2022
Almeida J, Mota I, Skoda J, Sousa E, Cidade H, Saraiva L
Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment Journal Article
Cancers 14(24), 6212 (2022).
@article{pmid36551697,
title = {Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment},
author = {Joana Almeida and Inês Mota and Jan Skoda and Emília Sousa and Honorina Cidade and Lucília Saraiva},
doi = {10.3390/cancers14246212},
issn = {2072-6694},
year = {2022},
date = {2022-12-01},
urldate = {2022-12-01},
journal = {Cancers},
volume = {14},
number = {24},
pages = {6212},
abstract = {Neuroblastoma (NB) is an embryonic cancer that develops from neural crest stem cells, being one of the most common malignancies in children. The clinical manifestation of this disease is highly variable, ranging from spontaneous regression to increased aggressiveness, which makes it a major therapeutic challenge in pediatric oncology. The p53 family proteins p53 and TAp73 play a key role in protecting cells against genomic instability and malignant transformation. However, in NB, their activities are commonly inhibited by interacting proteins such as murine double minute (MDM)2 and MDMX, mutant p53, ΔNp73, Itch, and Aurora kinase A. The interplay between the p53/TAp73 pathway and N-MYC, a known biomarker of poor prognosis and drug resistance in NB, also proves to be decisive in the pathogenesis of this tumor. More recently, a strong crosstalk between microRNAs (miRNAs) and p53/TAp73 has been established, which has been the focused of great attention because of its potential for developing new therapeutic strategies. Collectively, this review provides an updated overview about the critical role of the p53/TAp73 pathway in the pathogenesis of NB, highlighting encouraging clues for the advance of alternative NB targeted therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neuroblastoma (NB) is an embryonic cancer that develops from neural crest stem cells, being one of the most common malignancies in children. The clinical manifestation of this disease is highly variable, ranging from spontaneous regression to increased aggressiveness, which makes it a major therapeutic challenge in pediatric oncology. The p53 family proteins p53 and TAp73 play a key role in protecting cells against genomic instability and malignant transformation. However, in NB, their activities are commonly inhibited by interacting proteins such as murine double minute (MDM)2 and MDMX, mutant p53, ΔNp73, Itch, and Aurora kinase A. The interplay between the p53/TAp73 pathway and N-MYC, a known biomarker of poor prognosis and drug resistance in NB, also proves to be decisive in the pathogenesis of this tumor. More recently, a strong crosstalk between microRNAs (miRNAs) and p53/TAp73 has been established, which has been the focused of great attention because of its potential for developing new therapeutic strategies. Collectively, this review provides an updated overview about the critical role of the p53/TAp73 pathway in the pathogenesis of NB, highlighting encouraging clues for the advance of alternative NB targeted therapies.
Paukovcekova S, Krchniakova M, Chlapek P, Neradil J, Skoda J, Veselska R
Int J Mol Sci 23(15) (2022).
@article{pmid35955683,
title = {Thiosemicarbazones Can Act Synergistically with Anthracyclines to Downregulate CHEK1 Expression and Induce DNA Damage in Cell Lines Derived from Pediatric Solid Tumors},
author = {Silvia Paukovcekova and Maria Krchniakova and Petr Chlapek and Jakub Neradil and Jan Skoda and Renata Veselska},
doi = {10.3390/ijms23158549},
issn = {1422-0067},
year = {2022},
date = {2022-08-01},
journal = {Int J Mol Sci},
volume = {23},
number = {15},
abstract = {Anticancer therapy by anthracyclines often leads to the development of multidrug resistance (MDR), with subsequent treatment failure. Thiosemicarbazones have been previously suggested as suitable anthracycline partners due to their ability to overcome drug resistance through dual Pgp-dependent cytotoxicity-inducing effects. Here, we focused on combining anthracyclines (doxorubicin, daunorubicin, and mitoxantrone) and two thiosemicarbazones (DpC and Dp44mT) for treating cell types derived from the most frequent pediatric solid tumors. Our results showed synergistic effects for all combinations of treatments in all tested cell types. Nevertheless, further experiments revealed that this synergism was independent of Pgp expression but rather resulted from impaired DNA repair control leading to cell death via mitotic catastrophe. The downregulation of checkpoint kinase 1 (CHEK1) expression by thiosemicarbazones and the ability of both types of agents to induce double-strand breaks in DNA may explain the Pgp-independent synergism between anthracyclines and thiosemicarbazones. Moreover, the concomitant application of these agents was found to be the most efficient approach, achieving the strongest synergistic effect with lower concentrations of these drugs. Overall, our study identified a new mechanism that offers an avenue for combining thiosemicarbazones with anthracyclines to treat tumors regardless the Pgp status.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Anticancer therapy by anthracyclines often leads to the development of multidrug resistance (MDR), with subsequent treatment failure. Thiosemicarbazones have been previously suggested as suitable anthracycline partners due to their ability to overcome drug resistance through dual Pgp-dependent cytotoxicity-inducing effects. Here, we focused on combining anthracyclines (doxorubicin, daunorubicin, and mitoxantrone) and two thiosemicarbazones (DpC and Dp44mT) for treating cell types derived from the most frequent pediatric solid tumors. Our results showed synergistic effects for all combinations of treatments in all tested cell types. Nevertheless, further experiments revealed that this synergism was independent of Pgp expression but rather resulted from impaired DNA repair control leading to cell death via mitotic catastrophe. The downregulation of checkpoint kinase 1 (CHEK1) expression by thiosemicarbazones and the ability of both types of agents to induce double-strand breaks in DNA may explain the Pgp-independent synergism between anthracyclines and thiosemicarbazones. Moreover, the concomitant application of these agents was found to be the most efficient approach, achieving the strongest synergistic effect with lower concentrations of these drugs. Overall, our study identified a new mechanism that offers an avenue for combining thiosemicarbazones with anthracyclines to treat tumors regardless the Pgp status.
Kameneva P, Melnikova V I, Kastriti M E, Kurtova A, Kryukov E, Murtazina A, Faure L, Poverennaya I, Artemov A V, Kalinina T S, Kudryashov N V, Bader M, Skoda J, Chlapek P, Curylova L, Sourada L, Neradil J, Tesarova M, Pasqualetti M, Gaspar P, Yakushov V D, Sheftel B I, Zikmund T, Kaiser J, Fried K, Alenina N, Voronezhskaya E E, Adameyko I
Serotonin limits generation of chromaffin cells during adrenal organ development Journal Article
Nat Commun 13(1), 2901 (2022).
