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49 results on '"Zagozdzon, Agnieszka"'

1. 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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2. 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

3. 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

4. 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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5. 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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6. 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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7. 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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8. 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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9. 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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10. 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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11. Arginase 1/2 Inhibitor OATD-02: From Discovery to First-in-man Setup in Cancer Immunotherapy

Author

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

Published
2023
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12. Inhibition of Macrophage-Specific CHIT1 as an Approach to Treat Airway Remodeling in Severe Asthma

Author

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

Published
2023
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14. A Novel Function for Cyclin E in Cell Cycle Progression

Author

Geng, Yan, Lee, Youngmi, Welcker, Markus, Swanger, Jherek, Zagozdzon, Agnieszka, Roberts, James M., Kaldis, Philipp, Clurman, Bruce E., Sicinski, Piotr, Melmed, Shlomo, editor, Rochefort, Henri, editor, Chanson, Phillipe, editor, and Christen, Yves, editor

Published
2008
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15. Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis

Author

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

Published
2022
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17. Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis

Author

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

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 effec

Published
2022

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

Author

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

Abstract

Introduction: 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.

Published
2022

19. A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers

Author

Jirawatnotai, Siwanon, Hu, Yiduo, Michowski, Wojciech, Elias, Joshua E., Becks, Lisa, Bienvenu, Frederic, Zagozdzon, Agnieszka, Goswami, Tapasree, Wang, Yaoyu E., Clark, Alan B., Kunkel, Thomas A., van Harn, Tanja, Xia, Bing, Correll, Mick, Quackenbush, John, Livingston, David M., Gygi, Steven P., and Sicinski, Piotr

Subjects
Interactomes -- Observations -- Methods, DNA repair -- Methods, Cyclin D proteins -- Properties -- Methods, Cancer cells -- Properties -- Methods, DNA damage -- Observations -- Methods, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cyclin D1 is a component of the core cell cycle machinery (1). Abnormally high levels of cyclin D1 are detected in many human cancer types (2). To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process (3). We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation (4,5). These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition., To elucidate the molecular functions of cyclin D1 in human cancer cells, we set out to identify cyclin Dl-interacting proteins in four types of human tumours: mantle cell lymphoma (Granta [...]

Published
2011
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20. Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen

Author

Bienvenu, Frederic, Jirawatnotai, Siwanon, Elias, Joshua E., Meyer, Clifford A., Mizeracka, Karolina, Marson, Alexander, Frampton, Garrett M., Cole, Megan F., Odom, Duncan T., Odajima, Junko, Geng, Yan, Zagozdzon, Agnieszka, Jecrois, Marie, Young, Richard A., Liu, X. Shirley, Cepko, Constance L., Gygi, Steven P., and Sicinski, Piotr

Subjects
Cell cycle -- Research, Cyclin D proteins -- Physiological aspects -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers (1,2). The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag- and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinas--an organ that critically requires cyclin D1 function (3,4)--cyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null ([Ccnd1.sup.-/-]) retinas. Transduction of an activated allele of Notch1 into [Ccnd1.sup.-/-] retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term 'genetic-proteomic', can be used to study the in vivo function of essentially any protein., To study the molecular functions of cyclin D1 during development and in cancer formation, we generated knock-in mouse strains in which tandem (Flag and haemagglutinin (HA)) tags were inserted into [...]

Published
2010
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23. Discovery of OATD-01, a First-in-Class Chitinase Inhibitor as Potential New Therapeutics for Idiopathic Pulmonary Fibrosis

Author

Koralewski, Robert, primary, Dymek, Barbara, additional, Mazur, Marzena, additional, Sklepkiewicz, Piotr, additional, Olejniczak, Sylwia, additional, Czestkowski, Wojciech, additional, Matyszewski, Krzysztof, additional, Andryianau, Gleb, additional, Niedziejko, Piotr, additional, Kowalski, Michal, additional, Gruza, Mariusz, additional, Borek, Bartłomiej, additional, Jedrzejczak, Karol, additional, Bartoszewicz, Agnieszka, additional, Pluta, Elżbieta, additional, Rymaszewska, Aleksandra, additional, Kania, Magdalena, additional, Rejczak, Tomasz, additional, Piasecka, Sylwia, additional, Mlacki, Michal, additional, Mazurkiewicz, Marcin, additional, Piotrowicz, Michał, additional, Salamon, Magdalena, additional, Zagozdzon, Agnieszka, additional, Napiorkowska-Gromadzka, Agnieszka, additional, Bartlomiejczak, Aneta, additional, Mozga, Witold, additional, Dobrzański, Paweł, additional, Dzwonek, Karolina, additional, Golab, Jakub, additional, Nowotny, Marcin, additional, Olczak, Jacek, additional, and Golebiowski, Adam, additional

