Establishment of a first cancer Biobank at the Institute for Oncology and Radiology of Serbia – advantages, challenges and future perspective
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Oncology Insights Offi cial Journal of the Serbian Associa on for Cancer Research ISSN 3009-3848 ISSNe 3009-383X Year 2023/No. 1
ONCOLOGY INSIGHTS Offi cial Journal of the Serbian Associa on for Cancer Research Belgrade, Serbia October, 2023 ISSN 3009-3848 ISSNe 3009-383X
ONCOLOGY INSIGHTS Offi cial Journal of the Serbian Associa on for Cancer Research Publishing annually Publisher Serbian Associa on for Cancer Research Belgrade, Serbia Editor-in-Chief Dr Milena Čavić Associate Editors Dr Milica Pešić, Dr Ivana Z. Ma ć Managing Editor Dr Ana Damjanović Veličković Technical Editors Dr Marija Đorđić Crnogorac, Dr Milica Nedeljković Editors Dr Radmila Janković, Dr Marko Radulović, Prof. Katarina Zeljić, Dr Ana Krivokuća, Prof. Chiara Ambrogio, Dr Thomas Mohr, Prof. Engin Ulukaya, Prof. Vilma Petrikaite, Prof. Konstan nos Dimas, Dr Cris na Xavier, Dr Remond Fijneman, Prof. Ieronymos Zoidakis, Dr Sergi Castellvi-Bel, Dr Petar Ozre c, Prof. Sonja Levanat Editorial Council Dr Ana Đurić, Dr Marko Radulović, Dr Radmila Janković, Prof. Katarina Zeljić, Dr Lidija Todorović Lector/Corrector Jana Stefanović Editorial Offi ce Serbian Associa on for Cancer Research Printed by: Connect Online Studio Ćirila i Metodija 2a Belgrade, Serbia CIP - Каталогизација у публикацији Народна библиотека Србије, Београд 616-006-08 ONCOLOGY Insights : offi cial Journal of the Serbian Associaton for Cancer Research / editor in chief Milena Čavić. - [Štampano izd.]. - 2023, no. 1- . - Belgrade : Serbian Associaton for Cancer Research, 2023- (Belgrade : Connect Online Studio). - 30 cm Godišnje. - Drugo izdanje na drugom medijumu: Oncology Insights (Online) = ISSN 3009-383X ISSN 3009-3848 = Oncology Insights (Štampano izd.) COBISS.SR-ID 125366281
V SDIR6 ORGANIZING COMMITTEE President: Prof. dr Katarina Zeljić, Faculty of Biology, University of Belgrade Dr Milena Čavić, Ins tute for Oncology and Radiology of Serbia Dr Milica Pešić, Ins tute for Biological Research “Siniša Stanković”, University of Belgrade Dr Radmila Janković, Ins tute for Oncology and Radiology of Serbia Dr Marko Radulović, Ins tute for Oncology and Radiology of Serbia Prof. dr Katarina Zeljić, Faculty of Biology, University of Belgrade Dr Ivana Ma ć, Ins tute for Oncology and Radiology of Serbia Dr Ana Krivokuća, Ins tute for Oncology and Radiology of Serbia Dr Lidija Todorović, The Vinča Ins tute of Nuclear Sciences, University of Belgrade Dr Jelena Spasić, Ins tute for Oncology and Radiology of Serbia Dr Nina Petrović, The Vinča Ins tute of Nuclear Sciences, University of Belgrade Dr Milica Nedeljković, Ins tute for Oncology and Radiology of Serbia Dr Sofi ja Jovanović Stojanov, Ins tute for Biological Research “Siniša Stanković”, University of Belgrade Dr Ana Damjanović Veličković, Ins tute for Oncology and Radiology of Serbia Dr Marija Đorđić Crnogorac, Ins tute for Oncology and Radiology of Serbia Dr Jelena Grahovac, Ins tute for Oncology and Radiology of Serbia Dr Ana Đurić, Ins tute for Oncology and Radiology of Serbia Dr Tijana Išić Denčić, Ins tute for the Applica on of Nuclear Energy - INEP Dr Bojana Kožik, The Vinča Ins tute of Nuclear Sciences, University of Belgrade Ivana Pašić, Ins tute for Oncology and Radiology of Serbia Aleksandra Stanojević, Ins tute for Oncology and Radiology of Serbia Mladen Marinković, Ins tute for Oncology and Radiology of Serbia Valen na Karadžić, Ins tute for Oncology and Radiology of Serbia Marina Popović Krneta, Ins tute for Oncology and Radiology of Serbia Ana Stepanović, Ins tute for Biological Research “Siniša Stanković”, University of Belgrade