@article{pmid35614045,
title = {Serotonin limits generation of chromaffin cells during adrenal organ development},
author = {Polina Kameneva and Victoria I Melnikova and Maria Eleni Kastriti and Anastasia Kurtova and Emil Kryukov and Aliia Murtazina and Louis Faure and Irina Poverennaya and Artem V Artemov and Tatiana S Kalinina and Nikita V Kudryashov and Michael Bader and Jan Skoda and Petr Chlapek and Lucie Curylova and Lukas Sourada and Jakub Neradil and Marketa Tesarova and Massimo Pasqualetti and Patricia Gaspar and Vasily D Yakushov and Boris I Sheftel and Tomas Zikmund and Jozef Kaiser and Kaj Fried and Natalia Alenina and Elena E Voronezhskaya and Igor Adameyko},
doi = {10.1038/s41467-022-30438-w},
issn = {2041-1723},
year = {2022},
date = {2022-05-01},
journal = {Nat Commun},
volume = {13},
number = {1},
pages = {2901},
abstract = {Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor "bridge" cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3A human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists. In embryos (in vivo), the physiological increase of 5HT caused a prolongation of the cell cycle in "bridge" progenitors leading to a smaller chromaffin population and changing the balance of hormones and behavioral patterns in adulthood. These behavioral effects and smaller adrenals were mirrored in the progeny of pregnant female mice subjected to experimental stress, suggesting a maternal-fetal link that controls developmental adaptations. Finally, these results corresponded to a size-distribution of adrenals found in wild rodents with different coping strategies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor "bridge" cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3A human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists. In embryos (in vivo), the physiological increase of 5HT caused a prolongation of the cell cycle in "bridge" progenitors leading to a smaller chromaffin population and changing the balance of hormones and behavioral patterns in adulthood. These behavioral effects and smaller adrenals were mirrored in the progeny of pregnant female mice subjected to experimental stress, suggesting a maternal-fetal link that controls developmental adaptations. Finally, these results corresponded to a size-distribution of adrenals found in wild rodents with different coping strategies.
Çoku J, Booth D M, Skoda J, Pedrotty M C, Vogel J, Liu K, Vu A, Carpenter E L, Ye J C, Chen M A, Dunbar P, Scadden E, Yun T D, Nakamaru-Ogiso E, Area-Gomez E, Li Y, Goldsmith K C, Reynolds C P, Hajnoczky G, Hogarty M D
Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance Journal Article
EMBO J 41(8), e108272 (2022).
@article{pmid35211994,
title = {Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance},
author = {Jorida Çoku and David M Booth and Jan Skoda and Madison C Pedrotty and Jennifer Vogel and Kangning Liu and Annette Vu and Erica L Carpenter and Jamie C Ye and Michelle A Chen and Peter Dunbar and Elizabeth Scadden and Taekyung D Yun and Eiko Nakamaru-Ogiso and Estela Area-Gomez and Yimei Li and Kelly C Goldsmith and C Patrick Reynolds and Gyorgy Hajnoczky and Michael D Hogarty},
doi = {10.15252/embj.2021108272},
issn = {1460-2075},
year = {2022},
date = {2022-04-01},
journal = {EMBO J},
volume = {41},
number = {8},
pages = {e108272},
abstract = {Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug-resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER-mitochondria-associated membranes (MAMs; ER-mitochondria contacts, ERMCs) in therapy-resistant cells, and genetically or biochemically reducing MAMs in therapy-sensitive tumors phenocopied resistance. MAMs serve as platforms to transfer Ca and bioactive lipids to mitochondria. Reduced Ca transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ER-mitochondria-associated membranes as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug-resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER-mitochondria-associated membranes (MAMs; ER-mitochondria contacts, ERMCs) in therapy-resistant cells, and genetically or biochemically reducing MAMs in therapy-sensitive tumors phenocopied resistance. MAMs serve as platforms to transfer Ca and bioactive lipids to mitochondria. Reduced Ca transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ER-mitochondria-associated membranes as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance.
Curylova L, Ramos H, Saraiva L, Skoda J
Noncanonical roles of p53 in cancer stemness and their implications in sarcomas Journal Article
Cancer Lett 525, 131–145 (2022).
@article{pmid34742870,
title = {Noncanonical roles of p53 in cancer stemness and their implications in sarcomas},
author = {Lucie Curylova and Helena Ramos and Lucília Saraiva and Jan Skoda},
doi = {10.1016/j.canlet.2021.10.037},
issn = {1872-7980},
year = {2022},
date = {2022-01-01},
journal = {Cancer Lett},
volume = {525},
pages = {131--145},
abstract = {Impairment of the prominent tumor suppressor p53, well known for its canonical role as the "guardian of the genome", is found in almost half of human cancers. More recently, p53 has been suggested to be a crucial regulator of stemness, orchestrating the differentiation of embryonal and adult stem cells, suppressing reprogramming into induced pluripotent stem cells, or inhibiting cancer stemness (i.e., cancer stem cells, CSCs), which underlies the development of therapy-resistant tumors. This review addresses these noncanonical roles of p53 and their implications in sarcoma initiation and progression. Indeed, dysregulation of p53 family proteins is a common event in sarcomas and is associated with poor survival. Additionally, emerging studies have demonstrated that loss of wild-type p53 activity hinders the terminal differentiation of mesenchymal stem cells and leads to the development of aggressive sarcomas. This review summarizes recent findings on the roles of aberrant p53 in sarcoma development and stemness and further describes therapeutic approaches to restore normal p53 activity as a promising anti-CSC strategy to treat refractory sarcomas.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Impairment of the prominent tumor suppressor p53, well known for its canonical role as the "guardian of the genome", is found in almost half of human cancers. More recently, p53 has been suggested to be a crucial regulator of stemness, orchestrating the differentiation of embryonal and adult stem cells, suppressing reprogramming into induced pluripotent stem cells, or inhibiting cancer stemness (i.e., cancer stem cells, CSCs), which underlies the development of therapy-resistant tumors. This review addresses these noncanonical roles of p53 and their implications in sarcoma initiation and progression. Indeed, dysregulation of p53 family proteins is a common event in sarcomas and is associated with poor survival. Additionally, emerging studies have demonstrated that loss of wild-type p53 activity hinders the terminal differentiation of mesenchymal stem cells and leads to the development of aggressive sarcomas. This review summarizes recent findings on the roles of aberrant p53 in sarcoma development and stemness and further describes therapeutic approaches to restore normal p53 activity as a promising anti-CSC strategy to treat refractory sarcomas.
Krchniakova M, Paukovcekova S, Chlapek P, Neradil J, Skoda J, Veselska R
Front Pharmacol 13, 976955 (2022).
