1. The Slovenian translational platform GlioBank for brain tumour research : identification of molecular signatures of glioblastoma progressionMetka Novak, Bernarda Majc, Marta Malavolta, Andrej Porčnik, Jernej Mlakar, Matjaž Hren, Anamarija Habič, Mateja Mlinar, Ivana Jovchevska, Neja Šamec, Alja Zottel, Marija Skoblar Vidmar, Tina Vipotnik-Vesnaver, Andrej Zupan, Alenka Matjašič, Saša Trkov, Dejan Georgiev, Aleksander Sadikov, Roman Bošnjak, Borut Prestor, Radovan Komel, Tamara Lah Turnšek, Barbara Breznik, 2025, izvirni znanstveni članek Ključne besede: biobank, biomarker, glioblastoma, tumour models, oncology
Objavljeno v DiRROS: 28.01.2025; Ogledov: 257; Prenosov: 152
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2. Patient-derived tumor organoids mimic treatment-induced DNA damage response in glioblastomaBernarda Majc, Anamarija Habič, Marta Malavolta, Miloš Vittori, Andrej Porčnik, Roman Bošnjak, Jernej Mlakar, Alenka Matjašič, Andrej Zupan, Marija Skoblar Vidmar, Tamara Lah Turnšek, Aleksander Sadikov, Barbara Breznik, Metka Novak, 2024, izvirni znanstveni članek Povzetek: Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical in vitro models. In this study, we investigated the effects of standard therapy using patient-derived GB organoids (GBOs). GBOs reflect the complexity and heterogeneity of the original tumor tissue. No significant effect on GBO viability or invasion was observed after irradiation and temozolomide treatment. E3 ubiquitin-protein ligase (MDM2), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the serine/threonine kinases ATM and ATR were upregulated at the gene and protein levels after treatment. Our results show that the p53 pathway and DNA-damage response mechanisms were triggered, suggesting that GBOs recapitulate GB therapy resistance. GBOs thus provide a highly efficient platform to assess the specific responses of GB patients to therapy and to further explore therapy resistance.
Ključne besede: cellular physiology, cellular toxicology, in vitro toxicology including 3D culture, technical aspects of cell biology, cancer
Objavljeno v DiRROS: 09.09.2024; Ogledov: 616; Prenosov: 256
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3. Biodiverziteta in varstvo slovenskega morja na pragu 21. stoletja : zbornik referatov1999, druge monografije in druga zaključena dela Povzetek: V preteklem letu so potekale tudi številne dejavnosti, kot so delavnice, posveti, kongresi doma in v tujini, predstavitve znanstvenih in poljudnih publikacij z morsko tematiko, prispevki v sredstvih javnega obveščanja, razstave, ples pomorščakov, tekmovanje jadralcev na deski za državni pokaf. Dobro obiskana je bila tudi tematska knjižna razstava "Morje, oceani in knjige" v knjižnici Piran. Ker ljudje lahko varujemo samo tisto, kar poznamo, je izobraževanju posvečena velika pozornost. Za izobraževalne namene smo v pretekiem letu pripravili, v sodelovanju z Regionalnim RTV centrom Koper-Capodistria, izobraževalni film, ki vključuje kratke dokumentarne oddaje, seminar za učitelje in profesorje, mladinske raziskovalne naloge z morsko tematiko. V mesecu juniju je v Fiesi potekal raziskovalni tabor Dnevi ustvarjalnih otrok (DUO), namenjen nadarjenim osmošolcem iz Slovenije, in mednarodni tabor za srednješolce. Ta je namenjen mednarodnemu sodelovanju mladih in je prek Urada za mladino vključen v program EURO PLATFORMA 98. Oba tabora je organiziralo Obalno društvo pedagoških delavcev v sodelovanju s podjetjem za kulturo in izobraževanje