<p>Nastavni proces usmeren na davanje &scaron;to veće sume gotovih znanja ne može vi&scaron;e odolevati potrebama modernog doba. Problemska nastava osmi&scaron;ljena je sa ciljem da pomogne studentima da razviju unutra&scaron;nju motivaciju, ve&scaron;tine efikasnog re&scaron;avanja problema, saradnje kao i da razviju svoje stvaralačke sposobnosti, samostalno istražuju, analiziraju, zaključuju, izgrađuju sopstveni način mi&scaron;ljenja, a samim tim da se uspe&scaron;nije snalaze u sve složenijim odnosima koje nameće savremeni razvoj dru&scaron;tva.<br />Istraživanje u okviru ove disertacije imalo je za cilj da utvrdi kako primena problemske nastave doprinosi boljem usvajanju globalnih (organizacija, namena, čitaoci) i lokalnih (stil, gramatika, mehanika) aspekata pisanja u nastavi engleskog jezika struke prvenstveno jer postoji vrlo malo istraživanja koja se bave razvojem specifičnih aspekata pisanja i istraživači najče&scaron;će ispituju samo ukupno pobolj&scaron;anje ve&scaron;tine pisanja.<br />U istraživanju su učestvovali studenti prve godine na Visokoj poslovnoj &scaron;koli strukovnih studija u Novom Sadu koji su pohađali predmet Prvi strani poslovni jezik I &ndash; engleski. U skladu sa postavljenim problemom, ciljem i zadacima, u istraživanju je primenjena kauzalna metoda &ndash; eksperiment sa paralelnim grupama koji je imao za cilj utvrđivanje razlike inicijalnog i finalnog nivoa znanja globalnih i lokalnih aspekata pisanja u eksperimentalnoj i kontrolnoj grupi. Eksperimentalna grupa, učila je o globalnim i lokalnim aspektima pisanja po prethodno osmi&scaron;ljenim nastavnim jedinicama pripremljenim po principima problemske nastave dok su isti sadržaji obrađivani i u kontrolnoj grupi ali putem tradicionalne nastave.<br />Zbog kompleksnosti jezičke građe koju smo proučavali, opredelili smo se za pismeni sastav (pismo) kao merni instrument na inicijalnom i finalnom merenju i za analitičku skalu procene kao instrument za ocenjivanje pismenih sastava jer smo želeli da dobijemo pojedinačne ocene za svaki od ispitivanih aspekata i &scaron;to detaljnije informacije o postignuću studenta. U cilju postizanja validnosti, pored autorke, u ovom istraživanju su učestvovala jo&scaron; dva nastavnika engleskog jezika sa dugogodi&scaron;njim iskustvom u nastavi engleskog jezika struke. Oni su imali ulogu ocenjivača i pregledali su sve radove kako bi odredili razliku u kvalitetu inicijalnih i finalnih sastava.<br />Ispitivanjem efikasnosti posmatranog modela dobili smo pozitivan odgovor na pitanje da li problemska nastava utiče na pobolj&scaron;anje uspeha studenata u nastavi pisanja u jeziku struke. Upoređujući rezultate početnog testiranja i testiranja nakon izvođenja eksperimenta zaključili smo da su značajnije napredovali studenti koji su bili izloženi problemskoj nastavi a koji su pokazali značajna pobolj&scaron;anja u svih &scaron;est ispitivanih aspekata pisanja.<br />Uz pomoć problemske nastave kao konstruktivističkog pristupa učenju nastavnici engleskog jezika struke pronalaze načine da pomognu studentima da se upoznaju sa tekstualnim karakteristikama relevantnih disciplina, da nauče da analiziraju potrebe ciljnih čitalaca, procenjuju očekivanja publike i pi&scaron;u tekstove koji su prihvatljivi u diskursima određenih zajednica.<br />Ključne reči: problemska nastava, tradicionalna nastava, nastava pisanja, jezik struke, lokalni aspekti pisanja, globalni aspekti pisanja, analitička skala procene, ocenjivači.</p>

<p>Problemi klasifikacije i segmentacije digitalnih slika su veoma<br />aktuelni i zastupljeni u praksi. Potreba za modelima koji razmatraju<br />ovu problematiku u poslednjih nekoliko decenija ubrzanim tempom<br />poprima sve veći značaj i obim u svakodnevnom životu. Koriste se u<br />računarskoj grafici, prepoznavanju oblika, medicinskoj analizi slika,<br />saobraćaju, analizi dokumenata, pokreta i izraza lica i sl.<br />U okviru ove disertacije, predstavljeno istraživanje motivisano je<br />primenama razvijenih modela u klasifikaciji i segmentaciji<br />digitalnih slika. Istraživanje obuhvata dva segmenta. Ovi segmenti<br />povezani su terminom neodređenosti, koji je uz upotrebu adekvatnog<br />matematičkog aparata (teorije fazi skupova), ugrađen u modele razvije<br />za primenu u obradi slike.