@article{pmid36160437,
title = {Thiosemicarbazones and selected tyrosine kinase inhibitors synergize in pediatric solid tumors: NDRG1 upregulation and impaired prosurvival signaling in neuroblastoma cells},
author = {Maria Krchniakova and Silvia Paukovcekova and Petr Chlapek and Jakub Neradil and Jan Skoda and Renata Veselska},
doi = {10.3389/fphar.2022.976955},
issn = {1663-9812},
year = {2022},
date = {2022-01-01},
journal = {Front Pharmacol},
volume = {13},
pages = {976955},
abstract = {Tyrosine kinase inhibitors (TKIs) are frequently used in combined therapy to enhance treatment efficacy and overcome drug resistance. The present study analyzed the effects of three inhibitors, sunitinib, gefitinib, and lapatinib, combined with iron-chelating agents, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) or di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC). Simultaneous administration of the drugs consistently resulted in synergistic and/or additive activities against the cell lines derived from the most frequent types of pediatric solid tumors. The results of a detailed analysis of cell signaling in the neuroblastoma cell lines revealed that TKIs inhibited the phosphorylation of the corresponding receptor tyrosine kinases, and thiosemicarbazones downregulated the expression of epidermal growth factor receptor, platelet-derived growth factor receptor, and insulin-like growth factor-1 receptor, leading to a strong induction of apoptosis. Marked upregulation of the metastasis suppressor N-myc downstream regulated gene-1 (NDRG1), which is known to be activated and upregulated by thiosemicarbazones in adult cancers, was also detected in thiosemicarbazone-treated neuroblastoma cells. Importantly, these effects were more pronounced in the cells treated with drug combinations, especially with the combinations of lapatinib with thiosemicarbazones. Therefore, these results provide a rationale for novel strategies combining iron-chelating agents with TKIs in therapy of pediatric solid tumors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tyrosine kinase inhibitors (TKIs) are frequently used in combined therapy to enhance treatment efficacy and overcome drug resistance. The present study analyzed the effects of three inhibitors, sunitinib, gefitinib, and lapatinib, combined with iron-chelating agents, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) or di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC). Simultaneous administration of the drugs consistently resulted in synergistic and/or additive activities against the cell lines derived from the most frequent types of pediatric solid tumors. The results of a detailed analysis of cell signaling in the neuroblastoma cell lines revealed that TKIs inhibited the phosphorylation of the corresponding receptor tyrosine kinases, and thiosemicarbazones downregulated the expression of epidermal growth factor receptor, platelet-derived growth factor receptor, and insulin-like growth factor-1 receptor, leading to a strong induction of apoptosis. Marked upregulation of the metastasis suppressor N-myc downstream regulated gene-1 (NDRG1), which is known to be activated and upregulated by thiosemicarbazones in adult cancers, was also detected in thiosemicarbazone-treated neuroblastoma cells. Importantly, these effects were more pronounced in the cells treated with drug combinations, especially with the combinations of lapatinib with thiosemicarbazones. Therefore, these results provide a rationale for novel strategies combining iron-chelating agents with TKIs in therapy of pediatric solid tumors.
2021
Macsek P, Skoda J, Krchniakova M, Neradil J, Veselska R
Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma Journal Article
Int J Mol Sci 23(1) (2021).
@article{pmid35008802,
title = {Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma},
author = {Peter Macsek and Jan Skoda and Maria Krchniakova and Jakub Neradil and Renata Veselska},
doi = {10.3390/ijms23010376},
issn = {1422-0067},
year = {2021},
date = {2021-12-01},
journal = {Int J Mol Sci},
volume = {23},
number = {1},
abstract = {Despite constant advances in the field of pediatric oncology, the survival rate of high-risk neuroblastoma patients remains poor. The molecular and genetic features of neuroblastoma, such as amplification and stemness status, have established themselves not only as potent prognostic and predictive factors but also as intriguing targets for personalized therapy. Novel thiosemicarbazones target both total level and activity of a number of proteins involved in some of the most important signaling pathways in neuroblastoma. In this study, we found that di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) potently decreases N-MYC in -amplified and c-MYC in -nonamplified neuroblastoma cell lines. Furthermore, DpC succeeded in downregulating total EGFR and phosphorylation of its most prominent tyrosine residues through the involvement of NDRG1, a positive prognostic marker in neuroblastoma, which was markedly upregulated after thiosemicarbazone treatment. These findings could provide useful knowledge for the treatment of MYC-driven neuroblastomas that are unresponsive to conventional therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Despite constant advances in the field of pediatric oncology, the survival rate of high-risk neuroblastoma patients remains poor. The molecular and genetic features of neuroblastoma, such as amplification and stemness status, have established themselves not only as potent prognostic and predictive factors but also as intriguing targets for personalized therapy. Novel thiosemicarbazones target both total level and activity of a number of proteins involved in some of the most important signaling pathways in neuroblastoma. In this study, we found that di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) potently decreases N-MYC in -amplified and c-MYC in -nonamplified neuroblastoma cell lines. Furthermore, DpC succeeded in downregulating total EGFR and phosphorylation of its most prominent tyrosine residues through the involvement of NDRG1, a positive prognostic marker in neuroblastoma, which was markedly upregulated after thiosemicarbazone treatment. These findings could provide useful knowledge for the treatment of MYC-driven neuroblastomas that are unresponsive to conventional therapies.
Seebacher N A, Krchniakova M, Stacy A E, Skoda J, Jansson P J
Tumour Microenvironment Stress Promotes the Development of Drug Resistance Journal Article
Antioxidants (Basel) 10(11) (2021).
@article{pmid34829672,
title = {Tumour Microenvironment Stress Promotes the Development of Drug Resistance},
author = {Nicole A Seebacher and Maria Krchniakova and Alexandra E Stacy and Jan Skoda and Patric J Jansson},
doi = {10.3390/antiox10111801},
issn = {2076-3921},
year = {2021},
date = {2021-11-01},
journal = {Antioxidants (Basel)},
volume = {10},
number = {11},
abstract = {Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells.
2020
Paukovcekova S, Skoda J, Neradil J, Mikulenkova E, Chlapek P, Sterba J, Richardson D R, Veselska R
Novel Thiosemicarbazones Sensitize Pediatric Solid Tumor Cell-Types to Conventional Chemotherapeutics through Multiple Molecular Mechanisms Journal Article
Cancers 12(12), 3781 (2020).