Forum Piranense. Na OŠ Ciril Kosmač je v oktobru 1998 potekaj 5. mednarodni izobraževalno - raziskovalni tabor. Organizirali so vrsto delavnic, med drugim tudi delavnico o problematiki onesnaženja obalnega morja. Omeniti moramo tudi prispevek najmlajših "Morje skozi oči Ankarana"- prispevek učencev 4. razreda OŠ Ankaran. Nacionalni program Slovenije je bil predstavljen organizaciji The Oceanography Society (TOS) in Intergovernmental Oceanographic Commission (IOC) v Parizu, ki bo gradivo vključila v načrtovano razstavo na sedežu UNESCa v Parizu. Na tej razstavi naj bi predvsem slikovno predstavili nacionalne dejavnosti v zvezi z Mednarodnim letom oceanov, nato pa naj bi bila razstava predvidoma prenesena v palačo Združenih narodov v New Yorku. Preteklo leto je v številnih državah sveta in tudi v Sloveniji potekalo podpisovanje Listine o oceanih. Listina je nepravni dokument, vendar poziv vsakemu posamezniku, da podpiše, da se bo pri igri, svojem delu in odločitvah, ki jih sprejema pri vsakdanjem ravnanju z morji, oceani in vodami, ki se vanje izlivajo, zavedal: - da je zdravje oceanov ter umno in previdno izkoriščanje njihovih bogatih ribjih lovišč in drugih naravnih virov osnovno načelo, ki ga mora sprejeti vsak posameznik, kot tudi sprejeti in spoštovati vlade vseh držav v prid dolgoročnih koristi in obstoja narodov sveta; - da mora biti spoznavanje in razumevanje morskega okolja in njegovih živih bitij osnova smotrnega gospodarjenja z oceani in morji, kot tudi odločanja o njihovem varovanju ter izkoriščanju virov. Listino o oceanih so predlagali na Svetovni konferenci o morjih septembra 1997 v St. John'su na Novi Fundlandiji v Kanadi. Državniško Listino o oceanih je podpisal predsednik vlade dr. J. Drnovšek ob svojem obisku slovenske uradne delegacije svetovne razstave EXPO '98 v Lizboni v paviljonu Združenih narodov. Ob otvoritvi razstave "Barve zaliva" v galeriji insula je Minister za okolje in prostor dr. P. Gantar podpisal Listino o oceanih. Podpisovanje Moje listine o oceanih pa je potekalo ob različnih priložnostih (prireditvah, razstavah, predavanjih, predstavitvah ...) in prek domače strani interneta.
Ključne besede: morje, Morska biološka postaja, varstvo morja, vrstna pestrost, biodiverziteta, biološka raznovrstnost, fitoplankton, makroalge, morski nevretenčarji, favna, flora, habitatni tipi
Objavljeno v DiRROS: 04.09.2024; Ogledov: 557; Prenosov: 231
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4. Letno poročilo 2009-2010 : Nacionalni inštitut za biologijo2011, druge monografije in druga zaključena dela Povzetek: »Iz take smo snovi kot sanje« je rekel Shakespeare. Jaz pa pravim: »Iz take smo snovi kot znanje... Spoznanje je misel, ki jo ujamemo v letu, jo umestimo v svoje pasti in udejanimo v svojem znanstvenem poskusu. Potem okameni in postane stvarnost. Znanje postavimo v nek kontekst. Kamenček v mozaiku, kamor morda sploh ne sodi, a vendarle se prej ali slej umesti, kamor res sodi.«
Ali pa ne! Kam bo sodila naša misel jutri, ko bo fluidni mozaik našega spoznanja o vsem kar nas obdaja in kar počnemo, dobil spet drugo podobo – ne vemo ..! Ali nam bo dano kdaj spoznati predvsem človeka samega, spletne mreže naših nevronov? Ali nam bo dano to spoznanje ali ne, je težko reči, saj je eno človeško življenje za to prekratko. Rodimo se in umremo v ne-vedenju. Tako sama vidim svoje delo. Tako raziskovalci tu gledamo živa bitja in naravo – biologijo. Mnogo bolje bo danes o tem govoril naš znanstveno - umetniški film, zato bodi dovolj..!
