54 research outputs found
Novel comprehensive in vitro model of acquired resistance to carboplatin as a tool to identify new targets of ovarian cancer therapy
No full textRak jajnika je ginekološka bolest koja, uslijed nedostatka specifičnih simptoma i farmakogenetskih biljega (biomarkera), često biva otkrivena u kasnim stadijima, kada se bolest već proširila i na druge organe. Malobrojne bolesnice koje odgovore na primarnu terapiju vrlo često razviju otpornost na lijekove. Kako bismo bolje razumjeli taj ključni problem uspješne terapije, razvili smo model stanica postepenog razvoja otpornosti raka jajnika na karboplatinu, sastavljenog od roditeljskih stanica i sedam varijanti sa stabilnom rastućom otpornosti na karboplatinu. Svaka varijanta, uključujući i roditeljske stanice, karakterizirana je s obzirom na otpornost na najčešće korištene kemoterapeutike u terapiji raka jajnika, razine biljega epitelno-mezenhimske tranzicije i metastatskog potencijala. Nadalje, nakon izmjerene ekspresije gena u svim varijantama stanica korištenjem dva pristupa analizirali smo dobivene vrijednosti bioinformatičkim metodama. Dobivene liste značajno promijenjenih gena (DEG) i gena čija ekspresija korelira s odgovorom na karboplatinu (CCORG) uspoređene su u kontekstu signalnih puteva, interakcija proteina i bioloških procesa. Izdvojeni su potencijalno interesantni geni čija je uloga u procesima razvoja otpornosti i epitelno-mezenhimske tranzicije analizirana in vitro metodama, a njihov značaj kao mogućih farmakogenetskih biljega u klinici bioinformatičkim analizama informacija u dostupnim bazama podataka. Dodatnim eksperimentima korištenjem specifičnih inhibitora pojedinih proteina od interesa ispitana je važnost izdvojenih signalnih puteva u razvoju otpornosti i pokretljivosti stanica. Predstavljeni model, zajedno s dva različita pristupa analizi ekspresije gena doprinio je razumijevanju razvoja otpornosti i omogućio detekciju gena čija uloga dosad nije bila opisana u kontekstu otpornosti i pokretljivosti stanica te smo time pokazali međusobnu povezanost ova dva fenomena potaknuta lijekom.Due to the lack of specific early-stage symptoms and biomarkers, ovarian cancer is often diagnosed in late stages, when the disease has already spread. A small number of patients that positively respond to chemotherapy often develop drug resistance upon therapy. To tackle the problem, we developed high-grade serous ovarian cancer (HGSOC) model composed of variants with differing degrees of resistance to carboplatin. All variants, including the parental cells, were characterized in terms of carboplatin and paclitaxel sensitivity, markers of epithelial-mesenchymal transition and metastatic properties (migration and invasion). To understand the differences, we measured the expression of genes in all established variants and analysed it by two different bioinformatics approaches. Resulting differentially expressed gene (DEG) and carboplatin-correlating gene (CCORG) lists were compared in terms of signalling pathways, protein interactions and biological processes. Potentially interesting genes were selected and analysed in terms of their role in resistance development and metastasis by in vitro experiments. Their prognostic and predictive clinical value was examined by in silico approaches. Additional experiments using inhibitors were used to examine the role of selected signaling pathways. Presented cell model, along with two distinct approaches to gene expression analysis gave us a valuable insight in resistance development mechanisms and enabled us to select novel genes with reported functions in drug resistance and drug-induced epithelial-mesenchymal transition
Athlete`s heart syndrome
