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2. The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs

Author

Tesfaye, Ephrath, Martinez-Terroba, Elena, Bendor, Jordan, Winkler, Lauren, Olivero, Christiane, Chen, Kevin, Feldser, David M, Zamudio, Jesse R, and Dimitrova, Nadya

Subjects
Pediatric Research Initiative, Cancer, Genetics, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Aetiology, Animals, Carcinogenesis, Cell Line, Tumor, Cell Proliferation, Cellular Senescence, DNA Damage, E2F Transcription Factors, Gene Expression Regulation, Neoplastic, Genome-Wide Association Study, Mice, Neoplasms, Proto-Oncogene Proteins c-myc, RNA, Long Noncoding, Signal Transduction, Stress, Physiological, Tumor Suppressor Protein p53, p53, tumor suppression, lncRNA, senescence, transcription
Abstract

The p53 pathway is a universal tumor suppressor mechanism that limits tumor progression by triggering apoptosis or permanent cell cycle arrest, called senescence. In recent years, efforts to reactivate p53 function in cancer have proven to be a successful therapeutic strategy in murine models and have gained traction with the development of a range of small molecules targeting mutant p53. However, knowledge of the downstream mediators of p53 reactivation in different oncogenic contexts has been limited. Here, we utilized a panel of murine cancer cell lines from three distinct tumor types susceptible to alternative outcomes following p53 restoration to define unique and shared p53 transcriptional signatures. While we found that the majority of p53-bound sites and p53-responsive transcripts are tumor-type specific, analysis of shared targets identified a core signature of genes activated by p53 across all contexts. Furthermore, we identified repression of E2F and Myc target genes as a key feature of senescence. Characterization of p53-induced transcripts revealed core and senescence-specific long noncoding RNAs (lncRNAs) that are predominantly chromatin associated and whose production is coupled to cis-regulatory activities. Functional investigation of the contributions of p53-induced lncRNAs to p53-dependent outcomes highlighted Pvt1b, the p53-dependent isoform of Pvt1, as a mediator of p53-dependent senescence via Myc repression. Inhibition of Pvt1b led to decreased activation of senescence markers and increased levels of markers of proliferation. These findings shed light on the core and outcome-specific p53 restoration signatures across different oncogenic contexts and underscore the key role of the p53-Pvt1b-Myc regulatory axis in mediating proliferative arrest.

Published
2021

3. Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy

Author

Wang, Yi, primary, Zhang, Mingming, additional, Wang, Rong, additional, Lin, Jing, additional, Ma, Qing, additional, Guo, Haipeng, additional, Huang, Huihui, additional, Liang, Zhuomin, additional, Cao, Yangpo, additional, Zhang, Xiaoran, additional, Lu, Yao Wei, additional, Liu, Jianming, additional, Xiao, Feng, additional, Yan, Hualin, additional, Dimitrova, Nadya, additional, Huang, Zhan-Peng, additional, Mably, John D., additional, Pu, William T., additional, and Wang, Da-Zhi, additional

Published
2024
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7. Challenges in LncRNA Biology: Views and Opinions.

Author

Adjeroh, Donald A., Zhou, Xiaobo, Paschoal, Alexandre Rossi, Dimitrova, Nadya, Derevyanchuk, Ekaterina G., Shkurat, Tatiana P., Loeb, Jeffrey A., Martinez, Ivan, and Lipovich, Leonard

Subjects
LANGUAGE models, DEEP learning, LINCRNA, COVID-19, BIOLOGY
Abstract

This is a mini-review capturing the views and opinions of selected participants at the 2021 IEEE BIBM 3rd Annual LncRNA Workshop, held in Dubai, UAE. The views and opinions are expressed on five broad themes related to problems in lncRNA, namely, challenges in the computational analysis of lncRNAs, lncRNAs and cancer, lncRNAs in sports, lncRNAs and COVID-19, and lncRNAs in human brain activity. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment.

Author

Martinez-Terroba, Elena, Plasek-Hegde, Leah M., Chiotakakos, Ioannis, Li, Vincent, de Miguel, Fernando J., Robles-Oteiza, Camila, Tyagi, Antariksh, Politi, Katerina, Zamudio, Jesse R., and Dimitrova, Nadya

Subjects
TUMOR microenvironment, GENE expression, GENETIC overexpression, LINCRNA, METASTASIS
Abstract

Expression of the long noncoding RNA (lncRNA) metastasis–associated lung adenocarcinoma transcript 1 (MALAT1) correlates with tumor progression and metastasis in many tumor types. However, the impact and mechanism of action by which MALAT1 promotes metastatic disease remain elusive. Here, we used CRISPR activation (CRISPRa) to overexpress MALAT1/Malat1 in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. Malat1 overexpression was sufficient to promote the progression of LUAD to metastatic disease in mice. Overexpression of MALAT1/Malat1 enhanced cell mobility and promoted the recruitment of protumorigenic macrophages to the tumor microenvironment through paracrine secretion of CCL2/Ccl2. Ccl2 up-regulation was the result of increased global chromatin accessibility upon Malat1 overexpression. Macrophage depletion and Ccl2 blockade counteracted the effects of Malat1 overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment. Editor's summary: The long noncoding RNA (lncRNA) MALAT1 is overexpressed in many tumor types, and expression is associated with metastasis. Martinez-Terroba et al. used CRISPR activation to investigate how MALAT1/Malat1 promotes metastasis in human and murine lung adenocarcinoma (LUAD). Overexpression of Malat1 resulted in altered global chromatin accessibility and increased transcription of Ccl2 in murine tumor cells. Ccl2 secretion promoted recruitment of protumorigenic macrophages and metastasis, which could be rescued by blockade of Ccl2 or by macrophage depletion. These findings indicate that MALAT1/Malat1 overexpression induces reprogramming of the tumor microenvironment in LUAD to drive metastasis. —Hannah Isles [ABSTRACT FROM AUTHOR]

Published
2024
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11. Treatment challenges in and outside a network setting: Head and neck cancers