Published
2020
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25. Benzoxazepine-Derived Selective, Orally Bioavailable Inhibitor of Human Acidic Mammalian Chitinase

Author

Andryianau, Gleb, primary, Kowalski, Michal, additional, Piotrowicz, Michal C., additional, Rajkiewicz, Adam A., additional, Dymek, Barbara, additional, Sklepkiewicz, Piotr L., additional, Pluta, Elzbieta, additional, Stefaniak, Filip, additional, Czestkowski, Wojciech, additional, Olejniczak, Sylwia, additional, Mazur, Marzena, additional, Niedziejko, Piotr, additional, Koralewski, Robert, additional, Matyszewski, Krzysztof, additional, Gruza, Mariusz, additional, Zagozdzon, Agnieszka, additional, Salamon, Magdalena, additional, Rymaszewska, Aleksandra, additional, Welzer, Mikolaj, additional, Dzwonek, Karolina, additional, Golab, Jakub, additional, Olczak, Jacek, additional, Bartoszewicz, Agnieszka, additional, and Golebiowski, Adam, additional

Published
2020
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28. Discovery of selective, orally bioavailable inhibitor of mouse chitotriosidase

Author

Mazur, Marzena, Bartoszewicz, Agnieszka, Dymek, Barbara, Salamon, Magdalena, Andryianau, Gleb, Kowalski, Michał, Olejniczak, Sylwia, Matyszewski, Krzysztof, Pluta, Elżbieta, Borek, Bartłomiej, Stefaniak, Filip, Zagozdzon, Agnieszka, Mazurkiewicz, Marcin, Koralewski, Robert, Czestkowski, Wojciech, Piotrowicz, Michał, Niedziejko, Piotr, Gruza, Mariusz M., Dzwonek, Karolina, Golebiowski, Adam, Golab, Jakub, and Olczak, Jacek

Published
2018
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29. 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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30. Development of Dual Chitinase Inhibitors as Potential New Treatment for Respiratory System Diseases

Author

Mazur, Marzena, primary, Dymek, Barbara, additional, Koralewski, Robert, additional, Sklepkiewicz, Piotr, additional, Olejniczak, Sylwia, additional, Mazurkiewicz, Marcin, additional, Piotrowicz, Michał, additional, Salamon, Magdalena, additional, Jędrzejczak, Karol, additional, Zagozdzon, Agnieszka, additional, Czestkowski, Wojciech, additional, Matyszewski, Krzysztof, additional, Borek, Bartłomiej, additional, Bartoszewicz, Agnieszka, additional, Pluta, Elżbieta, additional, Rymaszewska, Aleksandra, additional, Mozga, Witold, additional, Stefaniak, Filip, additional, Dobrzański, Paweł, additional, Dzwonek, Karolina, additional, Golab, Jakub, additional, Golebiowski, Adam, additional, and Olczak, Jacek, additional

Published
2019
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31. CHIT1 is a novel therapeutic target in idiopathic pulmonary fibrosis (IPF): anti-fibrotic efficacy of OATD-01, a potent and selective chitinase inhibitor in the mouse model of pulmonary fibrosis

Author

Dymek, Barbara, primary, Sklepkiewicz, Piotr, additional, Mlacki, Michal, additional, Zagozdzon, Agnieszka, additional, Koralewski, Robert, additional, Mazur, Marzena, additional, Paplinska-Goryca, Magdalena, additional, Nejman-Gryz, Patrycja, additional, Proboszcz, Malgorzata, additional, Gorska, Katarzyna, additional, Maskey-Warzechowska, Marta, additional, Przysucha, Natalia, additional, Krenke, Rafal, additional, Golebiowski, Adam, additional, Dobrzanski, Pawel, additional, and Dzwonek, Karolina, additional

Published
2018
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32. Abstract B17: FOXO1 is transcriptional regulator of malignant B-cell surface antigen CD20, the target for therapeutic monoclonal antibodies

