9 results on '"Vočková P"'
Search Results
2. Book Review. Getting Dialogic Teaching into Classrooms: Making Change Possible, by Klára Šeďová, Zuzana Šalamounová, Roman Švaříček, Martin Sedláček
- Author
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Pavlína Vočková
- Subjects
Special aspects of education ,LC8-6691 ,Language and Literature - Published
- 2023
- Full Text
- View/download PDF
3. Cytarabine nanotherapeutics with increased stability and enhanced lymphoma uptake for tailored highly effective therapy of mantle cell lymphoma.
- Author
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Pola, Robert, Pokorná, Eva, Vočková, Petra, Böhmová, Eliška, Pechar, Michal, Karolová, Jana, Pankrác, Jan, Šefc, Luděk, Helman, Karel, Trněný, Marek, Etrych, Tomáš, and Klener, Pavel
- Subjects
MANTLE cell lymphoma ,CYTARABINE ,LYMPHOMAS ,CELLULAR therapy ,COPOLYMERS ,RITUXIMAB ,DISEASE relapse - Abstract
Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma (B-NHL) with chronically relapsing clinical course. Implementation of cytarabine (araC) into induction and salvage regimen became standard of care for majority of MCL patients. In this study, tailored N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer nanotherapeutics containing covalently bound araC (araC co-polymers) were designed, synthesized and evaluated for their anti-lymphoma efficacy in vivo using a panel of six patient-derived lymphoma xenografts (PDX) derived from newly diagnosed and relapsed / refractory (R/R) MCL. While free araC led to temporary inhibition of growth of MCL tumors, araC co-polymers induced long-term disappearance of the engrafted lymphomas with no observed toxicity even in the case of PDX models derived from patients, who relapsed after high-dose araC-based treatments. The results provide sound preclinical rationale for the use of HPMA-based araC co-polymers in induction, salvage or palliative therapy of MCL patients. Image, graphical abstract [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
4. ESTABLISHED CELL LINES AND PATIENT-DERIVED XENOGRAFTS REPRESENT EQUALLY RELEVANT MODELS OF AGGRESSIVE LYMPHOMAS
- Author
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Klener, P., primary, Klánová, M., additional, Molinský, J., additional, Svatoň, M., additional, Berková, A., additional, Zemanová, Z., additional, Jakša, R., additional, Špaček, M., additional, Březinová, J., additional, Tichá, I., additional, Jančušková, T., additional, Hardekopf, D.W., additional, Forsterová, K., additional, Froňková, E., additional, Kotrová, M., additional, Kubričanová-Žaliová, M., additional, Maswabi, B.C., additional, Průková, D., additional, Vočková, P., additional, Tušková, D., additional, Michalová, K., additional, Trka, J., additional, Trněný, M., additional, and Klener, P., additional
- Published
- 2017
- Full Text
- View/download PDF
5. Sensitivity to PI3K and AKT inhibitors is mediated by divergent molecular mechanisms in subtypes of DLBCL
- Author
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Erdmann, Tabea, Klener, Pavel, Lynch, James T., Grau, Michael, Vočková, Petra, Molinsky, Jan, Tuskova, Diana, Hudson, Kevin, Polanska, Urszula M., Grondine, Michael, Mayo, Michele, Dai, Beiying, Pfeifer, Matthias, Erdmann, Kristian, Schwammbach, Daniela, Zapukhlyak, Myroslav, Staiger, Annette M., Ott, German, Berdel, Wolfgang E., Davies, Barry R., Cruzalegui, Francisco, Trneny, Marek, Lenz, Peter, Barry, Simon T., and Lenz, Georg
- Abstract
Activated B-cell-like (ABC) and germinal center B-cell-like diffuse large B-cell lymphoma (DLBCL) represent the 2 major molecular DLBCL subtypes. They are characterized by differences in clinical course and by divergent addiction to oncogenic pathways. To determine activity of novel compounds in these 2 subtypes, we conducted an unbiased pharmacologic in vitro screen. The phosphatidylinositol-3-kinase (PI3K) α/δ (PI3Kα/δ) inhibitor AZD8835 showed marked potency in ABC DLBCL models, whereas the protein kinase B (AKT) inhibitor AZD5363 induced apoptosis in PTEN-deficient DLBCLs irrespective of their molecular subtype. These in vitro results were confirmed in various cell line xenograft and patient-derived xenograft mouse models in vivo. Treatment with AZD8835 induced inhibition of nuclear factor κB signaling, prompting us to combine AZD8835 with the Bruton's tyrosine kinase inhibitor ibrutinib. This combination was synergistic and effective both in vitro and in vivo. In contrast, the AKT inhibitor AZD5363 was effective in PTEN-deficient DLBCLs through downregulation of the oncogenic transcription factor MYC. Collectively, our data suggest that patients should be stratified according to their oncogenic dependencies when treated with PI3K and AKT inhibitors.