Ker dan zahteva od nas še mnogo več – treba je preliti to znanje med ljudi. Treba ga je dajati mladim raziskovalcem. So kot nežni cvetovi, žejni jutranje rose učenosti - a so tudi zahtevni, neusmiljeni, brezsramni in izčrpavajoči. A prav vzgoja mladih raziskovalcev, ki jih pri nas opremimo še z dodatnimi znanji in veščinami tako, da bodo kos vsem izzivom družbe in gospodarstva, je pomembno poslanstvo NIBa. Ti novi doktorji znanosti, ki izhajajo iz našega dela, bodo namreč nujno potrebna gonilna sila inovativnega razvoja Slovenije.
A sedanjost zahteva tudi, da pretopimo znanje v zlato. Žal nismo alkimisti in vmes – med znanjem in bogastvom je še mnogo, na kar ne moremo vplivati. Je kopica drugih elementov in podpornih sistemov, za katere znanost in znanstveniki sami ne moremo dosti narediti. Lahko le pomagamo graditi ta podporni sistem do mere, ko bo zlitje z njim rodilo resnično konkurenčnost in uspeh. A to se ne doseže čez noč...
Ko se obračam v zgodovino, ugotavljam, da smo bili včasih že kar na pravi poti. Da smo se znali odrekati in videti višje cilje. Znanost je že lepo shodila in rastoča industrija 70-80 let ji je znala podajat roko. A to so bili drugačni časi in kaj se je zgodilo potem – je preveč za današnji slavnostni dan!
Nekako v tistem času se je rodil NIB. Vizionarski pogled prof. Miroslava Zeia, pobudnika ustanovitve našega instituta, se je danes uresničil. NIB torej ni rodila politika za razliko od večine, posebno naravoslovno tehničnih inštitutov, ki so imeli zato tudi potrebno državno podporo. NIB je rasel kot samorastnik, samosvoje, kar nas je utrdilo za preživetje, tudi za prihajajoče obdobje.
Tako ga danes zaradi odličnega znanstvenega dela in kompetentnih raziskovalcev nova tehnološka predvidevanja vključujejo kot močnega partnerja v svojem razvoju. Posebno v zadnjem desetletju zaznamo prodor, tako v znanstvenem delu z naraščajočimi dobrimi publikacijami (npr. v prestižni reviji Nature) kot tudi na razvojnem področju.
V 70 letih se je inštitutu priključila Mor - ska biološka postaja (MBP), ki je ime - la pomemben vpliv tudi na delo na - ših drugih področij, kot so bile tedaj rastlinska fiziologija, entomologija in predvsem raziskave ekosistemov. MBP je namreč že takrat izvajala svo - je družbeno pomembno poslanstvo v strateškem delovanju na področju razvoja in raziskav širšega obalnega okolja in upravljanja z morskimi viri. Podobno smo danes tudi na skoraj vseh področjih svojega dela in eksper - tize stalni partner ministrskih služb in agencij, prvenstveno na področju oko - lja, kmetijstva in zdravstva. Postali in ostali smo - na eni strani nepogrešljivi izvajalec in na drugi svetovalec politi - ke pri načrtovanju njenega razvoja, ne nazadnje tudi na več segmentih nujne sinhronizacije z Evropsko politiko in direktivami.
V zadnjem desetletju smo uspeli ob pod - pori resornega ministrstva za znanost, visoko šolstvo in tehnologijo posodo - biti infrastrukturo MBP, tako da je ta danes ena najmodernejših ustanov na severnem Jadranu in okolici. Upamo, da bomo to lahko storili tudi v Lju - bljani na Biološkem središču, saj že po petnajstih letih po vselitvi to poka po šivih, predvsem zaradi prodora mla - dih ljudi, ki prihajajo na NIB, vse več tudi iz tujine.
