41 results on '"Whitfield, Jonathan R."'
Search Results
2. The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets
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Zacarías-Fluck, Mariano F, Jauset, Toni, Martínez-Martín, Sandra, Kaur, Jastrinjan, Casacuberta-Serra, Sílvia, Massó-Vallés, Daniel, del Pozo, Erika Serrano, Martín-Fernández, Génesis, González-Larreategui, Íñigo, López-Estévez, Sergio, Brown-Swigart, Lamorna, Beaulieu, Marie-Eve, Whitfield, Jonathan R, Madan, Babita, Virshup, David M, Evan, Gerard I, and Soucek, Laura
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Rare Diseases ,Genetics ,Pancreatic Cancer ,Digestive Diseases ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Adenoma ,Islet Cell ,Animals ,Carcinogenesis ,Cell Movement ,Cell Proliferation ,Female ,Frizzled Receptors ,Genes ,myc ,Islets of Langerhans ,Male ,Mice ,Wnt Signaling Pathway ,beta Catenin ,Biological sciences ,Biomedical and clinical sciences - Abstract
The huge cadre of genes regulated by Myc has obstructed the identification of critical effectors that are essential for Myc-driven tumorigenesis. Here, we describe how only the lack of the receptor Fzd9, previously identified as a Myc transcriptional target, impairs sustained tumor expansion and β-cell dedifferentiation in a mouse model of Myc-driven insulinoma, allows pancreatic islets to maintain their physiological structure and affects Myc-related global gene expression. Importantly, Wnt signaling inhibition in Fzd9-competent mice largely recapitulates the suppression of proliferation caused by Fzd9 deficiency upon Myc activation. Together, our results indicate that the Wnt signaling receptor Fzd9 is essential for Myc-induced tumorigenesis in pancreatic islets.
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- 2021
3. Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma
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Pighi, Chiara, Cheong, Taek-Chin, Compagno, Mara, Patrucco, Enrico, Arigoni, Maddalena, Olivero, Martina, Wang, Qi, López, Cristina, Bernhart, Stephan H., Grande, Bruno M., Poggio, Teresa, Langellotto, Fernanda, Bonello, Lisa, Dall'Olio, Riccardo, Martínez-Martín, Sandra, Molinaro, Luca, Francia di Celle, Paola, Whitfield, Jonathan R., Soucek, Laura, Voena, Claudia, Calogero, Raffaele A., Morin, Ryan D., Staudt, Louis M., Siebert, Reiner, Zamò, Alberto, and Chiarle, Roberto
- Published
- 2021
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4. MYC: there is more to it than cancer
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Zacarías-Fluck, Mariano F., primary, Soucek, Laura, additional, and Whitfield, Jonathan R., additional
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- 2024
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5. Therapeutic implications of the interplay between interferons and ER in breast cancer
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Todorović-Raković, Nataša, primary and Whitfield, Jonathan R., additional
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- 2024
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6. The effect of environmental chemicals on the tumor microenvironment
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Casey, Stephanie C, Vaccari, Monica, Al-Mulla, Fahd, Al-Temaimi, Rabeah, Amedei, Amedeo, Barcellos-Hoff, Mary Helen, Brown, Dustin G, Chapellier, Marion, Christopher, Joseph, Curran, Colleen S, Forte, Stefano, Hamid, Roslida A, Heneberg, Petr, Koch, Daniel C, Krishnakumar, PK, Laconi, Ezio, Maguer-Satta, Veronique, Marongiu, Fabio, Memeo, Lorenzo, Mondello, Chiara, Raju, Jayadev, Roman, Jesse, Roy, Rabindra, Ryan, Elizabeth P, Ryeom, Sandra, Salem, Hosni K, Scovassi, A Ivana, Singh, Neetu, Soucek, Laura, Vermeulen, Louis, Whitfield, Jonathan R, Woodrick, Jordan, Colacci, Annamaria, Bisson, William H, and Felsher, Dean W
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Stem Cell Research ,Cancer ,Prevention ,2.2 Factors relating to the physical environment ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Carcinogenesis ,Environmental Exposure ,Hazardous Substances ,Humans ,Neoplasms ,Tumor Microenvironment ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.