<br />Jedan pravac istraživanja baziran je na teoriji fazi skupova, t-<br />normama, t-konormama, operatorima agregacije i agregiranim<br />funkcijama rastojanja. U okviru toga, istraživanje je sprovedeno sa<br />struktuiranom matematičkom podlogom, izložene su osnovne<br />definicije, teoreme, kao i osobine korištenih operatora, prošireni<br />su teorijski koncepti t-normi i t-konormi. Definisani su novi tipovi<br />operatora agregacije i njihovom primenom konstruisane su nove<br />funkcije rastojanja, čija je upotreba diskutovana kroz uspešnost u<br />procesu segmentacije digitalnih slika.<br />Drugi pravac istraživanja, izložen u ovoj disertaciji, obuhvata više<br />inženjerski pristup rešavanju problema klasifikacije tekstura<br />digitalnih slika. U skladu sa tim, detaljno je analizirana i<br />diskutovana klasa lokalnih binarnih deskriptora teksture.<br />Inspirisana uspešnošću pomenute LBP klase deskriptora, uvedena je<br />jedna nova podfamilija &alpha;-deskriptora teksture. Uvedeni model<br />deskriptora formiran je na temeljima idejnih principa lokalnih<br />binarnih kodova i bazičnih pojmova iz teorije fazi skupova. Praktična<br />upotreba i značaj predstavljenog modela demonstrirani su kroz veoma<br />uspešne procese klasifikacije na nekoliko javno dostupnih baza slika.</p> / <p>Classification and segmentation problems of digital images is a very attractive<br />topic and has been making impact in many different applied disciplines. In the<br />past few decades, the demand for models that address these issues has been<br />gaining momentum and applications in everyday life. These models are used in<br />computer graphics, shape recognition, medical image analysis, traffic, document<br />analysis, facial movements and expressions, etc.<br />The research within this doctoral dissertation was motivated by the application of<br />developed methods in classification and segmentation tasks. The conducted<br />research covered two segments, which were linked by the term of indeterminacy,<br />with the usage of the theory of fuzzy sets, which is incorporated into methods<br />developed for application in image processing.<br />One direction of the research was founded on the theory of fuzzy sets, t-norms,<br />t-conorms, aggregation operators, and aggregated distance functions. Within this<br />framework, the research was conducted with a structured mathematical<br />background. Firstly, basic definitions, theorems and characteristics of the used<br />operators were presented, followed by the theoretical concepts of t-norms and tconorms<br />that were extended. New types of aggregation operators and distance<br />functions were defined, and finally, their contribution in the digital image<br />segmentation process was explored and discussed.<br />The second direction of the research presented in this dissertation involved more<br />of an engineering-type of approach to solving the problem of the classification of<br />digital image textures. To that end, a class of local binary texture descriptors<br />(LBPs) was analyzed and discussed in detail. Inspired by the results of the<br />above-mentioned LBP descriptors, one new sub-family of the $\alpha$-<br />descriptors was introduced by the author. The introduced descriptor model was<br />based on the conceptual principles of LBPs and basic definitions from the fuzzy<br />set theory. Its practical usage and importance were established and reflected in<br />very successful classification results, achieved in the application on several<br />publicly available image datasets.</p>

<p>UVOD: Glavni problem u lečenju karcinoma dojke je kako na osnovu kliničke klasifikacije i morfolo&scaron;kih osobina tumora predvideti njegovo dalje pona&scaron;anje. Vrlo često ni kombinacija standardnih prognostičkih faktora ne daje odgovor o potrebi davanja adjuvantne hemioterapije. U cilju sprovođenja adekvatne dalje terapije karcinoma dojke i otkrivanja agresivnih tipova tumora, a nakon hirur&scaron;kog lečenja, postoji stalna potreba za pronalaženjem novih pokazatelja pomoću kojih bi se identifikovale bolesnice koje imaju povećan rizik od razvoja relapsa bolesti. CILJEVI: Ciljevi su bili da se utvrdi prisustvo, lokalizacija i distribucija tumor infiltri&scaron;ućih limfocita, kako ukupnih, tako i CD4+ i CD8+ T limfocita u tumoru