Biologija je danes namreč v svetu ena najbolj hitro se razvijajočih disciplin in prodira v mnoge pore novih teh - nologij – od klasičnih vrst biotehno - logije do nano-tehnologij in celo do vesoljskih tehnologij – česar se prav doma premalo zavedamo! Sodelovati s poslovnim sektorjem poskušamo, bodisi preko vključevanja v nove Cen - tre odličnosti, Centre kompetentnosti ter preko možnih povezovanj s pod - jetji doma in tudi preko naših meja, poskušamo… A po mojem osebnem prepričanju je najbolj učinkovito usta - navljanje lastnih podjetij, strategija, ki je prav ob 50 letnici rodila naše prvo odcepljeno podjetje Biosistemika, ki je zrasla iz naših raziskav s področja sistemske biologije.
Predmet naših raziskav je torej zelo ra - znolik - od bakterij do človeka in njegovega okolja. Rdeča nit je seveda ohranjene zdravega okolja za zdrave - ga človeka, kar je nedvomno najvišja kakovost življenja.
Naj tu končam. Vabim vas torej v prije - ten popoldan, ko boste občutili biolo - gijo in se s tem zavedli sebe kot živega bitja, ki je le del narave in nič več, a nič manj kot to.
Objavljeno v DiRROS: 04.09.2024; Ogledov: 502; Prenosov: 278
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5. Cyanobacterial cyclic peptides can disrupt cytoskeleton organization in human astrocytes : a contribution to the understanding of the systemic toxicity of cyanotoxinsAnja Bubik, Robert Frangež, Monika C. Žužek, Ion Gutiérrez-Aguirre, Tamara Lah Turnšek, Bojan Sedmak, 2024, izvirni znanstveni članek Povzetek: The systemic toxicity of cyclic peptides produced by cyanobacteria (CCPs) is not yet completely understood. Apart from the most known damages to the liver and kidneys, symptoms of their neurotoxicity have also been reported. Hepatotoxic CCPs, like microcystins, as well as non-hepatotoxic anabaenopeptins and planktopeptins, all exhibit cytotoxic and cytostatic effects on mammalian cells. However, responses of different cell types to CCPs depend on their specific modes of interaction with cell membranes. This study demonstrates that non-hepatotoxic planktopeptin BL1125 and anabaenopeptins B and F, at concentrations up to 10 µM, affect normal and tumor human astrocytes (NHA and U87-GM) in vitro by their almost immediate insertion into the lipid monolayer. Like microcystin-LR (up to 1 µM), they inhibit Ser/Thr phosphatases and reorganize cytoskeletal elements, with modest effects on their gene expression. Based on the observed effects on intermediate filaments and intermediate filament linkage elements, their direct or indirect influence on tubulin cytoskeletons via post-translational modifications, we conclude that the basic mechanism of CCP toxicities is the induction of inter- and intracellular communication failure. The assessed inhibitory activity on Ser/Thr phosphatases is also crucial since the signal transduction cascades are modulated by phosphorylation/dephosphorylation processes.
Ključne besede: astrocytes, cyclic cyanobacterial peptides, cytoskeletal organization, Ser/Thr phosphatases, systemic toxicity, cyanobacteria
Objavljeno v DiRROS: 28.08.2024; Ogledov: 661; Prenosov: 464
Celotno besedilo (21,09 MB)
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6. Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumoursBarbara Breznik, Helena Motaln, Tamara Lah Turnšek, 2017, pregledni znanstveni članek Povzetek: Proteolytic enzymes are highly relevant in different processes of cancer progression. Their interplay with other signalling molecules such as cytokines represents important regulation of multicellular cross-talk. In this review, we discuss protease regulation mechanisms of cytokine signalling in various types of cancer. Additionally, we highlight the reverse whereby cytokines have an impact on protease expression in an autocrine and paracrine manner, representing complex feedback mechanisms among multiple members of these two protein families. The relevance of the protease-cytokine axis is illustrated in glioblastoma, where interactions between normal mesenchymal stem cells and cancer cells play an important role in this very malignant form of brain cancer.