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- 2015
7. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
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Goodson, William H, Lowe, Leroy, Carpenter, David O, Gilbertson, Michael, Manaf Ali, Abdul, Lopez de Cerain Salsamendi, Adela, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, Amelia K, Collins, Andrew R, Ward, Andrew, Salzberg, Anna C, Colacci, Annamaria, Olsen, Ann-Karin, Berg, Arthur, Barclay, Barry J, Zhou, Binhua P, Blanco-Aparicio, Carmen, Baglole, Carolyn J, Dong, Chenfang, Mondello, Chiara, Hsu, Chia-Wen, Naus, Christian C, Yedjou, Clement, Curran, Colleen S, Laird, Dale W, Koch, Daniel C, Carlin, Danielle J, Felsher, Dean W, Roy, Debasish, Brown, Dustin G, Ratovitski, Edward, Ryan, Elizabeth P, Corsini, Emanuela, Rojas, Emilio, Moon, Eun-Yi, Laconi, Ezio, Marongiu, Fabio, Al-Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L, Van Schooten, Frederik J, Goldberg, Gary S, Wagemaker, Gerard, Nangami, Gladys N, Calaf, Gloria M, Williams, Graeme, Wolf, Gregory T, Koppen, Gudrun, Brunborg, Gunnar, Lyerly, H Kim, Krishnan, Harini, Ab Hamid, Hasiah, Yasaei, Hemad, Sone, Hideko, Kondoh, Hiroshi, Salem, Hosni K, Hsu, Hsue-Yin, Park, Hyun Ho, Koturbash, Igor, Miousse, Isabelle R, Scovassi, A Ivana, Klaunig, James E, Vondráček, Jan, Raju, Jayadev, Roman, Jesse, Wise, John Pierce, Whitfield, Jonathan R, Woodrick, Jordan, Christopher, Joseph A, Ochieng, Josiah, Martinez-Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Sun, Jun, Prudhomme, Kalan R, Narayanan, Kannan Badri, Cohen-Solal, Karine A, Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D'Abronzo, Leandro S, Lin, Liang-Tzung, Li, Lin, Gulliver, Linda, McCawley, Lisa J, Memeo, Lorenzo, Vermeulen, Louis, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, Maria Fiammetta, Chapellier, Marion, Williams, Marc A, and Wade, Mark
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,2.2 Factors relating to the physical environment ,Animals ,Carcinogenesis ,Carcinogens ,Environmental ,Environmental Exposure ,Hazardous Substances ,Humans ,Neoplasms ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
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- 2015
8. Data from MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding
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Massó-Vallés, Daniel, primary, Beaulieu, Marie-Eve, primary, Jauset, Toni, primary, Giuntini, Fabio, primary, Zacarías-Fluck, Mariano F., primary, Foradada, Laia, primary, Martínez-Martín, Sandra, primary, Serrano, Erika, primary, Martín-Fernández, Génesis, primary, Casacuberta-Serra, Sílvia, primary, Castillo Cano, Virginia, primary, Kaur, Jastrinjan, primary, López-Estévez, Sergio, primary, Morcillo, Miguel Ángel, primary, Alzrigat, Mohammad, primary, Mahmoud, Loay, primary, Luque-García, Antonio, primary, Escorihuela, Marta, primary, Guzman, Marta, primary, Arribas, Joaquín, primary, Serra, Violeta, primary, Larsson, Lars-Gunnar, primary, Whitfield, Jonathan R., primary, and Soucek, Laura, primary
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- 2023
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9. Supplementary Data from MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding
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Massó-Vallés, Daniel, primary, Beaulieu, Marie-Eve, primary, Jauset, Toni, primary, Giuntini, Fabio, primary, Zacarías-Fluck, Mariano F., primary, Foradada, Laia, primary, Martínez-Martín, Sandra, primary, Serrano, Erika, primary, Martín-Fernández, Génesis, primary, Casacuberta-Serra, Sílvia, primary, Castillo Cano, Virginia, primary, Kaur, Jastrinjan, primary, López-Estévez, Sergio, primary, Morcillo, Miguel Ángel, primary, Alzrigat, Mohammad, primary, Mahmoud, Loay, primary, Luque-García, Antonio, primary, Escorihuela, Marta, primary, Guzman, Marta, primary, Arribas, Joaquín, primary, Serra, Violeta, primary, Larsson, Lars-Gunnar, primary, Whitfield, Jonathan R., primary, and Soucek, Laura, primary
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- 2023
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10. Abstract 3435: Identification of potential biomarkers of response to OMO-103, a first-in-modality pan-MYC inhibitor, in patients with advanced solid tumors
