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Genska terapija v onkologiji, prvi razvojni koraki v Sloveniji
Maja Čemažar, Tanja Dolinšek, Maša Bošnjak, Boštjan Markelc, Urška Kamenšek, Simona Kranjc, Špela Kos, Urša Lampreht Tratar, Katarina Žnidar, Andrej Renčelj, Urška Matkovič, Teja Valant, Kristina Levpušček, Živa Modic, Tilen Komel, Tim Božič, Urša Kešar, Barbara Starešinič, Katja Uršič Valentinuzzi, Monika Štimac, Primož Strojan, Gorana Gašljević, Maja Ota, Aleš Grošelj, Črt Jamšek, Rosana Hudej, Matjaž Peterka, Franc Smrekar, Barbara Hubad, Marjan Hosta, Jaka Kužnik, Alojz Hosta, Damijan Miklavčič, Matej Reberšek, Aleksandra Cvetkoska, Anja Zajc, Janja Dermol-Černe, Nataša Tozon, Nina Milevoj, Alenka Nemec Svete, Gregor Serša, 2022, strokovni članek

Povzetek: Genska terapija postaja čedalje bolj zanimiva tudi v onkologiji. Med aplikacijami je morda najzanimivejša imunostimulacija. Pripravimo lahko plazmidno DNA, ki nosi zapis za različne imunostimulatorne molekule, ki jih vnesemo v celice tumorjev ali normalnih tkiv. Ta tkiva postanejo proizvajalci teh molekul, ki lahko delujejo lokalno ali pa se izločajo tudi sistemsko v krvni obtok. Ker plazmidna DNA ne prehaja celične membrane, so potrebni dostavni sistemi, virusni ali nevirusni. V naših študijah uporabljamo predvsem nevirusni dostavni sistem – elektroporacijo. Interlevkin 12 (IL-12) je eden od zanimivih citokinov, za katerega je znano protitumorsko delovanje s spodbujanjem imunskega odziva in antiangiogenim delovanjem. Namen projekta SmartGene.si je bil pripraviti plazmid z zapisom za interlevkin 12 (plazmid phIL12) in pripraviti vse potrebno za njegovo klinično testiranje za zdravljenje kožnih tumorjev. V konzorciju smo združili moči s partnerji z akademskega in industrijskega področja. Treba je bilo pripraviti plazmid za uporabo v humani onkologiji po zahtevah Evropske agencije za zdravila (EMA). Za prijavo klinične študije na Javno agencijo za zdravila in medicinske pripomočke (JAZMP) smo morali izvesti tudi vse neklinične raziskave o varnosti in učinkovitosti zdravila. Nato je bilo treba razviti postopek priprave zdravila, zagotoviti primerne prostore za pripravo in izvedbo postopka priprave zdravila. V treh letih smo dosegli vse te zastavljene cilje in dobili dovoljenje za izvajanje klinične študije na kožnih tumorjih, ki ga je izdala JAZMP na osnovi pozitivnega mnenja Komisije Republike Slovenije za medicinsko etiko. Zdaj poteka klinična študija faze I preizkušanja plazmida phIL12 na kožnih tumorjih glave in vratu z namenom preveriti varnost in sprejemljivost genskega elektroprenosa plazmida v tumorje. Cilj študije je prav tako določiti primeren odmerek zdravila, ki bi ga v nadaljnji klinični študiji uporabili kot adjuvantno zdravljenje k ablativnim terapijam, kot sta radioterapija ali elektrokemoterapija.
Ključne besede: genska terapija, interlevkin-12, plazmidna DNA, elektroprenos genov, rak kože
Objavljeno v DiRROS: 01.07.2022; Ogledov: 104; Prenosov: 36
.pdf Celotno besedilo (420,40 KB)

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Carboxypeptidase cathepsin X defines a multifunctional role of gamma-enolase in cancer
Tjaša Vižin, Anja Pišlar, Ib Jarle Christensen, Hans Jørgen Nielsen, Pika Meško-Brguljan, Janko Kos, 2022, izvirni znanstveni članek