@article{pmid33334021,
title = {Novel Thiosemicarbazones Sensitize Pediatric Solid Tumor Cell-Types to Conventional Chemotherapeutics through Multiple Molecular Mechanisms},
author = {Silvia Paukovcekova and Jan Skoda and Jakub Neradil and Erika Mikulenkova and Petr Chlapek and Jaroslav Sterba and Des R Richardson and Renata Veselska},
doi = {10.3390/cancers12123781},
issn = {2072-6694},
year = {2020},
date = {2020-12-01},
urldate = {2020-12-01},
journal = {Cancers},
volume = {12},
number = {12},
pages = {3781},
abstract = {Combining low-dose chemotherapies is a strategy for designing less toxic and more potent childhood cancer treatments. We examined the effects of combining the novel thiosemicarbazones, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), or its analog, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), with the standard chemotherapies, celecoxib (CX), etoposide (ETO), or temozolomide (TMZ). These combinations were analyzed for synergism to inhibit proliferation of three pediatric tumor cell-types, namely osteosarcoma (Saos-2), medulloblastoma (Daoy) and neuroblastoma (SH-SY5Y). In terms of mechanistic dissection, this study discovered novel thiosemicarbazone targets not previously identified and which are important for considering possible drug combinations. In this case, DpC and Dp44mT caused: (1) up-regulation of a major protein target of CX, namely cyclooxygenase-2 (COX-2); (2) down-regulation of the DNA repair protein, O-methylguanine DNA methyltransferase (MGMT), which is known to affect TMZ resistance; (3) down-regulation of mismatch repair (MMR) proteins, MSH2 and MSH6, in Daoy and SH-SY5Y cells; and (4) down-regulation in all three cell-types of the MMR repair protein, MLH1, and also topoisomerase 2α (Topo2α), the latter of which is an ETO target. While thiosemicarbazones up-regulate the metastasis suppressor, NDRG1, in adult cancers, it is demonstrated herein for the first time that they induce NDRG1 in all three pediatric tumor cell-types, validating its role as a potential target. In fact, siRNA studies indicated that NDRG1 was responsible for MGMT down-regulation that may prevent TMZ resistance. Examining the effects of combining thiosemicarbazones with CX, ETO, or TMZ, the most promising synergism was obtained using CX. Of interest, a positive relationship was observed between NDRG1 expression of the cell-type and the synergistic activity observed in the combination of thiosemicarbazones and CX. These studies identify novel thiosemicarbazone targets relevant to childhood cancer combination chemotherapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Combining low-dose chemotherapies is a strategy for designing less toxic and more potent childhood cancer treatments. We examined the effects of combining the novel thiosemicarbazones, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), or its analog, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), with the standard chemotherapies, celecoxib (CX), etoposide (ETO), or temozolomide (TMZ). These combinations were analyzed for synergism to inhibit proliferation of three pediatric tumor cell-types, namely osteosarcoma (Saos-2), medulloblastoma (Daoy) and neuroblastoma (SH-SY5Y). In terms of mechanistic dissection, this study discovered novel thiosemicarbazone targets not previously identified and which are important for considering possible drug combinations. In this case, DpC and Dp44mT caused: (1) up-regulation of a major protein target of CX, namely cyclooxygenase-2 (COX-2); (2) down-regulation of the DNA repair protein, O-methylguanine DNA methyltransferase (MGMT), which is known to affect TMZ resistance; (3) down-regulation of mismatch repair (MMR) proteins, MSH2 and MSH6, in Daoy and SH-SY5Y cells; and (4) down-regulation in all three cell-types of the MMR repair protein, MLH1, and also topoisomerase 2α (Topo2α), the latter of which is an ETO target. While thiosemicarbazones up-regulate the metastasis suppressor, NDRG1, in adult cancers, it is demonstrated herein for the first time that they induce NDRG1 in all three pediatric tumor cell-types, validating its role as a potential target. In fact, siRNA studies indicated that NDRG1 was responsible for MGMT down-regulation that may prevent TMZ resistance. Examining the effects of combining thiosemicarbazones with CX, ETO, or TMZ, the most promising synergism was obtained using CX. Of interest, a positive relationship was observed between NDRG1 expression of the cell-type and the synergistic activity observed in the combination of thiosemicarbazones and CX. These studies identify novel thiosemicarbazone targets relevant to childhood cancer combination chemotherapy.
Mikulenkova E, Neradil J, Vymazal O, Skoda J, Veselska R
NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation Journal Article
Cells 9(3), 692 (2020).
@article{E2020,
title = {NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation},
author = {Mikulenkova, E. and Neradil, J. and Vymazal, O. and Skoda, J. and Veselska, R.},
doi = {10.3390/cells9030692},
year = {2020},
date = {2020-03-11},
journal = {Cells},
volume = {9},
number = {3},
pages = {692},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Skoda J, Neradil J, Zambo I S, Nunukova A, Macsek P, Borankova K, Dobrotkova V, Nemec P, Sterba J, Veselska R
Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells Journal Article
Cancers 12(1), 196 (2020).
@article{Skoda_2020,
title = {Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells},
author = {Jan Skoda and Jakub Neradil and Iva Staniczkova Zambo and Alena Nunukova and Peter Macsek and Karolina Borankova and Viera Dobrotkova and Pavel Nemec and Jaroslav Sterba and Renata Veselska},
doi = {10.3390/cancers12010196},
year = {2020},
date = {2020-01-01},
journal = {Cancers},
volume = {12},
number = {1},
pages = {196},
publisher = {MDPI AG},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Krchniakova M, Skoda J, Neradil J, Chlapek P, Veselska R
Repurposing tyrosine kinase inhibitors to overcome multidrug resistance in cancer: A focus on transporters and lysosomal sequestration Journal Article
International Journal of Molecular Sciences 21(9) (2020).
@article{Krchniakova2020,
title = {Repurposing tyrosine kinase inhibitors to overcome multidrug resistance in cancer: A focus on transporters and lysosomal sequestration},
author = {Krchniakova, M. and Skoda, J. and Neradil, J. and Chlapek, P. and Veselska, R.},
doi = {10.3390/ijms21093157},
year = {2020},
date = {2020-01-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {9},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Polaskova K, Merta T, Martincekova A, Zapletalova D, Kyr M, Mazanek P, Krenova Z, Mudry P, Jezova M, Tuma J, Skotakova J, Cervinkova I, Valik D, Zdrazilova-Dubska L, Noskova H, Pal K, Slaby O, Fabian P, Kozakova S, Neradil J, Veselska R, Kanderova V, Hrusak O, Freiberger T, Klement G L, Sterba J
Frontiers in Oncology 9 (2020).
@article{Polaskova2020,
title = {Comprehensive Molecular Profiling for Relapsed/Refractory Pediatric Burkitt Lymphomas—Retrospective Analysis of Three Real-Life Clinical Cases—Addressing Issues on Randomization and Customization at the Bedside},
author = {Polaskova, K. and Merta, T. and Martincekova, A. and Zapletalova, D. and Kyr, M. and Mazanek, P. and Krenova, Z. and Mudry, P. and Jezova, M. and Tuma, J. and Skotakova, J. and Cervinkova, I. and Valik, D. and Zdrazilova-Dubska, L. and Noskova, H. and Pal, K. and Slaby, O. and Fabian, P. and Kozakova, S. and Neradil, J. and Veselska, R. and Kanderova, V. and Hrusak, O. and Freiberger, T. and Klement, G.L. and Sterba, J.},
doi = {10.3389/fonc.2019.01531},
year = {2020},
date = {2020-01-01},
journal = {Frontiers in Oncology},
volume = {9},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gojo J, Pavelka Z, Zapletalova D, Schmook M T, Mayr L, Madlener S, Kyr M, Vejmelkova K, Smrcka M, Czech T, Dorfer C, Skotakova J, Azizi A A, Chocholous M, Reisinger D, Lastovicka D, Valik D, Haberler C, Peyrl A, Noskova H, Pál K, Jezova M, Veselska R, Kozakova S, Slaby O, Slavc I, Sterba J
Personalized Treatment of H3K27M-Mutant Pediatric Diffuse Gliomas Provides Improved Therapeutic Opportunities Journal Article
Frontiers in Oncology 9 (2020).