dojke, njihova povezanost sa standardnim prognostičkim parametrima, kao i njihov prognostički značaj tj. razlike u nivou infiltracije limfocita u tumoru u odnosu na pojavu relapsa bolesti i dužinu preživljavanja. METOD: Istraživanjem je obuhvaćeno 120 bolesnica sa invazivnim duktalnim karcinomom, sa tumorom lokalizovanim samo u dojci, bez zahvatanja kože i grudnog mi&scaron;ića, sa veličinom tumora do 5 cm, bez udaljenih visceralnih i ko&scaron;tanih metastaza, koje su operisane u Institutu za onkologiju Vojvodine. U istraživanje su uključene bolesnice bez metastaza u limfnim čvorovima pazu&scaron;ne jame i bolesnice sa metastazama u limfnim čvorovima pazu&scaron;ne jame. Istraživanjem nisu obuhvaćene bolesnice koje su primale neoadjuvantnu (preoperativnu) hemioterapiju, kao ni bolesnice sa multifokalnim i multicentričnim tumorima. REZULTATI: Gust limfocitni infiltrat uočen je u 14% tumora dojke, umeren limfocitni infiltrat uočen je u 38%, a oskudan u 43% tumora dojke. Limfocitni infiltrat nije uočen u 5% tumora. Gust infiltrat CD4+ limfocita uočen je u 8% tumora dojke, umeren u 44%, a oskudan u 43% tumora dojke. CD4+ limfociti nisu uočeni u 5% tumora. Gust infiltrat CD8+ limfocita uočen je u 1% tumora dojke, umeren u 23%, a oskudan u 66% tumora dojke. CD8+ limfociti nisu uočeni u 10% tumora. Utvrđena je pozitivna povezanost između nivoa TIL-a i CD4+ limfocita i veličine tumora, histolo&scaron;kog stepena diferentovanosti tumora, prisustva metastaza u limfnim čvorovima pazu&scaron;ne jame, HER-2 statusa, tripl negativnog tumora i relapsa bolesti. Utvrđena je negativna povezanost između nivoa TIL-a i CD4+ limfocita i estrogen i progesteron receptora, kao i godina starosti. Utvrđena je pozitivna povezanost između nivoa CD8+ limfocita i histolo&scaron;kog gradusa tumora, kao i HER-2 statusa. Utvrđena je negativna povezanost između nivoa CD8+ limfocita i estrogen i progesteron receptora, kao i godina starosti. ZAKLJUČAK:Rezultati ovog istraživanja pokazuju povezanost tumor infiltri&scaron;ućih limfocita i CD4+ limfocita sa brojnim negativnim prognostičkim faktorima, te kraćim vremenom slobodnog intervala bez bolesti, &scaron;to sve ukazuje na to da su tumor infiltri&scaron;ući limfociti kao i CD4+ limfociti lo&scaron; prognostički faktor kod bolesnica sa rakom dojke.</p> / <p>INTRODUCTION: The main problem in the treatment of breast cancer that based on clinical classification and morphological characteristics of the tumor to predict its future behavior. Very often, not a combination of standard prognostic factors does not answer the need of giving adjuvant chemotherapy. In order to implement adequate further treatment of breast cancer and detection aggressive types of tumor, after surgical treatment, there is a constant need to find new indicators by which we can identify patients who have an increased risk of relapse. OBJECTIVES: The objectives were to determine the presence, localization and distribution of tumor infiltrating lymphocytes, in total, as well as CD4+ and CD8+ T lymphocytes in breast cancer, their correlation with standard prognostic parameters, as well as their prognostic value i.e. differences in the level of infiltration of lymphocytes in a tumor in relation to the occurrence of disease relapse and survival. METHOD: The study included 120 patients with invasive ductal carcinoma, tumor localized only in the breast without involvement of the skin and pectoral muscle, the size of tumors up to 5 cm without distant visceral and bone metastases, which are operated at the Institute of Oncology. The study included patients without metastases in axillary lymph nodes and patients with metastases in axillary lymph nodes. The research not covered by patients receiving neoadjuvant chemotherapy, or patients with multifocal and multicentric tumors. RESULTS: The high amount of lymphocytic infiltrate was observed in the 14% a breast tumor, a moderate amount of lymphocytic infiltrate was observed in 38%, and the low in 43% breast tumors. Lymphocytic infiltrate was not observed in 5% of the tumor. High CD4+ lymphocyte infiltration was observed in 8% of breast, moderate in 44%, and the low in 43% of breast tumors. CD4+ lymphocytes were not observed in 5% tumors. High infiltration of CD8+ lymphocytes was observed in 1% of breast, moderate in 