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Povzetek: We extend the concept of a G-Drazin inverse from the set $M_n$ of all $n \times n$ complex matrices to the set ${\cal R}^D$ of all Drazin invertible elements in a ring ${\cal R}$ with identity. We also generalize a partial order induced by G-Drazin inverses from $M_n$ to the set of all regular elements in ${\cal R}^D$, study its properties, compare it to known partial orders, and generalize some known results.
Ključne besede: Drazin inverse, core-nilpotent decomposition, partial order, annihilator, ring
Objavljeno v DiRROS: 05.09.2024; Ogledov: 96; Prenosov: 54
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Povzetek: Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo. In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively. In the present study, we have evaluated its anti-cancer properties. It was more effective than nitroxoline in reducing tumor cell invasion and migration, as determined in vitro on two-dimensional cell models and tumor spheroids, under either endpoint or real time conditions. Moreover, it exhibited improved action over nitroxoline in impairing tumor growth in vivo in LPB mouse fibrosarcoma tumors in C57Bl/6 mice. Taken together, the addition of a 2-(ethylamino)acetonitrile group to nitroxoline at position 7 significantly improves its pharmacological characteristics and its potential for use as an anti-cancer drug.
Ključne besede: nitroxoline derivative, cathepsin B, inhibition, tumor invasion, cell migration
Objavljeno v DiRROS: 26.07.2024; Ogledov: 215; Prenosov: 178
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Povzetek: Glioblastoma (GBM) is the most lethal brain tumor also due to malignant and therapy-resistant GBM stem cells (GSCs) that are localized in protecting hypoxic GSC niches. Some members of the cysteine cathepsin family of proteases have been found to be upregulated in GBM. Cathepsin K gene expression is highly elevated in GBM tissue versus normal brain and it has been suggested to regulate GSC migration out of the niches. Here, we investigated the cellular distribution of cathepsins B, X and K in GBM tissue and whether these cathepsins are co-localized in GSC niches. Therefore, we determined expression of these cathepsins in serial paraffin sections of 14 human GBM samples and serial cryostat sections of two samples using immunohistochemistry and metabolic mapping of cathepsin activity using selective fluorogenic substrates. We detected cathepsins B, X and K in peri-arteriolar GSC niches in 9 out of 16 GBM samples, which were defined by co-expression of the GSC marker CD133, the niche marker stromal-derived factor-1α (SDF-1α) and smooth muscle actin as a marker for arterioles. The expression of cathepsin B and X was detected in stromal cells and cancer cells throughout the GBM sections, whereas cathepsin K expression was more restricted to arteriole-rich regions in the GBM sections. Metabolic mapping showed that cathepsin B, but not cathepsin K is active in GSC niches. On the basis of these findings, it is concluded that cathepsins B, X and K have distinct functions in GBM and that cathepsin K is the most likely GSC niche-related cathepsin of the three cathepsins investigated.
Ključne besede: cysteine cathepsins, glioblastoma stem cells, niches, stroma, proteolytic activity
Objavljeno v DiRROS: 24.07.2024; Ogledov: 225; Prenosov: 166
Celotno besedilo (10,33 MB)
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Ključne besede: glioblastoma, cathepsin X, γ-enolase, tumor microenvironment, glioblastoma stem cells, cathepsin X inhibitors
Objavljeno v DiRROS: 16.07.2024; Ogledov: 213; Prenosov: 162
Celotno besedilo (3,51 MB)
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Ključne besede: insect pollinators, wild bees, DNA, biodiversity, databases
Objavljeno v DiRROS: 19.06.2024; Ogledov: 290; Prenosov: 152
Celotno besedilo (1,11 MB)
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