@article{Gojo2020,
title = {Personalized Treatment of H3K27M-Mutant Pediatric Diffuse Gliomas Provides Improved Therapeutic Opportunities},
author = {Gojo, J. and Pavelka, Z. and Zapletalova, D. and Schmook, M.T. and Mayr, L. and Madlener, S. and Kyr, M. and Vejmelkova, K. and Smrcka, M. and Czech, T. and Dorfer, C. and Skotakova, J. and Azizi, A.A. and Chocholous, M. and Reisinger, D. and Lastovicka, D. and Valik, D. and Haberler, C. and Peyrl, A. and Noskova, H. and Pál, K. and Jezova, M. and Veselska, R. and Kozakova, S. and Slaby, O. and Slavc, I. and Sterba, J.},
doi = {10.3389/fonc.2019.01436},
year = {2020},
date = {2020-01-01},
journal = {Frontiers in Oncology},
volume = {9},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2019
Dobrotkova V, Chlapek P, Jezova M, Adamkova K, Mazanek P, Sterba J, Veselska R
Prediction of neuroblastoma cell response to treatment with natural or synthetic retinoids using selected protein biomarkers Journal Article
PLoS One 14(6), e0218269 (2019).
@article{RN5,
title = {Prediction of neuroblastoma cell response to treatment with natural or synthetic retinoids using selected protein biomarkers},
author = { V. Dobrotkova and P. Chlapek and M. Jezova and K. Adamkova and P. Mazanek and J. Sterba and R. Veselska},
doi = {10.1371/journal.pone.0218269},
issn = {1932-6203},
year = {2019},
date = {2019-01-01},
journal = {PLoS One},
volume = {14},
number = {6},
pages = {e0218269},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gomes S, Raimundo L, Soares J, Loureiro J B, Leao M, Ramos H, Monteiro M N, Lemos A, Moreira J, Pinto M, Chlapek P, Veselska R, Sousa E, Saraiva L
New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma Journal Article
Cancer Lett 446, 90-102 (2019).
@article{RN6,
title = {New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma},
author = { S. Gomes and L. Raimundo and J. Soares and J. B. Loureiro and M. Leao and H. Ramos and M. N. Monteiro and A. Lemos and J. Moreira and M. Pinto and P. Chlapek and R. Veselska and E. Sousa and L. Saraiva},
doi = {10.1016/j.canlet.2019.01.014},
issn = {0304-3835},
year = {2019},
date = {2019-01-01},
journal = {Cancer Lett},
volume = {446},
pages = {90-102},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Kyr M, Polaskova K, Kuttnerova Z, Merta T, Neradil J, Berkovcova J, Horky O, Jezova M, Veselska R, Klement G L, Valik D, Sterba J
Front Oncol 9, 644 (2019).
@article{RN4,
title = {Individualization of Treatment Improves the Survival of Children With High-Risk Solid Tumors: Comparative Patient Series Analysis in a Real-Life Scenario},
author = { M. Kyr and K. Polaskova and Z. Kuttnerova and T. Merta and J. Neradil and J. Berkovcova and O. Horky and M. Jezova and R. Veselska and G. L. Klement and D. Valik and J. Sterba},
doi = {10.3389/fonc.2019.00644},
issn = {2234-943X (Print)
2234-943x},
year = {2019},
date = {2019-01-01},
journal = {Front Oncol},
volume = {9},
pages = {644},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neradil J, Kyr M, Polaskova K, Kren L, Macigova P, Skoda J, Sterba J, Veselska R
Phospho-Protein Arrays as Effective Tools for Screening Possible Targets for Kinase Inhibitors and Their Use in Precision Pediatric Oncology Journal Article
Front Oncol 9, 930 (2019).
@article{RN3,
title = {Phospho-Protein Arrays as Effective Tools for Screening Possible Targets for Kinase Inhibitors and Their Use in Precision Pediatric Oncology},
author = { J. Neradil and M. Kyr and K. Polaskova and L. Kren and P. Macigova and J. Skoda and J. Sterba and R. Veselska},
doi = {10.3389/fonc.2019.00930},
issn = {2234-943X (Print)
2234-943x},
year = {2019},
date = {2019-01-01},
journal = {Front Oncol},
volume = {9},
pages = {930},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Skoda J, Borankova K, Jansson P J, Huang M L, Veselska R, Richardson D R
Pharmacological targeting of mitochondria in cancer stem cells: An ancient organelle at the crossroad of novel anti-cancer therapies Journal Article
Pharmacol Res 139, 298-313 (2019).
@article{RN7,
title = {Pharmacological targeting of mitochondria in cancer stem cells: An ancient organelle at the crossroad of novel anti-cancer therapies},
author = { J. Skoda and K. Borankova and P. J. Jansson and M. L. Huang and R. Veselska and D. R. Richardson},
doi = {10.1016/j.phrs.2018.11.020},
issn = {1043-6618},
year = {2019},
date = {2019-01-01},
journal = {Pharmacol Res},
volume = {139},
pages = {298-313},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Veselska R, Jezova M, Kyr M, Mazanek P, Chlapek P, Dobrotkova V, Sterba J
Front Oncol 9, 1221 (2019).
@article{RN2,
title = {Comparative Analysis of Putative Prognostic and Predictive Markers in Neuroblastomas: High Expression of PBX1 Is Associated With a Poor Response to Induction Therapy},
author = { Re Veselska and M Jezova and M Kyr and P Mazanek and P Chlapek and V Dobrotkova and J Sterba},
doi = {10.3389/fonc.2019.01221},
issn = {2234-943X (Print) 2234-943x},
year = {2019},
date = {2019-01-01},
journal = {Front Oncol},
volume = {9},
pages = {1221},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2018
Dobrotkova V, Chlapek P, Mazanek P, Sterba J, Veselska R
BMC Cancer 18(1), 1059 (2018).
@article{RN8,
title = {Traffic lights for retinoids in oncology: molecular markers of retinoid resistance and sensitivity and their use in the management of cancer differentiation therapy},
author = { V. Dobrotkova and P. Chlapek and P. Mazanek and J. Sterba and R. Veselska},
doi = {10.1186/s12885-018-4966-5},
issn = {1471-2407},
year = {2018},
date = {2018-01-01},
journal = {BMC Cancer},
volume = {18},
number = {1},
pages = {1059},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chlapek P, Slavikova V, Mazanek P, Sterba J, Veselska R
Why Differentiation Therapy Sometimes Fails: Molecular Mechanisms of Resistance to Retinoids Journal Article
Int J Mol Sci 19(1) (2018).
@article{RN11,
title = {Why Differentiation Therapy Sometimes Fails: Molecular Mechanisms of Resistance to Retinoids},
author = { P. Chlapek and V. Slavikova and P. Mazanek and J. Sterba and R. Veselska},
doi = {10.3390/ijms19010132},
issn = {1422-0067},
year = {2018},
date = {2018-01-01},
journal = {Int J Mol Sci},
volume = {19},
number = {1},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Skoda J, Veselska R
Cancer stem cells in sarcomas: Getting to the stemness core Journal Article
Biochim Biophys Acta Gen Subj 1862(10), 2134-2139 (2018).
