Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells.

Ecto-5'-nucleotidase (CD73), encoded by the NT5E gene, mediates tumor immunosuppression and has been targeted for the development of new anticancer drugs. Proteasome inhibitors impair protein degradation by inhibiting proteasome and have been used in the clinic for cancer therapy. Here we report that proteasome inhibitors reduce the protein and mRNA levels of CD73.

Loss of VOPP1 Contributes to BET Inhibitor Acquired Resistance in Non-Small Cell Lung Cancer Cells.

Unlabelled: Inhibitors targeting bromodomain and extraterminal (BET) proteins are promising anticancer drugs. The emergence of drug resistance during treatments will impair their therapeutic effectiveness. To investigate the mechanisms of acquired resistance to BET inhibitors (BETi), we generated a series of drug-resistant sublines by exposing non-small cell lung cancer (NSCLC) NCI-H1975 cells to the BETi ABBV-075.

Novel bivalent BET inhibitor N2817 exhibits potent anticancer activity and inhibits TAF1.

Bromodomain and extra-terminal domain (BET) family proteins are promising anticancer targets. Most BET inhibitors in clinical trials are monovalent. They competitively bind to one of the bromodomains (BD1 and BD2) in BET proteins and exhibit relatively weak anticancer activity, poor pharmacokinetics, and low metabolic stability.

Polymerase independent repression of FoxO1 transcription by sequence-specific PARP1 binding to FoxO1 promoter.

Poly(ADP-ribose) polymerase 1 (PARP1) regulates gene transcription in addition to functioning as a DNA repair factor. Forkhead box O1 (FoxO1) is a transcription factor involved in extensive biological processes. Here, we report that PARP1 binds to two separate motifs on the FoxO1 promoter and represses its transcription in a polymerase-independent manner.

Structure-Based Discovery and Development of a Series of Potent and Selective Bromodomain and Extra-Terminal Protein Inhibitors.

BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound harboring a five-membered-ring linker motif, we quickly identified lead compound , which exhibited good antitumor effects in an MM.

Inhibition of the BET family reduces its new target gene IDO1 expression and the production of L-kynurenine.

The bromodomain and extra terminal domain (BET) family members, including BRD2, BRD3, and BRD4, act as epigenetic readers to regulate gene expression. Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that participates in tumor immune escape primarily by catalyzing tryptophan to L-kynurenine. Here, we report that IDO1 is a new target gene of the BET family.

A new BET inhibitor, 171, inhibits tumor growth through cell proliferation inhibition more than apoptosis induction.

The bromodomain and extra-terminal domain (BET) family of proteins, especially bromodomain-containing protein 4 (BRD4), has emerged as exciting anti-tumor targets due to their important roles in epigenetic regulation. Therefore, the discovery of BET inhibitors with promising anti-tumor efficacy will provide a novel approach to epigenetic anticancer therapy. Recently, we discovered the new BET inhibitor compound 171, which is derived from a polo-like kinase 1 (PLK1)-BRD4 dual inhibitor based on our previous research.

Monostotic fibrous dysplasia of the thoracic spine: A case report.

Background And Objective: Fibrous dysplasia (FD) is a benign bone lesion manifested by local pain, swelling and deformity change. We report a case of monostotic fibrous dysplasia of the first thoracic vertebrae that treated by radical removal and reconstruction.

Case Report: A 29-year-old man with monostotic fibrous dysplasia of the first thoracic vertebrae was admitted to our department because of persistent, dull back pain for 3 months.

A Novel Type II NAD+-Specific Isocitrate Dehydrogenase from the Marine Bacterium Congregibacter litoralis KT71.

In most living organisms, isocitrate dehydrogenases (IDHs) convert isocitrate into ɑ-ketoglutarate (ɑ-KG). Phylogenetic analyses divide the IDH protein family into two subgroups: types I and II. Based on cofactor usage, IDHs are either NAD+-specific (NAD-IDH) or NADP+-specific (NADP-IDH); NADP-IDH evolved from NAD-IDH.