- Published
- 2017
- Full Text
- View/download PDF
6. Lenalidomide enhances antitumor functions of chimeric antigen receptor modified T cells
- Author
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Otáhal, Pavel, Průková, Dana, Král, Vlastimil, Fabry, Milan, Vočková, Petra, Latečková, Lucie, Trněný, Marek, and Klener, Pavel
- Abstract
ABSTRACTTumor immunotherapy based on the use of chimeric antigen receptor modified T cells (CAR T cells) is a promising approach for the treatment of refractory hematological malignancies. However, a robust response mediated by CAR T cells is observed only in a minority of patients and the expansion and persistence of CAR T cells in vivois mostly unpredictable.Lenalidomide (LEN) is an immunomodulatory drug currently approved for the treatment of multiple myeloma (MM) and mantle cell lymphoma, while it is clinically tested in the therapy of diffuse large B-cell lymphoma of activated B cell immunophenotype. LEN was shown to increase antitumor immune responses at least partially by modulating the activity of E3 ubiquitin ligase Cereblon, which leads to increased ubiquitinylation of Ikaros and Aiolos transcription factors, which in turn results in changed expression of various receptors on the surface of tumor cells. In order to enhance the effectiveness of CAR-based immunotherapy, we assessed the anti-lymphoma efficacy of LEN in combination with CAR19 T cells or CAR20 T cells in vitroand in vivousing various murine models of aggressive B-cell non-Hodgkin lymphomas (B-NHL).Immunodeficient NSG mice were transplanted with various human B-NHL cells followed by treatment with CAR19 or CAR20 T cells with or without LEN. Next, CAR19 T cells were subjected to series of tests in vitroto evaluate their response and signaling capacity following recognition of B cell in the presence or absence of LEN.Our data shows that LEN significantly enhances antitumor functions of CAR19 and CAR20 T cells in vivo. Additionally, it enhances production of interferon gamma by CAR19 T cells and augments cell signaling via CAR19 protein in T cells in vitro. Our data further suggests that LEN works through direct effects on T cells but not on B-NHL cells. The biochemical events underlying this costimulatory effect of LEN are currently being investigated. In summary, our data supports the use of LEN for augmentation of CAR-based immunotherapy in the clinical grounds.
- Published
- 2016
- Full Text
- View/download PDF
7. Quantitative In Vivo Monitoring of Hypoxia and Vascularization of Patient-Derived Murine Xenografts of Mantle Cell Lymphoma Using Photoacoustic and Ultrasound Imaging.
- Author
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Keša P, Pokorná E, Grajciarová M, Tonar Z, Vočková P, Trochet P, Kopeček M, Jakša R, Šefc L, and Klener P
- Subjects
- Animals, Cell Hypoxia, Female, Hemoglobins metabolism, Humans, Lymphoma, Mantle-Cell pathology, Mice, Microvascular Density, Microvessels diagnostic imaging, Multimodal Imaging, Neoplasm Transplantation, Oxyhemoglobins metabolism, Tumor Burden, Lymphoma, Mantle-Cell diagnostic imaging, Lymphoma, Mantle-Cell physiopathology, Neovascularization, Pathologic diagnostic imaging, Oxygen metabolism, Photoacoustic Techniques, Ultrasonography, Doppler, Color
- Abstract
Tumor oxygenation and vascularization are important parameters that determine the aggressiveness of the tumor and its resistance to cancer therapies. We introduce dual-modality ultrasound and photoacoustic imaging (US-PAI) for the direct, non-invasive real-time in vivo evaluation of oxygenation and vascularization of patient-derived xenografts (PDXs) of B-cell mantle cell lymphomas. The different optical properties of oxyhemoglobin and deoxyhemoglobin make it possible to determine oxygen saturation (sO
2 ) in tissues using PAI. High-frequency color Doppler imaging enables the visualization of blood flow with high resolution. Tumor oxygenation and vascularization were studied in vivo during the growth of three different subcutaneously implanted patient-derived xenograft (PDX) lymphomas (VFN-M1, VFN-M2 and VFN-M5 R1). Similar values of sO2 (sO2 Vital), determined from US-PAI volumetric analysis, were obtained in small and large VFN-M1 tumors ranging from 37.9 ± 2.2 to 40.5 ± 6.0 sO2 Vital (%) and 37.5 ± 4.0 to 35.7 ± 4.6 sO2 Vital (%) for small and large VFN-M2 PDXs. In contrast, the higher sO2 Vital values ranging from 57.1 ± 4.8 to 40.8 ± 5.7 sO2 Vital (%) (small to large) of VFN-M5 R1 tumors corresponds with the higher aggressiveness of that PDX model. The different tumor percentage vascularization (assessed as micro-vessel areas) of VFN-M1, VFN-M2 and VFN-M5 R1 obtained by color Doppler (2.8 ± 0.1%, 3.8 ± 0.8% and 10.3 ± 2.7%) in large-stage tumors clearly corresponds with their diverse growth and aggressiveness. The data obtained by color Doppler were validated by histology. In conclusion, US-PAI rapidly and accurately provided relevant and reproducible information on tissue oxygenation in PDX tumors in real time without the need for a contrast agent., Competing Interests: Conflict of interest disclosure Philippe Trochet and Milan Kopeček are employed in FUJIFILM VisualSonics, Inc. The other authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
8. Overcoming resistance to rituximab in relapsed non-Hodgkin lymphomas by antibody-polymer drug conjugates actively targeted by anti-CD38 daratumumab.
