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1. Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis

Author

Dymek B, Sklepkiewicz P, Mlacki M, Güner NC, Nejman-Gryz P, Drzewicka K, Przysucha N, Rymaszewska A, Paplinska-Goryca M, Zagozdzon A, Proboszcz M, Krzemiński Ł, von der Thüsen JH, Górska K, Dzwonek K, Zasłona Z, Dobrzanski P, and Krenke R

Subjects
chitinase, oatd-01, granuloma, macrophages, interstitial lung disease, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Barbara Dymek,1,2 Piotr Sklepkiewicz,1 Michal Mlacki,1 Nazan Cemre Güner,1 Patrycja Nejman-Gryz,3 Katarzyna Drzewicka,1 Natalia Przysucha,3 Aleksandra Rymaszewska,1 Magdalena Paplinska-Goryca,3 Agnieszka Zagozdzon,1 Małgorzata Proboszcz,3 Łukasz Krzemiński,1 Jan H von der Thüsen,4 Katarzyna Górska,3 Karolina Dzwonek,1 Zbigniew Zasłona,1 Pawel Dobrzanski,1 Rafał Krenke3 1Molecure SA, Warsaw, 02-089, Poland; 2Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, 02-097, Poland; 3Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, 02-097, Poland; 4Department of Pathology, Erasmus Medical Center, Rotterdam, 3015 GD, the NetherlandsCorrespondence: Barbara Dymek, Żwirki i Wigury 101, Warsaw, 02-089, Poland, Tel +48 22 552 67 24, Email b.dymek@molecure.comIntroduction: Sarcoidosis is a systemic disease of unknown etiology characterized by granuloma formation in the affected tissues. The pathologically activated macrophages are causatively implicated in disease pathogenesis and play important role in granuloma formation. Chitotriosidase (CHIT1), macrophage-derived protein, is upregulated in sarcoidosis and its levels correlate with disease severity implicating CHIT1 in pathology.Methods: CHIT1 was evaluated in serum and bronchial mucosa and mediastinal lymph nodes specimens from sarcoidosis patients. The therapeutic efficacy of OATD-01 was assessed ex vivo on human bronchoalveolar lavage fluid (BALF) macrophages and in vivo in the murine models of granulomatous inflammation.Results: CHIT1 activity was significantly upregulated in serum from sarcoidosis patients. CHIT1 expression was restricted to granulomas and localized in macrophages. Ex vivo OATD-01 inhibited pro-inflammatory mediators’ production (CCL4, IL-15) by lung macrophages. In the acute model of granulomatous inflammation in mice, OATD-01 showed anti-inflammatory effects reducing the percentage of neutrophils and CCL4 concentration in BALF. In the chronic model, inhibition of CHIT1 led to a decrease in the number of organized lung granulomas and the expression of sarcoidosis-associated genes.Conclusion: In summary, CHIT1 activity was increased in sarcoidosis patients and OATD-01, a first-in-class CHIT1 inhibitor, demonstrated efficacy in murine models of granulomatous inflammation providing a proof-of-concept for its clinical evaluation in sarcoidosis.Keywords: chitinase, OATD-01, granuloma, macrophages, interstitial lung disease

Published
2022

3. Sodium intake and urinary losses in children on dialysis: a European multicenter prospective study

Author

Paglialonga, Fabio, Shroff, Rukshana, Zagozdzon, Ilona, Bakkaloglu, Sevcan A., Zaloszyc, Ariane, Jankauskiene, Augustina, Gual, Alejandro Cruz, Consolo, Silvia, Grassi, Maria Rosa, McAlister, Louise, Skibiak, Aleksandra, Yazicioglu, Burcu, Puccio, Giuseppe, Edefonti, Alberto, Ariceta, Gema, Aufricht, Christoph, Holtta, Tuula, Klaus, Guenter, Ranchin, Bruno, Schmitt, Claus Peter, Snauwaert, Evelien, Stefanidis, Costantinos, Walle, Johan Vande, Stabouli, Stella, Verrina, Enrico, Vidal, Enrico, Vondrak, Karel, and Zurowska, Alexandra

Published
2023
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4. Reference values of lymphocyte subsets from healthy Polish adults

Author

Aleksander Roszczyk, Michał Zych, Dariusz Sołdacki, Radoslaw Zagozdzon, and Monika J. Kniotek

Subjects
b lymphocytes subsets, class-switching b lymphocytes, cvid – common variable immunodeficiency, flow cytometry, healthy adults, immunophenotype, lymphocyte subsets, peripheral blood, nk – natural killer, nkt – natural killer t cells, primary immunodeficiency – pid, reference values, Medicine
Abstract

The flow cytometry method could support physicians’ decisions in the diagnosis and treatment monitoring of immunodeficient patients. Most clinical recommendations are focused on the search for alterations in T- and B-lymphocyte subsets, less commonly natural killer (NK) cells and granulocytes. While reference values for clinically meaningful lymphocyte subsets have been published ubiquitously among numerous countries, we have not found significant data for a population of adult Polish habitats; thus we determined reference values for T, B, and NK subsets according to sex and age. The female group showed a higher percentage of lymphocytes (CD45 ++ ), T helper lymphocytes with a higher absolute count, as well as CD4/CD8 ratio, marginal zone-like B cells, class-switched B cells, and CD21 low B cells than the male group. The male group was found to have elevated percentages of naïve B lymphocytes, transitional B cells, and plasmablasts. A weak positive correlation with age was found among double positive T lymphocytes, natural killer T cells (NKT) lymphocytes, and CD21 low B cells. A negative correlation with age for double negative T lymphocytes, marginal zone-like B cells, and plasmablasts was noted. The results indicated the importance of creating distinct reference ranges regarding sex and age concerning immunophenotype.

Published
2024
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6. Bivalirudin versus heparin in ST and non-ST-segment elevation myocardial infarction—Outcomes at two years

Author

Omerovic, Elmir, James, Stefan, Råmundal, Truls, Fröbert, Ole, Linder, Rikard, Danielewicz, Mikael, Hamid, Mehmet, Pagonis, Christos, Henareh, Loghman, Wagner, Henrik, Stewart, Jason, Jensen, Jens, Lindros, Pontus, Robertsson, Lotta, Wikström, Helena, Ulvenstam, Anders, Bhiladval, Pallonji, Tödt, Tim, Ioanes, Dan, Kellerth, Thomas, Zagozdzon, Leszek, Götberg, Matthias, Andersson, Jonas, Angerås, Oskar, Östlund, Ollie, Held, Claes, Koul, Sasha, and Erlinge, David

Published
2024
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8. Regulatory T cells contribute to the immunosuppressive phenotype of neutrophils in a mouse model of chronic lymphocytic leukemia

Author

Agnieszka Goral, Marta Sledz, Aneta Manda-Handzlik, Adrianna Cieloch, Alicja Wojciechowska, Mieszko Lachota, Agnieszka Mroczek, Urszula Demkow, Radoslaw Zagozdzon, Katarzyna Matusik, Malgorzata Wachowska, and Angelika Muchowicz

Subjects
CD62L, Chronic lymphocytic leukemia (CLL), Neutrophils, Regulatory T cells (Treg), Immunosuppression, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Impaired neutrophil activity is an important issue in chronic lymphocytic leukemia (CLL), as it contributes to a dysfunctional immune response leading to life-threatening infections in patients. Some features typical of CLL neutrophils, e.g., the B-cell-supportive secretion profile, have already been described. However, most of these studies were performed on cells isolated from peripheral blood. It is still unclear which molecular factors and cell types are involved in shaping neutrophil function and phenotype in the CLL microenvironment. Since regulatory T cells (Treg) play an important role in CLL progression and influence the activity of neutrophils, we investigated the crosstalk between Treg and neutrophils in the spleen using a murine model of CLL. Methods In this work, we used an Eµ-TCL1 mouse model of human CLL. For our in vivo and ex vivo experiments, we inoculated wild-type mice with TCL1 leukemic cells isolated from Eµ-TCL1 transgenic mice and then monitored disease progression by detecting leukemic cells in peripheral blood. We analyzed both the phenotype and activity of neutrophils isolated from the spleens of TCL1 leukemia-bearing mice. To investigate the interrelation between Treg and neutrophils in the leukemia microenvironment, we performed experiments using TCL1-injected DEREG mice with Treg depletion or RAG2KO mice with adoptively transferred TCL1 cells alone or together with Treg. Results The obtained results underline the plasticity of the neutrophil phenotype, observed under the influence of leukemic cells alone and depending on the presence of Treg. In particular, Treg affect the expression of CD62L and IL-4 receptor in neutrophils, both of which are crucial for the function of these cells. Additionally, we show that Treg depletion and IL-10 neutralization induce changes in the leukemia microenvironment, partially restoring the “healthy” phenotype of neutrophils. Conclusions Altogether, the results indicate that the crosstalk between Treg and neutrophils in CLL may play an important role in CLL progression by interfering with the immune response.

Published
2023
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11. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

Author

Zagozdzon Agnieszka M, O’Leary Patrick, Callanan John J, Crown John, Gallagher William M, and Zagozdzon Radoslaw

Subjects
Transgenic mice, MMTV promoter, Luciferase, Bioluminescence, Breast cancer, in vivo imaging, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. Results A new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. Conclusions We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

Published
2012
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12. Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission

Author

Feigin, Valery L, Abd-Allah, Foad, Akinyemi, Rufus O, Bhattacharjee, Natalia V, Brainin, Michael, Cao, Jackie, Caso, Valeria, Dalton, Bronte, Davis, Alan, Dempsey, Robert, Duprey, Joseph, Feng, Wuwei, Ford, Gary A, Gall, Seana, Gandhi, Dorcas, Good, David C, Hachinski, Vladimir, Hacke, Werner, Hankey, Graeme J, Ishida, Marie, Johnson, Walter, Kim, Julie, Lavados, Pablo, Lindsay, Patrice, Mahal, Ajay, Martins, Sheila, Murray, Christopher, Nguyen, Thuy Phuong, Norrving, Bo, Olaiya, Muideen T, Olalusi, Oladotun V, Pandian, Jeyaraj, Phan, Hoang, Platz, Thomas, Ranta, Anna, Rehman, Sabah, Roth, Greg, Sebastian, Ivy Anne, Smith, Amanda E, Suwanwela, Nijasri C, Sylaja, P N, Thapa, Rajshree, Thrift, Amanda G, Uvere, Ezinne, Vollset, Stein Emil, Yavagal, Dileep, Yaria, Joseph, Owolabi, Mayowa O, Abera, Semaw Ferede, Akinyemi, Rufus, Dempsey, Robert J, Ibrahim, Norlinah Mohamed, Liu, Liping, Ovbiagele, Bruce, Piradov, Michael, Suwanwela, Nijasri, Abanto, Carlos, Addissie, Adamu, Adeleye, Amos O, Adilbekov, Yerzhan, Adilbekova, Bibigul, Adoukonou, Thierry A, Aguiar de Sousa, Diana, Akhmetzhanova, Zauresh, Akpalu, Albert, El Alaoui-Faris, Mustapha, Ameriso, Sebastian F, Andonova, Silva, Arsovska, Anita, Awoniyi, Folorunso E, Bakhiet, Moiz, Barboza, Miguel A, Basri, Hamidon, Bath, Philip M, Bereczki, Daniel, Beretta, Simone, Berkowitz, Aaron L, Bernhardt, Julie, Berzina, Guna, Bhavsar, Bhavan, Bisharyan, Mher S, Bohara, Manoj, Bovet, Pascal, Budincevic, Hrvoje, Cadilhac, Dominique A, Čerimagić, Denis, Charway-Felli, Augustina, Chen, Christopher, Chin, Jerome H, Christensen, Hanne, Chwojnicki, Kamil, Conforto, Adriana B, Correia, Manuel, Mora Cuervo, Daissy L, Członkowska, Anna, D'Amelio, Marco, Danielyan, Kristine E, Davis, Stephen, Demarin, Vida, Demchuk, Andrew M, Dichgans, Martin, Dokova, Klara, Donnan, Geoffrey, Duran, Juan Carlos, Ekeng, Gloria, Elkind, Mitchell S, Endres, Matthias, Fischer, Urs, Flomin, Yuriy, Gankpe, Fortuné, Gavidia, Martin, Gaye Saavedra, Andrés, Gebreyohanns, Mehari, George, Mary, Gierlotka, Marek, Giroud, Maurice, Gnedovskaya, Elena V, Gonçalves, Ivete Pillo, Gongora-Rivera, Fernando, Gunaratne, Padma S, Hamadeh, Randah R, Hamzat, Tal-hatu K, Heldner, Mirjam R, Ibrahim, Etedal, Ihle-Hansen, Hanne, Jee, Sungju, Jiann-Shing, Jeng, Johnston, S Clay, Jovanovic, Dejana, Jurjāns, Kristaps, Kalani, Rizwan, Kalkonde, Yogeshwar, Kamenova, Saltanat, Karaszewski, Bartosz, Kelly, Peter, Kiechl, Stefan, Kondybayeva, Aida, Kõrv, Janika, Kozera, Grzegorz, Kravchenko, Michael, Krespi, Yakup, Krishnamurthi, Rita, Kruja, Jera, Kutluk, Kursad, Langhorne, Peter, Law, Zhe K, Lebedynets, Dmytro, Lee, Tsong-Hai, Leung, Thomas W, Liebeskind, David S, López-Jaramillo, Patricio, Lotufo, Paulo A, Machline-Carrion, M Julia, Maia, Luis F, Malojcic, Branko, Markus, Hugh S, Marquez-Romero, Juan M, Medina, Marco T, Medukhanova, Sabina, Mehndiratta, Man Mohan, Miglāne, Evija, Mihejeva, Illa, Mikulik, Robert, Mirrakhimov, Erkin, Mohl, Stephanie, Munakomi, Sunil, Murphy, Sean, Musa, Kamarul I, Nasreldein, Ahmed, Nogueira, Raul G, Nolte, Christian H, Noubiap, Jean Jacques, Novarro-Escudero, Nelson, Ocampo, Cassandra, O'Donnell, Martin, Ogun, Yomi, Ogunniyi, Adesola, Oraby, Mohammed I, Ōrken, Dilek N, Ōzdemir, Atilla O, Ozturk, Serefnur, Paccot, Mélanie, Pereira, Telmo, Peeters, André, Potpara, Tatjana, Proios, Hariklia, Rathore, Farooq A, Sacco, Ralph L, Sahathevan, Ramesh, Sandset, Else S, Renato Santos, Irving, Saposnik, Gustavo, Sarfo, Fred S, Sargento-Freitas, João, Sharma, Mukul, Shaw, Louise, Sheth, Kevin N, Shin, Yong-Il, Shobhana, A, Silva, S Nishan, Tedim Cruz, Vitor, Thakur, Kiran, Thapa, Lekh Jung, Toni, Danilo, Topcuoglu, Mehmetakif A, Torales, Julio, Towfighi, Amytis, Truelsen, Thomas, Tsiskaridze, Alexander, Tulloch-Reid, Marshall, Useche, Juan N, Vanacker, Peter, Vassilopoulou, Sophia, Vukorepa, Gorana, Vuletic, Vladimira, Wahab, Kolawole W, Wang, Wenzhi, Wijeratne, Tissa, Wojtyniak, Bogdan, Wolfe, Charles, Yacouba, Mapoure N, Yang, Jie, Yifru, Yared M, Yock-Corrales, Adriana, Yonemoto, Naohiro, Yperzeele, Laetitia, and Zagożdżon, Pawel

Published
2023
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15. Targeting peroxiredoxin 1 impairs growth of breast cancer cells and potently sensitises these cells to prooxidant agents

Author

Bajor, Malgorzata, Zych, Agata O, Graczyk-Jarzynka, Agnieszka, Muchowicz, Angelika, Firczuk, Malgorzata, Trzeciak, Lech, Gaj, Pawel, Domagala, Antoni, Siernicka, Marta, Zagozdzon, Agnieszka, Siedlecki, Pawel, Kniotek, Monika, O’Leary, Patrick C, Golab, Jakub, and Zagozdzon, Radoslaw

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Animals, Antioxidants, Ascorbic Acid, Breast Neoplasms, CRISPR-Cas Systems, Cell Line, Tumor, Cell Proliferation, Diterpenes, Kaurane, Female, Gene Knockdown Techniques, Glucose Oxidase, Humans, MCF-7 Cells, Mice, Oxidative Stress, Peroxiredoxins, RNA Interference, Up-Regulation, Xenograft Model Antitumor Assays, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundOur previous work has shown peroxiredoxin-1 (PRDX1), one of major antioxidant enzymes, to be a biomarker in human breast cancer. Hereby, we further investigate the role of PRDX1, compared to its close homolog PRDX2, in mammary malignant cells.MethodsCRISPR/Cas9- or RNAi-based methods were used for genetic targeting PRDX1/2. Cell growth was assessed by crystal violet, EdU incorporation or colony formation assays. In vivo growth was assessed by a xenotransplantation model. Adenanthin was used to inhibit the thioredoxin-dependent antioxidant defense system. The prooxidant agents used were hydrogen peroxide, glucose oxidase and sodium L-ascorbate. A PY1 probe or HyPer-3 biosensor were used to detect hydrogen peroxide content in samples.ResultsPRDX1 downregulation significantly impaired the growth rate of MCF-7 and ZR-75-1 breast cancer cells. Likewise, xenotransplanted PRDX1-deficient MCF-7 cells presented a retarded tumour growth. Furthermore, genetic targeting of PRDX1 or adenanthin, but not PRDX2, potently sensitised all six cancer cell lines studied, but not the non-cancerous cells, to glucose oxidase and ascorbate.ConclusionsOur study pinpoints the dominant role for PRDX1 in management of exogeneous oxidative stress by breast cancer cells and substantiates further exploration of PRDX1 as a target in this disease, especially when combined with prooxidant agents.

Published
2018

16. FIBROMUSCULAR DYSPLASIA IN CHILDREN – A SINGLE-CENTER EXPERIENCE

Author

Skrzypczyk, Piotr, primary, Bujanowicz, Adam, additional, Ofiara, Anna, additional, Szyszka, Michal, additional, Tutka, Agnieszka, additional, Wabik, Anna Maria, additional, Zagozdzon, Ilona, additional, Krysiak, Remigiusz, additional, Zylkowski, Jaroslaw, additional, and Panczyk-tomaszewska, Malgorzata, additional

Published
2024
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17. Safety and efficacy of cinacalcet in children below 3 years of age on maintenance dialysis

Author

Bernardor, Julie, primary, Flammier, Sacha, additional, Zagozdzon, Ilona, additional, Lalayiannis, Alexander D., additional, Koster-Kamphuis, Linda, additional, Verrina, Enrico, additional, Dorresteijn, Eiske, additional, Guzzo, Isabella, additional, Haffner, Dieter, additional, Shroff, Rukshana, additional, Schmitt, Claus P., additional, and Bacchetta, Justine, additional

Published
2024
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18. Development of acquired resistance to lapatinib may sensitise HER2-positive breast cancer cells to apoptosis induction by obatoclax and TRAIL.

Author

Eustace, Alex J, Conlon, Neil T, McDermott, Martina SJ, Browne, Brigid C, O'Leary, Patrick, Holmes, Frankie A, Espina, Virginia, Liotta, Lance A, O'Shaughnessy, Joyce, Gallagher, Clair, O'Driscoll, Lorraine, Rani, Sweta, Madden, Stephen F, O'Brien, Neil A, Ginther, Charles, Slamon, Dennis, Walsh, Naomi, Gallagher, William M, Zagozdzon, Radoslaw, Watson, William R, O'Donovan, Norma, and Crown, John

Subjects
Cell Line, Tumor, Humans, Breast Neoplasms, Proto-Oncogene Proteins c-bcl-2, Antineoplastic Agents, Apoptosis, Gene Expression, Phosphorylation, Drug Resistance, Neoplasm, Genes, erbB-2, Female, CASP8 and FADD-Like Apoptosis Regulating Protein, TNF-Related Apoptosis-Inducing Ligand, Forkhead Box Protein O3, Lapatinib, AKT, ErbB2, FOXO3a, MCL-1, cFLIP, Cancer, Breast Cancer, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Aetiology, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundLapatinib has clinical efficacy in the treatment of trastuzumab-refractory HER2-positive breast cancer. However, a significant proportion of patients develop progressive disease due to acquired resistance to the drug. Induction of apoptotic cell death is a key mechanism of action of lapatinib in HER2-positive breast cancer cells.MethodsWe examined alterations in regulation of the intrinsic and extrinsic apoptosis pathways in cell line models of acquired lapatinib resistance both in vitro and in patient samples from the NCT01485926 clinical trial, and investigated potential strategies to exploit alterations in apoptosis signalling to overcome lapatinib resistance in HER2-positive breast cancer.ResultsIn this study, we examined two cell lines models of acquired lapatinib resistance (SKBR3-L and HCC1954-L) and showed that lapatinib does not induce apoptosis in these cells. We identified alterations in members of the BCL-2 family of proteins, in particular MCL-1 and BAX, which may play a role in resistance to lapatinib. We tested the therapeutic inhibitor obatoclax, which targets MCL-1. Both SKBR3-L and HCC1954-L cells showed greater sensitivity to obatoclax-induced apoptosis than parental cells. Interestingly, we also found that the development of acquired resistance to lapatinib resulted in acquired sensitivity to TRAIL in SKBR3-L cells. Sensitivity to TRAIL in the SKBR3-L cells was associated with reduced phosphorylation of AKT, increased expression of FOXO3a and decreased expression of c-FLIP. In SKBR3-L cells, TRAIL treatment caused activation of caspase 8, caspase 9 and caspase 3/7. In a second resistant model, HCC1954-L cells, p-AKT levels were not decreased and these cells did not show enhanced sensitivity to TRAIL. Furthermore, combining obatoclax with TRAIL improved response in SKBR3-L cells but not in HCC1954-L cells.ConclusionsOur findings highlight the possibility of targeting altered apoptotic signalling to overcome acquired lapatinib resistance, and identify potential novel treatment strategies, with potential biomarkers, for HER2-positive breast cancer that is resistant to HER2 targeted therapies.

Published
2018

19. Inhibition of CHIT1 as a novel therapeutic approach in idiopathic pulmonary fibrosis

Author

Sklepkiewicz, Piotr, Dymek, Barbara A., Mlacki, Michal, Koralewski, Robert, Mazur, Marzena, Nejman-Gryz, Patrycja, Korur, Serdar, Zagozdzon, Agnieszka, Rymaszewska, Aleksandra, von der Thüsen, Jan H., Siwińska, Anna M., Güner, Nazan Cemre, Cheda, Łukasz, Paplinska-Goryca, Magdalena, Proboszcz, Małgorzata, van den Bosch, Thierry P.P., Górska, Katarzyna, Golab, Jakub, Kamiński, Rafał M., Krenke, Rafał, Golebiowski, Adam, Dzwonek, Karolina, and Dobrzanski, Pawel

Published
2022
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21. Refining genotype–phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants

Author

Eid, Loai Akram, Arbeiter, Klaus, Godefroid, Nathalie, Lombet, Jacques, De Mul, Aurélie, Feldkoetter, Markus, Zieg, Jakub, Grundmann, Franziska, Galiano, Matthias, Buchholz, Björn, Buescher, Anja, Häffner, Karsten, Gross, Oliver, Patzer, Ludwig, Oh, Jun, Haffner, Dieter, Bernhardt, Wanja, Schaefer, Susanne, Wygoda, Simone, Halbritter, Jan, Derichs, Ute, Klaus, Günter, Lechner, Felix, Ponsel, Sabine, König, Jens, Staude, Hagen, Wurm, Donald, Bald, Martin, Gessner, Michaela, Soliman, Neveen A., Ariceta, Gema, Gonzalez Rodriguez, Juan David, Ojeda, Francisco de la Cerda, Harambat, Jerome, Morin, Denis, Dossier, Claire, Dorval, Guillaume, Shroff, Rukshana, Stabouli, Stella, Hooman, Nakysa, Mencarelli, Francesca, Morello, William, Longo, Germana, Emma, Francesco, Jankauskiene, Augustina, Taranta-Janusz, Katarzyna, Zagozdzon, Ilona, Zachwieja, Katarzyna, Stanczyk, Malgorzata, Bienias, Beata, Litwin, Mieczyslaw, Morawiec-Knysak, Aurelia, Afonso, Alberto Caldas, Dunand, Oliver, Rachisan, Andreea, Miloševski-Lomić, Gordana, Papizh, Svetlana, Rus, Rina, Jilani, Houweyda, Atmis, Bahriye, Duzova, Ali, Soylu, Alper, Candan, Cengiz, Caliskan, Salim, Yilmaz, Alev, Gökce, İbrahim, Akinci, Nurver, Mir, Sevgi, Dursun, Ismail, Tabel, Yilmaz, Nalcacioglu, Hulya, Burgmaier, Kathrin, Brinker, Leonie, Erger, Florian, Beck, Bodo B., Benz, Marcus R., Bergmann, Carsten, Boyer, Olivia, Collard, Laure, Dafinger, Claudia, Fila, Marc, Kowalewska, Claudia, Lange-Sperandio, Bärbel, Massella, Laura, Mastrangelo, Antonio, Mekahli, Djalila, Miklaszewska, Monika, Ortiz-Bruechle, Nadina, Prikhodina, Larisa, Ranchin, Bruno, Ranguelov, Nadejda, Schild, Raphael, Seeman, Tomas, Sever, Lale, Sikora, Przemyslaw, Szczepanska, Maria, Teixeira, Ana, Thumfart, Julia, Uetz, Barbara, Weber, Lutz Thorsten, Wühl, Elke, Zerres, Klaus, Dötsch, Jörg, Schaefer, Franz, and Liebau, Max Christoph

Published
2021
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22. Inhibition of Macrophage-Specific CHIT1 as an Approach to Treat Airway Remodeling in Severe Asthma

Author

Piotr Sklepkiewicz, Barbara Dymek, Michal Mlacki, Agnieszka Zagozdzon, Magdalena Salamon, Anna Maria Siwińska, Marcin Piotr Mazurkiewicz, Natalia de Souza Xavier Costa, Marzena Mazur, Thais Mauad, Adam Gołębiowski, Karolina Dzwonek, Jakub Gołąb, and Zbigniew Zasłona

Subjects
macrophage, chitotriosidase, asthma, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Chitotriosidase (CHIT1) is an enzyme produced by macrophages that regulates their differentiation and polarization. Lung macrophages have been implicated in asthma development; therefore, we asked whether pharmacological inhibition of macrophage-specific CHIT1 would have beneficial effects in asthma, as it has been shown previously in other lung disorders. CHIT1 expression was evaluated in the lung tissues of deceased individuals with severe, uncontrolled, steroid-naïve asthma. OATD-01, a chitinase inhibitor, was tested in a 7-week-long house dust mite (HDM) murine model of chronic asthma characterized by accumulation of CHIT1-expressing macrophages. CHIT1 is a dominant chitinase activated in fibrotic areas of the lungs of individuals with fatal asthma. OATD-01 given in a therapeutic treatment regimen inhibited both inflammatory and airway remodeling features of asthma in the HDM model. These changes were accompanied by a significant and dose-dependent decrease in chitinolytic activity in BAL fluid and plasma, confirming in vivo target engagement. Both IL-13 expression and TGFβ1 levels in BAL fluid were decreased and a significant reduction in subepithelial airway fibrosis and airway wall thickness was observed. These results suggest that pharmacological chitinase inhibition offers protection against the development of fibrotic airway remodeling in severe asthma.

Published
2023
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25. The Role of Chitinases in Chronic Airway Inflammation Associated with Tobacco Smoke Exposure

Author

Natalia Przysucha, Katarzyna Górska, Marta Maskey-Warzęchowska, Małgorzata Proboszcz, Patrycja Nejman-Gryz, Magdalena Paplińska-Goryca, Barbara Dymek, Agnieszka Zagozdzon, and Rafał Krenke

Subjects
COPD, airway inflammation, chitinase, cytokines, YKL-40, CHIT1, Cytology, QH573-671
Abstract

Chitinases and chitinase-like proteins are thought to play a role in innate inflammatory responses. Our study aimed to assess whether chitinase concentration and activity in induced sputum (IS) of patients exposed to tobacco smoke are related to the level of airway inflammation including the level and activity of chitinases and chitinase-like proteins. The study included 22 patients with chronic obstructive pulmonary disease (COPD), 12 non-COPD smokers, and nine nonsmoking subjects. Sputum CHIT1 and YKL-40 levels and chitinolytic activity were compared with sputum IL-6, IL-8, IL-18, and MMP-9 levels. A hierarchical cluster analysis was also performed. Sputum YKL-40 was higher in COPD patients than in the control groups. Sputum CHIT1 and YKL-40 levels correlated with IS inflammatory cell count as well as with MMP-9 and IL-8 levels. Two main clusters were revealed: Cluster 1 had lower chitinase levels and activity, lower IS macrophage and neutrophil count, and lower IS IL-8, IL-18, and MMP-9 than Cluster 2. Comparison of COPD patients from both clusters revealed significant differences in the IS inflammatory profile despite comparable clinical and functional data. Our findings seem to confirm the involvement of chitinases in smoking-associated chronic airway inflammation and show that airway chitinases may be a potential novel marker in COPD phenotyping.

Published
2022
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26. Twenty years of growth hormone treatment in dialyzed children in Poland—Results of national multicenter study

Author

Adamczuk, Dominika, Leszczyńska, Beata, Skrzypczyk, Piotr, Turczyn, Agnieszka, Antonowicz, Agnieszka, Majcher, Anna, Szczepańska, Maria, Adamczyk, Piotr, Zagożdżon, Ilona, Żurowska, Aleksandra, Tkaczyk, Marcin, Jander, Anna, Sikora, Przemysław, Wasilewska, Anna, Warzywoda, Alfred, Kiliś-Pstrusińska, Katarzyna, Zwolińska, Danuta, Zachwieja, Katarzyna, Drożdż, Dorota, Stankiewicz, Roman, Grenda, Ryszard, and Pańczyk-Tomaszewska, Małgorzata

Published
2019
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29. Optimization of Se- and Zn-Enriched Mycelium of Lentinula edodes (Berk.) Pegler as a Dietary Supplement with Immunostimulatory Activity

Author

Kałucka, Małgorzata, primary, Roszczyk, Aleksander, additional, Klimaszewska, Marzenna, additional, Kaleta, Beata, additional, Drelich, Ewelina, additional, Błażewicz, Anna, additional, Górska-Jakubowska, Sandra, additional, Malinowska, Eliza, additional, Król, Marek, additional, Prus, Aleksandra Maria, additional, Trześniowska, Katarzyna, additional, Wołczyńska, Aleksandra, additional, Dorożyński, Przemysław, additional, Zagozdzon, Radoslaw, additional, and Turło, Jadwiga, additional

Published
2023
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30. Supplementary Figure 21 from Arginase 1/2 Inhibitor OATD-02: From Discovery to First-in-man Setup in Cancer Immunotherapy

Author

Borek, Bartlomiej, primary, Nowicka, Julita, primary, Gzik, Anna, primary, Dziegielewski, Marek, primary, Jedrzejczak, Karol, primary, Brzezinska, Joanna, primary, Grzybowski, Marcin, primary, Stanczak, Paulina, primary, Pomper, Paulina, primary, Zagozdzon, Agnieszka, primary, Rejczak, Tomasz, primary, Matyszewski, Krzysztof, primary, Golebiowski, Adam, primary, Olczak, Jacek, primary, Lisiecki, Kamil, primary, Tyszkiewicz, Magdalena, primary, Kania, Magdalena, primary, Piasecka, Sylwia, primary, Cabaj, Anna, primary, Dera, Paulina, primary, Mulewski, Krzysztof, primary, Chrzanowski, Jacek, primary, Kusmirek, Damian, primary, Sobolewska, Elzbieta, primary, Magdycz, Marta, primary, Mucha, Lukasz, primary, Masnyk, Marek, primary, Golab, Jakub, primary, Nowotny, Marcin, primary, Nowak, Elzbieta, primary, Napiorkowska-Gromadzka, Agnieszka, primary, Pikul, Stanislaw, primary, Jazwiec, Radoslaw, primary, Dzwonek, Karolina, primary, Dobrzanski, Pawel, primary, Meyring, Michael, primary, Skowronek, Krzysztof, primary, Iwanowski, Piotr, primary, Zaslona, Zbigniew, primary, and Blaszczyk, Roman, primary

Published
2023
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31. Supplementary Figure 18 from Arginase 1/2 Inhibitor OATD-02: From Discovery to First-in-man Setup in Cancer Immunotherapy

Author

Borek, Bartlomiej, primary, Nowicka, Julita, primary, Gzik, Anna, primary, Dziegielewski, Marek, primary, Jedrzejczak, Karol, primary, Brzezinska, Joanna, primary, Grzybowski, Marcin, primary, Stanczak, Paulina, primary, Pomper, Paulina, primary, Zagozdzon, Agnieszka, primary, Rejczak, Tomasz, primary, Matyszewski, Krzysztof, primary, Golebiowski, Adam, primary, Olczak, Jacek, primary, Lisiecki, Kamil, primary, Tyszkiewicz, Magdalena, primary, Kania, Magdalena, primary, Piasecka, Sylwia, primary, Cabaj, Anna, primary, Dera, Paulina, primary, Mulewski, Krzysztof, primary, Chrzanowski, Jacek, primary, Kusmirek, Damian, primary, Sobolewska, Elzbieta, primary, Magdycz, Marta, primary, Mucha, Lukasz, primary, Masnyk, Marek, primary, Golab, Jakub, primary, Nowotny, Marcin, primary, Nowak, Elzbieta, primary, Napiorkowska-Gromadzka, Agnieszka, primary, Pikul, Stanislaw, primary, Jazwiec, Radoslaw, primary, Dzwonek, Karolina, primary, Dobrzanski, Pawel, primary, Meyring, Michael, primary, Skowronek, Krzysztof, primary, Iwanowski, Piotr, primary, Zaslona, Zbigniew, primary, and Blaszczyk, Roman, primary

Published
2023
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32. Data from Arginase 1/2 Inhibitor OATD-02: From Discovery to First-in-man Setup in Cancer Immunotherapy

Author

Borek, Bartlomiej, primary, Nowicka, Julita, primary, Gzik, Anna, primary, Dziegielewski, Marek, primary, Jedrzejczak, Karol, primary, Brzezinska, Joanna, primary, Grzybowski, Marcin, primary, Stanczak, Paulina, primary, Pomper, Paulina, primary, Zagozdzon, Agnieszka, primary, Rejczak, Tomasz, primary, Matyszewski, Krzysztof, primary, Golebiowski, Adam, primary, Olczak, Jacek, primary, Lisiecki, Kamil, primary, Tyszkiewicz, Magdalena, primary, Kania, Magdalena, primary, Piasecka, Sylwia, primary, Cabaj, Anna, primary, Dera, Paulina, primary, Mulewski, Krzysztof, primary, Chrzanowski, Jacek, primary, Kusmirek, Damian, primary, Sobolewska, Elzbieta, primary, Magdycz, Marta, primary, Mucha, Lukasz, primary, Masnyk, Marek, primary, Golab, Jakub, primary, Nowotny, Marcin, primary, Nowak, Elzbieta, primary, Napiorkowska-Gromadzka, Agnieszka, primary, Pikul, Stanislaw, primary, Jazwiec, Radoslaw, primary, Dzwonek, Karolina, primary, Dobrzanski, Pawel, primary, Meyring, Michael, primary, Skowronek, Krzysztof, primary, Iwanowski, Piotr, primary, Zaslona, Zbigniew, primary, and Blaszczyk, Roman, primary

Published
2023
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33. Supplementary Tables 1-11 from Arginase 1/2 Inhibitor OATD-02: From Discovery to First-in-man Setup in Cancer Immunotherapy

Author

Borek, Bartlomiej, primary, Nowicka, Julita, primary, Gzik, Anna, primary, Dziegielewski, Marek, primary, Jedrzejczak, Karol, primary, Brzezinska, Joanna, primary, Grzybowski, Marcin, primary, Stanczak, Paulina, primary, Pomper, Paulina, primary, Zagozdzon, Agnieszka, primary, Rejczak, Tomasz, primary, Matyszewski, Krzysztof, primary, Golebiowski, Adam, primary, Olczak, Jacek, primary, Lisiecki, Kamil, primary, Tyszkiewicz, Magdalena, primary, Kania, Magdalena, primary, Piasecka, Sylwia, primary, Cabaj, Anna, primary, Dera, Paulina, primary, Mulewski, Krzysztof, primary, Chrzanowski, Jacek, primary, Kusmirek, Damian, primary, Sobolewska, Elzbieta, primary, Magdycz, Marta, primary, Mucha, Lukasz, primary, Masnyk, Marek, primary, Golab, Jakub, primary, Nowotny, Marcin, primary, Nowak, Elzbieta, primary, Napiorkowska-Gromadzka, Agnieszka, primary, Pikul, Stanislaw, primary, Jazwiec, Radoslaw, primary, Dzwonek, Karolina, primary, Dobrzanski, Pawel, primary, Meyring, Michael, primary, Skowronek, Krzysztof, primary, Iwanowski, Piotr, primary, Zaslona, Zbigniew, primary, and Blaszczyk, Roman, primary

Published
2023
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34. Supplementary Materials and Methods from Arginase 1/2 Inhibitor OATD-02: From Discovery to First-in-man Setup in Cancer Immunotherapy

Author

Borek, Bartlomiej, primary, Nowicka, Julita, primary, Gzik, Anna, primary, Dziegielewski, Marek, primary, Jedrzejczak, Karol, primary, Brzezinska, Joanna, primary, Grzybowski, Marcin, primary, Stanczak, Paulina, primary, Pomper, Paulina, primary, Zagozdzon, Agnieszka, primary, Rejczak, Tomasz, primary, Matyszewski, Krzysztof, primary, Golebiowski, Adam, primary, Olczak, Jacek, primary, Lisiecki, Kamil, primary, Tyszkiewicz, Magdalena, primary, Kania, Magdalena, primary, Piasecka, Sylwia, primary, Cabaj, Anna, primary, Dera, Paulina, primary, Mulewski, Krzysztof, primary, Chrzanowski, Jacek, primary, Kusmirek, Damian, primary, Sobolewska, Elzbieta, primary, Magdycz, Marta, primary, Mucha, Lukasz, primary, Masnyk, Marek, primary, Golab, Jakub, primary, Nowotny, Marcin, primary, Nowak, Elzbieta, primary, Napiorkowska-Gromadzka, Agnieszka, primary, Pikul, Stanislaw, primary, Jazwiec, Radoslaw, primary, Dzwonek, Karolina, primary, Dobrzanski, Pawel, primary, Meyring, Michael, primary, Skowronek, Krzysztof, primary, Iwanowski, Piotr, primary, Zaslona, Zbigniew, primary, and Blaszczyk, Roman, primary

Published
2023
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35. Supplementary Figures 2 - 14 from Arginase 1/2 Inhibitor OATD-02: From Discovery to First-in-man Setup in Cancer Immunotherapy

Author

Borek, Bartlomiej, primary, Nowicka, Julita, primary, Gzik, Anna, primary, Dziegielewski, Marek, primary, Jedrzejczak, Karol, primary, Brzezinska, Joanna, primary, Grzybowski, Marcin, primary, Stanczak, Paulina, primary, Pomper, Paulina, primary, Zagozdzon, Agnieszka, primary, Rejczak, Tomasz, primary, Matyszewski, Krzysztof, primary, Golebiowski, Adam, primary, Olczak, Jacek, primary, Lisiecki, Kamil, primary, Tyszkiewicz, Magdalena, primary, Kania, Magdalena, primary, Piasecka, Sylwia, primary, Cabaj, Anna, primary, Dera, Paulina, primary, Mulewski, Krzysztof, primary, Chrzanowski, Jacek, primary, Kusmirek, Damian, primary, Sobolewska, Elzbieta, primary, Magdycz, Marta, primary, Mucha, Lukasz, primary, Masnyk, Marek, primary, Golab, Jakub, primary, Nowotny, Marcin, primary, Nowak, Elzbieta, primary, Napiorkowska-Gromadzka, Agnieszka, primary, Pikul, Stanislaw, primary, Jazwiec, Radoslaw, primary, Dzwonek, Karolina, primary, Dobrzanski, Pawel, primary, Meyring, Michael, primary, Skowronek, Krzysztof, primary, Iwanowski, Piotr, primary, Zaslona, Zbigniew, primary, and Blaszczyk, Roman, primary

Published
2023
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36. Kinase-independent function of E-type cyclins in liver cancer

Author

Geng, Yan, Michowski, Wojciech, Chick, Joel M., Wang, Yaoyu E., Jecrois, M. Emmanuelle, Sweeney, Katharine E., Liu, Lijun, Han, Richard C., Ke, Nan, Zagozdzon, Agnieszka, Sicinska, Ewa, Bronson, Roderick T., Gygi, Steven P., and Sicinski, Piotr

Published
2018

37. Bioinformatic Analysis Reveals Central Role for Tumor-Infiltrating Immune Cells in Uveal Melanoma Progression

Author

Mieszko Lachota, Anton Lennikov, Karl-Johan Malmberg, and Radoslaw Zagozdzon

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Tumor-infiltrating immune cells are capable of effective cancer surveillance, and their abundance is linked to better prognosis in numerous tumor types. However, in uveal melanoma (UM), extensive immune infiltrate is associated with poor survival. This study aims to decipher the role of different tumor-infiltrating cell subsets in UM in order to identify potential targets for future immunotherapeutic treatment. We have chosen the TCGA-UVM cohort as a training dataset and GSE22138 as a testing dataset by mining publicly available databases. The abundance of 22 immune cell types was estimated using CIBERSORTx. Then, to determine the significance of tumor-infiltrating cell subsets in UM, we built a multicell type prognostic signature, which was validated in the testing cohort. The created signature was built upon the negative prognostic role of CD8+ T cells and M0 macrophages and the positive role of neutrophils. Based on the created signature score, we divided the patients into low- and high-risk groups. Kaplan-Meier, Cox, and ROC analyses demonstrated superior performance of our risk score compared to either clinical or pathologic characteristics of both cohorts. Further, we found the molecular pathways associated with cancer immunoevasion and metastasis to be enriched in the high-risk group, explaining both the lack of adequate immune surveillance despite increased infiltration of CD8+ T cells as well as the higher metastatic potential. Genes associated with tryptophan metabolism (IDO1 and KYNU) and metalloproteinases were among the most differentially expressed between the high- and low-risk groups. Our correlation analyses interpreted in context of published in vitro data strongly suggest the central role of CD8+ T cells in shifting the UM tumor microenvironment towards suppressive and metastasis-promoting. Therefore, we propose further investigations of IDO1 and metalloproteinases as novel targets for immunotherapy in lymphocyte-rich metastatic UM patients.

Published
2021
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39. Analysis of TCP Connection Performance Using Emulation of TCP State

Author

Bąk, Andrzej, Gajowniczek, Piotr, Zagożdżon, Michał, Kacprzyk, Janusz, Series editor, Pal, Nikhil R., Advisory editor, Bello Perez, Rafael, Advisory editor, Corchado, Emilio S., Advisory editor, Hagras, Hani, Advisory editor, Kóczy, László T., Advisory editor, Kreinovich, Vladik, Advisory editor, Lin, Chin-Teng, Advisory editor, Lu, Jie, Advisory editor, Melin, Patricia, Advisory editor, Nedjah, Nadia, Advisory editor, Nguyen, Ngoc Thanh, Advisory editor, Wang, Jun, Advisory editor, Grzenda, Maciej, editor, Awad, Ali Ismail, editor, Furtak, Janusz, editor, and Legierski, Jarosław, editor

Published
2017
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40. Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease

Author

Ranguelov, Nadejda, Godefroid, Nathalie, Collard, Laure, Lombet, Jacques, Maquet, Julie, Schalk, Gesa, Querfeld, Uwe, Beck, Bodo B., Benzing, Thomas, Buettner, Reinhard, Grundmann, Franziska, Kurschat, Christine, Benz, Kerstin, Tzschoppe, Anja, Buchholz, Björn, Buescher, Rainer, Häffner, Karsten, Pohl, Martin, Gross, Oliver, Krügel, Jenny, Stock, Johanna, Patzer, Ludwig, Oh, Jun, Bernhardt, Wanja, Doyon, Anke, Vinke, Tobias, Sander, Anja, Henn, Michael, Derichs, Ute, Beetz, Rolf, Jeck, Nikola, Lange-Sperandio, Bärbel, Ponsel, Sabine, Kusser, Franziska, Uetz, Barbara, Benz, Marcus, Schmidt, Silke, Huppertz-Kessler, Christina, Kranz, Birgitta, Titieni, Andrea, Wurm, Donald, Leichter, Heinz E., Bald, Martin, Billing, Heiko, Nabhan, Marwa M., Lara, Luis Enrique, Papachristou, Fotios, Emma, Francesco, Cerkauskiene, Rimante, Azukaitis, Karolis, Wasilewska, Anna, Balasz-Chmielewska, Irena, Miklaszewska, Monika, Tkaczyk, Marcin, Sikora, Przemyslaw, Zaniew, Marcin, Niemirska, Ania, Antoniewicz, Jolanta, Lesiak, Justyna, Afonso, Alberto Caldas, Teixeira, Ana, Milosevski-Lomic, Gordana, Paripović, Dusan, Peco-Antic, Amira, Papizh, Svetlana, Bayazit, Aysun Karabay, Anarat, Ali, Soylu, Alper, Kavukcu, Salih, Candan, Cengiz, Caliskan, Salim, Canpolat, Nur, Emre, Sevinc, Alpay, Harika, Akinci, Nurver, Conkar, Secil, Poyrazoglu, Hakan M., Dusunsel, Ruhan, Burgmaier, Kathrin, Kunzmann, Kevin, Ariceta, Gema, Bergmann, Carsten, Buescher, Anja Katrin, Burgmaier, Mathias, Dursun, Ismail, Duzova, Ali, Eid, Loai, Erger, Florian, Feldkoetter, Markus, Galiano, Matthias, Geßner, Michaela, Goebel, Heike, Gokce, Ibrahim, Haffner, Dieter, Hooman, Nakysa, Hoppe, Bernd, Jankauskiene, Augustina, Klaus, Guenter, König, Jens, Litwin, Mieczyslaw, Massella, Laura, Mekahli, Djalila, Melek, Engin, Mir, Sevgi, Pape, Lars, Prikhodina, Larisa, Ranchin, Bruno, Schild, Raphael, Seeman, Tomas, Sever, Lale, Shroff, Rukshana, Soliman, Neveen A., Stabouli, Stella, Stanczyk, Malgorzata, Tabel, Yilmaz, Taranta-Janusz, Katarzyna, Testa, Sara, Thumfart, Julia, Topaloglu, Rezan, Weber, Lutz Thorsten, Wicher, Dorota, Wühl, Elke, Wygoda, Simone, Yilmaz, Alev, Zachwieja, Katarzyna, Zagozdzon, Ilona, Zerres, Klaus, Dötsch, Jörg, Schaefer, Franz, and Liebau, Max Christoph

Published
2018
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41. HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies

Author

Bobrowicz, Malgorzata, Dwojak, Michal, Pyrzynska, Beata, Stachura, Joanna, Muchowicz, Angelika, Berthel, Elise, Dalla-Venezia, Nicole, Kozikowski, Mieszko, Siernicka, Marta, Miazek, Nina, Zapala, Piotr, Domagala, Antoni, Bojarczuk, Kamil, Malenda, Agata, Barankiewicz, Joanna, Graczyk-Jarzynka, Agnieszka, Zagozdzon, Agnieszka, Gabrysiak, Magdalena, Diaz, Jean-Jacques, Karp, Marta, Lech-Maranda, Ewa, Firczuk, Malgorzata, Giannopoulos, Krzysztof, Efremov, Dimitar G., Laurenti, Luca, Baatout, Dunja, Frenzel, Lukas, Malinowska, Agata, Slabicki, Mikolaj, Zenz, Thorsten, Zerrouqi, Abdessamad, Golab, Jakub, and Winiarska, Magdalena

Published
2017
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42. Data from Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors

Author

Oei, Vincent Yi Sheng, primary, Siernicka, Marta, primary, Graczyk-Jarzynka, Agnieszka, primary, Hoel, Hanna Julie, primary, Yang, Weiwen, primary, Palacios, Daniel, primary, Almåsbak, Hilde, primary, Bajor, Malgorzata, primary, Clement, Dennis, primary, Brandt, Ludwig, primary, Önfelt, Björn, primary, Goodridge, Jodie, primary, Winiarska, Magdalena, primary, Zagozdzon, Radoslaw, primary, Olweus, Johanna, primary, Kyte, Jon-Amund, primary, and Malmberg, Karl-Johan, primary

Published
2023
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43. Supplementary Video 1 from Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors

Author

Oei, Vincent Yi Sheng, primary, Siernicka, Marta, primary, Graczyk-Jarzynka, Agnieszka, primary, Hoel, Hanna Julie, primary, Yang, Weiwen, primary, Palacios, Daniel, primary, Almåsbak, Hilde, primary, Bajor, Malgorzata, primary, Clement, Dennis, primary, Brandt, Ludwig, primary, Önfelt, Björn, primary, Goodridge, Jodie, primary, Winiarska, Magdalena, primary, Zagozdzon, Radoslaw, primary, Olweus, Johanna, primary, Kyte, Jon-Amund, primary, and Malmberg, Karl-Johan, primary

Published
2023
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45. Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis

Author

Chesnaye, Nicholas C, Schaefer, Franz, Bonthuis, Marjolein, Holman, Rebecca, Baiko, Sergey, Baskın, Esra, Bjerre, Anna, Cloarec, Sylvie, Cornelissen, Elisabeth A M, Espinosa, Laura, Heaf, James, Stone, Rosário, Shtiza, Diamant, Zagozdzon, Ilona, Harambat, Jérôme, Jager, Kitty J, Groothoff, Jaap W, and van Stralen, Karlijn J

Published
2017
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46. Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis

Author

Barbara Dymek, Piotr Sklepkiewicz, Michal Mlacki, Nazan Cemre Güner, Patrycja Nejman-Gryz, Katarzyna Drzewicka, Natalia Przysucha, Aleksandra Rymaszewska, Magdalena Paplinska-Goryca, Agnieszka Zagozdzon, Małgorzata Proboszcz, Łukasz Krzemiński, Jan H von der Thüsen, Katarzyna Górska, Karolina Dzwonek, Zbigniew Zasłona, Pawel Dobrzanski, Rafał Krenke, and Pathology

Subjects
SDG 3 - Good Health and Well-being, Immunology, Immunology and Allergy, Journal of Inflammation Research
Abstract

Barbara Dymek,1,2 Piotr Sklepkiewicz,1 Michal Mlacki,1 Nazan Cemre Güner,1 Patrycja Nejman-Gryz,3 Katarzyna Drzewicka,1 Natalia Przysucha,3 Aleksandra Rymaszewska,1 Magdalena Paplinska-Goryca,3 Agnieszka Zagozdzon,1 Małgorzata Proboszcz,3 Łukasz Krzemiński,1 Jan H von der Thüsen,4 Katarzyna Górska,3 Karolina Dzwonek,1 Zbigniew Zasłona,1 Pawel Dobrzanski,1 Rafał Krenke3 1Molecure SA, Warsaw, 02-089, Poland; 2Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, 02-097, Poland; 3Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, 02-097, Poland; 4Department of Pathology, Erasmus Medical Center, Rotterdam, 3015 GD, the NetherlandsCorrespondence: Barbara Dymek, Żwirki i Wigury 101, Warsaw, 02-089, Poland, Tel +48 22 552 67 24, Email b.dymek@molecure.comIntroduction: Sarcoidosis is a systemic disease of unknown etiology characterized by granuloma formation in the affected tissues. The pathologically activated macrophages are causatively implicated in disease pathogenesis and play important role in granuloma formation. Chitotriosidase (CHIT1), macrophage-derived protein, is upregulated in sarcoidosis and its levels correlate with disease severity implicating CHIT1 in pathology.Methods: CHIT1 was evaluated in serum and bronchial mucosa and mediastinal lymph nodes specimens from sarcoidosis patients. The therapeutic efficacy of OATD-01 was assessed ex vivo on human bronchoalveolar lavage fluid (BALF) macrophages and in vivo in the murine models of granulomatous inflammation.Results: CHIT1 activity was significantly upregulated in serum from sarcoidosis patients. CHIT1 expression was restricted to granulomas and localized in macrophages. Ex vivo OATD-01 inhibited pro-inflammatory mediators’ production (CCL4, IL-15) by lung macrophages. In the acute model of granulomatous inflammation in mice, OATD-01 showed anti-inflammatory effects reducing the percentage of neutrophils and CCL4 concentration in BALF. In the chronic model, inhibition of CHIT1 led to a decrease in the number of organized lung granulomas and the expression of sarcoidosis-associated genes.Conclusion: In summary, CHIT1 activity was increased in sarcoidosis patients and OATD-01, a first-in-class CHIT1 inhibitor, demonstrated efficacy in murine models of granulomatous inflammation providing a proof-of-concept for its clinical evaluation in sarcoidosis.Keywords: chitinase, OATD-01, granuloma, macrophages, interstitial lung disease

Published
2022

47. Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years: An ESPN/ERA-EDTA Registry Study

Author

Bonthuis, Marjolein, Groothoff, Jaap W., Ariceta, Gema, Baiko, Sergey, Battelino, Nina, Bjerre, Anna, Cransberg, Karlien, Kolvek, Gabriel, Maxwell, Heather, Miteva, Polina, Molchanova, Maria S., Neuhaus, Thomas J., Pape, Lars, Reusz, Gyorgy, Rousset-Rouviere, Caroline, Sandes, Ana Rita, Topaloglu, Rezan, Van Dyck, Maria, Ylinen, Elisa, Zagozdzon, Ilona, Jager, Kitty J., and Harambat, Jérôme

Published
2020
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48. Data from Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors

Author

Karl-Johan Malmberg, Jon-Amund Kyte, Johanna Olweus, Radoslaw Zagozdzon, Magdalena Winiarska, Jodie Goodridge, Björn Önfelt, Ludwig Brandt, Dennis Clement, Malgorzata Bajor, Hilde Almåsbak, Daniel Palacios, Weiwen Yang, Hanna Julie Hoel, Agnieszka Graczyk-Jarzynka, Marta Siernicka, and Vincent Yi Sheng Oei

Abstract

Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles. Kinetics experiments revealed that CAR expression was optimal after 3 days of IL15 stimulation prior to transfection, consistently achieving over 80% expression. CAR-engineered NK cells acquired increased degranulation toward CD19+ targets, and maintained their intrinsic degranulation response toward CD19− K562 cells. The response of redirected NK-cell subsets against CD19+ targets was dependent on their intrinsic thresholds for activation determined through both differentiation and education by killer cell immunoglobulin-like receptors (KIR) and/or CD94/NKG2A binding to self HLA class I and HLA-E, respectively. Redirected primary NK cells were insensitive to inhibition through NKG2A/HLA-E interactions but remained sensitive to inhibition through KIR depending on the amount of HLA class I expressed on target cells. Adaptive NK cells, expressing NKG2C, CD57, and self-HLA–specific KIR(s), displayed superior ability to kill CD19+, HLA low, or mismatched tumor cells. These findings support the feasibility of primary allogeneic NK cells for CAR engineering and highlight a need to consider NK-cell diversity when optimizing efficacy of cancer immunotherapies based on CAR-expressing NK cells. Cancer Immunol Res; 6(4); 467–80. ©2018 AACR.

Published
2023

49. Supplementary Video 1 from Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors

Author

Karl-Johan Malmberg, Jon-Amund Kyte, Johanna Olweus, Radoslaw Zagozdzon, Magdalena Winiarska, Jodie Goodridge, Björn Önfelt, Ludwig Brandt, Dennis Clement, Malgorzata Bajor, Hilde Almåsbak, Daniel Palacios, Weiwen Yang, Hanna Julie Hoel, Agnieszka Graczyk-Jarzynka, Marta Siernicka, and Vincent Yi Sheng Oei

Abstract

Supplementary Video 1. Time-lapse sequence of a serial killer NK cell attacking a cluster of six 221 cells in a 50Ã-50Ã-300 μm3 microwell. The movie plays the same sequence simultaneously side-by-side in fluorescence (left) and bright field (right). The NK cell is shown in blue (in both panels), live targets are shown in green and dead targets in red. At the end of the movie five target cells have been killed. Total imaging time was 4.5 hours with 10 minutes between frames.

Published
2023

50. Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association−European Dialysis and Transplant (ESPN/ERA-EDTA) Registry

Author

Levtchenko, E., Haffner, D., Bjerre, A., Massy, Z., Shtiza, D., Kramar, R., Oberbauer, R., Baiko, S., Sukalo, A., van Hoeck, K., Collart, F., des Grottes, J.M., Pokrajac, D., Roussinov, D., Batinić, D., Lemac, M., Slavicek, J., Seeman, T., Vondrak, K., Heaf, J.G., Toots, U., Finne, P., Grönhagen-Riska, C., Couchoud, C., Lasalle, M, Sahpazova, E, Abazi, N, Ristoka Bojkovska, N, von Gersdorff, G, Scholz, C, Tönshoff, B, Krupka, K, Höcker, B, Pape, L, Afentakis, N, Kapogiannis, A, Printza, N, Reusz, G, Berecki, Cs, Szabó, A, Szabó, T, Györke, Z.S., Kis, E., Palsson, R., Edvardsson, V., Gianoglio, B., Maringhini, S., Pecoraro, C., Picca, S., Testa, S., Vidal, E., Verrina, E., Jankauskiene, A., Pundziene, B., Said-Conti, V., Gatcan, S., Berbeca, O., Zaikova, N., Pavićević, S., Leivestad, T., Zurowska, A., Zagozdzon, I., Mota, C., Almeida, M., Afonso, C., Mircescu, G., Garneata, L., Molchanova, E.A., Tomilina, N.A., Bikbov, B.T., Kostic, M., Peco-Antic, A., Spasojevic-Dimitrijeva, B., Milosevski-Lomic, G., Paripovic, D., Puric, S., Kruscic, D., Podracka, L., Kolvek, G., Buturovic-Ponikvar, J., Novljan, G., Battelino, N., Alonso Melgar, A., Schön, S., Prütz, K.G., Backmän, L., Stendahl, M., Evans, M., Rippe, B., Kuenhi, C.E., Maurer, E., Laube, G.F., Tschumi, S., Parvex, P., Hoitsma, A., Hemke, A., Topaloglu, R., Duzova, A., Ivanov, D., Pruthi, R., Braddon, F., Mannings, S., Cassula, A., Sinha, M.D., Mekahli, Djalila, van Stralen, Karlijn J., Bonthuis, Marjolein, Jager, Kitty J., Balat, Ayşe, Benetti, Elisa, Godefroid, Nathalie, Edvardsson, Vidar O., Heaf, James G., Jankauskiene, Augustina, Kerecuk, Larissa, Marinova, Svetlana, Puteo, Flora, Seeman, Tomas, Zurowska, Aleksandra, Pirenne, Jacques, Schaefer, Franz, and Groothoff, Jaap W.

Published
2016
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