Analiza predikcije matičnosti karcinoma dojke i kolona u tretmanu hemioterapeuticima primenom alata matematičkog modeliranja
Ramović Hamzagić, Amra, 1993-
Ljujić, Biljana, 1974-
Živanović, Marko, 1980-
Gazdić Janković, Marina, 1987-
Nikolić, Dalibor, 1985-
Perović, Vladimir, 1975-
Introduction: The complex tumor microenvironment with heterogeneous cell types poseschallenges in the therapy because even after chemotherapy, CSC remain viable and can againinduce tumor formation and metastasis. Therefore, a detailed analysis of the tumormicroenvironment, driver markers and cells with different phenotypes are crucial.Aim: The main objective of this study was the detection of markers that participate in thetherapeutic outcome and the identification of noxi that contribute to tumor growth anddevelopment.Material and methods: Markers of resistance to chemotherapeutic drugs and malignancywere CD24, CD44, ABCG2 and ALDH1. Study included anylysis of 24 marker combinationsand effects of 5-fluorouracil, leucovorin, irinotecan, oxaliplatin and polyester nanoplastics ina model of colon (HCT-116) and breast cancer cell lines (MDA-MB-231). Mathematicalanalysis allowed us to better characterize the malignant phenotype.Results: The impact of chemotherapeutics and nanoplastics on the cure, formation andprogression of tumors represent the most significant contribution of this research. The degreeof malignancy was determined on the presence of the CSC population, which was defined bythe expression of stem markers by flow cytometry and qRT-PCR methods.Viability wasevaluated using in vitro methods (MTT and RTCA).Conclusion: Our results showed for the first time that the examined cancer lines are aheterogeneous population of tumor cells that also contain CSCs. Conventionalchemotherapeutic agents can help, but also promote the proliferation of CSCs. Polystyrenenanoplastics represent a significant factor in the formation of a malignant phenotype. Theimplementation of mathematical modeling is an important tool in understanding tumors andchoosing a therapy.
Uvod: Kompleksna tumorska mikrosredina sa heterogenim vrstama ćelija predstavljabrojne izazove u terapijskom pristupu jer i nakon hemioterapije, kancerske matičnećelije CSCc ostaju vijabilne i ponovo mogu indukovati nastanak tumora i metastaza.Zbog navedenog, detaljna analiza tumorske mikrosredine i identifikacija drajvermarkera i ćelija sa različitim fenotipom je neophodna.Cilj: Osnovni cilj ovog istraživanja je detekcija markera koji učestvuju uterapijskom ishodu i identifikacija noksi (poliestirenska nanoplastika) kojedoprinose razvoju tumora.Materijal i metode: Markeri rezistencije i malignosti koji su bili ispitivani su:CD24, CD44, ABCG2 i ALDH1. Obuhvaćena je analiza 24 različite kombinacije ovihmarkera kao i ispitivanje uticaja 5-fluorouracila, leukovorina, irinotekana,oksaliplatine i poliestirenske nanoplastike na modelu ćelijskih linija kancerakolona (HCT-116) i dojke (MDA-MB-231). Matematička analiza omogućila nam je boljukarakterizaciju malignog fenotipa.Rezultati: Uticaj hemioterapeutika i nanoplastike na izlečenje, nastanak iprogresiju tumora, predstavljaju najznačajniji doprinos ovog istraživanja. Stepenmalignosti određivan je na osnovu zastupljenosti populacije CSC, koja je definisanaekspresijom markera matičnosti metodama protočne citometrije i qRT-PCR. Uproceni vijabilnosti koristili smo in vitro metode (MTT i RTCA).Zaključak: Rezultati ovog istraživanja po prvi put pokazuju da su ispitivane linijekarcinoma heterogena populacija tumorskih ćelija koje sadrže i CSC. Takođe dakonvencionalni hemioterapeutici mogu da pomognu ali mogu i da promovišuproliferaciju CSC. Polistirenska nanoplastika predstavlja značajnu noksu unastanku malignog fenotipa. Implementacija matematičkog modeliranja predstavnjavažan faktor u razumevanju tumora i izboru terapije.
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srpski
2025
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