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Beaulieu, Marie-Eve, primary, Garralda, Elena, additional, Casacuberta-Serra, Sílvia, additional, Martínez-Martín, Sandra Sandra, additional, Calvo, Emiliano, additional, Moreno, Víctor, additional, López-Estévez, Sergio, additional, Foradada, Laia, additional, Alonso, Guzman, additional, Corral, Elena, additional, Doger, Bernard, additional, Hernández, Tatiana, additional, Grueso, Judit, additional, González-Larreategui, Íñigo Íñigo, additional, Pozo, Erika Serrano del, additional, Thabussot, Hugo, additional, Cano, Virginia Castillo, additional, Zacarías-Fluck, Mariano F. Mariano F., additional, Kaur, Jastrinjan, additional, Giuntini, Fabio, additional, Whitfield, Jonathan R., additional, Morales, Josefa, additional, Niewel, Manuela, additional, and Soucek, Laura, additional
- Published
- 2023
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11. Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma
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Zacarías-Fluck, Mariano F., primary, Massó-Vallés, Daniel, additional, Giuntini, Fabio, additional, González-Larreategui, Íñigo, additional, Kaur, Jastrinjan, additional, Casacuberta-Serra, Sílvia, additional, Jauset, Toni, additional, Martínez-Martín, Sandra, additional, Martín-Fernández, Génesis, additional, Serrano del Pozo, Erika, additional, Foradada, Laia, additional, Grueso, Judit, additional, Nonell, Lara, additional, Beaulieu, Marie-Eve, additional, Whitfield, Jonathan R., additional, and Soucek, Laura, additional
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- 2023
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12. Supplementary Figure 3 from Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma
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Massó-Vallés, Daniel, primary, Jauset, Toni, primary, Serrano, Erika, primary, Sodir, Nicole M., primary, Pedersen, Kim, primary, Affara, Nesrine I., primary, Whitfield, Jonathan R., primary, Beaulieu, Marie-Eve, primary, Evan, Gerard I., primary, Elias, Laurence, primary, Arribas, Joaquín, primary, and Soucek, Laura, primary
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- 2023
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13. Supplementary Figure 1 from Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma
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Massó-Vallés, Daniel, primary, Jauset, Toni, primary, Serrano, Erika, primary, Sodir, Nicole M., primary, Pedersen, Kim, primary, Affara, Nesrine I., primary, Whitfield, Jonathan R., primary, Beaulieu, Marie-Eve, primary, Evan, Gerard I., primary, Elias, Laurence, primary, Arribas, Joaquín, primary, and Soucek, Laura, primary
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- 2023
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14. Supplementary Figure legends from Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma
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Massó-Vallés, Daniel, primary, Jauset, Toni, primary, Serrano, Erika, primary, Sodir, Nicole M., primary, Pedersen, Kim, primary, Affara, Nesrine I., primary, Whitfield, Jonathan R., primary, Beaulieu, Marie-Eve, primary, Evan, Gerard I., primary, Elias, Laurence, primary, Arribas, Joaquín, primary, and Soucek, Laura, primary
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- 2023
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15. Supplementary Figure 2 from Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma
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Massó-Vallés, Daniel, primary, Jauset, Toni, primary, Serrano, Erika, primary, Sodir, Nicole M., primary, Pedersen, Kim, primary, Affara, Nesrine I., primary, Whitfield, Jonathan R., primary, Beaulieu, Marie-Eve, primary, Evan, Gerard I., primary, Elias, Laurence, primary, Arribas, Joaquín, primary, and Soucek, Laura, primary
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- 2023
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16. Editorial: MYC as a disease target beyond cancer.
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Whitfield, Jonathan R.