23%, and the low 66% breast tumors. CD8+ lymphocytes have not been observed in 10% tumors. There is a positive correlation between the level of TIL and CD4+ lymphocytes and tumor size, histological grade of tumor differentiation, presence of metastases in axillary lymph nodes, HER-2 status, triple negative tumors and relapses of disease. There was a negative correlation between the level of TIL and CD4+ cell counts and estrogen and progesterone receptors, as well as age. There is a positive correlation between the level of CD8+ cells and histological grade of the tumor, and HER-2 status. There was a negative correlation between the level of CD8+ lymphocytes and estrogen and progesterone receptors, as well as age. CONCLUSION: The results of this study demonstrate the association between tumor infiltrating lymphocytes and CD4+ lymphocytes with a number of negative prognostic factors, and shorter free interval without the disease, all of which indicates that the tumor infiltrating lymphocytes and CD4+ lymphocytes bad prognostic factor in patients with breast cancer.</p>

<p>UVOD: Karcinom kolona (KK) je velik javnozdravstveni problem usled visoke incidence i stope mortaliteta. Kod KK je stadijum bolesti najvažniji pojedinačni nezavisni faktor prognoze. U prisustvu nepovoljnih prognostičkih parametara, u koje spadaju visok histolo&scaron;ki gradus, ileus, limfo-vaskularna i perineuralna invazija, nakon potencijalno kurativne operacije se kod pacijenata u stadijumu II indikuje primena adjuvantne hemioterapije koja ima pozitivan uticaj na ukupno preživljavanje i na produženje perioda bez bolesti. Međutim, relapsi bolesti nastaju kod nekih bolesnika bez negativnih prognostičkih faktora, &scaron;to ukazuje na moguće postojanje drugih tkivnih faktora lo&scaron;e prognoze. U novije vreme se sve veća pažnja posvećuje fenomenu tumorskog pupljenja koje predstavlja pojavu tumorskih pupoljaka (TP), odnosno oligocelularnih grupa tumorskih ćelija koje se na invazivnom frontu tumora odvajaju od glavne tumorske mase. Ove tumorske ćelije poprimaju fenotip mezenhimnih ćelija i stiču sposobnost ameboidnog kretanja kroz ekstracelularni matriks, uz pomoć citoplazmatskih podija koje se na dvodimenzionalnim histolo&scaron;kim rezovima vizualizuju kao citoplazmatski pseudofragmenti (CPF). Značaj gustine TP i CPF je jo&scaron; uvek nedovoljno ispitan, ali postoje indicije da se radi o moćnom prediktoru biolo&scaron;kog pona&scaron;anja tumora. CILJ: Cilj je bio da se ispita zavisnost dužine perioda bez relapsa, veličine primarnog tumora, gustine peritumorske limfocitne infiltracije i konfiguracije tumorske margine od gustine TP i CPF kod bolesnika sa KK u stadijumu II. METODOLOGIJA: Istraživanjem je obuhvaćeno 114 bolesnika operisanih od KK u stadijumu II na Institutu za onkologiju Vojvodine, bez nepovoljnih prognostičkih faktora i bez indikacija za primenu adjuvantne hemioterapije. Mikroskopskom analizom rutinskih histolo&scaron;kih i imunohistohemijskih preparata utvrđivana je gustina TP i CPF, koja je zatim korelirana sa vremenom pojave relapsa, veličinom primarnog tumora, gustinom peritumorske limfocitne infiltracije i konfiguracijom tumorske margine. REZULTATI: Velika gustina TP i/ili CPF nađena je kod 45 tumora (39,5%). U ovoj grupi se relaps dogodio kod 26 bolesnika (57,8%). U grupi bolesnika sa malom gustinom TP/CPF relaps je registrovan u 4 slučaja (5,8%). Poređenje krivih preživljavanja pokazalo je da je verovatnoća relapsa značajno veća ako se u tumoru nalazi velika gustina TP/CPF (p&lt;0,0001). Tumori sa velikom gustinom TP/CPF su imali najveći prečnik koji je varirao u rasponu od 25 do 100 mm, dok su tumori sa malom gustinom TP/CPF bili najvećeg prečnika od 20 do 110 mm (p=0,6744). Intenzitet peritumorskog limfoidnog odgovora je bio velik kod 13 tumora sa velikom gustinom TP/CPF (28,9%) i kod 17 tumora sa malom gustinom TP/CPF (24,6%), p=0,7747. Konfiguracija tumorske margine je bila infiltrativna u svim tumorima sa velikom gustinom TP/CPF, kao i kod 42 tumora sa malom gustinom TP/CPF (60,9%). ZAKLJUČAK: Velika gustina TP/CPF je nezavisan tkivni indikator lo&scaron;e prognoze kod bolesnika sa KK u stadijumu II, koji je ne korelira ni sa veličinom primarnog tumora ni sa intenzitetom peritumorskog limfoidnog odgovora. Velika gustina TP/CPF nije kompatibilna sa ekspanzivnom konfiguracijom tumorske margine, ali infiltrativna konfiguracija tumorske margine nije prediktor velike gustine TP/CPF.