Ključne besede: cellular cross-talk, glioblastoma, invasion, mesenchymal stem cells, protease-cytokine signalling
Objavljeno v DiRROS: 06.08.2024; Ogledov: 542; Prenosov: 315
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7. Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiformeMiha Koprivnikar Krajnc, Metka Novak, Richard G. Pestell, Tamara Lah Turnšek, 2019, pregledni znanstveni članek Povzetek: Background
Glioblastoma is the most frequent and aggressive brain tumour in humans with median survival from 12 to 15 months after the diagnosis. This is mostly due to therapy resistant glioblastoma stem cells in addition to intertumour heterogeneity that is due to infiltration of a plethora of host cells. Besides endothelial cells, mesenchymal stem cells and their differentiated progenies, immune cells of various differentiation states, including monocytes, comprise resident, brain tumour microenvironment. There are compelling evidence for CCL5/CCR5 in the invasive and metastatic behaviour of many cancer types. CCR5, a G-protein coupled receptor, known to function as an essential co-receptor for HIV entry, is now known to participate in driving tumour heterogeneity, the formation of cancer stem cells and the promotion of cancer invasion and metastasis. Clinical trials have recently opened targeting CCR5 using a humanized monoclonal antibody (leronlimab) for metastatic triple negative breast cancer (TNBC) or a small molecule inhibitor (maraviroc) for metastatic colon cancer. There are important CCL5 and CCR5 structure and signalling mechanisms in glioblastoma. In addition, the CCL5/CCR5 axis directs infiltration and interactions with monocytes/macrophages and mesenchymal stem cells, comprising glioblastoma stem cell niches.
Conclusions
CCR5 is highly expressed in glioblastoma and is associated with poor prognosis of patients. CCL5/CCR5 is suggested to be an excellent new target for glioblastoma therapy. The molecular mechanisms, by which chemoattractant and receptor respond within the complex tissue microenvironment to promote cancer stem cells and tumour heterogeneity, should be considered in forthcoming studies.
Ključne besede: cytokines, CCL5-RANTES, glioblastoma, tumour microenvironment, mesenchymal stem cells, signalling
Objavljeno v DiRROS: 06.08.2024; Ogledov: 545; Prenosov: 279
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8. Epithelial-to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironmentBernarda Majc, Tilen Sever, Miki Zarić, Barbara Breznik, Boris Turk, Tamara Lah Turnšek, 2020, pregledni znanstveni članek Povzetek: Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process that is part of normal embryogenesis and wound healing, and also has a ubiquitous role in various types of carcinoma and glioblastoma. EMT is activated and regulated by specific microenvironmental endogenous triggers and a complex network of signalling pathways. These mostly include epigenetic events that affect protein translation-controlling factors and proteases, altogether orchestrated by the switching on and off of oncogenes and tumour-suppressor genes in cancer cells. The hallmark of cancer-linked EMT is that the process is incomplete, as it is opposed by the reverse process of mesenchymal-to-epithelial transition, which results in a hybrid epithelial/mesenchymal phenotype that shows notable cell plasticity. This is a characteristic of cancer stem cells (CSCs), and it is of the utmost importance in their niche microenvironment, where it governs CSC migratory and invasive properties, thereby creating metastatic CSCs. These cells have high resistance to therapeutic treatments, in particular in glioblastoma.