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DEVELOPMENTAL biology ,CYTOLOGY ,TRANSCRIPTION factors ,LITERATURE reviews ,BONE growth - Abstract
The article focuses on the diverse roles of the MYC transcription factor beyond its well-known involvement in cancer. Topics include MYC's potential in treating various non-cancerous diseases, the progress of MYC inhibitors in clinical trials, and a detailed exploration of MYC's impact on conditions like heart restenosis, bone disorders, and obesity.
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- 2024
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17. MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding
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Massó-Vallés, Daniel, primary, Beaulieu, Marie-Eve, additional, Jauset, Toni, additional, Giuntini, Fabio, additional, Zacarías-Fluck, Mariano F., additional, Foradada, Laia, additional, Martínez-Martín, Sandra, additional, Serrano, Erika, additional, Martín-Fernández, Génesis, additional, Casacuberta-Serra, Sílvia, additional, Castillo Cano, Virginia, additional, Kaur, Jastrinjan, additional, López-Estévez, Sergio, additional, Morcillo, Miguel Ángel, additional, Alzrigat, Mohammad, additional, Mahmoud, Loay, additional, Luque-García, Antonio, additional, Escorihuela, Marta, additional, Guzman, Marta, additional, Arribas, Joaquín, additional, Serra, Violeta, additional, Larsson, Lars-Gunnar, additional, Whitfield, Jonathan R., additional, and Soucek, Laura, additional
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- 2022
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18. Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease
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Todorović-Raković, Nataša, primary and Whitfield, Jonathan R., additional
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- 2021
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19. The long journey to bring a Myc inhibitor to the clinic
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Whitfield, Jonathan R., primary and Soucek, Laura, additional
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- 2021
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20. Tumor microenvironment: becoming sick of Myc
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Whitfield, Jonathan R. and Soucek, Laura
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- 2012
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21. Abstract 1823: Translating Myc inhibition to the clinic in metastatic breast cancer
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Massó-Vallés, Daniel, primary, Beaulieu, Marie-Eve, additional, Jauset, Toni, additional, Serrano, Erika, additional, Martínez-Martín, Sandra, additional, Foradada, Laia, additional, Castillo, Virginia, additional, Castillo, Francisco, additional, Martín, Génesis, additional, Casacuberta-Serra, Sílvia, additional, Zacarias-Fluck, Mariano F., additional, Luque-García, Antonio, additional, Escorihuela, Marta, additional, Whitfield, Jonathan R., additional, Arribas, Joaquín, additional, and Soucek, Laura, additional
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- 2020
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22. Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy
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Beaulieu, Marie-Eve, primary, Jauset, Toni, additional, Massó-Vallés, Daniel, additional, Martínez-Martín, Sandra, additional, Rahl, Peter, additional, Maltais, Loïka, additional, Zacarias-Fluck, Mariano F., additional, Casacuberta-Serra, Sílvia, additional, Serrano del Pozo, Erika, additional, Fiore, Christopher, additional, Foradada, Laia, additional, Cano, Virginia Castillo, additional, Sánchez-Hervás, Meritxell, additional, Guenther, Matthew, additional, Romero Sanz, Eduardo, additional, Oteo, Marta, additional, Tremblay, Cynthia, additional, Martín, Génesis, additional, Letourneau, Danny, additional, Montagne, Martin, additional, Morcillo Alonso, Miguel Ángel, additional, Whitfield, Jonathan R., additional, Lavigne, Pierre, additional, and Soucek, Laura, additional