No full textSindrom sportskog srca skup je kliničkih, elektrokardiografskih i ehokardiografskih promjena koje nalazimo kod srca ozbiljnih sportaša čije bavljenje sportom uključuje najčešće dugu primarno aerobnu fizičku aktivnost. Glavne kliničke promjene koje su ključne u medicinskom razlikovanju sindroma sportskog srca od sličnih patoloških stanja su sinusna bradikardija i aritmija, zakašnjenje u atrioventrikularnom provođenju signala, povećanje srčanog miokarda (posebno lijeve klijetke), vazovagalna sinkopa, pojava srčanih šumova i elektrokardiografske promjene ST-T valova. Spomenuti simptomi sindroma naglašeniji su kod pripadnika muškog spola, iako se javljaju u vrlo maloj mjeri i kod sportaša ženskog spola. Nadalje, sportaši koji se bavi sportovima izdržljivosti poput biciklizma, trčanja, veslanja, skijaškog trčanja itd., u pravilu imaju jače simptome od ostalih. Razlog je pojačana aerobna aktivnost. Korištenjem dijagnostičkih tehnika (ehokardiografije, magnetne rezonancije srca i elektrokardiografije) još uvijek je teško sa sigurnošću odijeliti simptome sindroma sportskog srca od simptoma drugih patoloških bolesti poput displazije desne klijetke, dilatacijske kardiomiopatije, miokarditisa i hipertrofične kardiomiopatije. Zbog toga se u prošlosti, ali i danas, sindrom sportskog srca smatra sivom zonom između patološkog stanja i pozitivne evolucijske prilagodbe na stres uzrokovan intenzivnom aerobnom fizičkom aktivnošću.Athlete's heart syndrome is a set of clinical, electrocardiographic and echocardiographic changes found in the heart of serious athletes whose sports participation mostly includes long primary aerobic physical activities and actions. The main clinical changes that are essential in the medical distinction between athlete's heart syndrome from similar pathological conditions are sinus bradycardia and arrhythmia, atrioventricular delay in conducting signals, increase in cardiac muscle (especially the left ventricle), vasovagal syncope, presence of heart murmurs and electrocardiographic changes in ST-T wave. The above mentioned symptoms of the syndrome are more often among the male athletes, although they occur in very small extent among female athletes. Furthermore, athletes who specializes in endurance sports such as cycling, running, rowing, cross country skiing, etc., generally have more symptoms than others. The reason is the increased aerobic activity. Using diagnostic techniques (echocardiography, magnetic resonance imaging of the heart and electrocardiography) is still difficult to safely separate the symptoms of athlete's heart syndrome from symptoms of other pathological conditions such as right ventricular dysplasia, dilated cardiomyopathy, myocarditis and hypertrophic cardiomyopathy. Therefore, in the past, but today, the athlete's heart syndrome is considered a gray zone between the pathology and positive evolutionary adaptation to stress caused by intense aerobic physical activity
Novel comprehensive in vitro model of acquired resistance to carboplatin as a tool to identify new targets of ovarian cancer therapy
No full textRak jajnika je ginekološka bolest koja, uslijed nedostatka specifičnih simptoma i farmakogenetskih biljega (biomarkera), često biva otkrivena u kasnim stadijima, kada se bolest već proširila i na druge organe. Malobrojne bolesnice koje odgovore na primarnu terapiju vrlo često razviju otpornost na lijekove. Kako bismo bolje razumjeli taj ključni problem uspješne terapije, razvili smo model stanica postepenog razvoja otpornosti raka jajnika na karboplatinu, sastavljenog od roditeljskih stanica i sedam varijanti sa stabilnom rastućom otpornosti na karboplatinu. Svaka varijanta, uključujući i roditeljske stanice, karakterizirana je s obzirom na otpornost na najčešće korištene kemoterapeutike u terapiji raka jajnika, razine biljega epitelno-mezenhimske tranzicije i metastatskog potencijala. Nadalje, nakon izmjerene ekspresije gena u svim varijantama stanica korištenjem dva pristupa analizirali smo dobivene vrijednosti bioinformatičkim metodama. Dobivene liste značajno promijenjenih gena (DEG) i gena čija ekspresija korelira s odgovorom na karboplatinu (CCORG) uspoređene su u kontekstu signalnih puteva, interakcija proteina i bioloških procesa. Izdvojeni su potencijalno interesantni geni čija je uloga u procesima razvoja otpornosti i epitelno-mezenhimske tranzicije analizirana in vitro metodama, a njihov značaj kao mogućih farmakogenetskih biljega u klinici bioinformatičkim analizama informacija u dostupnim bazama podataka. Dodatnim eksperimentima korištenjem specifičnih inhibitora pojedinih proteina od interesa ispitana je važnost izdvojenih signalnih puteva u razvoju otpornosti i pokretljivosti stanica. Predstavljeni model, zajedno s dva različita pristupa analizi ekspresije gena doprinio je razumijevanju razvoja otpornosti i omogućio detekciju gena čija uloga dosad nije bila opisana u kontekstu otpornosti i pokretljivosti