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101	Geschlechterunterschiede bei drucklast-induzierter Myokardhypertrophie im Mausmodell Fliegner, Daniela 06 February 2009 (has links) Die Entwicklung und der Verlauf einer Myokardhypertrophie (MH) und Herzinsuffizienz (HF) unterscheiden sich deutlich zwischen Frauen und Männern. Diese Geschlechterunterschiede können zumindest partiell auf Sexualhormone, insbesondere Östrogen, zurückgeführt werden. Östrogene wirken biologisch über zwei verschiedene Östrogenrezeptoren (ER): ERalpha und ERbeta. Viele Befunde weisen auf eine positiv modulierende Wirkung der Östrogene und speziell auf eine besondere Rolle des ERbeta bei der Entwicklung der druckinduzierten MH und HF hin. Diese Studie befasst sich mit der Untersuchung der Geschlechterunterschiede in der Ausprägung einer pathologischen MH und den myokardialen Veränderungen unter dem Einfluss des ERbeta. Grundlage der Arbeit bildete ein Mausmodell mit ERbeta-/-- und Wildtyp- Mäusen, denen durch eine transversale Aortenkonstruktion (TAC) eine artifizielle MH induziert wurde. Zur Dokumentation der Progression und den damit verbundenen Veränderungen wurden zwei Zeitpunkte gewählt, welche die adaptive und maladaptive kardiale Antwort darstellen. Die Entwicklung der Myokardhypertrophie wurde sowohl durch Echokardiographie als auch hämodynamischen Messungen charakterisiert und durch biochemische und molekulare Techniken sowie den Einsatz von Mikroarrays untersucht. Es konnte der Einfluss des Geschlechts auf die Entwicklung der MH bei andauernder Druckbelastung nachgewiesen werden. ERbeta modulierte dabei die kardiale Funktion sowie die molekulare Antwort in hypertrophie- assoziierten Prozessen, wie dem kardialen Metabolismus, der kardialen Fibrose und der Apoptose in weiblichen und männlichen Tieren. ERbeta trug in den weiblichen Tieren zum Erhalt des kardialen Energiehaushaltes bei und limitierte dadurch die Entwicklung einer kardialen Fibrose und Apoptose. Ein positiver Einfluss des ERbeta konnte in auch in den männlichen Tieren beobachtet werden: Ein starker Funktionsverlust des Herzens und apoptotische Prozesse wurden durch ERbeta verlangsamt oder inhibiert. / Development and progress of myocardial hypertrophy (MH) and the transition to heart failure (HF) differ between the sexes in humans. There is evidence that sex- related differences are mediated through sex hormones, especially the sex hormone estrogen. Effects of estrogen are mediated by two different estrogen receptors (ER): ERalpha und ERbeta. Many studies indicate a beneficial role of estrogen and particularly for ERbeta in the development of pressure overload induced MH and HF. This study investigates sex differences in the development of pathological MH and accompanying myocardial changes under the influence of ERbeta. For this purpose wildtype and estrogen receptor beta lacking (ERbeta-/-) mice were investigated. Myocardial hypertrophy was induced by using the method of transversal aortic constriction (TAC). To determine the progression of MH to HF two time points were studied, which describe the adaptive and the maladaptive response to cardiac pressure overload. The development of MH was characterized by echocardiography and hemodynamic measurements in vivo. Additionally microarrays, molecular and biochemical analyses were performed in left ventricles. We identified sex differences in the development of MH induced by chronic pressure overload. ERbeta modulated the cardiac function and the molecular response in hypertrophy associated processes like cardiac metabolism, fibrosis and apoptosis in female and male animals. ERbeta contribute to the maintenance of energy homeostasis in female mice and limits the development of maladaptive cardiac hypertrophy, fibrosis and apoptosis in female and in male mice and slows the progression to heart failure consequently down. Apoptose Herzinsuffizienz Fibrose Geschlechterunterschiede Myokardhypertrophie Östrogenrezeptoren kardialer Metabolismus Apoptosis Sex Differences Myocardial Hypertrophy Heart Failure Estrogen receptors Cardiac Metabolism Fibrosis 570 Biowissenschaften, Biologie 32 Biologie YC 1400 ddc:570