- Published
- 2019
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23. Abstract B16: Targeting Myc in metastatic breast cancer by Omomyc: From proof of principle to pharmacologic approach
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Massó-Vallés, Daniel, primary, Beaulieu, Marie-Eve, additional, Jauset, Toni, additional, Serrano, Erika, additional, Martínez-Martín, Sandra, additional, Foradada, Laia, additional, Castillo, Virginia, additional, Casacuberta-Serra, Sílvia, additional, Zacarias-Fluck, Mariano F., additional, Martín, Génesis, additional, Luque-García, Antonio, additional, Escorihuela, Marta, additional, Whitfield, Jonathan R., additional, Arribas, Joaquín, additional, and Soucek, Laura, additional
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- 2018
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24. Abstract 3351: Myc inhibition by Omomyc impairs melanoma growth and progression through genome-wide gene expression reprogramming
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Zacarias-Fluck, Mariano F., primary, Martín, Génesis, additional, Massó-Vallés, Daniel, additional, Foradada, Laia, additional, Whitfield, Jonathan R., additional, Beaulieu, Marie-Eve, additional, and Soucek, Laura, additional
- Published
- 2018
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25. Abstract 3956: Omomyc-based cell-penetrating peptides: From proof of concept to a clinically viable anti-Myc therapy
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Beaulieu, Marie-Eve, primary, Jauset, Toni, additional, Massó-Vallés, Daniel, additional, Martínez-Martín, Sandra, additional, Rahl, Peter, additional, Maltais, Löika, additional, Zacarias-Fluck, Mariano F., additional, Casacuberta-Serra, Sílvia, additional, Pozo, Erika Serrano del, additional, Fiore, Christopher, additional, Foradada, Laia, additional, Cano, Virginia Castillo, additional, Guenther, Matthew, additional, Sanza, Eduardo Romero, additional, Oteo, Marta, additional, Tremblay, Cynthia Tremblay, additional, Martín, Génesis, additional, Letourneau, Danny, additional, Montagne, Martin, additional, Alonso, Miguel Ángel Morcillo, additional, Whitfield, Jonathan R., additional, Lavigne, Pierre, additional, and Soucek, Laura, additional
- Published
- 2018
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26. BET inhibition is an effective approach against KRAS-driven PDAC and NSCLC
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Jauset, Toni, primary, Massó-Vallés, Daniel, additional, Martínez-Martín, Sandra, additional, Beaulieu, Marie-Eve, additional, Foradada, Laia, additional, Fiorentino, Francesco Paolo, additional, Yokota, Jun, additional, Haendler, Bernard, additional, Siegel, Stephan, additional, Whitfield, Jonathan R., additional, and Soucek, Laura, additional
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- 2018
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27. Abstract 2167: Preclinical validation of an Omomyc cell-penetrating peptide as a viable anti-Myc therapy
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Beaulieu, Marie-eve, primary, Jauset, Toni, additional, Massó-Vallés, Daniel, additional, Rahl, Peter, additional, Martinez-Martin, Sandra, additional, Maltais, Loika, additional, Zacarias-Fluck, Mariano F., additional, Casacuberta, Silvia, additional, Pozo, Erika Serrano del, additional, Fiore, Christopher, additional, Foradada, Laia, additional, Guenther, Matthew, additional, Sanz, Eduardo Romero, additional, Vives, Marta Oteo, additional, Tremblay, Cynthia, additional, Montagne, Martin, additional, Alonso, Miguel Ángel Morcillo, additional, Whitfield, Jonathan R., additional, Lavigne, Pierre, additional, and Soucek, Laura, additional
- Published
- 2017
