1. Rak neznanega izvora : nas izvor bolezni še zanimaErika Matos, Snežana Pavlović Djokić, Srdjan Novaković, Marina Čakš, Rok Devjak, Nežka Hribernik, Kaja Cankar, 2024, strokovni članek Povzetek: Rak neznanega izvora (RNI) je opredeljen kot karcinom ali nediferencirana neoplazma, pri kateri z naborom standardnih diagnostičnih postopkov ni mogoče odkriti izvornega mesta bolezni. Tradicionalno RNI delimo v dve podskupini, pri čemer le približno 15 % primerov predstavlja prognostično ugodno skupino. Velika večina bolnikov spada v prognostično neugodno skupino in ima ob prvi prezentaciji obsežno breme bolezni. Možnosti zdravljenja so omejene, izidi bolnikov, zdravljenih z empirično kemoterapijo (KT) s platino ali taksani, pa so še vedno slabi, srednje celokupno preživetje je manj kot 10 mesecev. Za mnoge bolnike ostaja optimalna izbira najboljše možno podporno zdravljenje. Novi pristopi k obravnavi teh bolnikov se zdijo obetavni in so temeljit premik v paradigmi zdravljenja RNI; od zdravljenja, specifičnega za organ/tkivo, k zdravljenju, usmerjenemu na posameznega bolnika, ki temelji na genomskih spremembah njegovega tumorja. Prispevek povzema trenutne dokaze o uporabi vsakega od teh pristopov. Predstavljeno je tudi zdravljenje treh bolnikov z neugodnim RNI.
Ključne besede: rak neznanega izvora, molekularne značilnosti, biološki označevalci
Objavljeno v DiRROS: 26.07.2024; Ogledov: 242; Prenosov: 134
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2. Succinylation of polyallylamine: influence on biological efficacy and the formation of electrospun fibersLucija Jurko, Matej Bračič, Silvo Hribernik, Damjan Makuc, Janez Plavec, Filip Jerenec, Sonja Žabkar, Nenad Gubeljak, Alja Štern, Rupert Kargl, 2021, izvirni znanstveni članek Povzetek: Succinylation of proteins is a commonly encountered reaction in biology and introduces negatively charged carboxylates on previously basic primary amine groups of amino acid residues. In analogy, this work investigates the succinylation of primary amines of the synthetic polyelectrolyte polyallylamine (PAA). It investigates the influence of the degree of succinylation on the cytotoxicity and antibacterial activity of the resulting polymers. Succinylation was performed in water with varying amounts of succinic anhydride and at different pH values. The PAA derivatives were analyzed in detail with respect to molecular structure using nuclear magnetic resonance and infrared absorbance spectroscopy. Polyelectrolyte and potentiometric charge titrations were used to elucidate charge ratios between primary amines and carboxylates in the polymers. The obtained materials were then evaluated with respect to their minimum inhibitory concentration against Staphylococcus aureus and Pseudomonas aeruginosa. The biocompatibility was assessed using mouse L929 fibroblasts. The degree of succinylation decreased cytotoxicity but more significantly reduced antibacterial efficacy, demonstrating the sensitivity of the fibroblast cells against this type of ampholytic polyelectrolytes. The obtained polymers were finally electrospun into microfiber webs in combination with neutral water-soluble polyvinyl alcohol. The resulting non-woven could have the potential to be used as wound dressing materials or coatings.
Ključne besede: polyallylamine hydrochloride, succinylation, aqueous chemistry, cytotoxicity, antimicrobial effect, electrospinning, nanofibers, mouse L929 fibroblasts, Staphylococcus aureus, Pseudomonas aeruginosa
Objavljeno v DiRROS: 19.07.2024; Ogledov: 148; Prenosov: 175
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3. Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab : real-world experienceNežka Hribernik, Marko Boc, Janja Ocvirk, Jasna Knez Arbeiter, Tanja Mesti, Marija Ignjatović, Martina Reberšek, 2020, izvirni znanstveni članek Povzetek: Based on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials. Patients and methods. This observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019. Results. The estimated median overall survival (OS) was 25.1 months (95% CI, 14.6%35.6) and the median progressionfree survival (PFS) was 10.7 months (95% CI, 5.9%15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3%4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment. Conclusions. Our real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.