stanica te smo time pokazali međusobnu povezanost ova dva fenomena potaknuta lijekom.Due to the lack of specific early-stage symptoms and biomarkers, ovarian cancer is often diagnosed in late stages, when the disease has already spread. A small number of patients that positively respond to chemotherapy often develop drug resistance upon therapy. To tackle the problem, we developed high-grade serous ovarian cancer (HGSOC) model composed of variants with differing degrees of resistance to carboplatin. All variants, including the parental cells, were characterized in terms of carboplatin and paclitaxel sensitivity, markers of epithelial-mesenchymal transition and metastatic properties (migration and invasion). To understand the differences, we measured the expression of genes in all established variants and analysed it by two different bioinformatics approaches. Resulting differentially expressed gene (DEG) and carboplatin-correlating gene (CCORG) lists were compared in terms of signalling pathways, protein interactions and biological processes. Potentially interesting genes were selected and analysed in terms of their role in resistance development and metastasis by in vitro experiments. Their prognostic and predictive clinical value was examined by in silico approaches. Additional experiments using inhibitors were used to examine the role of selected signaling pathways. Presented cell model, along with two distinct approaches to gene expression analysis gave us a valuable insight in resistance development mechanisms and enabled us to select novel genes with reported functions in drug resistance and drug-induced epithelial-mesenchymal transition
Investigation of biological effects of sesquiterpene from Centaurea ragusina L.
No full textMaligni tumori su, uz bolesti krvožilnog sustava, glavni uzrok smrtnosti ljudske populacije. Štetne popratne pojave i razvoj otpornosti tumora na lijekove glavni su problem uspješne kemoterapije. Potreba za učinkovitijim i manje štetnim spojevima, potencijalnim novim kemoterapeuticima, je zato velika. U ovom diplomskom radu je istraženo biološko djelovanje seskviterpen laktona raguzinina, izoliranog iz hrvatskog endema Centaurea ragusina L. (dubrovačka zečina). Biološki učinak seskviterpena raguzinina na ljudske stanice tumora vrata maternice (HeLa) istražen je korištenjem kolorimetrijske metode MTT (3-(4,5- dimetiltiazol-2-il)-2,5-difeniltetrazoli bromid) te je pokazano njegovo toksično djelovanje s IC50 kod 2,2 μM. Nadalje, korištenjem protočne citometrije pokazano je da raguzinin zaustavlja stanice u fazi G2 ciklusa stanice, te potiče apoptozu. Pojava apoptoze potvrđena je bojanjem stanica s propidij jodidom i Annexin-om V označenim fluorescein izotiocijanatom. Međutim, Western blot metodom se nije utvrdilo cijepanje opće prihvaćenih biljega apoptoze, kaspaze 3 i proteina PARP. Dobiveni rezultati ukazuju na mogućnost da raguzinin potiče apoptozu neovisnu o kaspazama. Pomoću specifičnih prekursora i inhibitora sinteze glutationa i molekula uključenih u njegov metabolizam pokazano je da je glutation uključen u mehanizam smanjenja citotoksičnosti raguzinina kod stanica HeLa, te da je njegova uloga u tom procesu detoksikacijska, a ne stabilizacija oksidativno-reduktivnog sustava stanice.Malign tumours are, along with cardiovascular diseases, the main cause of death of human population. Harmful consequences and development of drug resistance are the main problems of successful chemotherapies. There is a big need for more efficient and less harmful substances, potential chemotherapeutics. In this thesis, biological effect of sesquiterpene lactone isolated from Croatian endemic plant Centaurea ragusina L. (dubrovačka zečina) was examined. Biological effect of sesquiterpene lactone ragusinin on human cervical carcinoma (HeLa) cell line was examined using colorimetric assay MTT (3- (4,5-dimetyilthiazol-2-yl)-2,5-diphenyltetrazoli bromide) and the half-maximal inhibitory concentration (IC50) of the ragusinin was obtained at 2,2 μM. We also analysed the cell cycle progression by propidium iodide staining using flow cytometry. The obtained data indicated ragusinin as a potent inducer of apoptotic cell death and as a trigger for increase in G2 phase population. The ability of ragusinin to induce apoptosis of HeLa cells was examined by Annexin V-FITC Assay using flow cytometry. The cleavage of caspase 3 and PARP was not detected indicating that ragusinin triggers caspase-independent cell death. Using specific precursors and inhibitors of glutathione synthesis and of other molecules involved in glutathione metabolism, it was shown that glutathione is involved in the mechanism of ragusinin cytotoxicity inhibition probably through detoxification mechanism, and not by stabilization of oxidative-redox system in the cell
