20.500.12556/RUL-109168 Rak trebušne slinavke in novi načini zdravljenja. Pancreatic adenocarcinoma and new treatment methods. Rak trebušne slinavke velja za enega najbolj smrtonosnih rakov. Srednje preživetje je zaradi poznega odkritja le 3 – 6 mesecev. V primeru zgodnjega odkritja raka, se tumor operativno odstrani, sicer pa se bolnikom podaljšuje življenje s kemoterapijo, pri čemer se običajno uporabi gemcitabin. Lahko se zdravi tudi z radioterapijo, kjer z obsevanjem poskušajo izzvati mutacije v celici, ki privedejo do apoptoze. Zdravljenje raka trebušne slinavke je zahtevno zaradi gostega tumorskega mikrookolja, poleg tega pa zaviralci imunskih kontrolnih točk zavirajo citotoksično delovanje limfocitov T. Novi načini zdravljenja se zato osredotočajo predvsem na imunoterapijo. Zaviralci kontrolnih točk, kot so PD-L1, CTLA-4 in VISTA, so humana transgena monoklonska protitelesa, ki jih običajno proizvajajo z transgenimi CHO celicami. Izsledki raziskav kažejo, da terapija samo z zaviralci imunskih kontrolnih točk ni učinkovita, so pa veliko uspešnejše kombinirane terapije, predvsem v kombinaciji s cepivi ali kemoterapijo. Največji uspeh je dosegla terapija s cepivi z dendritičnimi celicami, ki jih izpostavijo tumorskim antigenom, v kombinaciji s kemoterapijo, ob uporabi te terapije se preživetje podaljša na 16,7 mesecev, kombinacija cepiv z zaviralci imunskih kontrolnih točk pa le na 6 mesecev. Terapija s CAR T celicami še ni dobro razvita, so pa raziskave z elektrokemoterapijo pokazale, da imajo celice raka trebušne slinavke visoko izražene transkripcijske markerje značilne za matične celice. Pancreatic cancer is said to be one of the deadliest types of cancer with median survival of 3 – 6 months due to late diagnosis. When the cancer is found early, it can be operable, however patients are usually diagnosed with stage III or IV pancreatic cancer. In such cases, chemotherapy is used to prolong survival, gemcitabine being the most commonly used chemotherapeutic, followed by bleomycin and cisplatin. Rarely it is treated with radiotherapy, where radiation is used to induce mutations that lead to apoptosis. Treatment of pancreatic adenocarcinoma is difficult due to thick tumor microenvironment. Immune checkpoint inhibitors also inhibit the cytotoxic properties of lymphocytes T. Therefore, new treatment methods are focused on immunotherapy. Human monoclonal antibodies produced in CHO cell lines, that inhibit immune checkpoints, such as PD-L1, CTLA-4 and VISTA, are not showing much success by themselves, but different combinatorial therapies are more promising. Specifically, vaccines with dendritic cells exposed to tumor antigens prolong combined with chemotherapy prolong life for a full year, while the combination with immune checkpoint inhibitors only prolongs survival for 6 months. CAR T therapy is not well developed yet, however electrochemotherapy is bringing life to new discoveries, proving high level of stemness markers in pancreatic cancer cells. trebušna slinavka rak imunoterapija elektrokemoterapija tumor zdravljenje pancreas cancer imunotherapy electrochemotherapy tumor treatment true false false [A. Osovnikar] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2019-08-24 07:45:33 2019-08-24 07:45:36 2022-08-21 03:40:24 0000-00-00 00:00:00 2019 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 606:616-056.7:602.8:616-006.6:602.68(043.2) 166350 9283193 7505.pdf 7505.pdf 1 C3BF7271BB8501347D9DCF1E352AE35F 9cec4433dc9c72790fa04bff8c68eb843b7b718bbc097eccddb05997a7298a31 cb8c18f2-a1b6-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=120658 Biotehniška fakulteta 0 0 0