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Priporočila za obravnavo bolnikov s pljučnim rakom
Martina Vrankar, Nina Boc, Izidor Kern, Aleš Rozman, Karmen Stanič, Tomaž Štupnik, Mojca Unk, Maja Ebert Moltara, Vesna Zadnik, Katja Adamič, Jernej Benedik, Marko Bitenc, Jasna But-Hadžić, Anton Crnjac, Marina Čakš, Dominik Časar, Eva Ćirić, Tanja Čufer, Ana Demšar, Rok Devjak, Goran Gačevski, Marta Globočnik Kukovica, Kristina Gornik-Kramberger, Maja Ivanetič Pantar, Marija Ivanović, Urška Janžič, Staša Jelerčič, Veronika Kloboves-Prevodnik, Mile Kovačević, Luka Ležaič, Mateja Marc-Malovrh, Katja Mohorčič, Loredana Mrak, Igor Požek, Nina Turnšek, Bogdan Vidmar, Dušanka Vidovič, Gregor Vlačić, Ana Lina Vodušek, Rok Zbačnik, Ivana Žagar, 2023, strokovni članek

Povzetek: Leta 2019 so bila objavljena Priporočila za obravnavo bolnikov s pljučnim rakom, ki so v slovenski prostor vnesla prepotrebno poenotenje diagnostike in zdravljenja z namenom izboljšanja preživetja bolnikov s pljučnim rakom. Posodobitev Priporočil tri leta po izidu izvirnika prinaša največ novosti v poglavju o sistemskem zdravljenju bolnikov s pljučnim rakom. To kaže na izjemen napredek na področju razumevanja onkogeneze in biologije pljučnega raka ter s tem razvoja novih zdravil. Breme pljučnega raka ostaja veliko, saj je pljučni rak pri nas in v svetu še vedno najpogostejši vzrok smrti zaradi raka. Za vsako peto smrt zaradi raka je odgovoren pljučni rak. Skoraj tretjina bolnikov s pljučnim rakom ne prejme specifičnega onkološkega zdravljenja, bodisi zaradi slabega stanja zmogljivosti, spremljajočih bolezni ali obsega bolezni. Polovica bolnikov ima ob diagnozi razsejano bolezen, zaradi česar izboljšanje preživetja z malimi koraki sledi napredku v zdravljenju bolnikov s pljučnim rakom. Ti podatki nas opominjajo, da se bomo morali za velike premike v obravnavi bolnikov s pljučnim rakom lotiti drugačnih pristopov. Kot najbolj obetavno se ponuja zgodnje odkrivanje bolezni, ko so možnosti ozdravitve pljučnega raka najboljše. Zapisana Priporočila so usmeritev za obravnavo bolnikov s pljučnim rakom. Le s sodobnim multidisciplinarnim pristopom obravnave lahko bolniku ponudimo zdravljenje, ki mu omogoča najboljši izhod prognostično neugodne bolezni.
Ključne besede: pljučni rak, priporočila
Objavljeno v DiRROS: 27.07.2023; Ogledov: 476; Prenosov: 165
.pdf Celotno besedilo (708,18 KB)
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Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small cell lung cancer : an international multicenter study
Zsolt Megyesfalvi, Nandor Barany, Andras Lantos, Zsuzsanna Valko, Orsolya Pipek, Christian Lang, Anna Schwendenwein, Felicitas Oberndorfer, Sandor Paku, Bence Ferencz, Izidor Kern, Mile Kovačević, Viktoria Laszlo, Balazs Dome, 2022, izvirni znanstveni članek

Povzetek: The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we have investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1 and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines reveal distinct vulnerability profiles defined by transcription regulators.
Ključne besede: Non-small-cell lung carcinoma, immunohistochemistry, molecular subtypes, prognostic relevance, expression pattern, neuroendocrine subtypes
Objavljeno v DiRROS: 27.05.2022; Ogledov: 942; Prenosov: 1273
.pdf Celotno besedilo (4,37 MB)
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Immunotherapy for metastatic non-small cell lung cancer : real-world data from an academic Central and Eastern European center
Marija Ivanović, Lea Knez, Ana Herzog, Mile Kovačević, Tanja Čufer, 2021, izvirni znanstveni članek

Povzetek: Background. Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). Here, we present the first results of a real-world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country. Materials and methods. Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first-line pembrolizumab (26 patients) or second-line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively. Results. Included patients had a median age of 64 years, most were male (55%), 6% were in performance status >/=2, and 18% had controlled central nervous system metastases at baseline. In first-line, the median progression-free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1-year overall survival (OS) was 62%. In second-line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1-year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3-4) in 12% of patients. Conclusion. The first real-world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real-world series, mainly coming from North America and Western European countries. Further data to inform on the real-world effectiveness of immunotherapy worldwide are needed.
Ključne besede: non-small cell lung carcinoma, immunotherapy, advanced non-small cell lung cancer, real-world data, Central Europe, Europe, Eastern Europe
Objavljeno v DiRROS: 12.10.2021; Ogledov: 977; Prenosov: 300
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