Suzana Mesojednik, Urška Kamenšek and Maja Čemažar
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Neza Podergajs, Narve Brekka, Bernhard Radlwimmer, Christel Herold-Mende, Krishna M. Talasila, Katja Tiemann, Uros Rajcevic, Tamara T. Lah, Rolf Bjerkvig and Hrvoje Miletic
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.
Atrial fibrillation (AF) is an increasingly widespread healthcare problem. AF can frequently present as a complication in acute coronary syndromes (ACS), especially in ST-elevation acute myocardial infarction (AMI), in which case it is the most frequent supraventricular rhythm disturbance with an estimated incidence of 6.8-21%. The presence of AF in ACS heralds worse outcomes in comparison to subjects in sinus rhythm, and several studies have shown that in AMI patients, both new-onset and pre-existing AF are associated with a higher risk of major adverse cardiovascular and cerebrovascular events during hospitalization. The cause of newonset AF in AMI is multifactorial. Although still incompletely understood, the mechanisms involved in the development of AF in acute myocardial ischemic events include the neurohormonal activation of the sympathetic nervous system that accompanies the AMI, ischemic involvement of the atrial myocytes, ventricular dysfunction, and atrial overload. The identification of patients at risk for AF is of great significance as it may lead to prompt therapeutic interventions and closer follow-up, thus improving prognosis and decreasing cardiovascular and cerebrovascular events. The present manuscript aims to summarize the current research findings related to new-onset AF in AMI patients, as well as the predictors and prognostic impact of this comorbid association.
Clara Pañella, Quim Castellví, Xavier Moll, Rita Quesada, Alberto Villanueva, Mar Iglesias, Dolores Naranjo, Patricia Sánchez-Velázquez, Anna Andaluz, Luís Grande, Antoni Ivorra and Fernando Burdío
Spread hepatic tumours are not suitable for treatment either by surgery or conventional ablation methods. The aim of this study was to evaluate feasibility and safety of selectively increasing the healthy hepatic conductivity by the hypersaline infusion (HI) through the portal vein. We hypothesize this will allow simultaneous safe treatment of all nodules by irreversible electroporation (IRE) when applied in a transhepatic fashion.
Material and methods
Sprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by trans-splenic puncture. Deionized serum (40 mL/Kg) and furosemide (2 mL/Kg) were simultaneously infused through the jugular vein to compensate hypernatremia. Changes in conductivity were monitored in the hepatic and tumour tissue. The period in which hepatic conductivity was higher than tumour conductivity was defined as the therapeutic window (TW). Animals were monitored during 1-month follow-up. The animals were sacrificed and selective samples were used for histological analysis.
The overall survival rate was 82.4% after the HI protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times higher than the baseline value, in group A and B, respectively. The mean maximum hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B creating a TW to implement selective IRE.
HI through the portal vein is safe when the hypersaline overload is compensated with deionized serum and it may provide a TW for focused IRE treatment on tumour nodules.
Barbara Novaković, Vladimir Kotnik, Tanja Šetina, Marjeta Vovk and Srdjan Novaković
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Simona Kranjc, Matej Kranjc, Janez Scancar, Jure Jelenc, Gregor Sersa and Damijan Miklavcic
clinic, was chosen in the study to test the application of induced electroporation mediated with magnetic field. The stock solution of the chemotherapeutic drug used in the study, CDDP (5 mg/mL, Cysplatyl, Aventis Laboratory, Paris, France) was dissolved in aqua pro injection and frozen in aliquots of 1 mL. In order that each animal received a dose of 80 μg of CDDP, a fresh solution at appropriate concentration of CDDP (1 mg/mL) was prepared in 0.9% sodium chloride solution daily before each experiment.
Mouse tumor model
Female C57B1/6 mice were purchased from
Xinyu Wu, Daixing Zhong, Bin Lin, Wenliang Zhai, Zhenqi Ding and Jin Wu
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Leila Towhidi, Seyed Firoozabadi, Hossein Mozdarani and Damijan Miklavcic
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