Abstract The present study compared the photothermal anticancer activity of near-infrared (NIR)-excited graphene nanoparticles and carbon nanotubes (CNT). Despite lower NIR-absorbing capacity, ...suspension of polyvinylpyrrolidone-coated graphene sheets exposed to NIR radiation (808 nm, 2 W/cm2 ) generated more heat than DNA or sodium dodecylbenzenesulfonate-solubilized single-wall CNT under the same conditions. Accordingly, graphene nanoparticles performed significantly better than CNT in inducing photothermal death of U251 human glioma cells in vitro. The superior photothermal sensitivity of graphene sheets could be largely explained by their better dispersivity, which has been supported by a simple calculation taking into account thermodynamic, optical and geometrical properties of the two type of carbon nanoparticles. The mechanisms of graphene-mediated photothermal killing of cancer cells apparently involved oxidative stress and mitochondrial membrane depolarization resulting in mixed apoptotic and necrotic cell death characterized by caspase activation/DNA fragmentation and cell membrane damage, respectively.
Gliomi su najčešći primarni tumori centralnog nervnog sistema. Glioblastom je gliom gradusa IV, terapijski rezistentan maligni tumor centralnog nervnog sistema. Nesteroidni anti-inflamatorni lekovi ...(NSAIL) su strukturno različite grupe molekula sa anti-inflamatornim i analgetskim dejstvom koji ispoljavaju i jak antitumorski efekat kako in vitro tako i in vivo. U ovoj doktorskoj disertaciji ispitivano je citotoksično dejstvo NSAIL na ćelije humane linije glioma U251 i ćelije primarne kulture glioblastoma izolovane iz tkiva obolelih pacijenata. Takođe, istraživali smo ulogu signalnog puta adenozin-monofosfatom aktivirane protein-kinaze (AMPK) i mTOR kompleksa 1 (mTORC1 - engl. mammalian target of rapamycin complex 1) u antigliomskom dejstvu NSAIL. Indometacin je snažnije od ostalih NSAIL (diklofenaka, naproksena i ketoprofena) smanjivao vijabilitet U251 ćelija humanog glioblastoma. Antigliomski efekat indometacina je bio povezan sa ekspresijom tumor supresorskog proteina p21 i zastojem ćelijskog ciklusa u G2M fazi, indukcijom oksidativnog stresa, depolarizacijom mitohondrija, aktivacijom kaspaza i indukcijom apoptoze. Indometacin je jedini od ispitivanih NSAIL povećavao fosforilaciju AMPK i nishodnih molekula koje ona fosforiliše, Raptor-a i acetil-CoA karboksilaze (ACC). Aktivaciju AMPK pratilo je smanjenje fosforilacije mTOR i molekula čiju aktivnost mTORC1 reguliše, kao što su ribozomalna p70S6 kinaza (S6K) i PRAS40 (Ser183). Genetska inhibicija AMPK RNK interferencijom, kao i tretman ćelija aktivatorom mTORC1 leucinom doveli su do delimičnog poništavanja citotoksičnih efekata izazvanih indometacinom. Sa druge strane, farmakološki aktivatori AMPK metformin i AICAR su poput indometacina ispoljavali antigliomski efekat inhibicijom mTORC1. Aktivacija AMPK u ćelijama tretiranim indometacinom korelirala je sa smanjenjem ćelijskog ATP i porastom AMP/ATP odnosa, ali je bila nezavisna od inhibicije COX i povećanja intraćelijskog nivoa kalcijuma. Takođe, citotoksični efekat indometacina na ćelije primarne kulture glioblastoma bio je posredovan aktivacijom AMPK/Raptor/ACC i inhibicijom mTORC1/S6K signalnih molekula.
Rapid progress made in various areas of regenerative medicine in recent years occurred both at the cellular level, with the Nobel prize-winning discovery of reprogramming (generation of induced ...pluripotent stem (iPS) cells) and also at the biomaterial level. The use of four transcription factors, Oct3/4, Sox2, c-Myc, and Klf4 (called commonly "Yamanaka factors") for the conversion of differentiated cells, back to the pluripotent/embryonic stage, has opened virtually endless and ethically acceptable source of stem cells for medical use. Various types of stem cells are becoming increasingly popular as starting components for the development of replacement tissues, or artificial organs. Interestingly, many of the transcription factors, key to the maintenance of stemness phenotype in various cells, are also overexpressed in cancer (stem) cells, and some of them may find the use as prognostic factors. In this review, we describe various methods of iPS creation, followed by overview of factors known to interfere with the efficiency of reprogramming. Next, we discuss similarities between cancer stem cells and various stem cell types. Final paragraphs are dedicated to interaction of biomaterials with tissues, various adverse reactions generated as a result of such interactions, and measures available, that allow for mitigation of such negative effects.
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