Author

Hackl, Monika, Eycken, Elizabeth Van, Henau, Kris, Dimitrova, Nadya, Sekerija, Mario, Dušek, Ladislav, Mägi, Margit, Malila, Nea, Leinonen, Maarit, Velten, Michel, Troussard, Xavier, Bouvier, Veronique, Guizard, Anne-Valérie, Bouvier, Anne-Marie, Arveux, Patrick, Maynadié, Marc, Woronoff, Anne-Sophie, Robaszkiewic, Michel, Baldi, Isabelle, Monnereau, Alain, Tretarre, Brigitte, Colonna, Marc, Molinié, Florence, Bara, Simona, Schvartz, Claire, Lapôtre-Ledoux, Bénédicte, Grosclaude, Pascale, Stabenow, Roland, Luttmann, Sabine, Nennecke, Alice, Engel, Jutta, Schubert-Fritschle, Gabriele, Heidrich, Jan, Holleczek, Bernd, Jónasson, Jón Gunnlaugur, Clough-Gorr, Kerri, Comber, Harry, Mazzoleni, Guido, Giacomin, Adriano, Sutera Sardo, Antonella, Barchielli, Alessandr, Serraino, Diego, De Angelis, Roberta, Mallone, Sandra, Tavilla, Andrea, Pierannunzio, Daniela, Rossi, Silvia, Santaquilani, Mariano, Knijn, Arnold, Pannozzo, Fabio, Gennaro, Valerio, Benfatto, Lucia, Ricci, Paolo, Autelitano, Mariangela, Spagnoli, Gianbattista, Fusco, Mario, Usala, Mario, Vitale, Francesco, Michiara, Maria, Tumino, Rosario, Mangone, Lucia, Falcini, Fabio, Ferretti, Stefano, Filiberti, Rosa Angela, Marani, Enza, Iannelli, Arturo, Sensi, Flavio, Piffer, Silvano, Gentilini, Maria, Madeddu, Anselmo, Ziino, Antonio, Maspero, Sergio, Candela, Pina, Stracci, Fabrizio, Tagliabue, Giovanna, Rugge, Massimo, Trama, Annalisa, Gatta, Gemma, Botta, Laura, Capocaccia, Riccardo, Pildava, Santa, Smailyte, Giedre, Calleja, Neville, Johannesen, Tom Børge, Rachtan, Jadwiga, Góźdź, Stanisław, Błaszczyk, Jerzy, Kępska, Kamila, de Lacerda, Gonçalo Forjaz, Bento, Maria José, Miranda, Ana, Diba, Chakameh Safaei, Almar, Enrique, Larrañaga, Nerea, de Munain, Arantza Lopez, Torrella-Ramos, Ana, Díaz García, José María, Marcos-Gragera, Rafael, Sanchez, Maria Josè, Navarro, Carmen, Salmeron, Diego, Moreno-Iribas, Conchi, Galceran, Jaume, Carulla, Marià, Mousavi, Mohsen, Bouchardy, Christine, Ess, Silvia M., Bordoni, Andrea, Konzelmann, Isabelle, Rashbass, Jem, Gavin, Anna, Brewster, David H., Huws, Dyfed Wyn, Visser, Otto, Bielska-Lasota, Magdalena, Primic-Zakelj, Maja, Kunkler, Ian, Benhamou, Ellen, Orlandi, Ester, Alfieri, Salvatore, Simon, Christian, and Licitra, Lisa

Published
2019
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12. Testicular germ-cell tumours and penile squamous cell carcinoma: Appropriate management makes the difference

Author

Hackl, Monika, Eycken, Elizabeth Van, Henau, Kris, Dimitrova, Nadya, Sekerija, Mario, Dušek, Ladislav, Mägi, Margit, Malila, Nea, Leinonen, Maarit, Velten, Michel, Troussard, Xavier, Bouvier, Veronique, Guizard, Anne-Valérie, Bouvier, Anne-Marie, Arveux, Patrick, Maynadié, Marc, Woronoff, Anne-Sophie, Robaszkiewic, Michel, Baldi, Isabelle, Monnereau, Alain, Tretarre, Brigitte, Colonna, Marc, Molinié, Florence, Bara, Simona, Schvartz, Claire, Lapôtre-Ledoux, Bénédicte, Grosclaude, Pascale, Stabenow, Roland, Luttmann, Sabine, Nennecke, Alice, Engel, Jutta, Schubert-Fritschle, Gabriele, Heidrich, Jan, Holleczek, Bernd, Jónasson, Jón Gunnlaugur, Clough-Gorr, Kerri, Comber, Harry, Mazzoleni, Guido, Giacomin, Adriano, Sutera Sardo, Antonella, Barchielli, Alessandr, Serraino, Diego, De Angelis, Roberta, Mallone, Sandra, Tavilla, Andrea, Pierannunzio, Daniela, Rossi, Silvia, Santaquilani, Mariano, Knijn, Arnold, Pannozzo, Fabio, Gennaro, Valerio, Benfatto, Lucia, Ricci, Paolo, Autelitano, Mariangela, Spagnoli, Gianbattista, Fusco, Mario, Usala, Mario, Vitale, Francesco, Michiara, Maria, Tumino, Rosario, Mangone, Lucia, Falcini, Fabio, Ferretti, Stefano, Filiberti, Rosa Angela, Marani, Enza, Iannelli, Arturo, Sensi, Flavio, Piffer, Silvano, Gentilini, Maria, Madeddu, Anselmo, Ziino, Antonio, Maspero, Sergio, Candela, Pina, Stracci, Fabrizio, Tagliabue, Giovanna, Rugge, Massimo, Trama, Annalisa, Gatta, Gemma, Botta, Laura, Capocaccia, Riccardo, Pildava, Santa, Smailyte, Giedre, Calleja, Neville, Johannesen, Tom Børge, Rachtan, Jadwiga, Góźdź, Stanisław, Błaszczyk, Jerzy, Kępska, Kamila, de Lacerda, Gonçalo Forjaz, Bento, Maria José, Miranda, Ana, Diba, Chakameh Safaei, Almar, Enrique, Larrañaga, Nerea, de Munain, Arantza Lopez, Torrella-Ramos, Ana, Díaz García, José María, Marcos-Gragera, Rafael, Sanchez, Maria Josè, Navarro, Carmen, Salmeron, Diego, Moreno-Iribas, Conchi, Galceran, Jaume, Carulla, Marià, Mousavi, Mohsen, Bouchardy, Christine, M. Ess, Silvia, Bordoni, Andrea, Konzelmann, Isabelle, Rashbass, Jem, Gavin, Anna, Brewster, David H., Huws, Dyfed Wyn, Visser, Otto, Bielska-Lasota, Magdalena, Primic-Zakelj, Maja, Kunkler, Ian, Benhamou, Ellen, Nicolai, Nicola, Biasoni, Davide, Catanzaro, Mario A., and Colecchia, Maurizio

Published
2019
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13. Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting

Author

Hackl, Monika, Eycken, Elizabeth Van, Henau, Kris, Dimitrova, Nadya, Sekerija, Mario, Dušek, Ladislav, Mägi, Margit, Malila, Nea, Leinonen, Maarit, Velten, Michel, Troussard, Xavier, Bouvier, Veronique, Guizard, Anne-Valérie, Bouvier, Anne-Marie, Arveux, Patrick, Maynadié, Marc, Woronoff, Anne-Sophie, Robaszkiewicz, Michel, Baldi, Isabelle, Monnereau, Alain, Tretarre, Brigitte, Colonna, Marc, Molinié, Florence, Bara, Simona, Schvartz, Claire, Lapôtre-Ledoux, Bénédicte, Grosclaude, Pascale, Stabenow, Roland, Luttmann, Sabine, Nennecke, Alice, Engel, Jutta, Schubert-Fritschle, Gabriele, Heidrich, Jan, Holleczek, Bernd, Jónasson, Jón Gunnlaugur, Clough-Gorr, Kerri, Comber, Harry, Mazzoleni, Guido, Giacomin, Adriano, Sardo, Antonella Sutera, Barchielli, Alessandro, Serraino, Diego, De Angelis, Roberta, Mallone, Sandra, Tavilla, Andrea, Pierannunzio, Daniela, Rossi, Silvia, Santaquilani, Mariano, Knijn, Arnold, Pannozzo, Fabio, Gennaro, Valerio, Benfatto, Lucia, Ricci, Paolo, Autelitano, Mariangela, Spagnoli, Gianbattista, Fusco, Mario, Usala, Mario, Vitale, Francesco, Michiara, Maria, Tumino, Rosario, Mangone, Lucia, Falcini, Fabio, Ferretti, Stefano, Angela Filiberti, Rosa, Marani, Enza, Iannelli, Arturo, Sensi, Flavio, Piffer, Silvano, Gentilini, Maria, Madeddu, Anselmo, Ziino, Antonio, Maspero, Sergio, Candela, Pina, Stracci, Fabrizio, Tagliabue, Giovanna, Rugge, Massimo, Trama, Annalisa, Gatta, Gemma, Botta, Laura, Capocaccia, Riccardo, Pildava, Santa, Smailyte, Giedre, Calleja, Neville, Johannesen, Tom Børge, Rachtan, Jadwiga, Góźdź, Stanisław, Błaszczyk, Jerzy, Kępska, Kamila, de Lacerda, Gonçalo Forjaz, Bento, Maria José, Miranda, Ana, Diba, Chakameh Safaei, Almar, Enrique, Larrañaga, Nerea, de Munain, Arantza Lopez, Torrella-Ramos, Ana, Díaz García, José María, Marcos-Gragera, Rafael, Sanchez, Maria Josè, Navarro, Carmen, Salmeron, Diego, Moreno-Iribas, Conchi, Galceran, Jaume, Carulla, Marià, Mousavi, Mohsen, Bouchardy, Christine, Ess, Silvia M., Bordoni, Andrea, Konzelmann, Isabelle, Rashbass, Jem, Gavin, Anna, Brewster, David H., Huws, Dyfed Wyn, Visser, Otto, Bielska-Lasota, Magdalena, Primic-Zakelj, Maja, Kunkler, Ian, Benhamou, Ellen, Imbimbo, Martina, Maury, Jean-Michel, Garassino, Marina, and Girard, Nicolas

Published
2019
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14. Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Author

Hackl, Monika, Van Eycken, Elizabeth, Henau, Kris, Dimitrova, Nadya, Sekerija, Mario, Dušek, Ladislav, Mägi, Margit, Malila, Nea, Leinonen, Maarit, Velten, Michel, Troussard, Xavier, Bouvier, Veronique, Guizard, Anne-Valérie, Bouvier, Anne-Marie, Arveux, Patrick, Maynadié, Marc, Woronoff, Anne-Sophie, Robaszkiewicz, Michel, Baldi, Isabelle, Monnereau, Alain, Tretarre, Brigitte, Colonna, Marc, Molinié, Florence, Bara, Simona, Schvartz, Claire, Lapôtre-Ledoux, Bénédicte, Grosclaude, Pascale, Stabenow, Roland, Luttmann, Sabine, Nennecke, Alice, Engel, Jutta, Schubert-Fritschle, Gabriele, Heidrich, Jan, Holleczek, Bernd, Jónasson, Jón Gunnlaugur, Clough-Gorr, Kerri, Comber, Harry, Mazzoleni, Guido, Giacomin, Adriano, Sardo, Antonella Sutera, Barchielli, Alessandro, Serraino, Diego, De Angelis, Roberta, Mallone, Sandra, Tavilla, Andrea, Pierannunzio, Daniela, Rossi, Silvia, Santaquilani, Mariano, Knijn, Arnold, Pannozzo, Fabio, Gennaro, Valerio, Benfatto, Lucia, Ricci, Paolo, Autelitano, Mariangela, Spagnoli, Gianbattista, Fusco, Mario, Usala, Mario, Vitale, Francesco, Michiara, Maria, Tumino, Rosario, Mangone, Lucia, Falcini, Fabio, Ferretti, Stefano, Filiberti, Rosa Angela, Marani, Enza, Iannelli, Arturo, Sensi, Flavio, Piffer, Silvano, Gentilini, Maria, Madeddu, Anselmo, Ziino, Antonio, Maspero, Sergio, Candela, Pina, Stracci, Fabrizio, Tagliabue, Giovanna, Rugge, Massimo, Trama, Annalisa, Gatta, Gemma, Botta, Laura, Capocaccia, Riccardo, Pildava, Santa, Smailyte, Giedre, Calleja, Neville, Johannesen, Tom Børge, Rachtan, Jadwiga, Góźdź, Stanisław, Błaszczyk, Jerzy, Kępska, Kamila, de Lacerda, Gonçalo Forjaz, Bento, Maria José, Miranda, Ana, Diba, Chakameh Safaei, Almar, Enrique, Larrañaga, Nerea, de Munain, Arantza Lopez, Torrella-Ramos, Ana, Díaz García, José María, Marcos-Gragera, Rafael, Sanchez, Maria Josè, Navarro, Carmen, Salmeron, Diego, Moreno-Iribas, Conchi, Galceran, Jaume, Carulla, Marià, Mousavi, Mohsen, Bouchardy, Christine, Ess, Silvia M., Bordoni, Andrea, Konzelmann, Isabelle, Rashbass, Jem, Gavin, Anna, Brewster, David H., Huws, Dyfed Wyn, Visser, Otto, Bielska-Lasota, Magdalena, Primic-Zakelj, Maja, Kunkler, Ian, Benhamou, Ellen, Lykoudis, Panagis M., Partelli, Stefano, Muffatti, Francesca, Caplin, Martyn, Falconi, Massimo, and Fusai, Giuseppe K.