</p> / <p>INTRODUCTION: Colonic carcinoma (CC) is a serious public health problem due to its high incidence and mortality rate. Stage is the single most important independent prognosticator in patients with CC. In the presence of indicators of poor prognosis, including high histologic grade, ileus, lympho-vascular invasion and perineural invasion, there is a need for adjuvant chemotherapy after a potentially curative operation in patients with stage II CC, because the therapy improves both overall survival and disease-free survival. However, some patients with no documented poor prognostic factors suffer recurrences, which indicates that there may be some other tissue features that confer poor prognosis. In the recent publications there is an increasing interest in the phenomenon of tumor budding, a term assigned to the presence of small groups of discohesive tumor cells at the invasive front of the tumor &ndash; tumor buds (TB&#39;s). These cells acquire mesenchymal phenotype and gain the ability to migrate through the extracellular matrix by means of cytoplasmic extrusions which are visible on the two-dimensional immunohistologic sections and are called cytoplasmic pseudofragments (CPF&#39;s). Significance of density of TB&#39;s and CPF&#39;s is still to be evaluated, but the pool of evidence suggests that this is a powerful predictor of biologic behaviour of CC. AIM: The aim of this study was to determine the influence of density of TB&#39;s and CPF&#39;s on the risk of recurrence in patients with stage II CC. This research also attempted to establish whether there is a correlation between the density of TB&#39;s and CPF&#39;s and several other morphologic features such as tumor diameter, peritumoral lymphocytic response and the configuration of the tumor margin. METHODS: 114 patients with stage II CC were enrolled in the study. All the patients received surgery at the Institute of Oncology in Sremska Kamenica and no patient had indication for adjuvant chemotherapy. Microscopic analysis of routine histologic and immunohistochemical slides was performed to establish the density of TB&#39;s and CPF&#39;s, to estimate the intensity of the peritumoral lymphocytic response and to determine the configuration of the tumor margin. RESULTS: High density of TB&#39;s and/or CPF&#39;s was found in 45 tumors (39.5%). In this group recurrence occured in 26 patients (57.8%). In the group of patients with low density of TB/CPF in the tumor tissue 4 patients relapsed (5.8%). Comparison of survival curves showed that the probability of recurrence was significantly greater if the density of TB/CPF&#39;s was high (p&lt;0.0001). Tumors with high density of TB/CPF&#39;s ranged from 25 to 100 mm in greatest diameter, while those with low density measured from 20 to 110 mm (p=0.6744). Intensity of peritumoral lymphocytic response was high in 13 tumors with high density of TB/CPF&#39;s (28.9%) and in 17 tumors with low density of TB/CPF&#39;s (24.6%), p=0.7747. All tumors with high density of TB/CPF&#39;s and 42 tumors with low density of TB/CPF&#39;s (60.9%) had infiltrative configuration of tumor margin. CONCLUSION: High density of TB/CPF&#39;s is an independent indicator of poor prognosis in patients with stage II CC and it correlates neither with tumor diameter nor with intensity of peritumoral lymphocytic response. High density of TB/CPF&#39;s is not compatible with the expansive configuration of tumor margin, but the infiltrative configuration of tumor margin is not a predictor of high density of TB/CPF&#39;s.</p>

