Cilj. Cilj je rada prikaz razvoja metapodatkovnih standarda za opis građe – ili shema metapodataka – Kongresne knjižnice u Washingtonu, SAD, iniciranog ubrzanim razvojem tehnologije i rasta mrežnog ...okruženja u posljednjim desetljećima.
Pristup/metodologija/dizajn. U skladu s ciljem rada, odabrani pristup svodi se na sažeti prikaz razvoja svakog metapodatkovnog standarda Kongresne knjižnice pojedinačno, s naglaskom na sheme metapodataka za opis građe knjižnične zajednice – MARC 21, MARCXML, MODS i MADS. Ovaj pristup omogućava autorima da detaljno analiziraju i ocijene trenutačno stanje metapodatkovnih standarda i njihovu evoluciju kroz vrijeme, kao i da identificiraju izazove i prilike za budući razvoj.
Rezultati. Rad pruža sažeti pregled razvoja svakog metapodatkovnog standarda u Kongresnoj knjižnici pojedinačno, s fokusom na sheme metapodataka za opis resursa unutar knjižnične zajednice – MARC 21, MARCXML, MODS i MADS. Također se daje pregled razvoja shema metapodataka za opis izvora u srodnim zajednicama (EAD, VRA Core) te metapodatkovnih standarda za digitalne knjižnice namijenjenih arhiviranju i zaštiti (METS, PREMIS). U radu se raspravlja i o potencijalnim smjerovima daljnjeg razvoja metapodatkovnih standarda u Kongresnoj knjižnici, s osvrtom na projekte vezane za tehnologije semantičkog weba i povezanih podataka (BIBFRAME, MODS/RDF, MADS/RDF). Ističe se potreba za kontinuiranim poboljšanjem metapodatkovnih standarda kako bi se pružale bolje usluge korisnicima i uskladile s tehnološkim razvojem i potrebamakorisnika.
Vrijednost. Rad pruža sveobuhvatan osvrt na razvoj metapodatkovnih standarda Kongresne knjižnice, što je iznimno važno za knjižničnu zajednicu i one koji se bave arhiviranjem i očuvanjem digitalnih izvora. Rasprava o mogućim pravcima razvoja metapodatkovnih standarda,posebno u kontekstu semantičkog weba i povezanih podataka, pruža uvid u buduće izazove i prilike za Kongresnu knjižnicu i širu zajednicu. Ovaj rad, u konačnici, pridonosi razumijevanju važnosti i složenosti metapodatkovnih standarda te njihova kontinuiranog razvoja u svjetlu brzih tehnoloških promjena.
Glioblastoma is the most aggressive cancer among primary brain tumours. As with other cancers, the incidence of glioblastoma is increasing; despite modern therapies, the overall mean survival of ...patients post-diagnosis averages around 16 months, a figure that has not changed in many years. Cannabigerol (CBG) has only recently been reported to prevent the progression of certain carcinomas and has not yet been studied in glioblastoma. Here, we have compared the cytotoxic, apoptotic, and anti-invasive effects of the purified natural cannabinoid CBG together with CBD and THC on established differentiated glioblastoma tumour cells and glioblastoma stem cells. CBG and THC reduced the viability of both types of cells to a similar extent, whereas combining CBD with CBG was more efficient than with THC. CBD and CBG, both alone and in combination, induced caspase-dependent cell apoptosis, and there was no additive THC effect. Of note, CBG inhibited glioblastoma invasion in a similar manner to CBD and the chemotherapeutic temozolomide. We have demonstrated that THC has little added value in combined-cannabinoid glioblastoma treatment, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies of glioblastoma therapy.
Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60-70% of all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and ...non-specific ion receptor protein transporters TRPs. First, we found up-regulated
, and
expression in glioma patient-derived tissue samples and cell lines compared with non-malignant brain samples.
and
did not correlate with glioma grade, whereas
negatively correlated with grade and positively correlated with longer overall survival. This suggests a tumour-suppressor role of
. With respect to markers of GBM stem cells, preferred targets of therapy,
and
, but not
, strongly correlated with different sets of stemness gene markers:
, and
and
,
, and
, respectively. This is in line with the higher expression of
and
genes in GSCs compared with differentiated GBM cells. Second, in a panel of patient-derived GSCs, we found that CBG and CBD exhibited the highest cytotoxicity at a molar ratio of 3:1. We suggest that this mixture should be tested in experimental animals and clinical studies, in which currently used Δ9-tetrahydrocannabinol (THC) is replaced with efficient and non-psychoactive CBG in adjuvant standard-of-care therapy.
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.
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•GBOs retain cellular diversity, heterogeneity, and transcriptional profile of GBs•GBOs recapitulate GB therapy resistance•Expression of ATM, ATR, MDM2, and CDKN1A is increased in GBOs
Cellular physiology; Cellular toxicology; In vitro toxicology including D culture; Technical aspects of cell biology; Cancer
Abstract
Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process in physiologic processes and invasion of various types of carcinoma and glioblastoma (GBM) cells. ...EMT is activated and regulated by specific endogenous triggers in complex network of intercellular interactions and signaling pathways. The hallmark of cancer-linked EMT are intermediate states that show notable cell plasticity, characteristic of cancer stem cells (CSCs), including glioblastoma stem cells – GSCs. GSCs resistance to irradiation (IR) and temozolomide (TMZ) chemotherapy is responsible for early relapses, even at distant brain sites. As GSCs are mostly homing to their “niches” as slowly-dividing GSC-subtype, mimicking a proneural-like non- invasive phenotype PN-genotype, we assume that this, by undergoing an EMT-like transition, GSCs are-reprogrammed to an invasive mesenchymal (MES) GBs/GSCs phenotype in a processes, called PMT (1). However, it is not known, if and by which environmental cues within the niche, this transition of GSCs is induced in vivo. In this work, we are presenting the transriptome data obtained when we exposed GSC spheroids to irradiation alone, TMZ alone and to the combined treatment in vitro and compared their differential genetic fingerprints related to EMT/PMT transition to the GSCs PMT transition, when embedded in their natural microenvironment in the GBM organoid model. The differential gene expression upon GSCs therapeutic perturbation (when alone and vs in the tumoroid microenvironment) will reveal the effects of the major candidate genes, associated with micronevironmendt stromal cells and matrix are contributing their observed EMT/PMT transition of GSCs in vivo.
•1. Majc, B., Sever, T., Zarić, M, Breznik, B., Turk, B, Lah Turnšek, T. Epithelial- to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironment. DOI: 10.1016/j.bbamcr.2020.118782
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