Published
2019
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15. Rare ovarian tumours: Epidemiology, treatment challenges in and outside a network setting

Author

Hackl, Monika, Van Eycken, Elizabeth, Henau, Kris, Dimitrova, Nadya, Sekerija, Mario, Dušek, Ladislav, Mägi, Margit, Malila, Nea, Leinonen, Maarit, Velten, Michel, Troussard, Xavier, Bouvier, Veronique, Guizard, Anne-Valérie, Bouvier, Anne-Marie, Arveux, Patrick, Maynadié, Marc, Woronoff, Anne-Sophie, Robaszkiewicz, Michel, Baldi, Isabelle, Monnereau, Alain, Tretarre, Brigitte, Colonna, Marc, Molinié, Florence, Bara, Simona, Schvartz, Claire, Lapôtre-Ledoux, Bénédicte, Grosclaude, Pascale, Stabenow, Roland, Luttmann, Sabine, Nennecke, Alice, Engel, Jutta, Schubert-Fritschle, Gabriele, Heidrich, Jan, Holleczek, Bernd, Jónasson, Jón Gunnlaugur, Clough-Gorr, Kerri, Comber, Harry, Mazzoleni, Guido, Giacomin, Adriano, Sardo, Antonella Sutera, Barchielli, Alessandro, Serraino, Diego, De Angelis, Roberta, Mallone, Sandra, Tavilla, Andrea, Pierannunzio, Daniela, Rossi, Silvia, Santaquilani, Mariano, Knijn, Arnold, Pannozzo, Fabio, Gennaro, Valerio, Benfatto, Lucia, Ricci, Paolo, Autelitano, Mariangela, Spagnoli, Gianbattista, Fusco, Mario, Usala, Mario, Vitale, Francesco, Michiara, Maria, Tumino, Rosario, Mangone, Lucia, Falcini, Fabio, Ferretti, Stefano, Filiberti, Rosa Angela, Marani, Enza, Iannelli, Arturo, Sensi, Flavio, Piffer, Silvano, Gentilini, Maria, Madeddu, Anselmo, Ziino, Antonio, Maspero, Sergio, Candela, Pina, Stracci, Fabrizio, Tagliabue, Giovanna, Rugge, Massimo, Trama, Annalisa, Gatta, Gemma, Botta, Laura, Capocaccia, Riccardo, Pildava, Santa, Smailyte, Giedre, Calleja, Neville, Johannesen, Tom Børge, Rachtan, Jadwiga, Góźdź, Stanisław, Błaszczyk, Jerzy, Kępska, Kamila, de Lacerda, Gonçalo Forjaz, José Bento, Maria, Miranda, Ana, Safaei Diba, Chakameh, Almar, Enrique, Larrañaga, Nerea, de Munain, Arantza Lopez, Torrella-Ramos, Ana, Díaz García, José María, Marcos-Gragera, Rafael, Josè Sanchez, Maria, Navarro, Carmen, Salmeron, Diego, Moreno-Iribas, Conchi, Galceran, Jaume, Carulla, Marià, Mousavi, Mohsen, Bouchardy, Christine, Ess, Silvia M., Bordoni, Andrea, Konzelmann, Isabelle, Rashbass, Jem, Gavin, Anna, Brewster, David H., Huws, Dyfed Wyn, Visser, Otto, Bielska-Lasota, Magdalena, Primic-Zakelj, Maja, Kunkler, Ian, Benhamou, Ellen, Ray-Coquard, I., Trama, AnnaLisa, Seckl, M.J., Fotopoulou, C., Pautier, P., Pignata, S., Kristensen, G., Mangili, G., Falconer, H., Massuger, L., Sehouli, J., Pujade-Lauraine, E., Lorusso, D., Amant, F., Rokkones, E., Vergote, I., and Ledermann, J.A.

Published
2019
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16. Epidemiology of rare cancers and inequalities in oncologic outcomes

Author

Hackl, Monika, Eycken, Elizabeth Van, Henau, Kris, Dimitrova, Nadya, Sekerija, Mario, Dušek, Ladislav, Mägi, Margit, Malila, Nea, Leinonen, Maarit, Velten, Michel, Troussard, Xavier, Bouvier, Veronique, Guizard, Anne-Valérie, Bouvier, Anne-Marie, Arveux, Patrick, Maynadié, Marc, Woronoff, Anne-Sophie, Robaszkiewicz, Michel, Baldi, Isabelle, Monnereau, Alain, Tretarre, Brigitte, Colonna, Marc, Molinié, Florence, Bara, Simona, Schvartz, Claire, Lapôtre-Ledoux, Bénédicte, Grosclaude, Pascale, Stabenow, Roland, Luttmann, Sabine, Nennecke, Alice, Engel, Jutta, Schubert-Fritschle, Gabriele, Heidrich, Jan, Holleczek, Bernd, Jónasson, Jón Gunnlaugur, Clough-Gorr, Kerri, Comber, Harry, Mazzoleni, Guido, Giacomin, Adriano, Sardo, Antonella Sutera, Barchielli, Alessandro, Serraino, Diego, De Angelis, Roberta, Mallone, Sandra, Tavilla, Andrea, Pierannunzio, Daniela, Rossi, Silvia, Santaquilani, Mariano, Knijn, Arnold, Pannozzo, Fabio, Gennaro, Valerio, Benfatto, Lucia, Ricci, Paolo, Autelitano, Mariangela, Spagnoli, Gianbattista, Fusco, Mario, Usala, Mario, Vitale, Francesco, Michiara, Maria, Tumino, Rosario, Mangone, Lucia, Falcini, Fabio, Ferretti, Stefano, Filiberti, Rosa Angela, Marani, Enza, Iannelli, Arturo, Sensi, Flavio, Piffer, Silvano, Gentilini, Maria, Madeddu, Anselmo, Ziino, Antonio, Maspero, Sergio, Candela, Pina, Stracci, Fabrizio, Tagliabue, Giovanna, Rugge, Massimo, Trama, Annalisa, Gatta, Gemma, Botta, Laura, Capocaccia, Riccardo, Pildava, Santa, Smailyte, Giedre, Calleja, Neville, Johannesen, Tom Børge, Rachtan, Jadwiga, Góźdź, Stanisław, Błaszczyk, Jerzy, Kępska, Kamila, de Lacerda, Forjaz, Bento, Maria José, Miranda, Ana, Diba, Chakameh Safaei, Almar, Enrique, Larrañaga, Nerea, de Munain, Arantza Lopez, Torrella-Ramos, Ana, Díaz García, José María, Marcos-Gragera, Rafael, Sanchez, Maria Josè, Navarro, Carmen, Salmeron, Diego, Moreno-Iribas, Conchi, Galceran, Jaume, Carulla, Marià, Mousavi, Mohsen, Bouchardy, Christine, Ess, Silvia M., Bordoni, Andrea, Konzelmann, Isabelle, Rashbass, Jem, Gavin, Anna, Brewster, David H., Huws, Dyfed Wyn, Visser, Otto, Bielska-Lasota, Magdalena, Primic-Zakelj, Maja, Kunkler, Ian, Benhamou, Ellen, Gatta, G., Trama, A., and Capocaccia, R.