102	Effect of phytoestrogens on low-density- lipoprotein receptor and apolipoprotein A-I expression in HepG2 cells. January 2005 (has links) Yuen Yee Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 108-125). / Abstracts in English and Chinese. / TITLE PAGE --- p.1 / ACKNOWLEGDEMENTS --- p.2 / ABSTRACT --- p.3 / 摘要 --- p.5 / table of contents --- p.7 / list of figures and tables --- p.13 / CHAPTER 1 GENERAL INTRODUCTION --- p.16 / Chapter 1.1 --- role of PHYTOESTROGENS in soy and red WINE the PREVENTION OF CARDIOVASCULAR DISEASES (CVD) --- p.17 / Chapter 1.1.1 --- INTRoduction and Classification of Phytoestrogens --- p.17 / Chapter 1.1.2 --- estrogenic1ty of phytoestrogens and theIr abundancesin Plasma --- p.18 / Chapter 1.1.3 --- phytoestrogens as one of the active components In cvd Protection --- p.21 / Chapter 1.1.4 --- effects of Phytoestrogens on LDL Receptor and Apolipoprotein A-1 --- p.22 / Chapter 1.2 --- role of estrogen receptors (ers) in gene regulation --- p.24 / Chapter 1.2.1 --- "structure, Classification and tissue distribution of ERS" --- p.24 / Chapter 1.2.2 --- ligands for ERS --- p.25 / Chapter 1.2.3 --- mechaniSMS OF LIgands-ERS complex in GENE regulation --- p.27 / Chapter 1.2.4 --- ligand-independent ER activation --- p.28 / Chapter 1.3 --- aims and scopes of investigation --- p.29 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.30 / Chapter 2.1 --- chemicals and materials --- p.30 / Chapter 2.1.1 --- Chemicals --- p.30 / Chapter 2.1.2 --- Plasmids --- p.30 / Chapter 2.2 --- mammalian cell culture maintainence --- p.30 / Chapter 2.2.1 --- Maintenance of Cells --- p.31 / Chapter 2.2.2 --- Preparation of Cell Stock --- p.31 / Chapter 2.2.3 --- Cell Recovery from Liquid Nitrogen Stock --- p.31 / Chapter 2.3 --- manipulation of dna --- p.31 / Chapter 2.3.1 --- isolation of HEPG2 cells genonmic DNA --- p.31 / Chapter 2.3.2 --- separation and purification of dna from agarose gel --- p.31 / Chapter 2.3.3 --- Restriction digestionof DNA --- p.32 / Chapter 2.3.4 --- Ligation of DNA Fragments --- p.32 / Chapter 2.3.5 --- Transformation of --- p.32 / Chapter 2.3.6 --- Small Scale Plasmids Purification from DH5a --- p.32 / Chapter 2.4 --- construction of expression and reporter plasmids --- p.33 / Chapter 2.4.1 --- Construction of Estrogen Receptorα (Erα) Expression Vectors --- p.33 / Chapter 2.4.2 --- construction of reporter vectors of LDLR promoter and the Respective Mutants --- p.33 / Chapter 2.4.3 --- Construction of Reporter Vectors of APOAI Promoter and the Respective Mutants --- p.33 / Chapter 2.5 --- determination of promoter transcrtiption activities --- p.34 / Chapter 2.5.1 --- Transient Transfection of Cell with ERa Expression Vector and Promoter Reporter using Lipofectamine PLUS Reagent --- p.34 / Chapter 2.5.2 --- Dual Luciferase Assay --- p.34 / Chapter 2.6 --- semi-quantitative and quantitative rt-pcr assay --- p.34 / Chapter 2.6.1 --- Transient transfection of Cell with ERa Expression Vector Using Lipofectamine PLUS Reagent --- p.34 / Chapter 2.6.2 --- "Isolation of RNA using TRIzol® Reagent (Life Technology, USA)" --- p.35 / Chapter 2.6.3 --- Quantitation of RNA --- p.35 / Chapter 2.6.4 --- First Strand cDNA Synthesis --- p.35 / Chapter 2.6.5 --- Sem卜Quantitative PCR Reactions --- p.35 / Chapter 2.6.6 --- Quantitative PCR Reactions --- p.36 / Chapter 2.7 --- western blotting analysis --- p.36 / Chapter 2.8 --- statistical methods --- p.36 / Chapter CHAPTER 3 --- REGULATION BY PHYSIOLOGICAL LEVEL OF 17B-ESTRADIOL ON APOLIPOPROTEIN A-I AND LOW-DENSITY- LIPOPROTEIN RECEPTOR IN HEPG2 CELLS --- p.37 / Chapter 3.1 --- introduction --- p.37 / Chapter 3.2 --- results --- p.39 / Chapter 3.2.1 --- Determination of transient transfection functionality of estrogen receptors in hepg2 cells --- p.39 / Chapter 3.2.2 --- Effect of 17β-Estradiolon LDLR promoter transcription activity --- p.39 / Chapter 3.2.3 --- Effect of 17β-Estradiol on apoai promoter transcription activity --- p.40 / Chapter 3.2 --- discussion --- p.47 / Chapter CHAPTER 4 --- SOY ISOFLAVONES