@article{RN10,
title = {Cancer stem cells in sarcomas: Getting to the stemness core},
author = { J. Skoda and R. Veselska},
doi = {10.1016/j.bbagen.2018.07.006},
issn = {0304-4165 (Print)
0304-4165},
year = {2018},
date = {2018-01-01},
journal = {Biochim Biophys Acta Gen Subj},
volume = {1862},
number = {10},
pages = {2134-2139},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sramek M, Neradil J, Macigova P, Mudry P, Polaskova K, Slaby O, Noskova H, Sterba J, Veselska R
Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis Journal Article
Int J Mol Sci 19(9) (2018).
@article{RN9,
title = {Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis},
author = { M. Sramek and J. Neradil and P. Macigova and P. Mudry and K. Polaskova and O. Slaby and H. Noskova and J. Sterba and R. Veselska},
doi = {10.3390/ijms19092599},
issn = {1422-0067},
year = {2018},
date = {2018-01-01},
journal = {Int J Mol Sci},
volume = {19},
number = {9},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2017
Chlapek P, Zitterbart K, Kren L, Filipova L, Sterba J, Veselska R
Uniformity under in vitro conditions: Changes in the phenotype of cancer cell lines derived from different medulloblastoma subgroups Journal Article
PLoS One 12(2), e0172552 (2017).
@article{RN12,
title = {Uniformity under in vitro conditions: Changes in the phenotype of cancer cell lines derived from different medulloblastoma subgroups},
author = { P. Chlapek and K. Zitterbart and L. Kren and L. Filipova and J. Sterba and R. Veselska},
doi = {10.1371/journal.pone.0172552},
issn = {1932-6203},
year = {2017},
date = {2017-01-01},
journal = {PLoS One},
volume = {12},
number = {2},
pages = {e0172552},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mudry P, Slaby O, Neradil J, Soukalova J, Melicharkova K, Rohleder O, Jezova M, Seehofnerova A, Michu E, Veselska R, Sterba J
BMC Cancer 17(1), 119 (2017).
@article{RN13,
title = {Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene},
author = { P. Mudry and O. Slaby and J. Neradil and J. Soukalova and K. Melicharkova and O. Rohleder and M. Jezova and A. Seehofnerova and E. Michu and R. Veselska and J. Sterba},
doi = {10.1186/s12885-017-3115-x},
issn = {1471-2407},
year = {2017},
date = {2017-01-01},
journal = {BMC Cancer},
volume = {17},
number = {1},
pages = {119},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sramek M, Neradil J, Veselska R
Much more than you expected: The non-DHFR-mediated effects of methotrexate Journal Article
Biochim Biophys Acta Gen Subj 1861(3), 499-503 (2017).
@article{RN14,
title = {Much more than you expected: The non-DHFR-mediated effects of methotrexate},
author = { M. Sramek and J. Neradil and R. Veselska},
doi = {10.1016/j.bbagen.2016.12.014},
issn = {0304-4165 (Print)
0304-4165},
year = {2017},
date = {2017-01-01},
journal = {Biochim Biophys Acta Gen Subj},
volume = {1861},
number = {3},
pages = {499-503},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2016
Skoda J, Hermanova M, Loja T, Nemec P, Neradil J, Karasek P, Veselska R
Co-Expression of Cancer Stem Cell Markers Corresponds to a Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma Journal Article
PLOS ONE 11(7) (2016).
@article{ISI:000379579500112,
title = {Co-Expression of Cancer Stem Cell Markers Corresponds to a
Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma},
author = { Jan Skoda and Marketa Hermanova and Tomas Loja and Pavel Nemec and Jakub Neradil and Petr Karasek and Renata Veselska},
doi = {10.1371/journal.pone.0159255},
issn = {1932-6203},
year = {2016},
date = {2016-07-01},
journal = {PLOS ONE},
volume = {11},
number = {7},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Skoda J, Nunukova A, Loja T, Zambo I, Neradil J, Mudry P, Zitterbart K, Hermanova M, Hampl A, Sterba J, Veselska R
Cancer stem cell markers in pediatric sarcomas: Sox2 is associated with tumorigenicity in immunodeficient mice Journal Article
TUMOR BIOLOGY 37(7), 9535-9548 (2016).
@article{ISI:000382174500105,
title = {Cancer stem cell markers in pediatric sarcomas: Sox2 is associated with
tumorigenicity in immunodeficient mice},
author = { Jan Skoda and Alena Nunukova and Tomas Loja and Iva Zambo and Jakub Neradil and Peter Mudry and Karel Zitterbart and Marketa Hermanova and Ales Hampl and Jaroslav Sterba and Renata Veselska},
doi = {10.1007/s13277-016-4837-0},
issn = {1010-4283},
year = {2016},
date = {2016-07-01},
journal = {TUMOR BIOLOGY},
volume = {37},
number = {7},
pages = {9535-9548},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sramek M, Neradil J, Sterba J, Veselska R
Non-DHFR-mediated effects of methotrexate in osteosarcoma cell lines: epigenetic alterations and enhanced cell differentiation Journal Article
CANCER CELL INTERNATIONAL 16 (2016).
@article{ISI:000371005700001,
title = {Non-DHFR-mediated effects of methotrexate in osteosarcoma cell lines:
epigenetic alterations and enhanced cell differentiation},
author = { Martin Sramek and Jakub Neradil and Jaroslav Sterba and Renata Veselska},
doi = {10.1186/s12935-016-0289-2},
issn = {1475-2867},
year = {2016},
date = {2016-02-01},
journal = {CANCER CELL INTERNATIONAL},
volume = {16},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chlapek P, Slavikova V, Sterba J, Veselska R
Sensitivity to the natural and synthetic retinoids in relation to the expression of selected protein markers in neuroblastoma cell lines Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 38(1), S55 (2016).
@article{ISI:000383733000202,
title = {Sensitivity to the natural and synthetic retinoids in relation to the
expression of selected protein markers in neuroblastoma cell lines},
author = { Petr Chlapek and Viera Slavikova and Jaroslav Sterba and Renata Veselska},
issn = {1107-3756},
year = {2016},
date = {2016-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {38},
number = {1},
pages = {S55},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neradil J, Melicharkova K, Mudry P, Veselska R, Sterba J
Detailed analysis of phosphorylated receptor tyrosine kinases and downstream signaling pathways in selected pediatric malignancies Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 38(1), S55 (2016).
@article{ISI:000383733000203,
title = {Detailed analysis of phosphorylated receptor tyrosine kinases and
downstream signaling pathways in selected pediatric malignancies},
author = { Jakub Neradil and Kristyna Melicharkova and Peter Mudry and Renata Veselska and Jaroslav Sterba},
issn = {1107-3756},
year = {2016},
date = {2016-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {38},
number = {1},
pages = {S55},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Veselska R, Nunukova A, Skoda J, Loja T, Zambo I, Neradil J, Hermanova M, Hampl A, Sterba J
Tumorigenicity and expression of the core stem cell markers in rhabdomyosarcoma cells Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 38(1), S54 (2016).