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Normal";mso-tstyle-rowband-size:0;mso-tstyle-colband-size:0;mso-style-noshow:yes;mso-style-priority:99;mso-style-qformat:yes;mso-style-parent:"";mso-padding-alt:0cm 5.4pt 0cm 5.4pt;mso-para-margin-top:0cm;mso-para-margin-right:0cm;mso-para-margin-bottom:10.0pt;mso-para-margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}</style><![endif]--><b><span style="font-size:11.0pt;font-family:&quot;Times New Roman&quot;,&quot;serif&quot;;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;color:black;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA">Uvod: </span></b><span style="font-size:11.0pt;font-family:&quot;Times New Roman&quot;,&quot;serif&quot;;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;color:black;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA">Karcinom dojke je heterogena bolest koju karakteri&scaron;u različita morfologija, imunohisto-hemijski profil, klinički tok i terapijski odgovor. Ki-67 proliferativni indeks je jedan od markera sa prognostičkim i prediktivnim značajem, čije metodolo&scaron;ko određivanje i analiza jo&scaron; uvek nisu standardizovani. <b>Cilj: </b>Utvrditi graničnu (&ldquo;cut-off&rdquo;) prognostičku vrednost Ki-67 indeksa, kao i povezanost vrednosti Ki-67 u ranom luminalnom karcinomu dojke sa prognostičkim i prediktivnim parametrima karcinoma dojke, kao &scaron;to su životna dob bolesnica, veličina tumora, histolo&scaron;ki gradus (HG) i nivo tumorske ekspresije receptora estrogena (ER) i progesterona (PR). Takođe, cilj istraživanja je i utvrđivanje značajnosti razlike u vrednosti Ki-67 proliferativnog indeksa u odnosu na pojavu lokalnog recidiva, udaljenih metastaza i dužinu preživljavanja u toku petogodi&scaron;njeg perioda praćenja pacijentkinja. <b>Metode: </b>Retrospektivno je analizirano 120 patohistolo&scaron;kih izve&scaron;taja bolesnica kojima je u periodu od 01.01.2009. godine do 31.12.2011. godine na Institutu za onkologiju Vojvodine imunohistohemijskom analizom dokazan luminalni karcinom dojke (pozitivan ER i PR, negativan HER2), bez metastaza u aksilarnim limfnim čvorovima. <b>Rezultati: </b>Metodama deskriptivne statistike prosečna starost pacijentkinja je iznosila 57,42&plusmn;10,17 godina; prosečna veličina tumora 17,98&plusmn;6,97mm; recidiv je registrovan kod 8 (6,7%) pacijentkinja uz prosečan vremenski period do pojave recidiva od 49&plusmn;20,23 meseci. Vrednost &ldquo;cut off&rdquo; indeksa Ki-67 od prognostičkog značaja za vremenski period bez recidiva je iznosio 20,75%. Nije dokazana signifikantna veza između vrednosti Ki-67 i godina starosti pacijentkinja (p=0,401, odnosno p=0,293), kao i jačine ekspresije ER (p=1,00, p=0,957) i PR (p=0,273, p=0,189). Ustanovljena je signifikantna povezanost Ki-67 postoji sa veličinom (p=0,035, p=0,20) i HG tumora (p=0,041, p=0,20). Prosečan period praćenja bolesnica iznosio je 72,92&plusmn;8,38 meseci; nije registrovana pojava udaljenih metastaza, kao ni smrtni ishod. U odnosu na pojavu lokalnog recidiva, Kaplan-Majerovom analizom i Koksovom regresionom analizom proliferativni indeks Ki-67 se pokazao kao signifikantan prediktor za procenu ponovnog javljanja bolesti, lokalnog recidiva (Log rank (df = 1) = 2,73; p=0,045). Takođe je ustanovljeno da je statistički značajan prediktor za procenu recidiva bolesti i starosna dob bolesnica (Log rank (df = 1) = 6,885; p=0,009). Intenzitet pozitivnosti ER i PR, veličina tumora i histolo&scaron;ki gradus se nisu pokazali kao prediktori za pojavu recidiva luminalnih karcinoma dojke (p &gt; 0,05). <b>Zaključak: </b>Zbog heterogene prirode oboljenja, kori&scaron;ćenjem standardnih histopatolo&scaron;kih faktora i biomarkera te&scaron;ko je predvideti tok i ishod karcinoma dojke. Ki-67 je proliferativni marker, čija visoka vrednost korelira sa faktorima lo&scaron;e prognoze.</span></p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>Tanja Lakic</o:Author> <o:Version>12.00</o:Version> </o:DocumentProperties></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-US</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> <w:Compatibility> <w:BreakWrappedTables/> <w:SnapToGridInCell/> <w:WrapTextWithPunct/> <w:UseAsianBreakRules/> <w:DontGrowAutofit/> <w:SplitPgBreakAndParaMark/> <w:DontVertAlignCellWithSp/> <w:DontBreakConstrainedForcedTables/> 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Normal";mso-tstyle-rowband-size:0;mso-tstyle-colband-size:0;mso-style-noshow:yes;mso-style-priority:99;mso-style-qformat:yes;mso-style-parent:"";mso-padding-alt:0cm 5.4pt 0cm 5.4pt;mso-para-margin-top:0cm;mso-para-margin-right:0cm;mso-para-margin-bottom:10.0pt;mso-para-margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}</style><![endif]--></p><p class="Default"><b><span style="font-size:11.0pt">Introduction: </span></b><span style="font-size:11.0pt">Breast cancer is a heterogeneous disease characterized by different morphology, immunohistochemical