VI SDIR6 SCIENTIFIC COMMITTEE President: Dr Milena Čavić, Ins tute for Oncology and Radiology of Serbia Dr Milena Čavić, Ins tute for Oncology and Radiology of Serbia Dr Milica Pešić, Ins tute for Biological Research “Siniša Stanković”, University of Belgrade Dr Radmila Janković, Ins tute for Oncology and Radiology of Serbia Dr Marko Radulović, Ins tute for Oncology and Radiology of Serbia Prof. dr Katarina Zeljić, Faculty of Biology, University of Belgrade Dr Ivana Ma ć, Ins tute for Oncology and Radiology of Serbia Dr Ana Krivokuća, Ins tute for Oncology and Radiology of Serbia Prof. dr Tatjana Simić, Faculty of Medicine, University of Belgrade Dr Ljubica Harhaji-Trajković, Ins tute for Biological Research “Siniša Stanković”, University of Belgrade Dr Miljana Tanić, Ins tute for Oncology and Radiology of Serbia Dr Lidija Todorović, The Vinča Ins tute of Nuclear Sciences, University of Belgrade Dr Jelena Spasić, Ins tute for Oncology and Radiology of Serbia Dr Nina Petrović, The Vinča Ins tute of Nuclear Sciences, University of Belgrade Dr Nevenka Gligorijević, Ins tute for Oncology and Radiology of Serbia Dr Ana Podolski-Renić, Ins tute for Biological Research “Siniša Stanković”, University of Belgrade Dr Jelena Dinić, Ins tute for Biological Research “Siniša Stanković”, University of Belgrade Prof. Chiara Ambrogio, Department of Molecular Biotechnology and Health Sciences, Molecular BiotechnologCenter, University of Torino Dr Thomas Mohr, Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna Prof. Engin Ulukaya, Medical Faculty of Is nye University Prof. Vilma Petrikaite, Life Sciences Center, Vilnius University Prof. Konstan nos Dimas, Faculty of Medicine - University of Thessaly Dr. Cris na Xavier, i3S - Ins tute for Research and Innova on in Health, Porto Dr Remond Fijneman, the Netherlands Cancer Ins tute Dr Ieronymos Zoidakis, Biomedical Research Founda on Academy of Athens, Greece Dr Sergi Castellvi-Bel, Fundació de Recerca Clínic Barcelona-Ins tut d’Inves gacions Biomèdiques August Pi i Sunyer, Barcelona Dr Petar Ozre c, Ruđer Bošković Ins tute, Zagreb Prof. Sonja Levanat, Ruđer Bošković Ins tute, Zagreb
Oncology Insights SDIRSACR 40, and C-reac ve Protein in Pa ents with Unresectable Pancrea c Cancer. Cancer Epidemiol Biomarkers Prev. 2020;29(1):176-84. doi: 10.1158/1055-9965.EPI-19-0672. 9. Chen HT, Zheng JM, Zhang YZ, Yang M, Wang YL, Man XH, Chen Y, Cai QC, Li ZS. Overexpression of YKL-40 Predicts Poor Prognosis in Pa ents Undergoing Cura ve Resec on of Pancrea c Cancer. Pancreas. 2017;46(3):323-34. doi: 10.1097/MPA.0000000000000751. 10. Rebelo R, Polónia B, Santos LL, Vasconcelos MH, Xavier CPR. Drug Repurposing Opportuni es in Pancrea c Ductal Adenocarcinoma. Pharmaceu cals (Basel). 2021;14(3):280. doi: 10.3390/ph14030280. Establishment of a fi rst cancer Biobank at the Ins tute for Oncology and Radiology of Serbia – advantages, challenges and future perspec ves S nežana Bjelogrlić1, Miljana Tanić1, Mladen Marinković2, Jelena Spasić3, Ana Đurić1, Suzana Stojanović-Rundić2,4, Aleksan dra Stanojević1, Marija Đorđić Crnogorac5, Katarina Mirjačić Mar nović1, Ana Vule ć1, Ana Damjanović Veličković1, Marko Radulović1, Radmila Janković1, Jerome Zoidakis6,7, Remond Fijneman8, Sergi Castellví-Bel9, Ana Krivokuća5, Milena Čavić1 1Department of Experimental Oncology, Ins tute for Oncology and Radiology of Serbia, Belgrade, Serbia 2Clinic for Radia on Oncology and Diagnos cs, Department of Radia on Oncology, Ins tute for Oncology and Radiology of Serbia, Belgrade, Serbia 3Clinic for Medical Oncology, Ins tute for Oncology and Radiology of Serbia, Belgrade, Serbia 4Faculty of Medicine, University of Belgrade, Belgrade, Serbia 5Department of Gene c Counseling for Hereditary Cancers, Ins tute for Oncology and Radiology of Serbia, Belgrade, Serbia 6Department of Biotechnology, Biomedical Research Founda on, Academy of Athens, Athens, Greece 7Department of Biology, Na onal and Kapodistrian University of Athens, Greece 8Department of Pathology, The Netherlands Cancer Ins tute, Amsterdam, the Netherlands 9Gastroenterology Department, Fundació de RecercaClínic Barcelona-Ins tutd'Inves gacionsBiomèdiques August Pi iSunyer, Centro de Inves gaciónBiomédica en Red de EnfermedadesHepá cas y Diges vas, Hospital Clínic, University of Barcelona, Barcelona, Spain Background: Procurement and storage of diff erent biospecimens from cancer pa ents has been a standard prac ce over decades at the Ins tute for Oncology and Radiology of Serbia (IORS). However, such organized repositories were exclusively project-based. The type and amount of collected samples was defi ned by research needs, or by limited capacity of the storage units, while collec ng of biospecimens relied on hands-on involvement of researchers and medical professionals. Although necessary ethical guidelines were respected and the whole process was well controlled by individual researchers, there were several disadvantages that needed to be addressed and resolved. Informa on on the stored samples was not collected systema cally and tracking was diffi cult. Most biospecimen were disposed a er project end due to storage space shortage rendering the previous collec on eff orts non-economic. Within the framework of the Horizon Europe STEPUPIORS (101079217) project, the goal was to solve the iden fi ed drawbacks of project-based repositories and to create a highly organized and well controlled biobanking system. The biobank was envisioned to func on in accordance with interna onally accepted technical, scien fi c and logis cal standards and guidelines while respec ng the na onal legisla ve, with the aim to contribute to elucida on of pathophysiology, diagnosis, and treatment of cancer. Organized biobanks provide assurance that pa ents’ biospecimens and derived data are collected, stored, and managed in a way that enables op mal sharing and usage with minimal risk of misuse. Here we present the road towards the establishment of a proper procedural workfl ow for se ng up a fi rst rectal cancer biobank at IORS, and the iden fi ed advantages, challenges and future perspec ves. Material and Methods: Future biobanking personnel a ended intensive online and in person training and performed expert visits to each partner ins tu on with insight into biobanking prac ces. Biobanking procedures were developed according to recommenda ons of the Interna onal Society of Biological and Environmental Repositories (ISBER), the Biobanking and BioMolecular resource Research Infrastructure (BBMRI), European Research Infrastructure Consor um (ERIC), and EU regula ons followed by partner ins tu ons. A rigorous evalua on of ethical and legal regula ons was performed, respec ng na onal and European legisla on. Essen al biobank equipment and laboratory informa on so ware were procured to ensure maximum accordance with infrastructural, storage and data protec on requirements. Decisions were made during regular weekly mee ng of IORS biobanking staff and consensus consor um approvals reached on all aspects. Management and internal and external oversight commi ees were formed of members of all four partner ins tu ons. Results: Fi een professionals of diff erent disciplines (5 physicians, 3 biochemists, 4 molecular biologists, 3 pharmacists), L14
Serbian Associa on for Cancer Research SDIRSACR all IORS employees, have been gathered sharing a mutual inten on to defi ne a sequence of ac on necessary for the process of se ng up a biobank. Within the fi rst year, the STEPUPIORS team has undertaken landmark steps to improve both our knowledge and technical aspects as those involved to establish high-quality criteria for rou ne biobanking prac ce. At the very beginning, we were pursuing ways to reconcile some diversi es in legal regula ons between Serbia and the European Union, which is of crucial importance for future biospecimens and data exchange. Two expert visits of IORS professionals to STEPUPIORS partner biobanks provided on site educa on regarding diff erent management strategies, funding models, and biosafety requirements that are mandatory for running a biobank. A ending a Basic biobanking course at the Medical University of Graz notably expanded our understanding of minimal requirements for building a biobank, sample handling and logis cs, biobank sustainability and risk assessment. We implemented the acquired knowledge to develop a fi rst set of 13 Standard opera ng procedure (SOP) protocols with appropriate annexes covering pa ent recruitment, documenta on and biospecimens management. We evaluated diff erent models of biobanking Informed consent documents and adapted ours to