@article{ISI:000383733000201,
title = {Tumorigenicity and expression of the core stem cell markers in
rhabdomyosarcoma cells},
author = { Renata Veselska and Alena Nunukova and Jan Skoda and Tomas Loja and Iva Zambo and Jakub Neradil and Marketa Hermanova and Ales Hampl and Jaroslav Sterba},
issn = {1107-3756},
year = {2016},
date = {2016-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {38},
number = {1},
pages = {S54},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Zambo I, Hermanova M, Zapletalova D, Skoda J, Mudry P, Kyr M, Zitterbart K, Sterba J, Veselska R
Expression of nestin, CD133 and ABCG2 in relation to the clinical outcome in pediatric sarcomas Journal Article
CANCER BIOMARKERS 17(1), 107-116 (2016).
@article{ISI:000381114300014,
title = {Expression of nestin, CD133 and ABCG2 in relation to the clinical
outcome in pediatric sarcomas},
author = { Iva Zambo and Marketa Hermanova and Danica Zapletalova and Jan Skoda and Peter Mudry and Michal Kyr and Karel Zitterbart and Jaroslav Sterba and Renata Veselska},
doi = {10.3233/CBM-160623},
issn = {1574-0153},
year = {2016},
date = {2016-01-01},
journal = {CANCER BIOMARKERS},
volume = {17},
number = {1},
pages = {107-116},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2015
Neradil J, Sramek M, Mrkvicova M, Zitterbart K, Sterba J, Veselska R
METHOTREXATE AND ALL-TRANS RETINOIC ACID COMBINED TREATMENT FOR INDUCTION OF OSTEOSARCOMA CELL LINES DIFFERENTIATION IN VITRO Journal Article
PEDIATRIC BLOOD & CANCER 62(4), S268 (2015).
@article{ISI:000361247200493,
title = {METHOTREXATE AND ALL-TRANS RETINOIC ACID COMBINED TREATMENT FOR INDUCTION OF OSTEOSARCOMA CELL LINES DIFFERENTIATION IN VITRO},
author = { Jakub Neradil and Martin Sramek and Martina Mrkvicova and Karel Zitterbart and Jaroslav Sterba and Renata Veselska},
issn = {1545-5009},
year = {2015},
date = {2015-11-01},
journal = {PEDIATRIC BLOOD & CANCER},
volume = {62},
number = {4},
pages = {S268},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Skoda J, Neradil J, Zambo I, Hermanova M, Sterba J, Veselska R
IDENTIFICATION OF CANCER STEM CELLS IN OSTEOSARCOMA CELL LINES: CHARACTERIZATION OF CANCER STEM CELL MARKERS EXPRESSION AND IN VIVO TUMORIGENICITY Journal Article
PEDIATRIC BLOOD & CANCER 62(4), S269 (2015).
@article{ISI:000361247200495,
title = {IDENTIFICATION OF CANCER STEM CELLS IN OSTEOSARCOMA CELL LINES: CHARACTERIZATION OF CANCER STEM CELL MARKERS EXPRESSION AND IN VIVO TUMORIGENICITY},
author = { Jan Skoda and Jakub Neradil and Iva Zambo and Marketa Hermanova and Jaroslav Sterba and Renata Veselska},
issn = {1545-5009},
year = {2015},
date = {2015-11-01},
journal = {PEDIATRIC BLOOD & CANCER},
volume = {62},
number = {4},
pages = {S269},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sramek M, Neradil J, Mrkvicova M, Zitterbart K, Sterba J, Veselska R
METHOTREXATE INDUCES EPIGENETIC ALTERATIONS IN OSTEOSARCOMA CELL LINES Journal Article
PEDIATRIC BLOOD & CANCER 62(4), S269 (2015).
@article{ISI:000361247200496,
title = {METHOTREXATE INDUCES EPIGENETIC ALTERATIONS IN OSTEOSARCOMA CELL LINES},
author = { M. Sramek and J. Neradil and M. Mrkvicova and K. Zitterbart and J. Sterba and R. Veselska},
issn = {1545-5009},
year = {2015},
date = {2015-11-01},
journal = {PEDIATRIC BLOOD & CANCER},
volume = {62},
number = {4},
pages = {S269},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mikulenkova E, Neradil J, Zitterbart K, Sterba J, Veselska R
Overexpression of the Delta Np73 isoform is associated with centrosome amplification in brain tumor cell lines Journal Article
TUMOR BIOLOGY 36(10), 7483-7491 (2015).
@article{ISI:000362969900018,
title = {Overexpression of the Delta Np73 isoform is associated with centrosome
amplification in brain tumor cell lines},
author = { Erika Mikulenkova and Jakub Neradil and Karel Zitterbart and Jaroslav Sterba and Renata Veselska},
doi = {10.1007/s13277-015-3474-3},
issn = {1010-4283},
year = {2015},
date = {2015-09-01},
journal = {TUMOR BIOLOGY},
volume = {36},
number = {10},
pages = {7483-7491},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neradil J, Veselska R
Nestin as a marker of cancer stem cells Journal Article
CANCER SCIENCE 106(7), 803-811 (2015).
@article{ISI:000357883900003,
title = {Nestin as a marker of cancer stem cells},
author = { Jakub Neradil and Renata Veselska},
doi = {10.1111/cas.12691},
issn = {1347-9032},
year = {2015},
date = {2015-07-01},
journal = {CANCER SCIENCE},
volume = {106},
number = {7},
pages = {803-811},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nunukova A, Neradil J, Skoda J, Jaros J, Hampl A, Sterba J, Veselska R
Atypical nuclear localization of CD133 plasma membrane glycoprotein in rhabdomyosarcoma cell lines Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 36(1), 65-72 (2015).
@article{ISI:000358134900007,
title = {Atypical nuclear localization of CD133 plasma membrane glycoprotein in
rhabdomyosarcoma cell lines},
author = { Alena Nunukova and Jakub Neradil and Jan Skoda and Josef Jaros and Ales Hampl and Jaroslav Sterba and Renata Veselska},
doi = {10.3892/ijmm.2015.2210},
issn = {1107-3756},
year = {2015},
date = {2015-07-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {36},
number = {1},
pages = {65-72},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neradil J, Pavlasova G, Sramek M, Kyr M, Veselska R, Sterba J
ONCOLOGY REPORTS 33(5), 2169-2175 (2015).
@article{ISI:000353180900010,
title = {DHFR-mediated effects of methotrexate in medulloblastoma and
osteosarcoma cells: The same outcome of treatment with different doses
in sensitive cell lines},
author = { Jakub Neradil and Gabriela Pavlasova and Martin Sramek and Michal Kyr and Renata Veselska and Jaroslav Sterba},
doi = {10.3892/or.2015.3819},
issn = {1021-335X},
year = {2015},
date = {2015-05-01},
journal = {ONCOLOGY REPORTS},
volume = {33},
number = {5},
pages = {2169-2175},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Veselska R, Skoda J, Nunukova A, Loja T, Zambo I, Neradil J, Hermanova M, Mudry P, Zitterbart K, Zapletalove D, Kyr M, Jaros J, Hamp A, Sterba J
Cancer stem cell markers in pediatric sarcomas: Comparative analysis of their expression in tumor tissues and derived cell lines Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 36(1), S71 (2015).
@article{ISI:000361863000268,
title = {Cancer stem cell markers in pediatric sarcomas: Comparative analysis of
their expression in tumor tissues and derived cell lines},
author = { Renata Veselska and Jan Skoda and Alena Nunukova and Tomas Loja and Iva Zambo and Jakub Neradil and Marketa Hermanova and Peter Mudry and Karel Zitterbart and Danica Zapletalove and Michal Kyr and Josef Jaros and Ales Hamp and Jaroslav Sterba},
issn = {1107-3756},
year = {2015},
date = {2015-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {36},
number = {1},
pages = {S71},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2014
Krzyzankova M, Chovanova S, Chlapek P, Radsetoulal M, Neradil J, Zitterbart K, Sterba J, Veselska R
LOX/COX inhibitors enhance the antineoplastic effects of all-trans retinoic acid in osteosarcoma cell lines Journal Article
TUMOR BIOLOGY 35(8), 7617-7627 (2014).
@article{ISI:000341883500046,
title = {LOX/COX inhibitors enhance the antineoplastic effects of all-trans
retinoic acid in osteosarcoma cell lines},
author = { Miroslava Krzyzankova and Silvia Chovanova and Petr Chlapek and Matej Radsetoulal and Jakub Neradil and Karel Zitterbart and Jaroslav Sterba and Renata Veselska},
doi = {10.1007/s13277-014-2019-5},
issn = {1010-4283},
year = {2014},
date = {2014-08-01},
journal = {TUMOR BIOLOGY},
volume = {35},
number = {8},
pages = {7617-7627},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chlapek P, Neradil J, Redova M, Zitterbart K, Sterba J, Veselska R
The ATRA-induced differentiation of medulloblastoma cells is enhanced with LOX/COX inhibitors: an analysis of gene expression Journal Article
CANCER CELL INTERNATIONAL 14 (2014).
@article{ISI:000338146500001,
title = {The ATRA-induced differentiation of medulloblastoma cells is enhanced
with LOX/COX inhibitors: an analysis of gene expression},
author = { Petr Chlapek and Jakub Neradil and Martina Redova and Karel Zitterbart and Jaroslav Sterba and Renata Veselska},
doi = {10.1186/1475-2867-14-51},
issn = {1475-2867},
year = {2014},
date = {2014-06-01},
journal = {CANCER CELL INTERNATIONAL},
volume = {14},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neradil J, Veselska R, Mudry P, Melicharkova K, Sterba J
Mapping of receptor tyrosine kinases activation and downstream signaling in rhabdomyosarcoma Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34(1), S78 (2014).
@article{ISI:000341276000295,
title = {Mapping of receptor tyrosine kinases activation and downstream signaling
in rhabdomyosarcoma},
author = { Jakub Neradil and Renata Veselska and Peter Mudry and Kristyna Melicharkova and Jaroslav Sterba},
issn = {1107-3756},
year = {2014},
date = {2014-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {34},
number = {1},
pages = {S78},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Skoda J, Neradil J, Zitterbart K, Sterba J, Veselska R
EGFR signaling in glioblastoma cells with a loss of EGFR gene copy and unusually mild clinical course of disease Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34(1), S78 (2014).
@article{ISI:000341276000294,
title = {EGFR signaling in glioblastoma cells with a loss of EGFR gene copy and
unusually mild clinical course of disease},
author = { Jan Skoda and Jakub Neradil and Karel Zitterbart and Jaroslav Sterba and Renate Veselska},
issn = {1107-3756},
year = {2014},
date = {2014-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {34},
number = {1},
pages = {S78},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sramek M, Neradil J, Mrkvicova M, Zitterbart K, Sterba J, Veselska R
Methotrexate-dependent changes of DNA methylation and gene expression in osteosarcoma cell lines Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34(1), S79 (2014).
@article{ISI:000341276000299,
title = {Methotrexate-dependent changes of DNA methylation and gene expression in
osteosarcoma cell lines},
author = { Martin Sramek and Jakub Neradil and Martina Mrkvicova and Karel Zitterbart and Jaroslav Sterba and Renata Veselska},
issn = {1107-3756},
year = {2014},
date = {2014-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {34},
number = {1},
pages = {S79},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Veselska R, Nunukova A, Skoda J, Neradil J, Jaros J, Hermanova M, Zambo I, Mudry P, Zitterbart K, Hampl A, Sterba J
Nuclear localization of CD133 in sarcoma cells Journal Article
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34(1), S81 (2014).
@article{ISI:000341276000309,
title = {Nuclear localization of CD133 in sarcoma cells},
author = { Renata Veselska and Alena Nunukova and Jan Skoda and Jakub Neradil and Josef Jaros and Marketa Hermanova and Iva Zambo and Peter Mudry and Karel Zitterbart and Ales Hampl and Jaroslav Sterba},
issn = {1107-3756},
year = {2014},
date = {2014-01-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
volume = {34},
number = {1},
pages = {S81},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Skoda J, Neradil J, Zitterbart K, Sterba J, Veselska R
EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy Journal Article
ONCOLOGY REPORTS 31(1), 480-487 (2014).
@article{ISI:000330788100065,
title = {EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss
of EGFR gene copy},
author = { Jan Skoda and Jakub Neradil and Karel Zitterbart and Jaroslav Sterba and Renata Veselska},
doi = {10.3892/or.2013.2864},
issn = {1021-335X},
year = {2014},
date = {2014-01-01},
journal = {ONCOLOGY REPORTS},
volume = {31},
number = {1},
pages = {480-487},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2013
Veselska R, Neradil J, Nekulova M, Dobrucka L, Vojtesek B, Sterba J, Zitterbart K
Intracellular distribution of the Delta Np73 protein isoform in medulloblastoma cells: a study with newly generated rabbit polyclonal antibodies Journal Article
HISTOLOGY AND HISTOPATHOLOGY 28(7), 913-924 (2013).
@article{ISI:000320710900011,
title = {Intracellular distribution of the Delta Np73 protein isoform in
medulloblastoma cells: a study with newly generated rabbit polyclonal
antibodies},
author = { Renata Veselska and Jakub Neradil and Marta Nekulova and Lucia Dobrucka and Borivoj Vojtesek and Jaroslav Sterba and Karel Zitterbart},
issn = {0213-3911},
year = {2013},
date = {2013-07-01},
journal = {HISTOLOGY AND HISTOPATHOLOGY},
volume = {28},
number = {7},
pages = {913-924},
keywords = {},
pubstate = {published},
tppubtype = {article}
}