI3K)/Akt pathway. Given that the PI3K inhibitor GDC-0084 is being evaluated in phase I/II clinical trials of GBM treatment, we hypothesized that combined inhibition of the EGFR/ERK and PI3K/Akt pathways may have a synergistic effect in the treatment of GBM.

Corrigendum: MELK Inhibition Effectively Suppresses Growth of Glioblastoma and Cancer Stem-Like Cells by Blocking AKT and FOXM1 Pathways.

[This corrects the article DOI: 10.3389/fonc.2020.

GRP78 blockade overcomes intrinsic resistance to UBA1 inhibitor TAK-243 in glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor of the central nervous system. Despite continuous progression in treatment options for GBM like surgery, radiotherapy, and chemotherapy, this disease still has a high rate of recurrence. The endoplasmic reticulum (ER) stress pathway is associated with chemotherapeutic drug resistance.

GRP78 determines glioblastoma sensitivity to UBA1 inhibition-induced UPR signaling and cell death.

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor for which new therapeutic approaches are urgently required. Unfolded protein response (UPR) plays an important role in the progression of GBM and is a promising target for developing novel therapeutic interventions. We identified ubiquitin-activating enzyme 1 (UBA1) inhibitor TAK-243 that can strongly induce UPR in GBM cells.

Csnk1a1 inhibition modulates the inflammatory secretome and enhances response to radiotherapy in glioma.

Glioblastoma multiforme (GBM), a fatal brain tumour with no available targeted therapies, has a poor prognosis. At present, radiotherapy is one of the main methods to treat glioma, but it leads to an obvious increase in inflammatory factors in the tumour microenvironment, especially IL-6 and CXCL1, which plays a role in tumour to resistance radiotherapy and tumorigenesis. Casein kinase 1 alpha 1 (CK1α) (encoded on chromosome 5q by Csnk1a1) is considered an attractive target for Tp53 wild-type acute myeloid leukaemia (AML) treatment.

MELK Inhibition Effectively Suppresses Growth of Glioblastoma and Cancer Stem-Like Cells by Blocking AKT and FOXM1 Pathways.

Glioblastoma multiforme (GBM) is a devastating disease yet no effective drug treatment has been established to date. Glioblastoma stem-like cells (GSCs) are insensitive to treatment and may be one of the reasons for the relapse of GBM. Maternal embryonic leucine zipper kinase gene () plays an important role in the malignant proliferation and the maintenance of GSC stemness properties of GBM.

[DESIGN AND CLINICAL APPLICATION OF LESSER TROCHANTERIC REDUCTION FIXATION SYSTEM].

Objective: To design and produce a lesser trochanteric reduction fixation system and verify its value and effectiveness.

Methods: A lesser trochanteric reduction fixation system was designed and produced according to the anatomical features of the lesser trochanteric fractures. Sixty-six patients with intertrochanteric fractures of Evans type III were included between January 2010 and July 2012.

Highly efficient and completely flexible fiber-shaped dye-sensitized solar cell based on TiO2 nanotube array.

A type of highly efficient completely flexible fiber-shaped solar cell based on TiO(2) nanotube array is successfully prepared. Under air mass 1.5G (100 mW cm(-2)) illumination conditions, the photoelectric conversion efficiency of the solar cell approaches 7%, the highest among all fiber-shaped cells based on TiO(2) nanotube arrays and the first completely flexible fiber-shaped DSSC.

A cylindrical core-shell-like TiO2 nanotube array anode for flexible fiber-type dye-sensitized solar cells.

A versatile anodization method was reported to anodize Ti wires into cylindrical core-shell-like and thermally crystallized TiO2 nanotube (TNT) arrays that can be directly used as the photoanodes for semi- and all-solid fiber-type dye-sensitized solar cells (F-DSSC). Both F-DSSCs showed higher power conversion efficiencies than or competitive to those of previously reported counterparts fabricated by depositing TiO2 particles onto flexible substrates. The substantial enhancement is presumably attributed to the reduction of grain boundaries and defects in the prepared TNT anodes, which may suppress the recombination of the generated electrons and holes, and accordingly lead to more efficient carrier-transfer channels.

Interfacial reaction growth approach to preparing patterned nanomaterials and beyond.

