ELEVATE-TN Study. New data of acalabrutinib in first-line treatment of chronic lymphocytic leukemia. Resolution

Over the past decade, we have seen a significant change in modern approaches in the first-line treatment of chronic lymphocytic leukemia (CLL). The CLL-10 study data established the FCR regimen as the treatment of choice for younger patients with limited comorbidities, while for patients older than 65 years, the BR regimen is more often considered as less toxic one. According to published data, 46% of patients with newly diagnosed CLL have comorbidities. Moreover, high-risk patients with del(17p) and/or TP53 mutation do not have response on immunochemotherapy (ICT) most often. Thus, about 1/2 of the patients cannot be treated or will not respond to standard ICT regimens. Targeted therapy with Brutons tyrosine kinase (BTK) inhibitors is an important option of the first-line treatment of patients with CLL. Acalabrutinib is a highly selective second-generation BTK inhibitor that does not inhibit EGFR, ITK or TEC targets. Acalabrutinib in combination with obinutuzumab or as monotherapy can be considered as a highly effective and safe option of the first line of CLL therapy. Based on the hight selectivity of the agent, acalabrutinib can be considered as the preferable option for patients who are not eligible for ICT, including patients with commodities, such as cardiovascular diseases or risk factors for their development

Hairy cell leukemia. Clinical recommendations

Hairy cell leukemia. Clinical recommendation

The impact of megacities on the environment

Završni rad pod naslovom "Utjecaj megagradova na okoliš", bavi se problemima koji se javljaju u najmnogoljudnijim gradovima u svijetu, a koji znatno utječu na okolinu u kojoj živimo te doprinose negativnim posljedicama ljudskog utjecaja na prirodni okoliš. Zagađivanje okoliša ljudskom aktivnošću, nemarom, posljedicama prometnog opterećenja, neadekvatnim zbrinjavanjem otpada, samo su neki od utjecaja na okoliš koji dovode i do klimatskih promjena, a koji se detaljnije objašnjavaju u radu na primjeru tzv. megagradova.The bachelor's thesis named 'The impact of megacities on the environment", deals with problems that appear in the most crowded cities of the world that contribute to the negative side effect on the natural environment. Environmental pollution by human activity,negligence, consequences of traffic load, inadequate waste disposal, are just some ofthe environmental impacts that lead to climate change. These impacts are explained in more detail in the thesis on the example of the so-called megacities

The impact of megacities on the environment

Završni rad pod naslovom "Utjecaj megagradova na okoliš", bavi se problemima koji se javljaju u najmnogoljudnijim gradovima u svijetu, a koji znatno utječu na okolinu u kojoj živimo te doprinose negativnim posljedicama ljudskog utjecaja na prirodni okoliš. Zagađivanje okoliša ljudskom aktivnošću, nemarom, posljedicama prometnog opterećenja, neadekvatnim zbrinjavanjem otpada, samo su neki od utjecaja na okoliš koji dovode i do klimatskih promjena, a koji se detaljnije objašnjavaju u radu na primjeru tzv. megagradova.The bachelor's thesis named 'The impact of megacities on the environment", deals with problems that appear in the most crowded cities of the world that contribute to the negative side effect on the natural environment. Environmental pollution by human activity,negligence, consequences of traffic load, inadequate waste disposal, are just some ofthe environmental impacts that lead to climate change. These impacts are explained in more detail in the thesis on the example of the so-called megacities

PH forscht : Bericht 2013-2015

"We teach what we research and we research what we teach!" Dieser Leitspruch der Pädagogischen Fakultät der Universität Helsinki, die ich im Frühjahr 2014 besuchen durfte, stellt auch meine Vision für unsere Hochschule dar. In den nächsten 5 bis 10 Jahren sollen die Rahmenbedingungen dafür ausgebaut werden, dass Forschung für alle Kolleginnen und Kollegen ein Thema sein kann. Zahlreiche Publikationen, Dissertations- und Habilitationsprojekte geben ein weiteres beredtes Zeugnis davon, dass an unserer Hochschule in den letzten Jahren ein forschungsorientiertes institutionelles Klima weiter ausgebaut werden konnte. Und dies bei Rahmenbedingungen und einer Ausstattung mit Forschungsressourcen, die noch alles andere als ideal sind. Wenn wir gerade in der Konzipierung der Pädagoginnen- und Pädagogenbildung davon sprechen, wie wichtig die vier Säulen sind – Fachwissenschaft, Fachdidaktik, Bildungswissenschaft und pädagogisch-praktische Studien – dann immer auf dem Hintergrund, dass Forschung in allen Bereichen Thema sein sollte – in unterschiedlichen Ausprägungen: von der Reflexion der eigenen Praxis über forschungsgeleitete Lehre bis hin zur Teilnahme am nationalen und internationalen Bildungsforschungsdiskurs. Prof. Prenzel von der School of Education der TU München ist davon überzeugt, dass es aus einer übergeordneten Perspektive nicht nur darum geht, Wissen aus der Forschung zu rezipieren und zu interpretieren, sondern mit der Forschung in einen Dialog zu treten und selbst dazu beizutragen. Forschung, zumal Bildungsforschung, hat aber keinen Selbstzweckcharakter. Forschung sollte immer auch dem Projekt der „Kultivierung der Menschlichkeit“ dienen, wie dies M. Nußbaum in ihrem gleichnamigen Buch eindrucksvoll darstellt. Die Fähigkeit kritischen Denkens – wahrscheinlich die Grundhaltung allen Forschens – sei deswegen von größter Bedeutung, um ein geprüftes Leben führen zu können – in Anlehnung an Sokrates formuliert Nußbaum »An unexamined life is not worth to be lived!« (Aus dem Vorwort von Rektor Franz Keplinger

Study of Structure–Activity Relationships of the Marine Alkaloid Fascaplysin and Its Derivatives as Potent Anticancer Agents

Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b’]diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure–activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization