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4. POSTER: MM-438 Addressing the Distress of Patients With Multiple Myeloma Can Improve Their Quality of Life, Parameters of Their Immune Profile and Autonomic Nervous System

Author

Kotoucek, Pavel, primary, Sedlak, Jan, additional, Stanislava, Gregor Sorgerova, additional, Hunakova, Luba, additional, Chlebcova, Veronika, additional, Cholujova, Danka, additional, Jakubikova, Jana, additional, Mravec, Boris, additional, Nanistova, Eva, additional, Panekova, Ludmila, additional, and Enright, Robert, additional

Published
2023
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5. MM-438 Addressing the Distress of Patients With Multiple Myeloma Can Improve Their Quality of Life, Parameters of Their Immune Profile and Autonomic Nervous System

Author

Kotoucek, Pavel, primary, Sedlak, Jan, additional, Stanislava, Gregor Sorgerova, additional, Hunakova, Luba, additional, Chlebcova, Veronika, additional, Cholujova, Danka, additional, Jakubikova, Jana, additional, Mravec, Boris, additional, Nanistova, Eva, additional, Panekova, Ludmila, additional, and Enright, Robert, additional

Published
2023
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7. Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia

Author

Cholujova, Danka, primary, Beke, Gabor, additional, Hunter, Zachary R., additional, Hideshima, Teru, additional, Flores, Ludmila, additional, Zeleznikova, Tatiana, additional, Harrachova, Denisa, additional, Klucar, Lubos, additional, Leiba, Merav, additional, Drgona, Lubos, additional, Treon, Steven P., additional, Kastritis, Efstathios, additional, Dorfman, David M., additional, Anderson, Kenneth C., additional, and Jakubikova, Jana, additional

Published
2022
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9. Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia.

Author

Cholujova, Danka, Beke, Gabor, Hunter, Zachary R., Hideshima, Teru, Flores, Ludmila, Zeleznikova, Tatiana, Harrachova, Denisa, Klucar, Lubos, Leiba, Merav, Drgona, Lubos, Treon, Steven P., Kastritis, Efstathios, Dorfman, David M., Anderson, Kenneth C., and Jakubikova, Jana

Subjects
IMMUNOLOGIC memory, TUMOR microenvironment, BONE marrow cells, MYELOID cells, CANCER cells
Abstract

Waldenström macroglobulinemia (WM) is a rare subtype of non‐Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In‐depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD‐1/PD‐L1&PD‐L2, TIGIT/PVR, CD137/CD137‐L, CTLA‐4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Myeloma Heterogeneity within Its Complex Immune Ecosystem

Author

Jakubikova, Jana Cholujova, Danka Beke, Gabor Hunter, Zachary R. Hideshima, Teru Leiba, Merav Jamroziak, Krzysztof and Richardson, Paul G. Kastritis, Eftathios Dorfman, David M. and Anderson, Kenneth C.

Published
2019

16. High-Dimensional Heterogeneity of Waldenström Macroglobulinemia within Its Immune Tumor Microenvironment

Author

Jakubikova, Jana, primary, Cholujova, Danka, additional, Beke, Gabor, additional, Hunter, Zachary R, additional, Hideshima, Teru, additional, Flores, Ludmila, additional, Leiba, Merav, additional, Richardson, Paul G., additional, Kastritis, Eftathios, additional, Dorfman, David M., additional, Treon, Steven P, additional, and Anderson, Kenneth C., additional

Published
2019
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17. Myeloma Heterogeneity within Its Complex Immune Ecosystem

Author

Jakubikova, Jana, primary, Cholujova, Danka, additional, Beke, Gabor, additional, Hunter, Zachary R, additional, Hideshima, Teru, additional, Leiba, Merav, additional, Jamroziak, Krzysztof, additional, Richardson, Paul G., additional, Kastritis, Eftathios, additional, Dorfman, David M., additional, and Anderson, Kenneth C., additional

Published
2019
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18. Clonal Heterogeneity and Immune Tumor Microenvironment in Waldenström Macroglobulinemia

Author

Jakubikova, Jana, primary, Cholujova, Danka, additional, Beke, Gabor, additional, Hunter, Zachary, additional, Hideshima, Teru, additional, Flores, Ludmila, additional, Leiba, Merav, additional, Richardson, Paul G., additional, Kastritis, Efstathios, additional, Dorfman, David M., additional, Treon, Steven, additional, and Anderson, Kenneth C., additional

Published
2019
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20. Realgar nanoparticlesversusATO arsenic compounds inducein vitroandin vivoactivityagainstmultiple myeloma

Author

Cholujova, Danka, primary, Bujnakova, Zdenka, additional, Dutkova, Erika, additional, Hideshima, Teru, additional, Groen, Richard W., additional, Mitsiades, Constantine S., additional, Richardson, Paul G., additional, Dorfman, David M., additional, Balaz, Peter, additional, Anderson, Kenneth C., additional, and Jakubikova, Jana, additional

Published
2017
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22. A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche : biologic and clinical applications

Author

Jakubikova, Jana, Cholujova, Danka, Hideshima, Teru, Gronesova, Paulina, Soltysova, Andrea, Harada, Takeshi, Joo, Jungnam, Kong, Sun-Young, Szalat, Raphael E., Richardson, Paul G., Munshi, Nikhil C., Dorfman, David M., Anderson, Kenneth C., Jakubikova, Jana, Cholujova, Danka, Hideshima, Teru, Gronesova, Paulina, Soltysova, Andrea, Harada, Takeshi, Joo, Jungnam, Kong, Sun-Young, Szalat, Raphael E., Richardson, Paul G., Munshi, Nikhil C., Dorfman, David M., and Anderson, Kenneth C.

Abstract

Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system. In the 3D model, MSC with conserved phenotype (CD73+CD90+CD105+) formed compact clusters with active fibrous connections, and retained lineage differentiation capacity. Extracellular matrix molecules, integrins, and niche related molecules including N-cadherin and CXCL12 are expressed in 3D MSC model. Furthermore, activation of osteogenesis (MMP13, SPP1, ADAMTS4, and MGP genes) and osteoblastogenic differentiation was confirmed in 3D MSC model. Co-culture of patient-derived BM mononuclear cells with either autologous or allogeneic MSC in 3D model increased proliferation of MM cells, CXCR4 expression, and SP cells. We carried out immune profiling to show that distribution of immune cell subsets was similar in 3D and 2D MSC model systems. Importantly, resistance to novel agents (IMiDs, bortezomib, carfilzomib) and conventional agents (doxorubicin, dexamethasone, melphalan) was observed in 3D MSC system, reflective of clinical resistance. This 3D MSC model may therefore allow for studies of MM pathogenesis and drug resistance within the BM niche. Importantly, ongoing prospective trials are evaluating its utility to inform personalized targeted and immune therapy in MM.

Published
2016

23. A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche: biologic and clinical applications

Author

Jakubikova, Jana, primary, Cholujova, Danka, additional, Hideshima, Teru, additional, Gronesova, Paulina, additional, Soltysova, Andrea, additional, Harada, Takeshi, additional, Joo, Jungnam, additional, Kong, Sun-Young, additional, Szalat, Raphael E., additional, Richardson, Paul G., additional, Munshi, Nikhil C., additional, Dorfman, David M., additional, and Anderson, Kenneth C., additional

Published
2016
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25. Abstract 2004: Phenotypic and molecular characterization of inter- and intraclonal heterogeneity in multiple myeloma and Waldenstrom macroglobulinemia

Author

Jakubikova, Jana, primary, Cholujova, Danka, additional, Hideshima, Teru, additional, Laubach, Jacob, additional, Munshi, Nikhil C., additional, Treon, Steven P., additional, Richardson, Paul G., additional, Kastritis, Efstathios, additional, Dorfman, David M., additional, and Anderson, Kenneth C., additional

