CK2 inhibitor CX-4945 destabilizes NOTCH1 and synergizes with JQ1 against human T-acute lymphoblastic leukemic cells

Here we show that CK2 inhibition by CX-4945 destabilizes NOTCH1 and synergizes with JQ1 to induce apoptosis in human T-ALL cells, implicating an alternative strategy to target NOTCH1 signaling in refractory/relapsed T-ALL

Gliosarcoma in a patient with triple-negative breast cancer: A case report

Gliosarcoma is a rare subtype of glioblastoma with the histological features of both glioblastoma and soft-tissue sarcoma. Triple-negative breast cancer (TNBC) is a special type of breast cancer that is different from other breast cancers. It is characterized by strong invasiveness, high recurrence rate, and poor prognosis. The concurrent occurrence of gliosarcoma and TNBC was rarely seen and reported. A 63-year-old woman with a history of TNBC was found to have an intracranial mass due to headache. Intracranial tumor resection surgery was undergone, and histopathological examination postoperation revealed gliosarcoma. After craniotomy, the patient underwent standard radiotherapy and chemotherapy. Postoperative follow-up observation showed no obvious recurrence of either tumor. In conclusion, gliosarcoma and TNBC are tumors with poor prognosis. It is rare to encounter two types of malignant tumors in the same patient. When we encounter intracranial space-occupying patients with a history of malignant tumors, we should first consider tumor metastasis. When excluding the possibility of cancer metastasis, the possibility of two primary tumors should be considered

Transcription factor TCF3 controls the cell proliferation and migration in glioblastoma multiforme cell lines

TCF3 is a member of the TCF/LEF transcription factor family. Recent studies have demonstrated its potential carcinogenic properties. Here we showed that TCF3 was upregulated in glioma tissues compared to normal brain tissues. This upregulation of TCF3 gene probably has functional significance in brain tumor progression. Our studies on glioblastoma multiforme cell lines showed that knock-down of TCF3 induced apoptosis, and inhibited cell migration. Further analysis revealed that down-regulation of TCF3 gene expression inhibits AKT and ERK1/2 activation, suggesting that carcinogenic properties of TCF3 in glioblastoma multiforme (GBM) are partially mediated by phosphatidylinositol 3-kinase/AKT and MAPK/ERK signaling pathways. Considering together, the results of the present study demonstrated that high levels of TCF3 in gliomas might potentially promote glioma development through AKT and ERK pathways.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm

Objective. Abdominal aortic aneurysm (AAA) development has been characterized by increased expression of vascular endothelial growth factor (VEGF), which contributes to angiogenesis via cyclooxygenase-2 (COX-2). Quercetin, one of the most common and well-researched flavonoids and abundant in vegetables and fruits, has beneficial effects in inhibiting angiogenesis. This study investigated the antiangiogenic effects of quercetin on experimental aneurysms. Methods. We utilized the in vivo AAA mouse model induced by the periaortic application of CaCl2 to examine the effectiveness of quercetin in blocking angiogenesis. Quercetin was administered at 60 mg/kg once daily on the day of the AAA induction and then continued for 6 weeks. Celecoxib, a selective COX-2 inhibitor, was used as the positive control. Results. Our results demonstrated that quercetin significantly attenuated aneurysm growth in AAA mice and medial neovascularization. Accordingly, quercetin decreased the expression of proangiogenic mediators, including VEGF-A, intercellular adhesion molecule-1, vascular cell adhesion molecule 1, and vascular endothelial cadherin. Quercetin treatment also inhibited the expression of COX-2 and hypoxia-inducible factor 1α (HIF-1α). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1α, VEGF-A, and matrix metalloproteinase activities in aortic vascular smooth muscle cells isolated from AAA mice. Conclusion. Quercetin attenuates neovascularization during AAA growth, and this effect is mediated via the inhibition of COX-2, which decreases HIF-1α/VEGF signaling-related angiogenesis

Biodegradable and Light-Responsive Polymeric Nanoparticles for Environmentally Safe Herbicide Delivery

The low utilization efficiency of pesticides exerts an adverse impact on the environment and human health. Polymer-related controlled-release nanosized pesticide systems provide a promising and efficient way to overcome the problem. In this work, a biodegradable and light-responsive amphiphilic polymer was synthesized via 1,1,3,3-tetramethylguanidine-promoted polyesterification under mild conditions (low temperature, no vacuum, and no inert gas protection). We used this polymer to fabricate a light-triggered controlled-release nanosized pesticide system. The herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was selected as a model drug to show its potential as a controlled-release pesticide system. It was found that the 2,4-D-loaded polymeric nanoparticles were stable without the treatment of UV, while the release rate of 2,4-D from the nanoparticles gradually increased after treatment with UV light. Pot trial showed that the 2,4-D-loaded polymer nanoparticles showed a good herbicidal effect. Finally, toxicity studies suggested that the polymer can reduce toxicity to nontarget organisms

Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover

Many bacterial pathogens produce diffusible signal factor (DSF)-type quorum sensing (QS) signals in modulation of virulence and biofilm formation. Previous work on Xanthomonas campestris showed that the RpfC/RpfG two-component system is involved in sensing and responding to DSF signals, but little is known in other microorganisms. Here we show that in Burkholderia cenocepacia the DSF-family signal cis-2-dodecenoic acid (BDSF) negatively controls the intracellular cyclic dimeric guanosine monophosphate (c-di-GMP) level through a receptor protein RpfR, which contains Per/Arnt/Sim (PAS)-GGDEF-EAL domains. RpfR regulates the same phenotypes as BDSF including swarming motility, biofilm formation, and virulence. In addition, the BDSF(-) mutant phenotypes could be rescued by in trans expression of RpfR, or its EAL domain that functions as a c-di-GMP phosphodiesterase. BDSF is shown to bind to the PAS domain of RpfR with high affinity and stimulates its phosphodiesterase activity through induction of allosteric conformational changes. Our work presents a unique and widely conserved DSF-family signal receptor that directly links the signal perception to c-di-GMP turnover in regulation of bacterial physiology