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Institution

Charles University in Prague

EducationPrague, Czechia
About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.


Papers
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Journal ArticleDOI
TL;DR: It is proposed that this endogenous FGF signaling pathway can be implicated in self‐renewal or differentiation of hESCs, suggesting an involvement of autocrine FGF signals in the maintenance of proliferating h ESCs in the undifferentiated state.
Abstract: Although the detection of several components of the fibroblast growth factor (FGF) signaling pathway in human embryonic stem cells (hESCs) has been reported, the functionality of that pathway and effects on cell fate decisions are yet to be established. In this study we characterized expression of FGF-2, the prototypic member of the FGF family, and its receptors (FGFRs) in undifferentiated and differentiating hESCs; subsequently, we analyzed the effects of FGF-2 on hESCs, acting as both exogenous and endogenous factors. We have determined that undifferentiated hESCs are abundant in several molecular-mass isoforms of FGF-2 and that expression pattern of these isoforms remains unchanged under conditions that induce hESC differentiation. Significantly, FGF-2 is released by hESCs into the medium, suggesting an autocrine activity. Expression of FGFRs in undifferentiated hESCs follows a specific pattern, with FGFR1 being the most abundant species and other receptors showing lower expression in the following order: FGFR1 --> FGFR3 --> FGFR4 --> FGFR2. Initiation of differentiation is accompanied by profound changes in FGFR expression, particularly the upregulation of FGFR1. When hESCs are exposed to exogenous FGF-2, extracellular signal-regulated kinases are phosphorylated and thereby activated. However, the presence or absence of exogenous FGF-2 does not significantly affect the proliferation of hESCs. Instead, increased concentration of exogenous FGF-2 leads to reduced outgrowth of hESC colonies with time in culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether FGF-2 that is released by hESCs exerts its activities via autocrine pathways. Strikingly, the resultant inhibition of FGFR suppresses activation of downstream protein kinases and causes rapid cell differentiation, suggesting an involvement of autocrine FGF signals in the maintenance of proliferating hESCs in the undifferentiated state. In conclusion from our data, we propose that this endogenous FGF signaling pathway can be implicated in self-renewal or differentiation of hESCs.

243 citations

Journal ArticleDOI
TL;DR: The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes, and results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.

242 citations

Journal ArticleDOI
Javier Egea, Isabel Fabregat1, Yves Frapart2, Pietro Ghezzi3  +148 moreInstitutions (57)
TL;DR: The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks and EU-ROS represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine.
Abstract: The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed

242 citations

Journal ArticleDOI
TL;DR: The term ‘migrastatics’ is coined for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation.
Abstract: In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers.

242 citations

Journal ArticleDOI
TL;DR: This Review summarises the reviewed literature and the recommendations of the ECIL 7 for management of cytomegalovirus in patients with haematological malignancies and covers diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management.
Abstract: Summary Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management of cytomegalovirus disease. Antiviral drugs including maribavir and letermovir are in development and prospective clinical trials have recently been completed. However, management of patients with resistant or refractory cytomegalovirus infection or cytomegalovirus disease is a challenge. In this Review we summarise the reviewed literature and the recommendations of the ECIL 7 for management of cytomegalovirus in patients with haematological malignancies.

242 citations


Authors

Showing all 32719 results

NameH-indexPapersCitations
Ronald C. Petersen1781091153067
P. Chang1702154151783
Vaclav Vrba141129895671
Milos Lokajicek139151198888
Christopher D. Manning138499147595
Yves Sirois137133495714
Rupert Leitner136120190597
Gerald M. Reaven13379980351
Roberto Sacchi132118689012
S. Errede132148198663
Mark Neubauer131125289004
Peter Kodys131126285267
Panos A Razis130128790704
Vit Vorobel13091979444
Jehad Mousa130122686564
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023203
2022554
20214,838
20204,793
20194,421
20183,991