Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetrahedral copper(I) TpCuP complexes 1-15, where Tp is a N,N,N-tris(azolyl)borate and P is a tertiary phosphine, have been synthesized and characterized by means of NMR, ESI-MS, and XAS-EXAFS, and X-ray diffraction analyses on the representative complexes 1 and 10, respectively. All copper(I) complexes were evaluated for their antiproliferative activity against a panel of human cancer cell lines (including cisplatin and multidrug-resistant sublines). The two most effective complexes [HB(pz)3]Cu(PCN), 1, and [HB(pz)3]Cu(PTA), 2, showed selectivity toward tumor vs normal cells, inhibition of 26S proteasome activity associated with endoplasmic reticulum (ER) stress, and unfolded protein response (UPR) activation. No biochemical hallmarks of apoptosis were detected, and morphology studies revealed an extensive cytoplasmic vacuolization coherently with a paraptosis-like cell death mechanism. Finally, the antitumor efficacy of complex 1 was validated in the murine Lewis Lung Carcinoma (LLC) model.
...
PMID:In vitro and in vivo anticancer activity of copper(I) complexes with homoscorpionate tridentate tris(pyrazolyl)borate and auxiliary monodentate phosphine ligands. 2479 39

Cancer-related fatigue at the time of tumor diagnosis is commonly attributed to inflammation associated with the disease process. However, we have previously demonstrated that running wheel deficits occur well before increased expression of proinflammatory cytokines in the liver and brain in a murine model of human papilloma virus-related head and neck cancer (mEER). Further, we have demonstrated that genetic deletion of type I interleukin-1 receptor and MyD88 has no effect. In the current investigation we sought to test the generality of this finding by assessing whether there is a role for toll-like receptor (TLR) 4-dependent inflammation in the fatigue-like behavior observed in mice with Lewis Lung Carcinoma (LLC) or mEER tumors. Genetic deletion of TLR4 attenuated tumor-induced elevations in liver pro-inflammatory cytokine expression in both models. However, it only abrogated wheel running deficits in LLC tumor bearing mice. To determine whether TLR4 signaling in the LLC model involves innate immune cells, mice were treated with the colony stimulating factor (CSF)-1 receptor antagonist PLX-5622 before and throughout tumor development to deplete microglia and peripheral macrophages. Administration of PLX-5622 had no protective effect on wheel running deficits in either mEER or LLC tumor models despite effective depletion of microglia and a down regulation of peripheral proinflammatory cytokine expression. These results indicate that the TLR4 signaling that mediates fatigue-like behavior in LLC mice is not dependent upon microglial or peripheral macrophage activation. Based on the literature and our data demonstrating attenuation of ubiquitin proteasome pathway activation in the gastrocnemius muscle of Tlr4-/- mice implanted with LLC cells, we interpret our current findings as indication that skeletal muscle TLR4 signaling may be involved. These results are important in that they add to the evidence that tumor-induced fatigue develops independently from classical neuroinflammation.
 ...
PMID:Toll-like receptor 4 mediates the development of fatigue in the murine Lewis Lung Carcinoma model independently of activation of macrophages and microglia. 3297 44