Author

Pyrzynska, Beata, primary, Zerrouqi, Abdessamad, additional, Dwojak, Michal, additional, Morlino, Giulia, additional, Zapala, Piotr, additional, Miazek, Nina, additional, Zagozdzon, Agnieszka, additional, Bojarczuk, Kamil, additional, Bobrowicz, Malgorzata, additional, Siernicka, Marta, additional, Machnicki, Marcin M., additional, Barankiewicz, Joanna, additional, Lech-Maranda, Ewa, additional, Juszczynski, Przemyslaw, additional, Calado, Dinis, additional, Golab, Jakub, additional, and Winiarska, Magdalena, additional

Published
2018
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34. FOXO1 promotes resistance of non-Hodgkin lymphomas to anti-CD20-based therapy

Author

Pyrzynska, Beata, primary, Dwojak, Michal, additional, Zerrouqi, Abdessamad, additional, Morlino, Giulia, additional, Zapala, Piotr, additional, Miazek, Nina, additional, Zagozdzon, Agnieszka, additional, Bojarczuk, Kamil, additional, Bobrowicz, Malgorzata, additional, Siernicka, Marta, additional, Machnicki, Marcin M., additional, Gobessi, Stefania, additional, Barankiewicz, Joanna, additional, Lech-Maranda, Ewa, additional, Efremov, Dimitar G., additional, Juszczynski, Przemyslaw, additional, Calado, Dinis, additional, Golab, Jakub, additional, and Winiarska, Magdalena, additional

Published
2018
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35. Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma

Author

Mazur, Marzena, primary, Olczak, Jacek, additional, Olejniczak, Sylwia, additional, Koralewski, Robert, additional, Czestkowski, Wojciech, additional, Jedrzejczak, Anna, additional, Golab, Jakub, additional, Dzwonek, Karolina, additional, Dymek, Barbara, additional, Sklepkiewicz, Piotr L., additional, Zagozdzon, Agnieszka, additional, Noonan, Tom, additional, Mahboubi, Keyvan, additional, Conway, Bruce, additional, Sheeler, Ryan, additional, Beckett, Paul, additional, Hungerford, William M., additional, Podjarny, Alberto, additional, Mitschler, Andre, additional, Cousido-Siah, Alexandra, additional, Fadel, Firas, additional, and Golebiowski, Adam, additional

Published
2018
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37. Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma

Author

Mazur, Marzena, Olczak, Jacek, Olejniczak, Sylwia, Koralewski, Robert, Czestkowski, Wojciech, Jedrzejczak, Anna, Golab, Jakub, Dzwonek, Karolina, Dymek, Barbara, Sklepkiewicz, Piotr L., Zagozdzon, Agnieszka, Noonan, Tom, Mahboubi, Keyvan, Conway, Bruce, Sheeler, Ryan, Beckett, Paul, Hungerford, William M., Podjarny, Alberto, Mitschler, Andre, Cousido-Siah, Alexandra, Fadel, Firas, and Golebiowski, Adam

Abstract

This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7fas a highly potent AMCase inhibitor (IC50values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150× against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in HDM-induced allergic airway inflammation in mice, reducing inflammatory cell influx in the BALF and total IgE concentration in plasma, which correlated with decrease of chitinolytic activity. Therapeutic efficacy of compound 7fin the clinically relevant aeroallergen-induced acute asthma model in mice provides a rationale for developing AMCase inhibitor for the treatment of asthma.

Published
2024
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39. Peroxiredoxin-1 protects estrogen receptor alpha from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer

Author

O'Leary, Patrick C., Terrile, Marta, Bajor, Malgorzata, Gaj, Pawel, Hennessy, Bryan T., Mills, Gordon B., Zagozdzon, Agnieszka, O'Connor, Darran P., Brennan, Donal J., Connor, Kate, Li, Jane, Gonzalez-Angulo, Ana Maria, Sun, Han-Dong, Pu, Jian-Xin, Pontén, Fredrik, Uhlen, Mathias, Jirstrom, Karin, Nowis, Dominika A., Crown, John P., Zagozdzon, Radoslaw, Gallagher, William M., O'Leary, Patrick C., Terrile, Marta, Bajor, Malgorzata, Gaj, Pawel, Hennessy, Bryan T., Mills, Gordon B., Zagozdzon, Agnieszka, O'Connor, Darran P., Brennan, Donal J., Connor, Kate, Li, Jane, Gonzalez-Angulo, Ana Maria, Sun, Han-Dong, Pu, Jian-Xin, Pontén, Fredrik, Uhlen, Mathias, Jirstrom, Karin, Nowis, Dominika A., Crown, John P., Zagozdzon, Radoslaw, and Gallagher, William M.