Novel comprehensive in vitro model of acquired resistance to carboplatin as a tool to identify new targets of ovarian cancer therapy
No full textRak jajnika je ginekološka bolest koja, uslijed nedostatka specifičnih simptoma i farmakogenetskih biljega (biomarkera), često biva otkrivena u kasnim stadijima, kada se bolest već proširila i na druge organe. Malobrojne bolesnice koje odgovore na primarnu terapiju vrlo često razviju otpornost na lijekove. Kako bismo bolje razumjeli taj ključni problem uspješne terapije, razvili smo model stanica postepenog razvoja otpornosti raka jajnika na karboplatinu, sastavljenog od roditeljskih stanica i sedam varijanti sa stabilnom rastućom otpornosti na karboplatinu. Svaka varijanta, uključujući i roditeljske stanice, karakterizirana je s obzirom na otpornost na najčešće korištene kemoterapeutike u terapiji raka jajnika, razine biljega epitelno-mezenhimske tranzicije i metastatskog potencijala. Nadalje, nakon izmjerene ekspresije gena u svim varijantama stanica korištenjem dva pristupa analizirali smo dobivene vrijednosti bioinformatičkim metodama. Dobivene liste značajno promijenjenih gena (DEG) i gena čija ekspresija korelira s odgovorom na karboplatinu (CCORG) uspoređene su u kontekstu signalnih puteva, interakcija proteina i bioloških procesa. Izdvojeni su potencijalno interesantni geni čija je uloga u procesima razvoja otpornosti i epitelno-mezenhimske tranzicije analizirana in vitro metodama, a njihov značaj kao mogućih farmakogenetskih biljega u klinici bioinformatičkim analizama informacija u dostupnim bazama podataka. Dodatnim eksperimentima korištenjem specifičnih inhibitora pojedinih proteina od interesa ispitana je važnost izdvojenih signalnih puteva u razvoju otpornosti i pokretljivosti stanica. Predstavljeni model, zajedno s dva različita pristupa analizi ekspresije gena doprinio je razumijevanju razvoja otpornosti i omogućio detekciju gena čija uloga dosad nije bila opisana u kontekstu otpornosti i pokretljivosti stanica te smo time pokazali međusobnu povezanost ova dva fenomena potaknuta lijekom.Due to the lack of specific early-stage symptoms and biomarkers, ovarian cancer is often diagnosed in late stages, when the disease has already spread. A small number of patients that positively respond to chemotherapy often develop drug resistance upon therapy. To tackle the problem, we developed high-grade serous ovarian cancer (HGSOC) model composed of variants with differing degrees of resistance to carboplatin. All variants, including the parental cells, were characterized in terms of carboplatin and paclitaxel sensitivity, markers of epithelial-mesenchymal transition and metastatic properties (migration and invasion). To understand the differences, we measured the expression of genes in all established variants and analysed it by two different bioinformatics approaches. Resulting differentially expressed gene (DEG) and carboplatin-correlating gene (CCORG) lists were compared in terms of signalling pathways, protein interactions and biological processes. Potentially interesting genes were selected and analysed in terms of their role in resistance development and metastasis by in vitro experiments. Their prognostic and predictive clinical value was examined by in silico approaches. Additional experiments using inhibitors were used to examine the role of selected signaling pathways. Presented cell model, along with two distinct approaches to gene expression analysis gave us a valuable insight in resistance development mechanisms and enabled us to select novel genes with reported functions in drug resistance and drug-induced epithelial-mesenchymal transition
Trade as a Modus Vivendi of Zadar region in the 18th century