profile, clinical course and response to applied therapy. Ki-67 proliferative index is one of the prognostic and predictive factors, whose methodological determination and analysis are still unstandardized. <b>Objective: </b>Determination of cut-off value for Ki-67 index, its corelation in luminal breast carcinoma with patient&#39;s age, tumor size, histological grade (HG) and expression of estrogen (ER) and progesterone (PR). Also, the aim of the study was to determine the significance of the difference in the value of the Ki-67 proliferative index in relation to the occurrence of local relapse, distant metastases and survival rates during the five-year follow-up period of the patient. <b>Methods: </b>Retrospectively, we analysed 120 pathohistological reports of patients who were treated in the period from 01.01.2009 until 31.12.2011 at the Oncology Institute of Vojvodina, and to whom immunohistochemically was proven luminal breast cancer (positive ER and PR, negative HER2), without axillary lymph node metastases. </span><b><span style="font-size:11.0pt">Results: </span></b><span style="font-size:11.0pt">The average patient&rsquo;s age was 57.42&plusmn;10.17 years; average tumor size 17.98&plusmn;6.97mm; recurrence was registered in 8 (6.7%) patients with average recurrence time of 49&plusmn;20.23 months. &quot;Cut off&quot; Ki-67 value of prognostic significance for period without recurrence was 20.75%. Test didn&rsquo;t show significant relationship between Ki-67 and patient&rsquo;s age (p=0.401 and p=0.293), as well as the strength of expression ER (p=1.00, p=0.957) and PR (p=0.273, p=0.189). Significant correlation was present for Ki-67 with size (p=0.035, p=0.20) and tumor&rsquo;s HG (p=0.041, p=0.20). The average follow-up period for patients was 72.92&plusmn;8.38 months; there was no registered occurrence of distant metastases or fatal outcome. In relation to the occurrence of local relapse, Kaplan-Meier analysis and Cox regression analysis, the proliferative index Ki-67 proved to be a significant predictor for the assessment of recurrence of the disease, local relapse (Log rank (df = 1) = 2.73; p = 0.045). Also, it was founded that a statistically significant predictor for assessing the recurrence of the disease is the age of the patients (Log rank (df = 1) = 6.885; p = 0.009). The intensity of ER and PR expression, tumor size and histological grade have not been shown to be predictors of the recurrence of luminal breast carcinoma (p&gt; 0.05). </span><b><span style="font-size:11.0pt">Conclusion: </span></b><span style="font-size:11.0pt">Breast carcinoma is heterogeneous disease, so it is difficult to predict its course and outcome using standard histopathological factors and biomarkers. Ki-67 is proliferative marker whose high value correlates with factors of bad prognosis. </span></p>

<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>

<p>Саобраћајно-географски и стратешки положај Книнске Крајине, условљавају сталну присутност овог подручја у балканским и европским збивањима, мада значај природних потенцијала није томе адекватан. Овим простором су пролазиле многе војске и владале бројне империје. Кроз бурне догађаје неки природни елементи су деградирани (вегетација, земљиште, укупан пејсаж), а дешавале су се и потпуне смене становништва, те рушења и паљења, што се веома негативно одражавало на привредну активност. Виталност становништва дуго је успешно надокнађивала стална исељавања. Међутим, стално погоршавање укупних природно-друштвених елемената, као и савремени привредни токови, поспешили су процес исељавања, па је крајем двадесетог века број становника у многим насељима пао на ниво из средине деветнаестог века. Сточарство је вековима било доминантна активност, али су деградација природне средине, слаба улагања и стално исељавање утицали на знатно опадање значаја ове гране. Ипак за равномеран развој, осим индустријализације, мора бити добро организована и пољопривредна производња. Пољопривредна делатност, на овом простору, мора тражити своју будућност и у производњи здраве хране, како у ратарству тако и у сточарству. Концентрација индустрије у Книну није добра за равномеран развој, а пошто изградња малих погона у неколико мањих наеља показује позитивне ефекте, мора се наставити у том правцу. Територијалне и политичке промене на простору бивше СФРЈ, утичу на појачање централних функција Книна, те он постаје значајан међурегионални и републички центар. Побољшању укупног развоја треба да допринесе и туристичка привреда, али и правилно валоризовање саобраћајног положаја и неких природних богатстава. Да би што боље оживела сеоска насеља, мора се побољшати функционално-комунална опремљеност локалних центара.