AND RESVERATROL DISPLAY DIFFERENT MECHANISM IN THE UP-REGULATION OF LOVV-DENSITY-LIPOPROTEIN RECEPTOR IN HEPG2 CELLS --- p.49 / Chapter 4.1 --- introduction --- p.49 / Chapter 4.2 --- results --- p.54 / Chapter 4.2.1 --- Association of ERα and isoflavones or resveratrol on LDLR promoter transcription activity --- p.54 / Chapter 4.2.2 --- Association of ERβ and isoflavones or resveratrol on LDLR promoter transcription activity --- p.54 / Chapter 4.2.3 --- "Role of MAP Kinase, PKA and PKC in isoflavones and resveratrol induced LDLR promoter transcription" --- p.55 / Chapter 4.2.4 --- Identification of promoter regions responsible for induction of LDLR transcription by isoflavones in the presence OF ERα --- p.55 / Chapter 4.2.5 --- Identification of promoter regions responsible for induction of LDLR TRANSCRIPTION BY resveratrol IN THE ABSENCE OF ERα --- p.56 / Chapter 4.3 --- DISCUSSION --- p.75 / Chapter CHAPTER 5 --- SOY ISOFLAVONES AND RESVERATROL UP-REGULATE APOLIPOPROTEIN A-I SIMILAR TO 17B-ESTRADIOL IN HEPG2 CELLS --- p.80 / Chapter 5.1 --- INTRODUCTION --- p.80 / Chapter 5.2 --- RESULTS --- p.84 / Chapter 5.2.1 --- Association of ERα phytoestrogens on APCAI gene expression --- p.84 / Chapter 5.2.2 --- Association of ERβ and isoflavones or resveratrol on APOAI promoter transcription activity --- p.85 / Chapter 5.2.3 --- "Role of MAP Kinase, PKA and PKC in isoflavones and resveratrol in APOAI promoter transcription in the presence of ERα" --- p.85 / Chapter 5.2.4 --- Identification of promoter regions responsible for induction of APOAI transcription by isoflavones and resveratrol in the presence of ERα --- p.85 / Chapter 5.3 --- DISCUSSION --- p.100 / Chapter CHAPTER 6 --- GENERAL DISCUSSION --- p.103 / Chapter CHAPTER 7 --- SUMMARY --- p.106 / BIBLIOGRAPHY --- p.108 / APPENDIX 1 ABBREVIATIONS --- p.126 / APPENDIX 2 MATERIALS AND METHODS --- p.129 / APPENDIX 3 PRIMER LISTS --- p.145 / APPENDIX 4 REAGENTS AND BUFFERS --- p.147 Phytoestrogens Lipoproteins--Physiological effect Apolipoproteins--Physiological effect Estrogen--Receptors Phytoestrogens--pharmacology Phytoestrogens--therapeutic use Receptors, LDL--drug effects Apolipoprotein A-I--drug effects Receptors, Estrogen--genetics Isoflavones--therapeutic use Stilbenes--therapeutic use Cardiovascular Diseases--drug therapy
103	Régulation de l’activité transcriptionnelle des récepteurs des estrogènes (ER) par le récepteur aux chimiokines CXCR7 et par la propyl isomérase Pin1 Benhadjeba, Samira 12 1900 (has links) No description available. Récepteurs aux estrogènes ER Estrogènes CXCR7 Gène cible Activation Pin1 Cancer du sein Cancer épithélial de l’ovaire Estrogen receptors Estrogen Target gene Breast cancer Ovarian cancer
104	Transcription par les récepteurs des estrogènes : identification d’un gène cible et d’un nouveau corépresseur Edjekouane, Lydia 12 1900 (has links) Malgré de nombreux progrès réalisés dans les traitements des cancers gynécologiques, ceux-ci demeurent la principale cause de mortalité due au cancer chez la femme. Les instabilités chromosomiques et génomiques au niveau du locus 3p21.3 sont des événements fréquents liés à des cancers épithéliaux, notamment les cancers du sein et de l'ovaire. C’est dans cette région que se trouvent les gènes hyaluronidases HYAL-1, HYAL-2 et HYAL-3. HYAL-1 est particulièrement surexprimé dans plusieurs cancers, notamment, le cancer de la prostate, la vessie, le cou, la tête et le sein où il est impliqué dans la progression tumorale et les métastases. Nous avons démontré que dans le locus 3p21.3, HYAL-1 est un gène cible sélectivement réprimé par ERα et l’estrogène. L’analyse de la cohorte METABRIC a révélé une corrélation inverse significative entre l’expression du gène HYAL-1 et ERα. Nous avons identifié des sites de liaison pour ERα au niveau du locus 3p21.3, parmi eux, un ERE proximal était responsable de la répression de HYAL-1 par ERα en plus d’un site Sp-1 requis pour atteindre une répression optimale. Cette répression de HYAL-1 est accompagnée par un enrichissement de la marque répressive H3K27me3 au niveau des deux sites ERE et