- Author
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Lidický O, Klener P, Machová D, Vočková P, Pokorná E, Helman K, Mavis C, Janoušková O, and Etrych T
- Subjects
- Antibodies, Monoclonal therapeutic use, Humans, Polymers therapeutic use, Rituximab, Antineoplastic Agents therapeutic use, Lymphoma, Non-Hodgkin drug therapy, Pharmaceutical Preparations
- Abstract
B-cell non-Hodgkin lymphomas (B-NHL) represent the most common type of hematologic malignancies in the Western hemisphere. The therapy of all B-NHL is based on the combination of different genotoxic cytostatics and anti-CD20 monoclonal antibody (mAb) rituximab. Unfortunately, many patients relapse after the mentioned front-line treatment approaches. The therapy of patients with relapsed/refractory (R/R) B-NHL represents an unmet medical need. We designed, developed and tested novel actively targeted hybrid mAb-polymer-drug conjugate (APDC) containing anti-CD20, anti-CD38 or anti-CD19 mAbs. Biocompatible copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) with cytostatic agent doxorubicin attached via stimuli-sensitive hydrazone bond were employed for the mAb grafting. Anti-lymphoma efficacy of the APDC nanotherapeutics was evaluated in vivo on a panel of three patient-derived lymphoma xenografts derived from two patients with R/R B-NHL and one patient with so far untreated B-NHL. In both PDX models derived from patients with R/R B-NHL, the targeting with anti-CD38 antibody daratumumab demonstrated highly improved anti-lymphoma efficacy compared to the targeting with anti-CD20 rituximab, two experimental anti-CD19 antibodies and non-targeted controls. The results represent a proof-of-concept of a new algorithm of personalized anti-tumor therapy based on highly innovative APDC biomaterials., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
9. Lenalidomide enhances antitumor functions of chimeric antigen receptor modified T cells.
- Author
-
Otáhal P, Průková D, Král V, Fabry M, Vočková P, Latečková L, Trněný M, and Klener P
- Abstract
Tumor immunotherapy based on the use of chimeric antigen receptor modified T cells (CAR T cells) is a promising approach for the treatment of refractory hematological malignancies. However, a robust response mediated by CAR T cells is observed only in a minority of patients and the expansion and persistence of CAR T cells in vivo is mostly unpredictable.Lenalidomide (LEN) is an immunomodulatory drug currently approved for the treatment of multiple myeloma (MM) and mantle cell lymphoma, while it is clinically tested in the therapy of diffuse large B-cell lymphoma of activated B cell immunophenotype. LEN was shown to increase antitumor immune responses at least partially by modulating the activity of E3 ubiquitin ligase Cereblon, which leads to increased ubiquitinylation of Ikaros and Aiolos transcription factors, which in turn results in changed expression of various receptors on the surface of tumor cells. In order to enhance the effectiveness of CAR-based immunotherapy, we assessed the anti-lymphoma efficacy of LEN in combination with CAR19 T cells or CAR20 T cells in vitro and in vivo using various murine models of aggressive B-cell non-Hodgkin lymphomas (B-NHL).Immunodeficient NSG mice were transplanted with various human B-NHL cells followed by treatment with CAR19 or CAR20 T cells with or without LEN. Next, CAR19 T cells were subjected to series of tests in vitro to evaluate their response and signaling capacity following recognition of B cell in the presence or absence of LEN.Our data shows that LEN significantly enhances antitumor functions of CAR19 and CAR20 T cells in vivo . Additionally, it enhances production of interferon gamma by CAR19 T cells and augments cell signaling via CAR19 protein in T cells in vitro . Our data further suggests that LEN works through direct effects on T cells but not on B-NHL cells. The biochemical events underlying this costimulatory effect of LEN are currently being investigated. In summary, our data supports the use of LEN for augmentation of CAR-based immunotherapy in the clinical grounds.
- Published
- 2015
- Full Text
- View/download PDF
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