Published
2019
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17. Treatment challenges in and outside a network setting: Soft tissue sarcomas

Author

Hackl, Monika, Van Eycken, Elizabeth, Henau, Kris, Dimitrova, Nadya, Sekerija, Mario, Dušek, Ladislav, Mägi, Margit, Malila, Nea, Leinonen, Maarit, Velten, Michel, Troussard, Xavier, Bouvier, Veronique, Guizard, Anne-Valérie, Bouvier, Anne-Marie, Arveux, Patrick, Maynadié, Marc, Woronoff, Anne-Sophie, Robaszkiewicz, Michel, Baldi, Isabelle, Monnereau, Alain, Tretarre, Brigitte, Colonna, Marc, Molinié, Florence, Bara, Simona, Schvartz, Claire, Lapôtre-Ledoux, Bénédicte, Grosclaude, Pascale, Stabenow, Roland, Luttmann, Sabine, Nennecke, Alice, Engel, Jutta, Schubert-Fritschle, Gabriele, Heidrich, Jan, Bernd Holleczek, Jónasson, Jón Gunnlaugur, Clough-Gorr, Kerri, Comber, Harry, Mazzoleni, Guido, Giacomin, Adriano, Sardo, Antonella Sutera, Barchielli, Alessandro, Serraino, Diego, De Angelis, Roberta, Mallone, Sandra, Tavilla, Andrea, Pierannunzio, Daniela, Rossi, Silvia, Santaquilani, Mariano, Knijn, Arnold, Pannozzo, Fabio, Gennaro, Valerio, Benfatto, Lucia, Ricci, Paolo, Autelitano, Mariangela, Spagnoli, Gianbattista, Fusco, Mario, Usala, Mario, Vitale, Francesco, Michiara, Maria, Tumino, Rosario, Mangone, Lucia, Falcini, Fabio, Ferretti, Stefano, Filiberti, Rosa Angela, Marani, Enza, Iannelli, Arturo, Sensi, Flavio, Piffer, Silvano, Gentilini, Maria, Madeddu, Anselmo, Ziino, Antonio, Maspero, Sergio, Candela, Pina, Stracci, Fabrizio, Tagliabue, Giovanna, Rugge, Massimo, Trama, Annalisa, Gatta, Gemma, Botta, Laura, Capocaccia, Riccardo, Pildava, Santa, Smailyte, Giedre, Calleja, Neville, Johannesen, Tom Børge, Rachtan, Jadwiga, Góźdź, Stanisław, Błaszczyk, Jerzy, Kępska, Kamila, de Lacerda, Gonçalo Forjaz, Bento, Maria José, Miranda, Ana, Diba, Chakameh Safaei, Almar, Enrique, Larrañaga, Nerea, de Munain, Arantza Lopez, Torrella-Ramos, Ana, Díaz García, José María, Marcos-Gragera, Rafael, Sanchez, Maria Josè, Navarro, Carmen, Salmeron, Diego, Moreno-Iribas, Conchi, Galceran, Jaume, Carulla, Marià, Mousavi, Mohsen, Bouchardy, Christine, Ess, Silvia M., Bordoni, Andrea, Konzelmann, Isabelle, Rashbass, Jem, Gavin, Anna, Brewster, David H., Huws, Dyfed Wyn, Visser, Otto, Bielska-Lasota, Magdalena, Primic-Zakelj, Maja, Kunkler, Ian, Benhamou, Ellen, Pasquali, Sandro, Bonvalot, Sylvie, Tzanis, Dimitri, Casali, Paolo G., and Gronchi, Alessandro

Published
2019
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19. Incidence and time trends of childhood lymphomas : findings from 14 Southern and Eastern European cancer registries and the Surveillance, Epidemiology and End Results, USA

Author

Georgakis, Marios K., Karalexi, Maria A., Agius, Domenic, Antunes, Luis, Bastos, Joana, Coza, Daniela, Demetriou, Anna, Dimitrova, Nadya, Eser, Sultan, Florea, Margareta, Ryzhov, Anton, Sekerija, Mario, Žagar, Tina, Zborovskaya, Anna, Zivkovic, Snezana, Bouka, Evdoxia, Kanavidis, Prodromos, Dana, Helen, Hatzipantelis, Emmanuel, Kourti, Maria, Moschovi, Maria, Polychronopoulou, Sophia, Stiakaki, Eftichia, Kantzanou, Maria, Pourtsidis, Apostolos, and Petridou, Eleni Th.

Published
2016

20. Quality analysis of population-based information on cancer stage at diagnosis across Europe, with presentation of stage-specific cancer survival estimates: A EUROCARE-5 study

Author

Hackl, M., Zielonke, N., Van Eycken, E., Henau, K., Valerianova, Z., Dimitrova, N., Sekerija, M., Dušek, L., Zvolský, M., Mägi, M., Aareleid, T., Malila, N., Seppä, K., Bouvier, A.M., Faivre, J., Bossard, N., Uhry, Z., Colonna, M., Stabenow, R., Luttmann, S., Eberle, A., Brenner, H., Nennecke, A., Engel, J., Schubert-Fritschle, G., Heidrich, J., Holleczek, B., Katalinic, A., Clough-Gorr, K., Mazzoleni, G., Bulatko, A., Buzzoni, C., Giacomin, A., Ferretti, S., Barchielli, A., Caldarella, A., Gatta, G., Sant, M., Amash, H., Amati, C., Baili, P., Berrino, F., Bonfarnuzzo, S., Botta, L., Capocaccia, R., Di Salvo, F., Foschi, R., Margutti, C., Meneghini, E., Minicozzi, P., Trama, A., Serraino, D., Maso, L. Dal, De Angelis, R., Caldora, M., Carrani, E., Francisci, S., Knijn, A., Mallone, S., Pierannunzio, D., Roazzi, P., Rossi, S., Santaquilani, M., Tavilla, A., Pannozzo, F., Natali, M., Filiberti, R.A., Marani, E., Autelitano, M., Spagnoli, G., Cirilli, C., Fusco, M., Vitale, M.F., Traina, A., Staiti, R., Vitale, F., Cusimano, R., Michiara, M., Tumino, R., Falcini, F., Caiazzo, A.L., Maspero, S., Fanetti, A.C., Zanetti, R., Rosso, S., Rugge, M., Tognazzo, S., Pildava, S., Smailyte, G., Johannesen, T.B., Rachtan, J., Góźdź, S., Mężyk, R., Błaszczyk, J., Kępska, K., Bielska-Lasota, M., Forjaz de Lacerda, G., Bento, M.J., Antunes, L., Miranda, A., Mayer-da-Silva, A., Safaei Diba, C., Primic-Zakelj, M., Almar, E., Mateos, A., Lopez de Munain, A., Larrañaga, N., Torrella-Ramos, A., Díaz García, J.M., Jimenez-Chillaron, R., Marcos-Gragera, R., Vilardell, L., Moreno-Iribas, C., Ardanaz, E., Lambe, M., Mousavi, M., Bouchardy, C., Usel, M., Ess, S.M., Frick, H., Lorez, M., Herrmann, C., Bordoni, A., Spitale, A., Konzelmann, I., Visser, O., Damhuis, R., Otter, R., Coleman, M., Allemani, C., Rachet, B., Rashbass, J., Broggio, J., Verne, J., Gavin, A., Fitzpatrick, D., Huws, D.W., White, C., Minicozzi, Pamela, Innos, Kaire, Sánchez, Maria-José, Trama, Annalisa, Walsh, Paul M., Marcos-Gragera, Rafael, Dimitrova, Nadya, Botta, Laura, Visser, Otto, Rossi, Silvia, Tavilla, Andrea, and Sant, Milena

