Despite the demonstrated constitutive activation of NF-kappaB in nasopharyngeal carcinoma (NPC), the therapeutic potential of targeting this pathway has not been investigated. Here, we employed a small molecule inhibitor of NF-kappaB, DHMEQ (which mainly blocks nuclear translocation of activated NF-kappaB) and demonstrated significant inhibition of NPC cell proliferation, migration, invasion, as well as anchorage-independent growth. These antitumor effects were associated with induction of G(2)/M cell cycle arrest and apoptosis, and downregulation of NF-kappaB target genes (EGFR, cyclin D1 and survivin). This first demonstration of therapeutic benefits of NF-kappaB targeting in NPC implicates the importance of targeting this pathway in NPC.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.canlet.2009.05.022 | DOI Listing |
Expert Opin Ther Pat
December 2024
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.
Introduction: Xanthine oxidase (XO) catalyzes the oxidation of both hypoxanthine and xanthine in the last two steps of the purine metabolic pathway, serving as a rate-limiting enzyme for uric acid production as well as a key target for the treatment of gout and other hyperuricemia-related conditions.
Areas Covered: This paper reviews XO inhibitors in patents from 2021 to the present. We summarize in detail the structural classes and characteristics, in vitro and in vivo biological results, and structure‒activity relationships of synthetic inhibitors, as well as the sources, specific structures, research methods, and biological activities of XO inhibitors from natural products.
BMC Genomics
December 2024
Department of Medicine and Animal Surgery, Veterinary Science, University of Murcia, Murcia, Spain.
Background: Extracellular vesicles (EVs) are essential for cell-to-cell communication because they transport functionally active molecules, including proteins, RNA, and lipids, from secretory cells to nearby or distant target cells. Seminal plasma contains a large number of EVs (sEVs) that are phenotypically heterogeneous. The aim of the present study was to identify the RNA species contained in two subsets of porcine sEVs of different sizes, namely small sEVs (S-sEVs) and large sEVs (L-sEVs).
View Article and Find Full Text PDFHum Cell
December 2024
Section of Oncopathology and Morphological Pathology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miazaki, 889-1692, Japan.
Hepatocyte growth factor activator inhibitor type 1 (HAI-1), which is encoded by the SPINT1 gene, is a membrane-associated serine proteinase inhibitor abundantly expressed in epithelial tissues. We had previously demonstrated that HAI-1 is critical for placental development, epidermal keratinization, and maintenance of keratinocyte morphology by regulating cognate proteases, matriptase and prostasin. After performing ultrastructural analysis of Spint1-deleted skin tissues, our results showed that Spint1-deleted epidermis exhibited partially disrupted epidermal basement-membrane structures.
View Article and Find Full Text PDFSci Rep
December 2024
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Targeting nuclear mechanics is emerging as a promising therapeutic strategy for sensitizing cancer cells to immunotherapy. Inhibition of the mechano-sensory kinase ATR leads to mechanical vulnerability of cancer cells, causing nuclear envelope softness and collapse and activation of the cGAS-STING-mediated innate immune response. Finding novel compounds that interfere with the non-canonical role of ATR in controlling nuclear mechanics presents an intriguing therapeutic opportunity.
View Article and Find Full Text PDFNPJ Regen Med
December 2024
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.
As an emerging type of pluripotent stem cells, chemically induced pluripotent stem cells (CiPSCs) avoid the risks of genomic disintegration by exogenous DNAs from viruses or plasmids, providing a safer stem cell source. To verify CiPSCs' capacity to differentiate into retinal organoids (ROs), we induced CiPSCs from mouse embryonic fibroblasts by defined small-molecule compounds and successfully differentiated the CiPSCs into three-dimensional ROs, in which all major retinal cell types and retinal genes were in concordance with those in vivo. We transplanted retinal photoreceptors from ROs into the subretinal space of retinal degeneration mouse models and the cells could integrate into the host retina, establish synaptic connections, and significantly improve the visual functions of the murine models.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!