1261. New inhibitors of cathepsin V impair tumor cell proliferation and elastin degradation and increase immune cell cytotoxicityAna Mitrović, Emanuela Senjor, Marko Jukič, Lara Bolčina, Mateja Prunk, Matic Proj, Milica Perišić, Stanislav Gobec, Janko Kos, 2022, izvirni znanstveni članek Povzetek: Cathepsin V is a human lysosomal cysteine peptidase with specific functions during pathological processes and is as such a promising therapeutic target. Peptidase inhibitors represent powerful pharmacological tools for regulating excessive proteolytic activity in various diseases. Cathepsin V is highly related to cathepsin L but differs in tissue distribution, binding site morphology, substrate specificity, and function. To validate its therapeutic potential and extend the number of potent and selective cathepsin V inhibitors, we used virtual high-throughput screening of commercially available compound libraries followed by an evaluation of kinetic properties to identify novel potent and selective cathepsin V inhibitors. We identified the ureido methylpiperidine carboxylate derivative, compound 7, as a reversible, selective, and potent inhibitor of cathepsin V. It also exhibited the most preferable characteristics for further evaluation with in vitro functional assays that simulate the processes in which cathepsin V is known to play an important role. Compound 7 exerted significant effects on cell proliferation, elastin degradation, and immune cell cytotoxicity. The latter was increased because compound 7 impaired conversion of immunosuppressive factor cystatin F to its active monomeric form. Taken together, our results present novel potent inhibitors of cathepsin V and provide new hit compounds for detailed development and optimization. Further, we demonstrate that cathepsin V is a potential target for new approaches to cancer therapy.
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1264. Cysteine cathepsins as regulators of the cytotoxicity of NK and T cellsMilica Perišić, Jerica Sabotič, Anahid Jewett, Janko Kos, 2014, pregledni znanstveni članek Povzetek: Cysteine cathepsins are lysosomal peptidases involved at different levels in the processes of the innate and adaptive immune responses. Some, such as cathepsins B, L, and H are expressed constitutively in most immune cells. In cells of innate immunity they play a role in cell adhesion and phagocytosis. Other cysteine cathepsins are expressed more specifically. Cathepsin X promotes dendritic cell maturation, adhesion of macrophages, and migration of T cells. Cathepsin S is implicated in major histocompatibility complex class II antigen presentation, whereas cathepsin C, expressed in cytotoxic T lymphocytes and natural killer (NK) cells, is involved in processing pro-granzymes into proteolytically active forms, which trigger cell death in their target cells. The activity of cysteine cathepsins is controlled by endogenous cystatins, cysteine protease inhibitors. Of these, cystatin F is the only cystatin that is localized in endosomal/lysosomal vesicles. After proteolytic removal of its N-terminal peptide, cystatin F becomes a potent inhibitor of cathepsin C with the potential to regulate pro-granzyme processing and cell cytotoxicity. This review is focused on the role of cysteine cathepsins and their inhibitors in the molecular mechanisms leading to the cytotoxic activity of T lymphocytes and NK cells in order to address new possibilities for regulation of their function in pathological processes.
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1267. Zdravljenje raka prostate : kdaj obsevanjeBorut Kragelj, 2019, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: rak prostate, kirurško zdravljenje, radioterapija, obsevanje
Objavljeno v DiRROS: 03.09.2025; Ogledov: 361; Prenosov: 95
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1269. Votrient (pazopanib) : spremljevalni vodnik za zdravljenjeBreda Škrbinc, 2013, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: rak ledvic, tarčna zdravila, bolniki, onkološki bolniki, vodniki
Objavljeno v DiRROS: 03.09.2025; Ogledov: 303; Prenosov: 89
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1270. Temozolomid pri zdravljenju bolnikov z možganskim tumorjem : bolnikov dnevnikUroš Smrdel, Lorna Zadravec-Zaletel, Marija Skoblar Vidmar, Gregor Kos, Ana Lina Vodušek, 2024, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: rak glave, temozolomid, možganski tumorji, bolniki
Objavljeno v DiRROS: 03.09.2025; Ogledov: 397; Prenosov: 90
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