Abstract

Introduction: Peroxiredoxin-1 (PRDX1) is a multifunctional protein, acting as a hydrogen peroxide (H2O2) scavenger, molecular chaperone and immune modulator. Although differential PRDX1 expression has been described in many tumors, the potential role of PRDX1 in breast cancer remains highly ambiguous. Using a comprehensive antibody-based proteomics approach, we interrogated PRDX1 protein as a putative biomarker in estrogen receptor (ER)-positive breast cancer. Methods: An anti-PRDX1 antibody was validated in breast cancer cell lines using immunoblotting, immunohistochemistry and reverse phase protein array (RPPA) technology. PRDX1 protein expression was evaluated in two independent breast cancer cohorts, represented on a screening RPPA (n = 712) and a validation tissue microarray (n = 498). In vitro assays were performed exploring the functional contribution of PRDX1, with oxidative stress conditions mimicked via treatment with H2O2, peroxynitrite, or adenanthin, a PRDX1/2 inhibitor. Results: In ER-positive cases, high PRDX1 protein expression is a biomarker of improved prognosis across both cohorts. In the validation cohort, high PRDX1 expression was an independent predictor of improved relapse-free survival (hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.40 to 0.96, P = 0.032), breast cancer-specific survival (HR = 0.44, 95% CI = 0.24 to 0.79, P = 0.006) and overall survival (HR = 0.61, 95% CI = 0.44 to 0.85, P = 0.004). RPPA screening of cancer signaling proteins showed that ER alpha protein was upregulated in PRDX1 high tumors. Exogenous H2O2 treatment decreased ER alpha protein levels in ER-positive cells. PRDX1 knockdown further sensitized cells to H2O2- and peroxynitrite-mediated effects, whilst PRDX1 overexpression protected against this response. Inhibition of PRDX1/2 antioxidant activity with adenanthin dramatically reduced ER alpha levels in breast cancer cells. Conclusions: PRDX1 is shown to be an independent predictor of improved outcomes in

Published
2014
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41. Cyclin C is a haploinsufficient tumour suppressor

Author

Li, Na, primary, Fassl, Anne, additional, Chick, Joel, additional, Inuzuka, Hiroyuki, additional, Li, Xiaoyu, additional, Mansour, Marc R., additional, Liu, Lijun, additional, Wang, Haizhen, additional, King, Bryan, additional, Shaik, Shavali, additional, Gutierrez, Alejandro, additional, Ordureau, Alban, additional, Otto, Tobias, additional, Kreslavsky, Taras, additional, Baitsch, Lukas, additional, Bury, Leah, additional, Meyer, Clifford A., additional, Ke, Nan, additional, Mulry, Kristin A., additional, Kluk, Michael J., additional, Roy, Moni, additional, Kim, Sunkyu, additional, Zhang, Xiaowu, additional, Geng, Yan, additional, Zagozdzon, Agnieszka, additional, Jenkinson, Sarah, additional, Gale, Rosemary E., additional, Linch, David C., additional, Zhao, Jean J., additional, Mullighan, Charles G., additional, Harper, J. Wade, additional, Aster, Jon C., additional, Aifantis, Iannis, additional, von Boehmer, Harald, additional, Gygi, Steven P., additional, Wei, Wenyi, additional, Look, A. Thomas, additional, and Sicinski, Piotr, additional

Published
2014
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42. Inhibitors of SRC kinases impair antitumor activity of anti-CD20 monoclonal antibodies

Author

Winiarska, Magdalena, primary, Bojarczuk, Kamil, additional, Pyrzynska, Beata, additional, Bil, Jacek, additional, Siernicka, Marta, additional, Dwojak, Michal, additional, Bobrowicz, Malgorzata, additional, Miazek, Nina, additional, Zapala, Piotr, additional, Zagozdzon, Agnieszka, additional, Krol, Magdalena, additional, Syta, Aleksandra, additional, Podszywalow-Bartnicka, Paulina, additional, Pilch, Zofia, additional, Dabrowska-Iwanicka, Anna, additional, Juszczynski, Przemyslaw, additional, Efremov, Dimitar G, additional, Slabicki, Mikolaj, additional, Zenz, Thorsten, additional, Roy, Aude Le, additional, Olive, Daniel, additional, Rygiel, Tomasz P, additional, Leusen, Jeanette HW, additional, and Golab, Jakub, additional