Published
2015
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26. Mimicking Myeloma Niche Ex Vivo

Author

Jakubikova, Jana, primary, Cholujova, Danka, additional, Groen, Richard W, additional, Joo, Jungnam, additional, Kong, Sun-Young, additional, Hideshima, Teru, additional, Suzuki, Rikio, additional, Sedlak, Jan, additional, Mitsiades, Constantine S, additional, Dorfman, David M, additional, Laubach, Jacob P., additional, Munshi, Nikhil C., additional, Richardson, Paul G., additional, and Anderson, Kenneth, additional

Published
2014
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29. Nanoparticle Arsenic Compound Realgar Effectively Targets Myeloma Stem-Like Side Population

Author

Jakubikova, Jana, primary, Hideshima, Teru, additional, Groen, Richard W.J., additional, Cholujova, Danka, additional, Bujnakova, Zdenka, additional, Laubach, Jacob P., additional, Munshi, Nikhil C., additional, Richardson, Paul G., additional, Mitsiades, Constantine S., additional, Balaz, Peter, additional, Sedlak, Jan, additional, and Anderson, Kenneth C., additional

Published
2013
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30. Myeloma Patient-Derived Mesenchymal Stem Cells Grown In 3-D Culture Induce Primary Myeloma Cell Proliferation and Resistance To Therapy

Author

Jakubikova, Jana, primary, Groen, Richard W.J., additional, Hideshima, Teru, additional, Cholujova, Danka, additional, Sedlak, Jan, additional, Mitsiades, Constantine S., additional, Laubach, Jacob P., additional, Munshi, Nikhil C., additional, Richardson, Paul G., additional, and Anderson, Kenneth C., additional

Published
2013
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32. Targeting the Clonogenic Side Population of Multiple Myeloma by Immunomodulatory Drugs (IMiDs) in the Context of Stromal Cell Microenvironment: Pathophysiologic and Clinical Implications.

Author

Jakubikova, Jana, primary, Cervi, David N., additional, Daley, John F., additional, Cholujova, Danka, additional, Ooi, Melissa G., additional, Klippel, Steffen, additional, Blotta, Simona, additional, Leiba, Merav, additional, Delmore, Jake, additional, McMillin, Douglas, additional, Kastritis, Efstathios, additional, Laubach, Jacob, additional, Richardson, Paul, additional, Sedlak, Jan, additional, Anderson, Kenneth C., additional, and Mitsiades, Constantine S., additional

Published
2009
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34. Effects of short-term Pilates exercise on selected blood parameters.

Author

Gronesova P, Cholujova D, Kozic K, Korbuly M, Vlcek M, Penesova A, Imrich R, Sedlak J, and Hunakova L

Subjects
Antioxidants metabolism, Chemokines blood, Erythrocytes cytology, Female, Healthy Volunteers, Hormones blood, Humans, Killer Cells, Natural cytology, Middle Aged, Time Factors, Blood Chemical Analysis, Exercise
Abstract

The aim of our prospective, interventional, pre-post, single arm study was to supplement the lack of knowledge of the effect of short-term Pilates intervention on selected blood parameters of healthy women. Female volunteers were recruited for 2-weeks Pilates intervention. Blood has been collected and anthropometric parameters were measured before and after exercise period (EP). Plasma insulin, cortisol, and dehydroepiandrosterone sulphate levels, erythrocyte antioxidant activity, glutathione levels, NK cytotoxicity and plasma cytokines were analysed. We found a decrease in erythrocyte antioxidant enzymes SOD and GPx activity; GSH levels; in the pro-inflammatory chemokine MCP-1 and trend to reduction in MIP-1β, PDGF and VEGF levels in plasma. NK cell cytotoxic activity increased after Pilates EP in the percentage of specific lysis at 25:1 effector: target (E:T) ratio and the same trend was observed at all E:T ratios as well as in the amount of lytic units per 107 cells. Our findings show that Pilates exercise may improve NK cell immune response and inflammatory milieu in plasma of healthy women.

Published
2018
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