Sp-1. En plus de réguler l’expression de nombreux gènes, l’activité transcriptionnelle des ERs est aussi régulée par les corégulateurs qui sont recrutés sur les ERs. Nous avons identifié un nouveau partenaire d’interaction inattendu pour les ERs, soit le facteur de transcription hématopoïétique TAL1. Malgré sa réputation d’oncogène dans les leucémies lymphoblastiques aiguës des cellules T, ce facteur de transcription est un corépresseur d’ERα, dû à son effet répresseur direct sur l’activité transcriptionnelle du récepteur en réponse à l’estrogène et donc sur l’expression de ces gènes cible dans le cancer du sein. De plus, TAL1 réprime aussi l’activation d’ERα en réponse à la phosphorylation induite par la voie des MAPK/Erk. Cette répression d’ERα par TAL1 résulte en une diminution de la prolifération et la migration des cellules cancéreuses mammaires. / Despite many advances in treatment of gynecological cancers, they remain the leading cause of cancer death in women. Chromosomal and genome instabilities at the 3p21.3 locus are frequent events related to epithelial cancers, including breast and ovarian cancers. It is in this region that the hyaluronidase HYAL-1, HYAL-2 and HYAL-3 genes are found. HYAL-1 is particularly overexpressed in several cancers, including prostate, bladder, neck, head and breast cancers where it promotes tumor progression and metastasis. We demonstrate here, that in the 3p21.3 locus, HYAL-1 is a target gene selectively repressed by ERα and estrogen. Integrative data mining using METABRIC dataset revealed a significant inverse correlation between ERα and HYAL-1 gene expression in human breast tumors. We identified binding sites for ERα at the 3p21.3 locus, among which a proximal ERE responsible for repression of HYAL-1 by ERα, in addition to an Sp-1 site required to achieve optimal repression. This repression of HYAL-1 is accompanied by an enrichment of the repressive mark H3K27me3 at the two sites ERE and Sp-1. In addition to regulate the expression of many target genes, the transcriptional activity of estrogen receptors is also regulated by coregulators who are recruited on ERs. We identified a new unexpected interaction partner for ERs, the hematopoietic transcription factor TAL1. Despite its reputation as an oncogene in T-cell acute lymphoblastic leukemia, this transcription factor is an ERα-corepressor due to its direct repressive effect on the transcriptional activity of the receptor in response to estrogen and thus to expression of its target genes in breast cancer. Moreover, TAL1 also inhibits ERs activation in response to phosphorylation induced by the MAPK/Erk pathway. This repression of ERα by TAL1 results in decreased growth and migration of mammary cancer cells. Récepteurs des estrogènes ER Estrogène Hyaluronidase-1 HYAL-1 Gène cible Répression Locus 3p21.3 TAL1 Corépresseur Régulation Estrogen receptors Estrogen Hyaluronidase-1 HYAL-1 Target gene 3p21.3 locus Corepressor Transcriptional regulation Breast cancer
105	Chemotherapy, estrogen, and cognition : neuroimaging and genetic variation Conroy, Susan Kim 25 February 2014 (has links) Indiana University-Purdue University Indianapolis (IUPUI) / The time course and biological mechanisms by which breast cancer (BC) and/or alterations in estrogen status lead to cognitive and brain changes remain unclear. The studies presented here use neuroimaging, cognitive testing, genetics, and biomarkers to investigate how post-chemotherapy interval (PCI), chemotherapy-induced amenorrhea (CIA), and genetic variation in the estrogen pathway affect the brain. Chapter 1 examines the association of post-chemotherapy interval (PCI) with gray matter density (GMD) and working memory-related brain activation in BC survivors (mean PCI 6.4, range 3-10 years). PCI was positively associated with GMD and activation in the right frontal lobe, and GMD in this region was correlated with global neuropsychological function. In regions where BC survivors showed decreased GMD compared to controls, this was inversely related to oxidative DNA damage and learning and memory scores. This is the