serve both the pa ents and the medical community, while respec ng all bioethical regula ons and data protec on legisla ve. We performed a thorough market and quality analysis of available biobanking laboratory informa on systems to be implemented which would best support data collec on, analysis and management while providing strong security and protec on of pa ents’ privacy. We further defi ned equipment and space requirements to maintain a safe environment for the biospecimen. Special a en on has been dedicated to poten al biosafety hazards and measures that should be implemented to minimize poten al risks while handling biohazardous materials. In August 2023, biobanking so ware procurement was fi nalized and the biobank is planned to be fully opera onal in October 2023. A procedural basis for the collec on of a planned project cohort of around 100 locally advanced rectal cancer (LARC) pa ents was successfully introduced. Scien fi c and management oversight commi ees including members of partner ins tu ons were formed from the ini a on of the biobank to ensure high-quality biobank-related research and innova on that will advance the treatment of LARC pa ents. Although the biobank has primarily been established within the framework of the STEPUPIORS project as a project deliverable, the collected rectal cancer cohort is planned to be used for a broad spectrum of future research projects. The developed SOPs and IT infrastructure will allow further advancement in cancer research at our Ins tute, as it has been envisioned to be expanded to other cancer types and the organized collec on of diagnos c samples. The fi rst IORS biobank might be useful as a pilot project for other biobanks planned to be formed in Serbia in the future. Conclusion: Building a biobank is a challenging project even in countries with appropriate scien fi c and healthrelated funds. Aside from legisla ve issues and the need for improvement of current infrastructure and performance, it requires a highly dedicated and well-orchestrated team of professionals with on-call duty to ensure maximum safety. Within the framework of the STEPUPIORS Horizon Europe project, the fi rst rectal cancer Biobank has been successfully established at the Ins tute for Oncology and Radiology of Serbia and is expected to become fully func onal by the end of 2023. Plans for its future expanding to accommodate other cancer subtypes are under way. Keywords: Biobank, bioethics, data protec on, rectal cancer Acknowledgements: This study was funded by the Horizon Europe Twinning Project STEPUPIORS (Agreement No. 101079217) and the Ministry of Educa on and Science of the Republic of Serbia (Agreement No. 451-03-68/202214/200043). Advancing reversible immunocapture toward scalable purifi ca on of extracellular vesicles Lidija Filipović1, Milica Spasojević1, Radivoje Prodanović2, Suzana Ma jašević3, Goran Brajušković3, Milica Popović2 1Innova ve Centre of the Faculty of Chemistry, Belgrade, Serbia 2University of Belgrade-Faculty of Chemistry, Belgrade, Serbia 3University of Belgrade-Faculty of Biology, Belgrade, Serbia Background: Extracellular vesicles (EVs) are supramolecular structures secreted by majority of cells1. Based on their mechanism of release and size, EVs are categorized as exosomes (EXO), microvesicles/shedding par cles, and apopto c bodies. Their content diff ers according to the characteris cs of the cells from which they originated2. EVs are involved in a myriad of physological and pathological proceses and correct elucida on of their role in these processes is highly dependent on the reliability of the method used for their purifi ca on3. Currently available chemical/physical protocols for sample frac ona on are me-consuming, o en scarcely reproducible and their yields are low. Immunecapture based approaches could represent an eff ec ve purifi ca on alterna ve to obtain homogeneous EV samples4. Methodology: We have set-up an easy-to-operate chromatography system for the purifi ca on of intact EVs based on a single domain (VHH) an bodies-copolymer matrix suitable for biological samples as diff erent as condi oned L15