Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 103-118). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

<p>Karcinom debelog creva predstavlja treći uzrok smrnosti od maligniteta kod mu&scaron;karaca i drugi kod žena. Postoji osnovana sumnja da kancerske matične ćelije (KMĆ) imaju veliki značaj u karcinogenezi, invazivnosti, &scaron;irenju i rezistenciji na hemioterapiju primarnog tumora. Njihova identifikacija u primatnom kolorektalnom karcinomu (KRK) putem markera kancerskih matičnih ćelija bi selektovala visokorizičnu grupu bolesnika, omogućila ciljano delovanje na ove ćelije i veću &scaron;ansu za izlečenje. Cilj ovog istraživanja je bio utvrđivanje uticaja prisustva kancerskih matičnih ćelija u primarnom tumoru obolelih od karcinoma kolona na pojavu relapsa bolesti, dužino preživljavanja bez bolesti i sveukupno preživljavanje.&nbsp; Istraživanje je sprovedeno kao prospektivno&minus;retrospektivna randomizovana analitička studija na Klinici za operativnu onkologiju i Službi za patolo&scaron;ko &ndash; anatomsku i laboratorijsku dijagnostiku Instituta za onkologiju Vojvodine u Sremskoj Kamenici u periodu od 2016-2019. godine. U studiju su uključeno 112 bolesnica operisanih na Institutu za onkologiju Vojvodine u periodu od 2007-2012. godine sa patohistolo&scaron;ki potvrđenom dijagnozom primarnog, nemetastatskog (stadijumi I, II i III) KRK. Bolesnici su randomizovani u odnosu na pojavu recidiva bolesti i prisustvo metastaza u regionalnim limfnim čvorovima u odnosu 1:1. Uzorci tumorskog tkiva dobijeni hirur&scaron;kom resekcijom su nakon standardne patohistolo&scaron;ke obrade tretirani primenom monoklonskih antitela na CD44, CD166 i &alpha;-Lgr5. Određivani su prisustvo, intezitet i lokalizacija kancerskih matičnih ćelija (KMĆ) u primarnom tumoru i njihov uticaj na pojavu relapsa bolesti, dužinu preživljavanja bez bolesti i sveukupno preživljavanje u grupi svih bolesnika a potom bolesnika podeljenih prema stadijumu bolesti. Bolesnici u prvom i drugom stadijumu bolesti koji su imali relaps su imali statistički značajno veće prisustvo CD44+ KMĆ u primarnom tumoru. Kod ovih bolesnika je prisutan kraći period preživljavanja bez bolesti kao i kraće sveukupno preživljavanje. Takođe, uočen je statistički značajan uticaj koekspresije CD44/CD166 u KMĆ na pojavu relapsa bolesti, dužinu preživljavanja bez bolesti i sveukupno preživljavanje kod bolesnika u prvom i drugom stadijumu bolesti. Nije uočena statistička značajnost prisustva KMĆ u primarnom tumoru na pojavu relapsa bolesti, dužinu preživljavanja bez bolesti i sveukupno preživljavanje kod bolesnika u trećem stadijumu bolesti. Prisustvo CD166 i &alpha;-Lgr5 obojenih KMĆ nije pokazalo statističku značajnost u pogledu pojave relapsa bolesti, dužine preživljavanja bez bolesti i sveukupnog preživljavanja, kako u grupi svih bolesnika tako i prilikom podele bolesnika na stadijume bolesti.</p> / <p>Colon cancer is the third most common case of death of malignancy in the world. There is justified theory that cancer stemm cells have significant impact on colon cancer tumorogenesis, invasiviness, spread and resistancy on chemotherapy. Identification of colon cancer stem cells in primary tumor by various biological markers would lead to identification of high risk group of patients, target therapy of colon cancer an higher chance to cure. Aim of this study was to determine wether presence of colon cancer stem cells in primary tumour have impact on recurrence, disease free survival (DFS) and overall survival (OS) in patients with colorectal cancer. An randomized, analytical prospective-retrospective study was performed on Clinic for Operative Oncology and Department for Anatomical Pathology of Oncology Institute of Vojvodina in Sremska Kamenica in period of 2016&minus;2019. Study included 112 patient with patohistological proven, non metastatic colon adenocarcinoma who were operated on Oncology Institute of Vojvodina in period of 2007-2012. Patients were randomized by recurrence and presence of metastatic lymph nodes by 1:1 ratio. After standard patohistological preparation, tumour specimens were stained for monoclonal CD44, CD166 and &alpha;-Lgr5 antibody. Presence, intensity of expression and localization of colon cancer stem cells were observed and their impact on relapse, disease free survival and overall survival in group of all patients as well as in groups divided by stages of the disease. We demonstrate that patients in Stage I and II of the disease who experience disease recurrence have statistically significant higher expression of CD44+ in primary tumor specimen. They also have shorter DFS and OS. Coexpression of CD44/CD166 antibody also have strong negative impact on recurrence, disease free survival and overall survival in Stage I and II patients. There is no correlation between presence of colon cancer stem cells and recurrence nor presence of colon cancer stem cells had impact on disease free survival and overall survival. Presence of CD166 and &alpha;-Lgr5 expression did not show significant impact on recurrence nor disease free survival and overall survival as in group of all patients as well in group of patients divided by stages of the disease. High expression of CD44+ and coexpression of CD44/CD166+ colon cancer stem cell markers in primary tumor specimen correlates with higher chance for disease recurrence and also leads to shorter DFS and OS.</p>