No full textU radu se evaluiraju dosadašnje historiografske spoznaje o trgovini Zadra i njegove regije u XVIII. stoljeću. Specifičan tranzitni karakter gradske luke uvjetovan je novim i jedinstvenim geostrateškim položajem grada u kontekstu imperijalnog pograničja. To potvrđuju predmeti razmjene, prometni pravci, infrastruktura i nositelji trgovačke djelatnosti. Posebna pažnja pridaje se stočnom tranzitu preko zadarske skele. Ukazuje se i na utjecaj pojačane trgovačke konjunkture u oblikovanju društvene svakodnevice. Autor konstruira narativ o Zadru kao o reprezentativnoj sponi između zapadnoeuropske pomorske i osmanske karavanske civilizacije.This master's thesis evaluates previous historiographical achievements on the trade of Zadar and its region (Contado di Zara) in the 18th century. Specific transit character of the city-port was conditioned by the new and unique geostrategical location of Zadar in the context of the triple imperial borderland concept. That can be verified by looking at the trade goods, transportation routes, infrastructure and merchants. Additionaly, attention was given to the transit of livestock through the boarding ramp. That intensified trade conjuncture had a strong impact on the shaping of the city's everyday life. Author constructs a narrative about Zadar being a representative link between Mediterranean Western Europe and continental Ottoman civilization
The Population of Murter in 1858 and 1915 – Data from the Murter Parish Anagraph
No full textU radu se iznosi građa iz murterskih anagrafa koji sadrže popis obitelji i zabilježene promjene unutar pojedinih obitelji u vremenu od 1854. godine do druge polovice XX. stoljeća. Okosnicu i glavninu rada čine popisi obitelji i analiza imenske, prezimenske i nadimačke strukture murterskog stanovništva u godinama 1858. i 1915., te se uočavaju promjene unutar tih struktura u vremenskom hodu omeđenom navedenim godinama.The anagraphs of the Murter parish, which contain data about Murter families in the period between 1854 to the second half of the twentieth century, are an indispensable source for researching the historical anthroponymy and demography of this settlement. Surrounded by an enormous quantity of data the author confines himself exclusively to the presentation of data which defines and rounds off a corpus of Murter names, surnames and nicknames in the years 1858 and 1915. The chronological framework thusly defined – in reality we are dealing with two wholly narrow frameworks – represents temporal points which were at the same time grounds for the mutual comparison of analyzed data. In such a way it was established that in less than 60 years the number of families in Murter grew by 60% – from 185 families in 1858 to 309 families in 1915. This growth is the consequence of natural growth, that is the role of immigration was insignificant. A comparison of the surname structure of the Murter populace during the said years – but also in respect to data concerning the anthroponymy of Murter in the period preceding the years under observation in this article published elsewhere – evinces a continuity of “old” families. Thusly only three new surnames appear in 1858 – a family that moved in and two men who married Murter women, while in 1915 we see two new families moving to Murter. However, the fund of first names greatly expanded within the targeted period – from the 89 male and female names known in 1858 to 266 names in 1915. In spite of this, newly born children were most frequently given centuries old saints’s names. Besides names and surnames, numerous nicknames have been recorded which are certainly the fundamental markers of a specific person or family
The Senj Uskoks
No full textU radu naslovljenom Senjski uskoci nastoji se odgovoriti na pitanje tko su to bili senjski
uskoci i kojim je čimbenicima njihovo djelovanje bilo uvjetovano. Rad nastoji uputiti na
postojanje različitih, često konfliktnih predodžbi koje su nastale kao posljedica različitih
interesa i suvremenika koji su bilježili podatke o uskocima, ali i kasnije povjesničara.
Na odgovor tko su bili senjski uskoci u radu se nastoji doći razmatranjem same riječi uskok te
njenom povezanosti s pitanjem porijekla senjskih uskoka i same njihove službe. Rad donosi
prikaz složenog porijekla senjskih uskoka te vojnu organizaciju uz koju se naziv uskok počelo
vezati. Osim toga, rad nastoji razmotriti koji su čimbenici utjecali na njihovo djelovanje.