first study to show neural effects of PCI and relate DNA damage to brain alterations in BC survivors. Chapter 2 demonstrates prospectively, in an independent cohort, decreased combined magnitudes of brain activation and deactivation from pre-to post-chemotherapy in patients undergoing CIA compared to both postmenopausal BC patients undergoing chemotherapy and healthy controls. CIA’s change in activity magnitude was strongly correlated with change in processing speed, suggesting this activity increase reflects effective cognitive compensation. These results demonstrate that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Chapter 3 presents the effects of variation in ESR1, the gene that codes for estrogen receptor-α, on brain structure in healthy older adults. ESR1 variation was associated with hippocampus and amygdala volumes, particularly in females. Single nucleotide polymorphism (SNP) rs9340799 influenced cortical GMD and thickness differentially by gender. Apolipoprotein E (APOE)-ε4 carrier status modulated the effect of SNP rs2234693 on amygdala volumes in women. This study showed that genetic variation in estrogen relates to brain morphology in ways that differ by sex, brain region and APOE-ε4 carrier status. The three studies presented here explore the interplay of BC, estrogen, and cognition, showing that PCI, CIA, and ESR1 genotype influence brain phenotypes. Cognitive correlates of neuroimaging findings indicate potential clinical significance of these results. Breast -- Cancer -- Endocrine aspects Amenorrhea -- Chemotherapy Human genetics -- Variation Brain -- Imaging Cognition -- Effect of drugs on Cognition -- Testing Biochemical markers Cognitive neuroscience Estrogen -- Receptors Estrogen -- Analysis Breast -- Cancer -- Chemotherapy Memory -- Testing -- Analysis Psychoneuroendocrinology
106	Design, Synthesis, and Process Chemistry Studies of Agents Having Anti-Cancer Properties Luniwal, Amarjit 26 May 2011 (has links) No description available. Chemistry Design Pharmaceuticals Pharmacy Sciences Drug Design Scale-up Synthesis Molecular docking studies Estrogen receptors Selective estrogen receptor modulators Breast Cancer Prostate Cancer Process Chemistry Glyceollins Pterocarpans Glycinol Benzofuran Dihydroxylation Isoprenylation
107	Klinička vrednost određivanja Ki-67 proliferativnog indeksa u karcinomima dojke sa pozitivnim hormonskim receptorima / Clinical value of determination of Ki-67 proliferative index in carcinomas with positive hormone receptors Lakić Tanja 22 November 2018 (has links) <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/> 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Name="TOC Heading"/> </w:LatentStyles></xml><![endif]--><!--[if gte mso 10]><style> /* Style Definitions / table.MsoNormalTable{mso-style-name:"Table 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:"Times New Roman","serif";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:"Times New Roman","serif";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 (“cut-off”) 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±10,17 godina; prosečna veličina tumora 17,98±6,97mm; recidiv je registrovan kod 8 (6,7%) pacijentkinja uz prosečan vremenski period do pojave recidiva od 49±20,23 meseci. Vrednost “cut off” 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±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 > 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'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’s age was 57.42±10.17 years; average tumor size 17.98±6.97mm; recurrence was registered in 8 (6.7%) patients with average recurrence time of 49±20.23 months. "Cut off" Ki-67 value of prognostic significance for period without recurrence was 20.75%. Test didn’t show significant relationship between Ki-67 and patient’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’s HG (p=0.041, p=0.20). The average follow-up period for patients was 72.92±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> 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>

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