</p> / <p>Saobraćajno-geografski i strateški položaj Kninske Krajine, uslovljavaju stalnu prisutnost ovog područja u balkanskim i evropskim zbivanjima, mada značaj prirodnih potencijala nije tome adekvatan. Ovim prostorom su prolazile mnoge vojske i vladale brojne imperije. Kroz burne događaje neki prirodni elementi su degradirani (vegetacija, zemljište, ukupan pejsaž), a dešavale su se i potpune smene stanovništva, te rušenja i paljenja, što se veoma negativno odražavalo na privrednu aktivnost. Vitalnost stanovništva dugo je uspešno nadoknađivala stalna iseljavanja. Međutim, stalno pogoršavanje ukupnih prirodno-društvenih elemenata, kao i savremeni privredni tokovi, pospešili su proces iseljavanja, pa je krajem dvadesetog veka broj stanovnika u mnogim naseljima pao na nivo iz sredine devetnaestog veka. Stočarstvo je vekovima bilo dominantna aktivnost, ali su degradacija prirodne sredine, slaba ulaganja i stalno iseljavanje uticali na znatno opadanje značaja ove grane. Ipak za ravnomeran razvoj, osim industrijalizacije, mora biti dobro organizovana i poljoprivredna proizvodnja. Poljoprivredna delatnost, na ovom prostoru, mora tražiti svoju budućnost i u proizvodnji zdrave hrane, kako u ratarstvu tako i u stočarstvu. Koncentracija industrije u Kninu nije dobra za ravnomeran razvoj, a pošto izgradnja malih pogona u nekoliko manjih naelja pokazuje pozitivne efekte, mora se nastaviti u tom pravcu. Teritorijalne i političke promene na prostoru bivše SFRJ, utiču na pojačanje centralnih funkcija Knina, te on postaje značajan međuregionalni i republički centar. Poboljšanju ukupnog razvoja treba da doprinese i turistička privreda, ali i pravilno valorizovanje saobraćajnog položaja i nekih prirodnih bogatstava. Da bi što bolje oživela seoska naselja, mora se poboljšati funkcionalno-komunalna opremljenost lokalnih centara.</p> / <p>The regional trafffic, geographic and strategic position of Knin Krajina was the main cause for its constant presence in Balcan and European events, though the inportantce its natural resources had not been adequate. Many armies passed through this region and a number of empires ruled it. Thruogh the turmoils of these events some natural elements were degraded (vegetation, soil, the whole scenery), total changes in its population emerged, destructions and arsons which had an-extremely negative effect on public economy. Vitality of the population had for a long time been successful in substituting for the constant migrations. However, constant deteriorating of natural and social elements, as well as modem natural movements, had influenced the speed of depopulation process, so that at the end of the XX centry a number of people in many settlements had decreased to the level equal to the middle XIX century period. Forming used to be dominant for centuries but the degradation of the nature and its qualities, poor investments and constant depopulation had affested it and made it inferior. Still, in order to have a balanced growth, apart from industralisation and agricultural production also needed to be very well organised. Agriculture, in this area, had to search for its future prospects in production of healthy food, both in cattle-breeding and in farming. The concentrated industry in Knin is not sufficiently good for a balanced growth and since building of new little factories in a few of small communities has showed positive effects, this direction should be followed. Changes in territory and in politics in the area of exYugoslavia, affects the increasing growth of central functions in Knin and therefore it has become an important internacional and republic center. Tourism should also contribute to the total development, and a proper evaluation of its traffic position and some natural resources as well. To make village communities more active some functional and communal facilities in local centres have to be improved.</p>