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28. Strategies to Inhibit Myc and Their Clinical Applicability
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Whitfield, Jonathan R., primary, Beaulieu, Marie-Eve, additional, and Soucek, Laura, additional
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- 2017
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29. Abstract B23: Pushing Myc inhibition towards the clinic by direct delivery of cell-penetrating peptides
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Beaulieu, Marie-Eve, primary, Jauset, Toni, additional, Massó-Valles, Daniel, additional, Whitfield, Jonathan R., additional, Pozo, Erika Serrano del, additional, Tremblay, Cynthia, additional, Maltais, Loïka, additional, Montagne, Martin, additional, Lavigne, Pierre, additional, and Soucek, Laura, additional
- Published
- 2015
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30. Abstract 396: Ibrutinib exerts potent antifibrotic activity in a mouse model of pancreatic adenocarcinoma
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Massó-Vallés, Daniel, primary, Jauset, Toni, additional, Serrano, Erika, additional, Sodir, Nicole M., additional, Pedersen, Kim, additional, Affara, Nesrine I., additional, Whitfield, Jonathan R., additional, Beaulieu, Marie-Eve, additional, Evan, Gerard I., additional, Elias, Laurence, additional, Arribas, Joaquín, additional, and Soucek, Laura, additional
- Published
- 2015
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31. Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma
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Massó-Vallés, Daniel, primary, Jauset, Toni, additional, Serrano, Erika, additional, Sodir, Nicole M., additional, Pedersen, Kim, additional, Affara, Nesrine I., additional, Whitfield, Jonathan R., additional, Beaulieu, Marie-Eve, additional, Evan, Gerard I., additional, Elias, Laurence, additional, Arribas, Joaquín, additional, and Soucek, Laura, additional
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- 2015
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32. Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
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Annibali, Daniela, primary, Whitfield, Jonathan R., additional, Favuzzi, Emilia, additional, Jauset, Toni, additional, Serrano, Erika, additional, Cuartas, Isabel, additional, Redondo-Campos, Sara, additional, Folch, Gerard, additional, Gonzàlez-Juncà, Alba, additional, Sodir, Nicole M., additional, Massó-Vallés, Daniel, additional, Beaulieu, Marie-Eve, additional, Swigart, Lamorna B., additional, Mc Gee, Margaret M., additional, Somma, Maria Patrizia, additional, Nasi, Sergio, additional, Seoane, Joan, additional, Evan, Gerard I., additional, and Soucek, Laura, additional
- Published
- 2014
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33. Abstract 4956: Pharmacological inhibition of Bruton's Tyrosine Kinase (BTK) as a therapy for insulinoma and pancreatic ductal adenocarcinoma.
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Massó-Vallés, Daniel, primary, Serrano, Erika, additional, Whitfield, Jonathan R., additional, Buggy, Joseph J., additional, Sodir, Nicole M., additional, Affara, Nesrine I., additional, Brown Swigart, Lamorna, additional, Evan, Gerard I., additional, and Soucek, Laura, additional
- Published
- 2013
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34. Abstract 1085: MYC inhibition is a potent therapy against glioma and induces mitotic crisis in cancer cells.
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Annibali, Daniela, primary, Whitfield, Jonathan R., additional, Favuzzi, Emilia, additional, Jauset, Toni, additional, serrano, Erika, additional, Folch, Gerard, additional, Cuartas, Marta I., additional, Gonzalez, Alba, additional, Brown Swigart, Lamorna, additional, Nasi, Sergio, additional, Evan, Gerard I., additional, Seoane, Joan, additional, and Soucek, Laura, additional
