1. Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approachKlemen Zupančič, Andrej Blejec, Ana Herman, Matija Veber, Urška Verbovšek, Marjan Koršič, Miomir Knežević, Primož Rožman, Tamara Lah Turnšek, Kristina Gruden, Helena Motaln, 2014, izvirni znanstveni članek Povzetek: Background. Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. Materials and methods. We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM. Results. We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM. Conclusions. Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.
Ključne besede: glioblastoma, proteomics, biomarker
Objavljeno v DiRROS: 16.04.2024; Ogledov: 39; Prenosov: 20
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2. Expansive growth of two glioblastoma stem-like cell lines is mediated by bFGF and not by EGFNeža Podergajs, Narve Brekka, Bernhard Radlwimmer, Christel Herold-Mende, Krishna M. Talasila, Katja Tiemann, Uroš Rajčević, Tamara Lah Turnšek, Rolf Bjerkvig, Hrvoje Miletic, 2013, objavljeni znanstveni prispevek na konferenci Povzetek: Background. Patient-derived glioblastoma (GBM) stem-like cells (GSCs) represent a valuable model for basic and therapeutic research. GSCs are usually propagated in serum-free Neural Basal medium supplemented with bFGF and EGF. Yet, the exact influence of these growth factors on GSCs is still unclear. Recently it was suggested that GBM stemlike cells with amplified EGFR should be cultured in stem cell medium without EGF, as the presence of EGF induced rapid loss of EGFR amplification. However, patient biopsies are usually taken into culture before their genomic profiles are defined. Thus, an important question remains whether GBM cells without EGFR amplification also can be cultured in stem cell medium without EGF.Meterials and methods. To address this question, we used two heterogeneous glioblastoma GSC lines (NCH421k and NCH644) that lack EGFR amplification.Results. Although both cell lines showed very low EGFR expression under standard growth conditions, bFGF stimulation induced higher expression of EGFR in NCH644. In both cell lines, expression of the stem cell markers nestin and CD133 was higher upon stimulation with bFGF compared to EGF. Importantly, bFGF stimulated the growth of both cell lines, whereas EGF had no effect. We verified that the growth stimulation by bFGF was either mediated by proliferation (NCH421k) or resistance to apoptosis (NCH644).Conclusions. We demonstrate that GSC cultures without EGFR amplification can be maintained and expanded with bFGF, while the addition of EGF has no significant effect and therefore can be omitted.
Ključne besede: glioblastoma, stem cell cultures, bFGF
Objavljeno v DiRROS: 03.04.2024; Ogledov: 36; Prenosov: 20
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4. CD133/prominin1 is prognostic for GBM patient's survival, but inversely correlated with cysteine cathepsine' expression in gliobastoma derived spheroidsSeyed Yousef Ardebili, Irena Zajc, Boris Gole, Benito Campos, Christel Herold-Mende, Sara Drmota Prebil, Tamara Lah Turnšek, 2011, izvirni znanstveni članek Povzetek: Introduction. CD133 is a marker for a population of glioblastoma (GBM) and normal neural stem cells (NNSC). We aimed to reveal whether the migratory potential and differentiation of these stem cells is associated with CD133 expression and with cathepsin proteases (Cats). Materials and methods. The invasiveness of normal NNSC, GBM/CD133+ cell lines and GBM spheroids was evaluated in 3D collagen, as well as of U87-MG and normal astrocytes (NHA) grown in monolayers in 2D Matrigel. Expression of Cats B, L and S was measuredat mRNA and activity levels and their relation to invasiveness, to CD133 mRNA in 26 gliomas, and to the survival of these patients. Results. The average yield of CD133+ cells from GBM samples was 9.6%. Survival of patients with higher CD133 mRNA expression was significantly shorter (p< 0.005). Invasion, associated with proteolytic degradation of matrix, was higher in normal stem cells and GBM spheroids and cells than in isolated GBM CD133+ cells. In glioma samples, there was no correlation between CD133 mRNA expression and Cat mRNAs, but there was an inverse correlation with Cat activities. Conclusions. The study confirms CD133 as a prognostic marker for the survival of GBM patients. We demonstrated that NNSC have higher invasion potential and invade the collagen matrix in a mode different from that of GBM,initiating stem cell spheres. This result could have implications for the design of new therapeutics, including protease inhibitors that specifically target invasive tumour stem cells. Increased activity of cathepsins in CD133- cells suggests their role in the invasive behaviour of GBM.