Published
2014
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43. Peroxiredoxin-1 protects estrogen receptor α from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer

Author

O’Leary, Patrick C, primary, Terrile, Marta, additional, Bajor, Malgorzata, additional, Gaj, Pawel, additional, Hennessy, Bryan T, additional, Mills, Gordon B, additional, Zagozdzon, Agnieszka, additional, O’Connor, Darran P, additional, Brennan, Donal J, additional, Connor, Kate, additional, Li, Jane, additional, Gonzalez-Angulo, Ana Maria, additional, Sun, Han-Dong, additional, Pu, Jian-Xin, additional, Pontén, Fredrik, additional, Uhlén, Mathias, additional, Jirström, Karin, additional, Nowis, Dominika A, additional, Crown, John P, additional, Zagozdzon, Radoslaw, additional, and Gallagher, William M, additional

Published
2014
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44. Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen

Author

Massachusetts Institute of Technology. Department of Biology, Young, Richard A., Bienvenu, Frederic, Jirawatnotai, Siwanon, Elias, Joshua E., Meyer, Clifford A., Mizeracka, Karolina, Marson, Alexander, Frampton, Garrett M., Cole, Megan F., Odom, Duncan, Odajima, Junko, Geng, Yan, Zagozdzon, Agnieszka, Jecrois, Marie, Liu, X. Shirley, Cepko, Constance L., Gygi, Steven P., Sicinski, Piotr, Massachusetts Institute of Technology. Department of Biology, Young, Richard A., Bienvenu, Frederic, Jirawatnotai, Siwanon, Elias, Joshua E., Meyer, Clifford A., Mizeracka, Karolina, Marson, Alexander, Frampton, Garrett M., Cole, Megan F., Odom, Duncan, Odajima, Junko, Geng, Yan, Zagozdzon, Agnieszka, Jecrois, Marie, Liu, X. Shirley, Cepko, Constance L., Gygi, Steven P., and Sicinski, Piotr

Abstract

Author manuscript: 2010 September 22., Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers[superscript 1, 2]. The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag- and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinas—an organ that critically requires cyclin D1 function[superscript 3, 4]—cyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1-/-) retinas. Transduction of an activated allele of Notch1 into Ccnd1-/- retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term ‘genetic–proteomic’, can be used to study the in vivo function of essentially any protein.

Published
2012

45. Kinase-Independent Function of Cyclin E

Author

Geng, Yan, primary, Lee, Young-Mi, additional, Welcker, Markus, additional, Swanger, Jherek, additional, Zagozdzon, Agnieszka, additional, Winer, Joel D., additional, Roberts, James M., additional, Kaldis, Philipp, additional, Clurman, Bruce E., additional, and Sicinski, Piotr, additional

Published
2007
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46. A Novel Function for Cyclin E in Cell Cycle Progression.

Author

Melmed, Shlomo, Rochefort, Henri, Chanson, Phillipe, Christen, Yves, Geng, Yan, Lee, Youngmi, Welcker, Markus, Swanger, Jherek, Zagozdzon, Agnieszka, Roberts, James M., Kaldis, Philipp, Clurman, Bruce E., and Sicinski, Piotr

Abstract

In this study we demonstrated the presence of a kinase-independent function for cyclin E. Specifically, weobserved that a kinase-deficient cyclin E1mutant can reconstitute cyclin E's function in cyclin E-null cells. Kinase-deficient cyclin E1 is loaded onto chromatin during G0 → S progression, it restores MCM incorporation and it facilitates S phase entry of cyclin E-null cells. We also observed that, in wild-type cells, cyclin E is loaded onto DNA during the G0 → S transition, and it co-localizes with MCM on chromatin. We demonstrated a physical interaction between cyclin E and MCM. We propose that the DNA-bound fraction of cyclin E facilitates MCM loading in a kinase-independent fashion. Our work indicates that, in addition to their well-established function as activators of cyclin-dependent kinases, E-cyclins play a kinase-independent function in cell cycle progression. [ABSTRACT FROM AUTHOR]

Published
2008
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47. Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity.

Author

Juxiang Cao, Schulte, Jennifer, Knight, Alexander, Leslie, Nicholas R., Zagozdzon, Agnieszka, Bronson, Roderick, Manevich, Yefim, Beeson, Craig, and Neumann, Carola A.