- Published
- 2013
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35. Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice
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Soucek, Laura, primary, Whitfield, Jonathan R., additional, Sodir, Nicole M., additional, Massó-Vallés, Daniel, additional, Serrano, Erika, additional, Karnezis, Anthony N., additional, Swigart, Lamorna Brown, additional, and Evan, Gerard I., additional
- Published
- 2013
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36. Tumor microenvironment: becoming sick of Myc
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Whitfield, Jonathan R., primary and Soucek, Laura, additional
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- 2011
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37. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
- Author
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Goodson, William H., Lowe, Leroy, Carpenter, David O., Gilbertson, Michael, Manaf Ali, Abdul, Lopez de Cerain Salsamendi, Adela, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, Amelia K., Collins, Andrew R., Ward, Andrew, Salzberg, Anna C., Colacci, Annamaria, Olsen, Ann-Karin, Berg, Arthur, Barclay, Barry J., Zhou, Binhua P., Blanco-Aparicio, Carmen, Baglole, Carolyn J., Dong, Chenfang, Mondello, Chiara, Hsu, Chia-Wen, Naus, Christian C., Yedjou, Clement, Curran, Colleen S., Laird, Dale W., Koch, Daniel C., Carlin, Danielle J., Felsher, Dean W., Roy, Debasish, Brown, Dustin G., Ratovitski, Edward, Ryan, Elizabeth P., Corsini, Emanuela, Rojas, Emilio, Moon, Eun-Yi, Laconi, Ezio, Marongiu, Fabio, Al-Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L., Van Schooten, Frederik J., Goldberg, Gary S., Wagemaker, Gerard, Nangami, Gladys, Calaf, Gloria M., Williams, Graeme, Wolf, Gregory T., Koppen, Gudrun, Brunborg, Gunnar, Kim Lyerly, H., Krishnan, Harini, Ab Hamid, Hasiah, Yasaei, Hemad, Sone, Hideko, Kondoh, Hiroshi, Salem, Hosni K., Hsu, Hsue-Yin, Park, Hyun Ho, Koturbash, Igor, Miousse, Isabelle R., Scovassi, A.Ivana, Klaunig, James E., Vondráček, Jan, Raju, Jayadev, Roman, Jesse, Wise, John Pierce, Whitfield, Jonathan R., Woodrick, Jordan, Christopher, Joseph A., Ochieng, Josiah, Martinez-Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Sun, Jun, Prudhomme, Kalan R., Narayanan, Kannan Badri, Cohen-Solal, Karine A., Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D’Abronzo, Leandro S., Lin, Liang-Tzung, Li, Lin, Gulliver, Linda, McCawley, Lisa J., Memeo, Lorenzo, Vermeulen, Louis, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, Maria Fiammetta, Chapellier, Marion, Williams, Marc A., Wade, Mark, Manjili, Masoud H., Lleonart, Matilde, Xia, Menghang, Gonzalez, Michael J., Karamouzis, Michalis V., Kirsch-Volders, Micheline, Vaccari, Monica, Kuemmerle, Nancy B., Singh, Neetu, Cruickshanks, Nichola, Kleinstreuer, Nicole, van Larebeke, Nik, Ahmed, Nuzhat, Ogunkua, Olugbemiga, Krishnakumar, P.K., Vadgama, Pankaj, Marignani, Paola A., Ghosh, Paramita M., Ostrosky-Wegman, Patricia, Thompson, Patricia, Dent, Paul, Heneberg, Petr, Darbre, Philippa, Sing Leung, Po, Nangia-Makker, Pratima, Cheng, Qiang (Shawn), Robey, R.Brooks, Al-Temaimi, Rabeah, Roy, Rabindra, Andrade-Vieira, Rafaela, Sinha, Ranjeet K., Mehta, Rekha, Vento, Renza, Di Fiore, Riccardo, Ponce-Cusi, Richard, Dornetshuber-Fleiss, Rita, Nahta, Rita, Castellino, Robert C., Palorini, Roberta, Abd Hamid, Roslida, Langie, Sabine A.S., Eltom, Sakina, Brooks, Samira A., Ryeom, Sandra, Wise, Sandra S., Bay, Sarah N., Harris, Shelley A., Papagerakis, Silvana, Romano, Simona, Pavanello, Sofia, Eriksson, Staffan, Forte, Stefano, Casey, Stephanie C., Luanpitpong, Sudjit, Lee, Tae-Jin, Otsuki, Takemi, Chen, Tao, Massfelder, Thierry, Sanderson, Thomas, Guarnieri, Tiziana, Hultman, Tove, Dormoy, Valérian, Odero-Marah, Valerie, Sabbisetti, Venkata, Maguer-Satta, Veronique, Rathmell, W.Kimryn, Engström, Wilhelm, Decker, William K., Bisson, William H., Rojanasakul, Yon, Luqmani, Yunus, Chen, Zhenbang, and Hu, Zhiwei