Published
2017
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22. Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America

Author

Karalexi, Maria A., Baka, Margarita, Ryzhov, Anton, Zborovskaya, Anna, Dimitrova, Nadya, Zivkovic, Snezana, Eser, Sultan, Antunes, Luis, Sekerija, Mario, Zagar, Tina, Bastos, Joana, Demetriou, Anna, Agius, Domenic, Florea, Margareta, Coza, Daniela, Polychronopoulou, Sophia, Stiakaki, Eftichia, Moschovi, Maria, Hatzipantelis, Emmanuel, Kourti, Maria, Graphakos, Stelios, Pombo-de-Oliveira, Maria S., Adami, Hans Olov, and Petridou, Eleni Th.

Published
2016
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26. 7.345 Non-coding RNAs: Junk or Critical Regulators in Health and Disease?, Spring 2012

Author

Dimitrova, Nadya, Papagiannakopoulos, Thales, Dimitrova, Nadya, and Papagiannakopoulos, Thales

Abstract

Every time we scientists think that we have dissected the precise biological nature of a process, an incidental finding, a brilliantly designed experiment, or an unexpected result can turn our world upside down. Until recently thought by many to be cellular "junk" because they do not encode proteins, non-coding RNAs are gaining a growing recognition for their roles in the regulation of a wide scope of processes, ranging from embryogenesis and development to cancer and degenerative disorders. The aim of this class is to introduce the diversity of the RNA world, inhabited by microRNAs, lincRNAs, piRNAs, and many others. This course is one of many Advanced Undergraduate Seminars offered by the Biology Department at MIT. These seminars are tailored for students with an interest in using primary research literature to discuss and learn about current biological research in a highly interactive setting. Many instructors of the Advanced Undergraduate Seminars are postdoctoral scientists with a strong interest in teaching.

Published
2023

27. OverexpressedMalat1Drives Metastasis through Inflammatory Reprogramming of Lung Adenocarcinoma Microenvironment

Author

Martínez-Terroba, Elena, de Miguel, Fernando J., Li, Vincent, Robles-Oteiza, Camila, Politi, Katerina, Zamudio, Jesse R., and Dimitrova, Nadya

Subjects
Article
Abstract

Metastasis is the main cause of cancer deaths but the molecular events leading to metastatic dissemination remain incompletely understood. Despite reports linking aberrant expression of long noncoding RNAs (lncRNAs) with increased metastatic incidence, in vivoevidence establishing driver roles for lncRNAs in metastatic progression is lacking. Here, we report that overexpression of the metastasis-associated lncRNAMalat1(metastasis-associated lung adenocarcinoma transcript 1) in the autochthonous K-ras/p53 mouse model of lung adenocarcinoma (LUAD) is sufficient to drive cancer progression and metastatic dissemination. We show that increased expression of endogenousMalat1RNA cooperates with p53 loss to promote widespread LUAD progression to a poorly differentiated, invasive, and metastatic disease. Mechanistically, we observe thatMalat1overexpression leads to the inappropriate transcription and paracrine secretion of the inflammatory cytokine, Ccl2, to augment the mobility of tumor and stromal cellsin vitroand to trigger inflammatory responses in the tumor microenvironmentin vivo. Notably, Ccl2 blockade fully reverses cellular and organismal phenotypes ofMalat1overexpression. We propose thatMalat1overexpression in advanced tumors activates Ccl2 signaling to reprogram the tumor microenvironment to an inflammatory and pro-metastatic state.

Published
2023

29. List of Contributors

Author

Adhikary, Santanu, primary, Baliñas, Carlos, additional, Banerjee, Shakri, additional, Bapat, Sharmila A., additional, Bhome, Rahul, additional, Boila, Liberalis D., additional, Bonnici, Vincenzo, additional, Bose, Debojit, additional, Boyero, Laura, additional, Chakrabarti, Jayprokas, additional, Chakravarti, Damayanti, additional, Chan, JiaJia, additional, Chariot, Alain, additional, Chatterjee, Shankha S., additional, Chen, Taiping, additional, Close, Pierre, additional, Coira, Isabel F., additional, Cuadros, Marta, additional, Cui, Juan, additional, Das, Chandrima, additional, Das, Shaoli, additional, de Brot, Simone, additional, Desi, Ng, additional, Dimitrova, Nadya, additional, Dittmar, Rachel L., additional, Emo, Katherine, additional, Ganguli, Sayak, additional, Gharpure, Kshipra M., additional, Ghosal, Suman, additional, Giugno, Rosalba, additional, Glavacˇ, Damjan, additional, Grützner, Frank, additional, Gupta, Sohini, additional, Halder, Agnik, additional, Hauptman, Nina, additional, Herrera, Antonio, additional, House, Louise, additional, Huang, Changzhi, additional, Huang, Shenglin, additional, Jacob, Reuben, additional, James, Victoria, additional, Jevšinek Skok, Daša, additional, Kondetimmanahalli, Ragini, additional, Lee, Eunice, additional, Leidel, Sebastian A., additional, Li, Yan, additional, Li, Yuan, additional, Lopez-Berestein, Gabriel, additional, Lupiáñez, Jose A., additional, Martín-Padrón, Joel, additional, Medina, Pedro P., additional, Mirnezami, Alex, additional, Mitra, Sanga, additional, Mongan, Nigel P., additional, Mukherjee, Shravanti, additional, Panda, Suchismita, additional, Peinado, Paola, additional, Pulvirenti, Alfredo, additional, Reyes-Zurita, Fernando J., additional, Rodriguez, Maria I., additional, Roychoudhury, Susanta, additional, Roy, Siddhartha, additional, Rufino-Palomares, Eva E., additional, Rutland, Catrin S., additional, Sayan, Emre, additional, Scoyni, Flavia, additional, Sengupta, Amitava, additional, Sengupta, Sharmila, additional, Sen, Subrata, additional, Sharma Saha, Sweta, additional, Shiras, Anjali, additional, Shi, Yuming, additional, Sinha, Sayantani, additional, Slaby, Ondrej, additional, Sood, Anil K., additional, Souckova, Kamila, additional, Tay, Yvonne, additional, Wang, Yu, additional, Wang, Zhiguo, additional, Wu, Sherry Y., additional, Yang, Tianqi, additional, Yildirim, Eda, additional, and Ying, Zhengzhou, additional

Published
2018
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31. Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US

Author

Georgakis, Marios K., Karalexi, Maria A., Kalogirou, Eleni I., Ryzhov, Anton, Zborovskaya, Anna, Dimitrova, Nadya, Eser, Sultan, Antunes, Luis, Sekerija, Mario, Zagar, Tina, Bastos, Joana, Agius, Domenic, Florea, Margareta, Coza, Daniela, Bouka, Evdoxia, Bourgioti, Charis, Dana, Helen, Hatzipantelis, Emmanuel, Moschovi, Maria, Papadopoulos, Savvas, Sfakianos, Georgios, Papakonstantinou, Evgenia, Polychronopoulou, Sophia, Sgouros, Spyros, Stefanaki, Kalliopi, Stiakaki, Eftichia, Strantzia, Katerina, Zountsas, Basilios, Pourtsidis, Apostolos, Patsouris, Eustratios, and Petridou, Eleni Th.

