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Glioblastom je najpogostejši možganski tumor pri odraslih z zelo slabo prognozo preživetja bolnikov. Ta je posledica odpornosti glioblastoma na standardno zdravljenje, ki vključuje radioterapijo in kemoterapijo. Z namenom načrtovanja učinkovitejših pristopov zdravljenja preučujemo biološke mehanizme odpornosti glioblastoma na radioterapijo s poudarkom na mikrookolju tumorja in rakavih matičnih celicah. V predkliničnih raziskavah uporabljamo napredne in personalizirane celične modele, ki posnemajo mikrookolje tumorja v bolnikih in z večjo natančnostjo napovedo odziv bolnika na zdravljenje. Hkrati so takšni modeli pomembni za testiranje novih pristopov za zdravljenje kot je imunoterapija.

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown. In this study, cathepsin X expression and activity were found to be upregulated in human GBM tissues compared to low-grade gliomas and nontumor brain tissues. Cathepsin X was localized in GBM cells as well as in tumor-associated macrophages and microglia. Subsequently, potent irreversible (AMS36) and reversible (Z7) selective cathepsin X inhibitors were tested in vitro. Selective cathepsin X inhibitors decreased the viability of patientderived GBM cells as well as macrophages and microglia that were cultured in conditioned media of GBM cells. We next examined the expression pattern of neuron-specific enzyme γ-enolase, which is the target of cathepsin X. We found that there was a correlation between high proteolytic activity of cathepsin X and C-terminal cleavage of γ-enolase and that cathepsin X and γ-enolase were colocalized in GBM tissues, preferentially in GBM-associated macrophages and microglia. Taken together, our results on patient-derived material suggest that cathepsin X is involved in GBM progression and is a potential target for therapeutic approaches against GBM.

Supplemental material, sj-pdf-1-jhc-10.1369_0022155421994679 for Immunohistochemical Detection of Neural Stem Cells and Glioblastoma Stem Cells in the Subventricular Zone of Glioblastoma Patients by Vashendriya V.V. Hira, Remco J. Molenaar, Barbara Breznik, Tamara Lah, Eleonora Aronica and Cornelis J.F. Van Noorden in Journal of Histochemistry & Cytochemistry

Supplemental material, sj-pdf-1-jhc-10.1369_00221554211054585 for Cell Biology Meets Cell Metabolism: Energy Production Is Similar in Stem Cells and in Cancer Stem Cells in Brain and Bone Marrow by Cornelis J.F. van Noorden, Barbara Breznik, Metka Novak, Amber J. van Dijck, Saloua Tanan, Milo�� Vittori, Urban Bogataj, No��lle Bakker, Joseph D. Khoury, Remco J. Molenaar and Vashendriya V.V. Hira in Journal of Histochemistry & Cytochemistry

Magistrsko delo Izdelovanje praktičnih izdelkov pri predmetu naravoslovje in tehnika na osnovnih šolah v Slovenskih goricah je sestavljeno iz dveh zaključenih celot: teoretičnega in empiričnega dela. Teoretični del je razdeljen v štiri sklope. Psihološki sklop je sklop, v katerem smo se osredotočili na otrokove razvojne sposobnosti in ustvarjalnost otrok. V didaktično-pedagoškem sklopu je opredeljen predmet naravoslovje in tehnika, metode in oblike dela pri pouku ter sovpadanja z mednarodnimi didaktičnimi trendi na področju izobraževanja. V tehnološkem sklopu so predstavljena delovna gradiva, pripomočki in orodja za delo pri pouku, vključno z elementi varnosti pri delu. V geografskem sklopu smo se osredotočili na osnovne šole, ki so sodelovale v anketni raziskavi in projekti, ki se izvajajo na šolah. V empiričnem delu so predstavljeni rezultati ter podrobna analiza in ugotovitve raziskave. V empiričnem delu so sodelovali učenci 4. in 5. razredov osnovnih šol: J. Hudalesa Jurovski Dol, Lenart, Voličina in Benedikt. Tako je bil glavni namen našega raziskovanja usmerjen v iskanje informacij na kakšen način, s katerimi materiali in orodji učenci izdelujejo praktične izdelke pri pouku naravoslovja in tehnike. Ugotavljamo, da učenci radi izdelujejo praktične izdelke. Pri tem starost in spol ne igrata pomembne vloge. V povprečju se v šolskem letu izdelajo 3-4 tehniški izdelki, kar menim, da je zelo malo in bi učitelji morali več časa posvetiti izdelavi lastnih izdelkov, vzpodbujanju učenčeve ustvarjalnosti, saj učenci praktične izdelke pri pouku izdelujejo največkrat vsi po enakem načrtu, ki pa ga naredi učitelj, ali pa je načrt iz škatle Izotech. Učenci najraje izdelujejo izdelke iz papirja in kartona, pri tem pa največkrat uporabljajo škarje in lepilo. The thesis titled Making craft products at Science and Technology in primary schools in Slovenske gorice consists of two completed units from theoretical and empirical part. The theoretical part is divided into four compounds. Psychological compound is the one in which the focal point revolves around child’s development skills and creativity. School subject Science and Technology is defined in the didactic-pedagogical compound along with work forms and methods used during lessons as well as correspondence with international didactic trends in field of education. Technological compound introduces work materials, accessories and instruments for classroom activities including safety elements at work. The focus in the geographical compound were primary schools involved the survey and ongoing project in the respective schools. The empirical part introduces results, detailed analysis and findings of the survey. The participants were the students of fourth and fifth grade attending lessons as the following primary schools: J. Hudalesa Jurovski Dol, Lenart, Voličina and Benedikt. Thus, the main purpose of research was directed to information involving manner, materials and instruments pupils use to produce practical products at Science and Technology classes. The analysis regarding age and gender has not shown any major alternations. In average, the number of technical products during a school year varies between 3 and 4. In my opinion this is not enough therefore, teachers should invest more time in production of their own products and in encouragement of pupil’s creativity due to the fact that practical products are mainly manufactured according to a plan devised by a teacher or even Izotech box. The pupils prefer to manufacture products out of paper or cardboard using scissors and glue.