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  1. Article ; Online: Prognostic Impact of Canonical TGF-β Signaling in Urothelial Bladder Cancer

    Slavica Stojnev / Miljan Krstić / Jovana Čukuranović Kokoris / Irena Conić / Ivan Petković / Sonja Ilić / Jelena Milosević-Stevanović / Ljubinka Janković Veličković

    Medicina, Vol 55, Iss 6, p

    2019  Volume 302

    Abstract: Background and objectives : Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal ... ...

    Abstract Background and objectives : Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients’ outcome. Materials and Methods : Immunohistochemical analysis of TGF-β1, Smad2, and Smad4 expression was performed on 404 urothelial bladder cancer samples, incorporated in tissue microarrays. Expression status was correlated with clinicopathological and follow-up data. The median follow-up was 61 months. Results : High expression of TGF-β1, Smad2, and Smad4 was detected in 68.1%, 31.7% and 45.2% of the tumors, respectively. TGF-β1 overexpression was significantly associated with high tumor grade, and advanced pathologic stage ( p < 0.001, respectively). Conversely, high Smad2 and Smad4 expression was linked to low tumor grade ( p = 0,003, p = 0.048, respectively), and low tumor stage ( p < 0.001, p = 0.003, respectively). Smad2 showed an inverse correlation with variant morphology and divergent differentiation of urothelial tumors ( p = 0.014). High TGF-β1 correlated directly, while Smad2 and Smad4 correlated inversely to cancer-specific death ( p = 0.043, p = 0.003, and p = 0.022, respectively). There was a strong relationship between Smad2 and Smad4 expression ( p < 0.001). Survival analyses showed that high Smad2 and Smad4 expression was associated with longer overall survival ( p = 0.003, p = 0.034, respectively), while in multivariate regression analysis TGF-β1 manifested as an independent predictor of poor outcome. Conclusions : Unraveling the complex roles and significance of TGF-β signaling in urothelial bladder cancer might have important implications for therapy of this ...
    Keywords urothelial bladder cancer ; TGF-β ; Smad2 ; Smad4 ; immunohistochemistry ; prognosis ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2019-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Number of decidual natural killer cells & macrophages in pre-eclampsia

    Jelena Milosevic-Stevanovic / Miljan Krstic / Dragana Radovic-Janosevic / Jasmina Popovic / Marija Tasic / Slavica Stojnev

    Indian Journal of Medical Research, Vol 144, Iss 6, Pp 823-

    2016  Volume 830

    Abstract: Background & objectives: The process of human placentation is complex and still not well understood. This study was aimed to examine the relationship between clinical features of pre-eclampsia and degree of trophoblastic invasion after its ... ...

    Abstract Background & objectives: The process of human placentation is complex and still not well understood. This study was aimed to examine the relationship between clinical features of pre-eclampsia and degree of trophoblastic invasion after its immunohistochemical visualization in the context of possible alterations in the number of natural killer (NK) cells and macrophages in the decidua. Methods: This prospective study included a study group comprising 30 pregnant women with pre-eclampsia delivered by caesarean section and a control group comprising 20 healthy pregnant women also delivered by caesarean section. Samples of placental bed obtained during caesarean section were analyzed after immunohistochemical labelling CD56 + NK cells, CD68 + macrophages and cytokeratin 7 trophoblastic cells. Results: In pre-eclampsia, there was a significantly lower number of CD56 + NK cells in the decidua (P<0.001) and a higher number of CD68 + macrophages (P<0.001) compared to control group. In the subgroup of pre-eclampsia with intrauterine growth retardation (IUGR), a significantly greater number of NK cells (P<0.05) was recorded, as well as an increased number of macrophages, but not significantly compared to pre-eclampsia without IUGR. There was no significant difference in the distribution of these cells in the decidua in relation to the severity of pre-eclampsia. CD56 + NK cells were significantly less (P<0.05) and macrophages were more (P<0.05) in the group with poor trophoblastic invasion. Interpretation & conclusions: Alterations in the number of immune cells in relation to the degree of trophoblastic invasion indicated their role in aetiopathogenesis of pre-eclampsia, while the direct association between their number and severity of pre-eclampsia was not confirmed.
    Keywords Decidua - macrophages - natural killer cells - preeclampsia - trophoblast ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Wolters Kluwer Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: INSULIN RESISTANCE SYNDROM IN PREECLAMPSIA – THE INFLUENCE ON THE OFFSPRING

    Milan Stefanović / Predrag Vukomanović / Jasmina Popović / Ranko Kutlešić / Jelena Milošević-Stevanović / Sonja Pop Trajković-Dinić

    Acta Medica Medianae, Vol 55, Iss 2, Pp 19-

    2016  Volume 24

    Abstract: Preeclampsia is a multisystem disorder of unknown cause that is unique to human pregnancy. It is a major cause of perinatal and maternal morbidity and mortality, affecting 5% to 8% of all pregnancies. The clinical findings can manifest as either a ... ...