In conventional template-assisted synthesis, a template is used as a physical confiner to control the morphologies of the prepared materials. However, the template can also initiate interfacial reactions to form various patterned materials at its exposed surfaces. This concept can evolve into a general interfacial reaction growth approach in nanofabrications.

Chemical characterization of Auricularia auricula polysaccharides and its pharmacological effect on heart antioxidant enzyme activities and left ventricular function in aged mice.

Age is a major risk factor for cardiovascular disease including heart disease. The aim of this study was to investigate chemical composition and structure of Auricularia auricula polysaccharides and its effect in improving heart function by examining blood and heart antioxidant enzyme activity and heart function parameters, e.g.

[Effect of blood glucose control on level of lactic acid in patients with cardic-valve replacement].

Objective: To evaluate the effect of different control levels of glucose on the serum lactic acid during operation, and to investigate the relation between glucose and lactic acid to find a new way of myocardial protection.

Methods: Volunteers were divided into an experiment group(n=38) and a control group(n=33) by random sampling and double blind method. The experiment group received intensive insulin therapy and the control group received traditional therapy.

[Measurement of activated clotting time during cardiopulmonary bypass in infective endocarditis patients].

Objective: To investigate the proper dosage of heparin and protamin in treating the patients with infective endocarditis (IE) during the operation.

Methods: Activated clotting time (ACT) was measured during and after cardiopulmonary bypass (CPB) in 30 patients with IE and 30 patients with rheumatic heart disease (RHD) respectively.

Results: The dosage of heparin before bypass in IE group was significantly higher than that of RHD group (P<0.

Transfection of human VEGF165 gene into bone marrow mesenchymal stem cells in rats.

Objective: To create a method for transfecting human vascular endothelial growth factor165 (hVEGF165) gene into bone marrow mesenchymal stem cells (MSCs) in rats.

Methods: MSCs of Wistar rats were isolated by density gradient centrifugation and purified based on their ability of adhesion to plastic. Detections of cell surface antigens, including CD34, CD45, CD44, and SH3, were performed using flow cytometry.

[Effects of myocardial transplantation of mesenchymal stem cells transfected with vascular endothelial factor gene on improvement of heart function and angiogenesis after myocardial infarction: experiment with rats].

Unlabelled: To establish a method to transfect vascular endothelial factor (VEGF) gene into mesenchymal stem cells ( MSCs) , to investigate the effects of the gene-transfected MSCs on heart function restoration and angiogenesis after myocardial infarction, and to compare the differences among cell therapy, gene therapy, and combined therapy.

Methods: Seventy-one Wistar rats underwent ligation of the left anterior descending coronary artery so as to establish heart ischemia models. Fifteen rats underwent sham operation.

Effects of myocardial transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor for the improvement of heart function and angiogenesis after myocardial infarction.

Objective: To establish the transfection method of vascular endothelial growth factor (VEGF) gene into mesenchymal stem cells (MSCs), to investigate the effect of this gene-transfected MSCs for heart function restoration and angiogenesis after myocardial infarction, and to compare the therapeutic differences among cell therapy, gene therapy, and combined therapy.

Methods: Ischemic heart models were constructed in inbred Wistar rats by ligation of the left anterior descending coronary artery. MSCs of Wistar rats were isolated by density gradient centrifugation and purified on the basis of their ability to adhere to plastic, and identified by checking the surface markers and their differentiation capacity, and then followed by transfection of pcDNA(3.

Low-dose anticoagulation in Chinese patients with mechanical heart valves.

The aim of this study was to provide guidelines for optimal anticoagulation in Chinese patients after mechanical heart valve replacement. A Carbomedics valve was implanted in 178 patients between July 2000 and July 2003. During follow-up, 22 bleeding events and 1 thromboembolic complication occurred.

[Anticoagulation in chinese patients with carbomedics mechanical prosthetic heart valves].

Objective: To provide some references for defining the Chinese optimal intensity of anticoagulation after mechanical heart valve prostheses replacement.

Methods: For the 178 patients with carbomedics mechanical prosthetic heart valves, the means of INR were compared between the patients with complications and those without complications at the standard of INR1. 4 - 2.