Published
2017
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32. Impact of the first wave of the COVID-19 pandemic on cancer registration and cancer care: a European survey

Author

Neamţiu, Luciana, Martos, Carmen, Giusti, Francesco, Negrão Carvalho, Raquel, Randi, Giorgia, Dimitrova, Nadya, Flego, Manuela, Dyba, Tadeusz, Bettio, Manola, Gavin, Anna, Visser, Otto, Sánchez, María José, Eden, Michael, Stracci, Fabrizio, Šekerija, Mario, Trojanowski, Maciej, Bray, Freddie, van Eycken, Elizabeth, Miranda, Ana, Storm, Hans, and the ENCR Steering Committee

Subjects
COVID-19, cancer care, cancer registries, SARS-CoV-2, Public Health, Environmental and Occupational Health, cancer treatment, SDG 3 - Good Health and Well-being, cancer screening, Neoplasms, Surveys and Questionnaires, cancer diagnosis, Humans, cancer registry, Pandemics
Abstract

Background The coronavirus disease COVID-19 pandemic posed a number of challenges to the oncology community, particularly the diagnosis and care of cancer patients while ensuring safety from the virus for both patients and professionals: minimization of visits to the hospital, cancellation of the screening programmes and the difficulties in the management and operation of cancer registries (CRs) while working remotely. This article describes the effects in the medium term of the first wave of the COVID-19 pandemic on cancer registration in Europe, focusing on changes in cancer detection and treatment, possible reduction of CR resources and difficulties in the access to data sources. Methods A questionnaire was distributed in June 2020 to the directors of 108 CRs from 34 countries affiliated to the European Network of Cancer Registries, providing a 37% response rate. Results The results of the survey showed that cancer-screening programmes were mostly stopped or slowed down in the majority of regions covered by the respondent CRs. Cancer diagnostics and treatments were severely disrupted. The cancer registration process was also disrupted, due to changes in the work modalities for the personnel, as well as to the difficulties in accessing sources and/or receiving the notifications. In some CRs, staff was allocated to different activities related to controlling the pandemic. Several CRs reported that they were investigating the impact of COVID-19 on cancer care via dedicated studies. Conclusions A careful analysis will be necessary for proper interpretation of temporal and geographical variations of the 2020 cancer burden indicators.

Published
2021

33. EVTIMA: A System for IE from Hospital Patient Records in Bulgarian

Author

Boytcheva, Svetla, Angelova, Galia, Nikolova, Ivelina, Paskaleva, Elena, Tcharaktchiev, Dimitar, Dimitrova, Nadya, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Goebel, Randy, editor, Siekmann, Jörg, editor, Wahlster, Wolfgang, editor, Dicheva, Darina, editor, and Dochev, Danail, editor

Published
2010
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34. Childhood cancer survival in Europe 1999–2007: results of EUROCARE-5—a population-based study

Author

Gatta, Gemma, Botta, Laura, Rossi, Silvia, Aareleid, Tiiu, Bielska-Lasota, Magdalena, Clavel, Jacqueline, Dimitrova, Nadya, Jakab, Zsuzsanna, Kaatsch, Peter, Lacour, Brigitte, Mallone, Sandra, Marcos-Gragera, Rafael, Minicozzi, Pamela, Sánchez-Pérez, Maria-José, Sant, Milena, Santaquilani, Mariano, Stiller, Charles, Tavilla, Andrea, Trama, Annalisa, Visser, Otto, and Peris-Bonet, Rafael

Published
2014
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37. Childhood leukemia and lymphoma: time trends and factors affecting survival in five Southern and Eastern European Cancer Registries

Author

Petridou, Eleni Th., Dimitrova, Nadya, Eser, Sultan, Kachanov, Denis, Karakilinc, Hulya, Varfolomeeva, Svetlana, Belechri, Maria, Baka, Margarita, Moschovi, Maria, Polychronopoulou, Sofia, Athanasiadou-Piperopoulou, Fani, Fragandrea, Ioanna, Stiakaki, Eftichia, Pourtsidis, Apostolos, Stefanadis, Christodoulos, Coebergh, Jan-Willem, and Sergentanis, Theodoros N.

Published
2013

41. The European cancer burden in 2020: Incidence and mortality estimates for 40 countries and 25 major cancers

Author

Dyba, Tadeusz, primary, Randi, Giorgia, additional, Bray, Freddie, additional, Martos, Carmen, additional, Giusti, Francesco, additional, Nicholson, Nicholas, additional, Gavin, Anna, additional, Flego, Manuela, additional, Neamtiu, Luciana, additional, Dimitrova, Nadya, additional, Negrão Carvalho, Raquel, additional, Ferlay, Jacques, additional, and Bettio, Manola, additional

Published
2021
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42. Phenotypic Plasticity, Behavioral Syndromes and Their Evolutionary Implications in Pacific Field Cricket Females

Author

Dimitrova, Nadya Dimitrova

Subjects
Evolution & development, Behavioral sciences, behavioral syndromes, female choice, phenotypic plasticity, predation pressure, Teleogryllus oceanicus
Abstract

Two models have been suggested to predict the presence of behavioral syndromes (correlations between different behaviors or the same behavior in different contexts). According to "genetic constraint" models, such correlations, where present, should persist regardless of environmental changes, while "adaptive divergence" models posit that syndromes will exist only where beneficial, and one such case is a high predation environment. We examined the plasticity and potential correlation between two behaviors - female responsiveness to male calls (responsiveness) and latency to emerge from shelter after a simulated predator threat (boldness). The subjects were female Pacific field crickets (Teleogryllus oceanicus) from populations with different predation pressures, and as an additional, experimental proxy for predation pressure, they were reared in an environment simulating either high or low population density. As expected, females reared in incubators where low population density was simulated, were more responsive to male calls, since such environments signal less mating opportunities. However, regardless of rearing conditions, females from the population where parasitoid predation pressure was strongest, were more responsive to male calls and also less bold, which suggests that there are genetic differences between the populations as well. As predicted by divergence models, the only population in which a behavioral syndrome (bold/more responsive) was detected, suffered the highest rate of parasitoid larvae infestation. If predation has driven the formation of bold/more responsive and shy/less responsive coping styles in females in this population, such strategies could be adaptive due to a tradeoff mechanism. A boldness/responsiveness syndrome was also present in both the high and low population density environments, which could be explained by both genetic constraint and adaptive divergence models - different experiments, and in some instances larger sample sizes, are needed to clarify this result.