Povzetek: Gamma-enolase enzymatic activity is involved in glycolysis, a prevalent process in cancer cell metabolism. Additionally, gamma-enolase has a pro-survival function, exhibited through the active site at the C-terminal end of the molecule. This activity is regulated by cysteine peptidase cathepsin X, which cleaves two amino acids at C-terminal end of gamma-enolase. In clinical practice, the determination of gamma-enolase as a tumour marker does not differ between total, uncleaved and C-terminally cleaved forms. However, levels of uncleaved gamma-enolase alone may provide additional clinical information. In this study we analysed cathepsin X, C- terminally uncleaved and total gamma-enolase in tumour cell lines and sera from 255 patients with colorectal cancer (CRC) by western blot, immunoprecipitation, enzymatic activity, ELISAs and ECLIA. Results show that uncleaved gamma-enolase, rather than total gamma- enolase, exhibits different levels in cells, being the highest in those, derived from metastatic sites or highly invasive tumours. Gamma-enolase is secreted into the extracellular space predominantly as an uncleaved form and levels were congruent to those within the cells. Furthermore, levels of uncleaved gamma-enolase in cells are inversely related to cathepsin X protein level and its enzymatic activity. Uncleaved gamma-enolase is also predominant form in sera of patients with CRC. Both forms exhibit similar stage dependent distribution, with slightly elevated levels in stage IV patients. Higher levels of total gamma-enolase are significantly related to shorter survival in patients with metastatic CRC. Results support evidence of additional pro-survival function of gamma-enolase in cancer. Future studies should focus on analysis of uncleaved gamma-enolase in tumour samples, which may provide additional relations to clinical indicators of disease progression.
Ključne besede: cancer, cathepsin X, cell survival, gamma-enolase, prognosis
Objavljeno v DiRROS: 06.04.2022; Ogledov: 165; Prenosov: 124
.pdf Celotno besedilo (1,16 MB)
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Poročilo o poteku študije za uvajanje tekočinske tehnologije v Sloveniji
Veronika Kloboves-Prevodnik, Mojca Florjančič, Tine Jerman, Jerneja Kos, Urška Ivanuš, 2021, objavljeni znanstveni prispevek na konferenci

Ključne besede: epidemija, presejalni programi, rak materničnega vratu, citopatologija
Objavljeno v DiRROS: 16.03.2022; Ogledov: 154; Prenosov: 79
.pdf Celotno besedilo (763,17 KB)
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Podobe gozdnega revirja
Anton Lesnik, Gal Fidej, Jože Prah, Jože Mori, Jože Kos, Jurij Diaci, Kristina Sever, Marija Imperl, 2022, poljudni članek

Ključne besede: revirni gozdar
Objavljeno v DiRROS: 08.03.2022; Ogledov: 271; Prenosov: 40
.pdf Celotno besedilo (522,26 KB)

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Incidence and control of steroid-induced hyperglycaemia in hospitalised patients at a tertiary care centre for lung diseases
Matej Dobravc Verbič, Jasna Gruban, Mojca Kerec Kos, 2021, izvirni znanstveni članek

Povzetek: Background The aim of this study was to determine the incidence of steroid-induced hyperglycaemia (SIH) in patients hospitalised at the tertiary centre for lung diseases, to assess glycaemic control during hospitalisation, and to determine the factors associated with the control of SIH. Methods A 4-month retrospective study was conducted. All patients who received systemic glucocorticoids for%%%2 days during hospitalisation, with%%%2 elevated blood glucose (BG) readings, were included in the analysis. SIH control was determined by mean BG levels, the number and proportion of elevated and pronouncedly elevated BG readings, and the number of hypoglycaemic events. Results 60 of 283 patients (21.2%) developed SIH, of which 55 patients were included in further analysis. Mean fasting and daytime BG levels were 7.8%%%2.9 mmol/l and 10.9%%%2.2 mmol/l, respectively. 41/55 patients (74.5%) had elevated average BG levels. 45/55 patients (81.8%) had%>%5 readings or%>%20% of all readings exceeding hyperglycaemia threshold, and 33/55 patients (60.0%) had pronouncedly elevated BG levels on more than one occasion. 6/55 patients (10.9%) experienced more than one hypoglycaemic event or a severe hypoglycaemia. Only 9/55 patients (16.4%) achieved adequate SIH control according to all defined criteria. Pre-existing diabetes and longer duration of hospital treatment with low glucocorticoid dose were significantly associated with poorer glycaemic control (p%<%0.001 and p%=%0.003, respectively). Conclusions Appropriate SIH management was demonstrated to be challenging. According to the defined criteria, adequate glycaemic control during hospitalisation was not achieved in the large majority of patients with SIH.
Ključne besede: hyperglycaemia, glucocorticoids, acetylcholine, blood glucose levels, antidiabetic therapy, steroid diabetes
Objavljeno v DiRROS: 10.03.2021; Ogledov: 478; Prenosov: 121
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