Izlaže motivacijske činitelje koji su potaknuli pojedince na postajanje uskokom. Osobit
naglasak stavlja se na ekonomske uvjete te se propituje u kojoj je mjeri shvaćanje uskoka kao
„predziđa“ kršćanstva uvjetovalo njihove postupke. Kako bi se steklo pobliže razumijevanje
uskočkog djelovanja, ono se nastoji razmotriti i kroz njihove suparničke i savezničke odnose,
osobito s Habsburškom Monarhijom i Mletačkom Republikom te lokalnim stanovništvom
grada Senja, mletačkog te osmanskog teritorija.Paper called The Senjs Uskoks tries to give an answer to the question who were the Senj
Uskoks and which factors had impact on their actions. It tries to indicate the existence of
different, often contrary, images of them, which are consequences of different interests of
Uskoks contemporaries and later historians.
To answer the question who were the Senj Uskoks this paper attempts to come by considering
the meanings given to the word Uskoks and its connection with the issue of their origin and
military service. Paper provides a view of a complex origin of the Senj Uskoks and their
military organization which became closely connected to the word Uskoks. Also, this paper
consider factors which had impact on activity of Senjs Uskoks. It gives a special emphasis on
the importance of economic conditions which encouraged individuals to become an Uskok
and it examines the extent to which understanding of the Uskoks as a “Bulwark of
Christianity” caused their actions.
More detailed understanding of Uskoks actions author tries to achieve by considering
relations with their rivals and allies, particularly with the Habsburg Monarchy, the Venetian
Republic, the local people of Senj and the Venetian and Ottoman subjects
Map of the Venetian-Ottoman Border Demarcation in Part of Northern and Central Dalmatia, 1588/1589
No full textMeđu povijesnim izvorima koji omogućuju prijedloge rekonstrukcije mletačko-osmanskih razgraničenja na sjeveroistočnoj obali i u jadranskome zaobalju u ranome novom vijeku osobito se ističu stare karte. One su kao grafički prikazi prostornih odnosa prvorazredan povijesni izvor geografskih podataka. Takva je i rukopisna karta nepoznatoga autora na kojoj je prikazano mletačko-osmansko razgraničenje poslije Ciparskoga rata u dijelu sjeverne i u srednjoj Dalmaciji. Karta se čuva u fondu Miscellanea – Materie miste e notabili Državnoga arhiva u Veneciji, a dosad nije bila predmetom znanstvenih i stručnih istraživanja. Manje u pogledu prirodno-geografskih sadržaja, a više u pogledu prikaza naselja, utvrda, prometnica i, posebno, granica, važno je svjedočanstvo o poznavanju topografije obalnoga i zaobalnoga dijela šibenske, trogirske i splitske komune kao strateški važnih dijelova mletačkoga Stato da Mar, izloženih osmanskim vojnim i pljačkaškim pohodima i teritorijalnim posizanjima.Among historical sources which allow a proposed reconstruction of the Venetian-Ottoman border demarcation on the northeast coastal and hinterland area of the Adriatic in the early modern period, old maps are especially prominent. As graphic depictions of spatial relations, they are a first-class historical source of geographical data. Such is the manuscript map by an unknown author which depicts the Venetia-Ottoman border demarcation in part of northern and central Dalmatia after the War of Cyprus. The map is housed in the Miscellanea Materie miste e notabili fund at the State Archives in Venice and has not yet been the subject of scientific and expert research. To a lesser extent, because of its natural-geographic
contents, and to a greater extent because of its depiction of settlements, fortifications, roads and especially borders, it is an important testimony to knowledge at the time of the topography of the coastal and hinterland parts of the Šibenik, Trogir and Split communes, as strategic parts of the Venetian Stato da Mar threatened by Ottoman military and looting forays and territorial incursions
IMPLEMENTATION OF QUALITATIVE RULES IN COMPANY`S INFORMATION MANAGEMENT
No full textIn the article there were presented chosen issues of quality management. Important role of information and work processes in companies were emphasized . Based on eight rules of quality management, TQM standards and ideas of discipline pioneers like Deming, Juran, Crosby and Shewart, author has constructed way of using chosen rules and assumptions to company`s information circulation. Analogy, suggested by author, has not only emphasized importance of information as a company`s resource, but also has pointed to possibility of improving ways of managing this information
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