Published
2015

45. Mitochondrial apoptotic priming is a key determinant of cell fate upon p53 restoration

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Sánchez-Rivera, Francisco J, Ryan, Jeremy, Soto-Feliciano, Yadira M, Clare Beytagh, Mary, Xuan, Lucius, Feldser, David M, Hemann, Michael T, Zamudio, Jesse, Dimitrova, Nadya, Letai, Anthony, Jacks, Tyler, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Sánchez-Rivera, Francisco J, Ryan, Jeremy, Soto-Feliciano, Yadira M, Clare Beytagh, Mary, Xuan, Lucius, Feldser, David M, Hemann, Michael T, Zamudio, Jesse, Dimitrova, Nadya, Letai, Anthony, and Jacks, Tyler

Abstract

Reactivation of p53 in established tumors typically results in one of two cell fates, cell cycle arrest or apoptosis, but it remains unclear how this cell fate is determined. We hypothesized that high mitochondrial priming prior to p53 reactivation would lead to apoptosis, while low priming would lead to survival and cell cycle arrest. Using a panel of Kras-driven, p53 restorable cell lines derived from genetically engineered mouse models of lung adenocarcinoma and sarcoma (both of which undergo cell cycle arrest upon p53 restoration), as well as lymphoma (which instead undergo apoptosis), we show that the level of mitochondrial apoptotic priming is a critical determinant of p53 reactivation outcome. Cells with high initial priming (e.g., lymphomas) lacked sufficient reserve antiapoptotic capacity and underwent apoptosis after p53 restoration. Forced BCL-2 or BCL-XL expression reduced priming and resulted in survival and cell cycle arrest. Cells with low initial priming (e.g., lung adenocarcinoma and sarcoma) survived and proceeded to arrest in the cell cycle. When primed by inhibition of their antiapoptotic proteins using genetic (BCL-2 or BCL-XL deletion or BAD overexpression) or pharmacologic (navitoclax) means, apoptosis resulted upon p53 restoration in vitro and in vivo. These data demonstrate that mitochondrial apoptotic priming is a key determining factor of cell fate upon p53 activation. Moreover, it is possible to enforce apoptotic cell fate following p53 activation in less primed cells using p53-independent drugs that increase apoptotic priming, including BH3 mimetic drugs.

Published
2021

47. 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility

Author

Dimitrova, Nadya, Chen, Yi-Chun M., Spector, David L., and de Lange, Titia

Subjects
Chromatin -- Research, Ataxia telangiectasia -- Development and progression -- Research, DNA damage -- Research, Telomeres -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation, Development and progression, Research
Abstract

Double-strand breaks activate the ataxia telangiectasia mutated (ATM) kinase, which promotes the accumulation of DNA damage factors in the chromatin surrounding the break. The functional significance of the resulting DNA [...]

Published
2008

48. Monitoring and evaluation of breast cancer screening programmes : selecting candidate performance indicators

Author

Muratov, Sergei, Canelo-Aybar, Carlos, Tarride, Jean-Eric, Alonso-Coello, Pablo, Dimitrova, Nadya, Borisch, Bettina, Castells, Xavier, Duffy, Stephen W., Fitzpatrick, Patricia, Follmann, Markus, Giordano, Livia, Hofvind, Solveig, Lebeau, Annette, Quinn, Cecily, Torresin, Alberto, Vialli, Claudia, Siesling, Sabine, Ponti, Antonio, Giorgi Rossi, Paolo, Schünemann, Holger, Nyström, Lennarth, Broeders, Mireille, Autelitano, Mariangela, Colzani, Edoardo, Daneš, Jan, Gräwingholt, Axel, Ioannidou-Mouzaka, Lydia, Knox, Susan, Langendam, Miranda, McGarrigle, Helen, Pérez Gómez, Elsa, van Engen, Ruben, Warman, Sue, Young, Kenneth, van Landsveld-Verhoeven, Cary, Lerda, Donata, Saz-Parkinson, Zuleika, Parmelli, Elena, Janusch-Roi, Annett, Epidemiology and Data Science, APH - Mental Health, APH - Methodology, APH - Quality of Care, and Health Technology & Services Research

Subjects
0301 basic medicine, Cancer Research, Time Factors, medicine.medical_treatment, Biopsy, Quality indicators, methods, Breast cancer screening, 0302 clinical medicine, Health care, Breast neoplasms/diagnostic imaging, Mass Screening, Breast, Mastectomy, Health care/standards, medicine.diagnostic_test, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Europe, Early detection of Cancer, standards, Oncology, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Mass screening/methods, Early detection of Cancer/methods, Female, Research Article, Mammography, medicine.medical_specialty, Breast Neoplasms, lcsh:RC254-282, 03 medical and health sciences, Breast cancer, All institutes and research themes of the Radboud University Medical Center, Genetics, medicine, Humans, Selection (genetic algorithm), Aged, Quality Indicators, Health Care, Cancer och onkologi, business.industry, Early detection of Cancer*/methods, Health Plan Implementation, diagnostic imaging, Monitoring and evaluation, Mass screening, Patient Acceptance of Health Care, medicine.disease, 030104 developmental biology, Ranking, Family medicine, Cancer and Oncology, Programme evaluation, Performance indicator, Breast neoplasms, business, Program Evaluation
Abstract

Background In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. Methods The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. Results A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. Conclusion This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.

Published
2020

49. Additional file 1 of Monitoring and evaluation of breast cancer screening programmes: selecting candidate performance indicators

Author

Muratov, Sergei, Canelo-Aybar, Carlos, Jean-Eric Tarride, Alonso-Coello, Pablo, Dimitrova, Nadya, Borisch, Bettina, Castells, Xavier, Duffy, Stephen W., Fitzpatrick, Patricia, Follmann, Markus, Giordano, Livia, Hofvind, Solveig, Lebeau, Annette, Quinn, Cecily, Torresin, Alberto, Vialli, Claudia, Siesling, Sabine, Ponti, Antonio, Rossi, Paolo Giorgi, Schünemann, Holger, Nyström, Lennarth, and Broeders, Mireille

Abstract

Additional file 1: Appendix 1: Search strategy. Appendix 2: Number of performance indicators identified per stage. Appendix 3A: Candidate indicators identified by a systematic review: pre-selected for the rating and ranking survey (n = 39). Appendix 3B: Candidate indicators identified by a systematic review: irrelevant and/or redundant (n = 63). Appendix 4: Conceptual framework considerations.

Published
2020
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