    Abstract Preeclampsia is a multisystem disorder of unknown cause that is unique to human pregnancy. It is a major cause of perinatal and maternal morbidity and mortality, affecting 5% to 8% of all pregnancies. The clinical findings can manifest as either a maternal syndrome or fetal syndrome. There is increasing data supporting the role of the insulin resistance in preeclampsia, although this evidence has not been seen in all studies. The aim of this research was to determine the influence of the insulin resistance on the offspring in preeclampsia. Sixty preeclamptic pregnancies underwent the research taking the serum insulin of 20uU/ml as the state of insulin resistance’s cut off. Insulin sensitivity was examined by using HOMA and QUICKY indexes. Thirty preeclamptic pregnancies had the insulin resistance syndrome and thirty were the control group. Linear regression analysis and logistic linear analysis were used to examine the influence of the insulin resistance. In the insulin resistance preeclamptic pregnancies, the duration of pregnancy was shorter (2.59; p<0.01) and the placental weight was lower (2.72; p<0.01). This group also had a statistically lower percentage of vaginal birth (9.64; p<0.01) and higher of caesarian sections (4,44; p<0,05). Newborns in the insulin resistance group were shorter (0.108; p<0.001) weighed less (2.81; p<0.01), had a lower Apgar score (3.11; p<0.01) and stayed in the hospital for a longer time (2,48; p<0,05). The insulin resistance syndrome is not present in every preeclamptic pregnancy, but if it is present it affects the offspring in a negative way.
    Keywords : preeclampsia ; insulin resistance ; newborn ; Medicine ; R
    Subject code 630
    Language English
    Publishing date 2016-06-01T00:00:00Z
    Publisher University in Nis, Faculty of Medicine
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: THE ROLE OF CARDIOTOCOGRAPHY IN ASSESSING THE CONDITION OF A FETUS IN PREECLAMPSIA

    Jelena Milošević-Stevanović / Marija Tasić / Radomir Živadinović / Predrag Vukomanović / Aleksandra Andrić / Sonja Pop-Trajković-Dinić

    Acta Medica Medianae, Vol 54, Iss 2, Pp 41-

    2015  Volume 47

    Abstract: The role of cardiotocography (CTG) in preeclampsia is still vaguely defined. The aim of this study was to investigate the possible role of CTG in assessing the condition of the fetus in preeclampsia with and without intrauterine growth retardation (IUGR) ...

    Abstract The role of cardiotocography (CTG) in preeclampsia is still vaguely defined. The aim of this study was to investigate the possible role of CTG in assessing the condition of the fetus in preeclampsia with and without intrauterine growth retardation (IUGR) and to compare the CTG findings with Doppler parameters and perinatal outcome. The prospective study included 30 singleton pregnancies with preeclampsia completed by caesarean section. The study group was divided into subgroups based on the presence of IUGR in relation to the severity of preeclampsia. The control group consisted of 20 healthy women delivered by elective caesarean section. In 53.3% of preeclamptic cases, cardiotocographic findings differed from normal (p<0.001) and they were either warning or pathological. There were no significant differences in the presence of a pattern deviating from normal based on the severity of preeclampsia, and it was significantly more prevalent in preeclampsia with IUGR (p<0.01) than the one without it. The prevalence of CTG pattern types in the study group was significantly altered by presence of olygoamnion (p<0.05) as well as the parameters of the flow through the uterine arteries, umbilical artery and middle cerebral artery (p<0.05). Apgar score significantly depends on the CTG findings and decreases with the unfavourable CTG pattern. CTG and Doppler ultrasonography complement each other in order to improve perinatal outcome in preeclampsia. CTG is irreplaceable as a first measure of rapid assessment of the fetal condition in newly diagnosed cases of preeclampsia, aiming also to and in order to detect complications from umbilical cord during its follow-up.
    Keywords cardiotocography ; IUGR ; preeclampsia ; Medicine ; R
    Language English
    Publishing date 2015-06-01T00:00:00Z
    Publisher University in Nis, Faculty of Medicine
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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