Subjects
CARCINOGENESIS, PEROXIDASE, BREAST cancer, EPITHELIAL cells, MAMMARY glands
Abstract

It is widely accepted that reactive oxygen species (ROS) promote tumorigenesis. However, the exact mechanisms are still unclear. As mice lacking the peroxidase peroxiredoxin1 (Prdx1) produce more cellular ROS and die prematurely of cancer, they offer an ideal model system to study ROS-induced tumorigenesis. Prdx1 ablation increased the susceptibility to Ras-induced breast cancer. We, therefore, investigated the role of Prdx1 in regulating oncogenic Ras effector pathways. We found Akt hyperactive in fibroblasts and mammary epithelial cells lacking Prdx1. Investigating the nature of such elevated Akt activation established a novel role for Prdx1 as a safeguard for the lipid phosphatase activity of PTEN, which is essential for its tumour suppressive function. We found binding of the peroxidase Prdx1 to PTEN essential for protecting PTEN from oxidation-induced inactivation. Along those lines, Prdx1 tumour suppression of Ras- or ErbB-2-induced transformation was mediated mainly via PTEN. [ABSTRACT FROM AUTHOR]

Published
2009
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48. Der Generalbass.

Author

ZAGOZDZON, AGNIESZKA and SCHHIDT, KAI

Subjects
*MUSIC education, *STRINGED instruments, *LESSON planning
Abstract

The article presents a lesson plan to accompany the audio and visual materials developed by the project Short Music Story (SMS) on the musical instrumental group known as the bass stringed instruments.

Published
2011

49. Peroxiredoxin-1 protects estrogen receptor α from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer.

Author

O'Leary, Patrick C, Terrile, Marta, Bajor, Malgorzata, Gaj, Pawel, Hennessy, Bryan T, Mills, Gordon B, Zagozdzon, Agnieszka, O'Connor, Darran P, Brennan, Donal J, Connor, Kate, Li, Jane, Gonzalez-Angulo, Ana Maria, Sun, Han-Dong, Pu, Jian-Xin, Pontén, Fredrik, Uhlén, Mathias, Jirström, Karin, Nowis, Dominika A, Crown, John P, and Zagozdzon, Radoslaw

Abstract

Introduction: Peroxiredoxin-1 (PRDX1) is a multifunctional protein, acting as a hydrogen peroxide (H2O2) scavenger, molecular chaperone and immune modulator. Although differential PRDX1 expression has been described in many tumors, the potential role of PRDX1 in breast cancer remains highly ambiguous. Using a comprehensive antibody-based proteomics approach, we interrogated PRDX1 protein as a putative biomarker in estrogen receptor (ER)-positive breast cancer.Methods: An anti-PRDX1 antibody was validated in breast cancer cell lines using immunoblotting, immunohistochemistry and reverse phase protein array (RPPA) technology. PRDX1 protein expression was evaluated in two independent breast cancer cohorts, represented on a screening RPPA (n = 712) and a validation tissue microarray (n = 498). In vitro assays were performed exploring the functional contribution of PRDX1, with oxidative stress conditions mimicked via treatment with H2O2, peroxynitrite, or adenanthin, a PRDX1/2 inhibitor.Results: In ER-positive cases, high PRDX1 protein expression is a biomarker of improved prognosis across both cohorts. In the validation cohort, high PRDX1 expression was an independent predictor of improved relapse-free survival (hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.40 to 0.96, P = 0.032), breast cancer-specific survival (HR = 0.44, 95% CI = 0.24 to 0.79, P = 0.006) and overall survival (HR = 0.61, 95% CI = 0.44 to 0.85, P = 0.004). RPPA screening of cancer signaling proteins showed that ERα protein was upregulated in PRDX1 high tumors. Exogenous H2O2 treatment decreased ERα protein levels in ER-positive cells. PRDX1 knockdown further sensitized cells to H2O2- and peroxynitrite-mediated effects, whilst PRDX1 overexpression protected against this response. Inhibition of PRDX1/2 antioxidant activity with adenanthin dramatically reduced ERα levels in breast cancer cells.Conclusions: PRDX1 is shown to be an independent predictor of improved outcomes in ER-positive breast cancer. Through its antioxidant function, PRDX1 may prevent oxidative stress-mediated ERα loss, thereby potentially contributing to maintenance of an ER-positive phenotype in mammary tumors. These results for the first time imply a close connection between biological activity of PRDX1 and regulation of estrogen-mediated signaling in breast cancer. [ABSTRACT FROM AUTHOR]

Published
2014
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