Ključne besede: carcinomas, cancer stem cellsInvasion, proteases, tumour microenvironment
Objavljeno v DiRROS: 06.08.2024; Ogledov: 618; Prenosov: 547
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9. Brain malignancies : glioblastoma and brain metastasesTamara Lah Turnšek, Metka Novak, Barbara Breznik, 2020, pregledni znanstveni članek Povzetek: Brain, the major organ of the central nervous system controls and processes most of body activities. Therefore, the most aggressive brain tumor – glioblastoma and metastases from other organs to the brain are lethal leaving the patients with very short time of survival. The brain tissue landscape is very different from any other tissues and the specific microenvironment, comprising stem cells niches and blood-brain barrier, significantly influences the low rate of glioblastoma metastasis out of the brain, but better accommodates brain-invading cancer. In contrast to low frequency (0.5%) of all glioblastoma metastases, 10%–45% of other primary cancers do metastasize to the brain. This review addresses general cellular and molecular pathways that are to some extent similar in both types of metastases, involving circulating tumor cells (CTCs) with cancer stem cells (CSCs) characteristics, and metastatic niches. The invasion is a dynamic process involving reversible epithelial-to-mesenchymal (EMT) cell process, creating a transient gradient state that is inter-connected with epigenetic plasticity of the metastasizing (m)CSCs. These cells can switch between stationary, low proliferating/dormant state to a migratory, mesenchymal-like state. Settling in their respective niches as dormant CSCs in the secondary organ is a common feature in all types of metastases. In glioblastoma metastasis, the malignant mGSC cells express markers of mesenchymal GSC subtype (MES-GSC), such as CD44 and YK-40 and their major obstacle seems to be propagating in the in various organs’ microenvironments, different from the niches that home GSCs in the primary glioblastoma. Focusing on one stromal component in the glioblastoma niches, the mesenchymal stem cells (MSCs), we report herein on their differential effects on glioblastoma cells, highly depending on their genetic subtype. On the other hand, in brain metastases, the major hindrance to metastatic progression of mCSCs seem to be crossing the blood-brain-barrier. Novel therapeutic approaches for brain metastases from various cancer types are advancing slowly, and the general trends involve targeting metastatic sub-clones and selective determinants of their niches. The update on the four most common brain metastases from lung, breast, melanoma and colorectal carcinoma is presented.
Ključne besede: glioblastoma, cancer stem cells, invasion, metastasis, tumor microenvironment
Objavljeno v DiRROS: 06.08.2024; Ogledov: 694; Prenosov: 380
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10. Bioactive peptides from venoms against glioma progressionBernarda Majc, Metka Novak, Tamara Lah Turnšek, Igor Križaj, 2022, pregledni znanstveni članek Povzetek: Venoms are complex mixtures of different molecules and ions. Among them, bioactive peptides have been found to affect cancer hallmarks, such as cell proliferation, cell invasion, cell migration, and can also modulate the immune response of normal and cancer-bearing organisms. In this article, we review the mechanisms of action on these cancer cell features, focusing on bioactive peptides being developed as potential therapeutics for one of the most aggressive and deadly brain tumors, glioblastoma (GB). Novel therapeutic approaches applying bioactive peptides may contribute to multiple targeting of GB and particularly of GB stem cells. Bioactive peptides selectively target cancer cells without harming normal cells. Various molecular targets related to the effects of bioactive peptides on GB have been proposed, including ion channels, integrins, membrane phospholipids and even immunomodulatory treatment of GB. In addition to therapy, some bioactive peptides, such as disintegrins, can also be used for diagnostics or are used as labels for cytotoxic drugs to specifically target cancer cells. Given the limitations described in the last section, successful application in cancer therapy is rather low, as only 3.4% of such peptides have been included in clinical trials and have passed successfully phases I to III. Combined approaches of added bioactive peptides to standard cancer therapies need to be explored using advanced GB in vitro models such as organoids. On the other hand, new methods are also being developed to improve translation from research to practice and provide new hope for GB patients and their families.
Objavljeno v DiRROS: 05.08.2024; Ogledov: 545; Prenosov: 322
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