Objavljeno v DiRROS: 19.03.2024; Ogledov: 107; Prenosov: 27
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6. Ecotoxicologically relevant cyclic peptides from cyanobacterial bloom (Planktothrix rubecens) - a threat to human and environmental healthBojan Sedmak, Tina Eleršek, Olga Grach-Pogrebinsky, Shmuel Carmeli, Nataša Sever, Tamara Lah Turnšek, 2008, izvirni znanstveni članek Povzetek: Background. The information of the overall production of major cyanobacterial cyclic peptides in a water body is essential for risk assessment and for the prediction of future development of the bloom. A procedure that gives a reviewof both toxic and non-hepatotoxic hydrophilic cyclic peptide production is important to evaluate the ecological conditions in the water environment and to predict the release of dangerous toxic and tumour promoting substances.Methods. The cyclic peptides were identified on the basis of their retention times, characteristic spectra, molecular masses and biological activity. The non-hepatotoxic cyclic peptides were characterised by their inhibition of porcine pancreatic elastase, while cytotoxicity to mammalian cells was tested with the MTT test on B16 cell line. Conclusions. The method presented gives a rapid, simultaneous assessment, preliminary identification and estimation of bioactive cyclic peptides. The synthesis of non-hepatotoxic cyclic peptides can mediate the release various toxic and otherwise biologically active substances that induce systemic genotoxicity in mammals.
Ključne besede: tumor promoters, microcystin, anabaenopeptin, planktopeptin, toxic cyanobacterial blooms, environmental health
Objavljeno v DiRROS: 07.03.2024; Ogledov: 101; Prenosov: 20
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7. Cysteine cathepsins, stefins and extracellular matrix degradation during invasion of transformed human breast cell linesIrena Zajc, Aleš Bervar, Tamara Lah Turnšek, 2006, izvirni znanstveni članek Povzetek: Background. Human breast cellular model, comprising four cell lines originating from spontaneously immortalized human breast epithelial MCF10A cell line, its c-Ha-ras transfectant, MCF10AT, and two tumourigenic derivatives, cultured from two sequential mouse xenographs, MCF10AT-Ca1a and MCF10AT-Ca1d, were used to compare the relative protein concentration of cathepsins and stefins in single cells. Methods. The relative protein concentration of cathepsins and stefins in single cells was analysed by confocal microscopy, and compared to their protein expression in cell homogenates. Results. The most invasive, MCF10AT cell line contained several fold higher protein concentration of cathepsin B and increased levels of stefins, but similar levels of cathepsin L, compared with the parental MCF10A cells. This was associated with five fold higher endocytosis of Matrigel-DQ-collagen IV (DQC) and a simultaneous increase in signal overlap between DQC and cathepsin L as well as DQC and stefin B, but a decrease in that of DQC and cathepsin B overlap in the MCF10AT cells. Simultaneously, increased signal overlaps between both cathepsins and between cathepsins-stefins pairs, were observed in this cell line. Conclusions. These results suggest that the increased collagen endocytosis and degradation in theinvasive phenotype significantly affect also the subcellular localization of cysteine cathepsins and stefins. Based on these and the reports of other authors, we hypothesize that the intracellular degradation may also be assoeiated with cathepsin L, whereas cathepsin B in the ras transformed breastcells is involved in both, the intracellular and pericellular degradation of extracellular matrix during cell migration and invasion.
Ključne besede: breast neoplasms, tumor cells cultured, neoplasms invasiveness, cathepsins, extracellular matrix
Objavljeno v DiRROS: 15.02.2024; Ogledov: 122; Prenosov: 35
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9. Cathepsin L in human meningiomasMiha Trinkaus, Andrej Vranič, Vinko V. Dolenc, Tamara Lah Turnšek, 2003, izvirni znanstveni članek Ključne besede: meningioma-pathology, cathepsin L, reverse transcriptase, polymerase chain reaction, neoplasm invasiveness
Objavljeno v DiRROS: 06.02.2024; Ogledov: 143; Prenosov: 36
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