Ključne besede: immunotherapy, pembrolizumab, metastatic melanoma, treatment-naive
Objavljeno v DiRROS: 11.07.2024; Ogledov: 208; Prenosov: 110
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5. Effectiveness of electrochemotherapy after IFN-[alpha] adjuvant therapy of melanoma patientsAndrejc Hribernik, Maja Čemažar, Gregor Serša, Maša Omerzel, Marko Snoj, 2016, izvirni znanstveni članek Povzetek: The combination of electrochemotherapy with immuno-modulatory treatments has already been explored and proven effective. However, the role of interferon alpha (IFN-alpha) adjuvant therapy of melanoma patients and implication on electrochemotherapy effectiveness has not been explored yet. Therefore, the aim of the study was to retrospectively evaluate the effectiveness and safety of electrochemotherapy after the previous adjuvant treatment with IFN-alpha in melanoma patients. Patients and methods. The study was a retrospective single-center observational analysis of the patients with advanced melanoma, treated with electrochemotherapy after previous IFN-alpha adjuvant therapy. Five patients, treated between January 2008 and December 2014, were included into the study, regardless of the time point of IFN-alpha adjuvant therapy. Results. Electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy proved to be a safe and effective treatment. Patients with one or two metastases responded completely. Among patients with multiple metastases, there was a variable response rate. In one patient all 23 metastases responded completely, in second patient more than 85% of all together 80 metastases responded completely and in third patient all 5 metastases had partial response. Taking into account all metastases from all patients together there was an 85% complete response rate. Conclusions. The study showed that electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy is a safe and effective treatment modality, which results in a high complete response rate, not only in single metastasis, but also in multiple metastases. The high complete response rate might be due to an IFN-alpha immune-editing effect, however, further studies with a larger number of patients are needed to support this presumption.
Ključne besede: electrochemotherapy, IFN-alpha, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 364; Prenosov: 114
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9. Sistemsko zdravljenje melanomskih bolnikov z zasevki v centralnem živčnem sistemuNežka Hribernik, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Bolniki z metastatskim melanomom, ki imajo možganske zasevke, so posebna podskupina melanomskih bolnikov z zelo slabim preživetjem. Pri obravnavi teh bolnikov je ključen multidisciplinaren pristop, ki vključuje tako lokalno zdravljenje (nevrokirurgija, radioterapija) kot specifično sistemsko onkološko zdravljenje. Z novimi možnostmi lokalne in sistemske terapije so se preživetja bolnikov z možganskimi zasevki izboljšala. Glede zaviralcev imunskih kontrolnih točk je kombinirana imunoterapija s PD-1/ CTLA 4 protitelesi uspešnejša napram mono-imunoterapiji. S kombinirano imunoterapijo je bil v randomiziranih kliničnih raziskavah pri bolnikih z asimptomatskimi možganskimi zasevki ugotovljen visok odgovor na zdravljenje. Ugotavljali so dolgotrajne remisije. Pri bolnikih s simptomatskimi možganskimi zasevki, ki so potrebovali sistemski glukokortikoid, tega uspeha niso beležili. Glede tarčne terapije z BRAF in MEK zaviralci je bil pri kombinaciji dabrafeniba in trametiniba dokazan hiter in visok delež odgovorov, vključno pri bolnikih, ki so prejemali sistemski glukokortikoid. Žal pa je bilo trajanje odgovorov kratko, povprečno manj kot 6 mesecev. Raziskujejo se novi načini zdravljenja, ki bodo dodatno izboljšali preživetja teh bolnikov.
Ključne besede: rak kože, melanom, sistemsko zdravljenje
Objavljeno v DiRROS: 17.05.2023; Ogledov: 492; Prenosov: 236
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10. Imunsko pogojeni neželeni učinkiNežka Hribernik, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Specifično sistemsko onkološko zdravljenje z zaviralci imunskih nadzornih točk dokazano podaljša celokupno preživetje in izboljša kakovost življenja bolnikov z različnimi vrstami raka. Število bolnikov, ki se zdravi s to vrsto imunoterapije, strmo narašča. Zaviralci imunskih nadzornih točk lahko povzročijo posebno vrsto neželenih učinkov, imenovanih imunsko pogojeni neželeni učinki. Ti so posledica prekomerne aktivacije imunskega sistema. Lahko privedejo do resnih in celo življenje ogrožajočih zapletov, čeprav so v večini blage do zmerne stopnje. Prizadet je lahko kateri koli organ. Ključno pri njihovi obravnavi ostaja hitra prepoznava, ustrezno zdravljenje in večje ozaveščanje med kliniki različnih področij in bolniki ter njihovimi svojci.
Ključne besede: imunoterapija, onkologija, onkološko zdravljenje
Objavljeno v DiRROS: 16.02.2023; Ogledov: 711; Prenosov: 294
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