- Abstract
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
- Published
- 2015
- Full Text
- View/download PDF
38. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
- Author
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Wade, Mark, Gonzalez, Michael J., Brooks, Samira A., Gonzalez, Laetitia, Sabbisetti, Venkata, Weisz, Judith, Felsher, Dean W., Odero-Marah, Valerie, Sone, Hideko, Goldberg, Gary S., Ivana Scovassi, A., Hsu, Hsue Yin, Wolf, Gregory T., Kim Lyerly, H., Eltom, Sakina, Hamid, Roslida Abd, Prudhomme, Kalan R., Chiaradonna, Ferdinando, Calaf, Gloria M., Al-Temaimi, Rabeah, Miousse, Isabelle R., Krishnan, Harini, Kravchenko, Julia, Engström, Wilhelm, Ogunkua, Olugbemiga, Van Larebeke, Nik, Rojas, Emilio, Collins, Andrew R., Ryan, Elizabeth P., Bay, Sarah N., Martinez-Leal, Juan Fernando, Darroudi, Firouz, Vento, Renza, Nangia-Makker, Pratima, Charles, Amelia K., Lowe, Leroy, Van Schooten, Frederik J., Goodson, William H., Eriksson, Staffan, Woodrick, Jordan, Sun, Jun, Ghosh, Paramita M., Carlin, Danielle J., Ochieng, Josiah, Hamid, Hasiah Ab, Rojanasakul, Yon, Manjili, Masoud H., Vadgama, Pankaj, Lee, Tae Jin, Carnero, Amancio, Martin, Francis L., Castellino, Robert C., Carpenter, David O., Valverde, Mahara, Christopher, Joseph A., Kimryn Rathmell, W., Ryeom, Sandra, Cruickshanks, Nichola, Koch, Daniel C., Ponce-Cusi, Richard, Heneberg, Petr, Brown, Dustin G., Dormoy, Valérian, Gilbertson, Michael, Langie, Sabine A.S., Koturbash, Igor, Otsuki, Takemi, Naus, Christian C., Mehta, Rekha, Chen, Zhenbang, Ostrosky-Wegman, Patricia, Massfelder, Thierry, Zhou, Binhua P., McCawley, Lisa J., Harris, Shelley A., Casey, Stephanie C., Xia, Menghang, Romano, Maria Fiammetta, Whitfield, Jonathan R., Laird, Dale W., Li, Lin, Dong, Chenfang, Brooks Robey, R., Pavanello, Sofia, Ratovitski, Edward, Roman, Jesse, Lleonart, Matilde, Vondráček, Jan, Narayanan, Kannan Badri, Marignani, Paola A., Brunborg, Gunnar, Laconi, Ezio, Wise, John Pierce, Nangami, Gladys, Marongiu, Fabio, Vaccari, Monica, Berg, Arthur, Jian, Le, Curran, Colleen S., Moon, Eun Yi, Wise, Sandra S., de Cerain Salsamendi, Adela Lopez, Yasaei, Hemad, Forte, Stefano, Krishnakumar, P. K., Thompson, Patricia, Zhang, Luoping, Raju, Jayadev, Lasfar, Ahmed, Palorini, Roberta, Mondello, Chiara, Romano, Simona, Memeo, Lorenzo, Andrade-Vieira, Rafaela, Salem, Hosni K., Karamouzis, Michalis V., Dent, Paul, Blanco-Aparicio, Carmen, Baglole, Carolyn J., Kondoh, Hiroshi, Wagemaker, Gerard, Decker, William K., Cheng, Qiang Shawn, Di Fiore, Riccardo, Hultman, Tove, Ali, Abdul Manaf, Kleinstreuer, Nicole, Luanpitpong, Sudjit, Gulliver, Linda, Salzberg, Anna C., D'Abronzo, Leandro S., Chapellier, Marion, Yedjou, Clement, Kirsch-Volders, Micheline, Guarnieri, Tiziana, Nahta, Rita, Ward, Andrew, Leyns, Luc, Cohen-Solal, Karine A., Hsu, Chia Wen, Lin, Liang Tzung, Chen, Tao, Corsini, Emanuela, Maguer-Satta, Veronique, Papagerakis, Silvana, Williams, Marc A., Roy, Rabindra, Williams, Graeme, Sinha, Ranjeet K., Roy, Debasish, Klaunig, James E., Singh, Neetu, Kuemmerle, Nancy B., Park, Hyun Ho, Barclay, Barry J., Bisson, William H., Vermeulen, Louis, Soucek, Laura, Khatami, Mahin, Sanderson, Thomas, Koppen, Gudrun, Darbre, Philippa, Ahmed, Nuzhat, Amedei, Amedeo, Dornetshuber-Fleiss, Rita, Al-Mulla, Fahd, Olsen, Ann Karin, Luqmani, Yunus, Hu, Zhiwei, Azqueta, Amaya, Leung, Po Sing, Moorwood, Kim, and Colacci, Annamaria
- Subjects
1. No poverty ,3. Good health - Abstract
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
39. Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
- Author
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Annibali, Daniela, Whitfield, Jonathan R, Favuzzi, Emilia, Jauset, Toni, Serrano, Erika, Cuartas, Isabel, Redondo-Campos, Sara, Folch, Gerard, Gonzàlez-Juncà, Alba, Sodir, Nicole M, Massó-Vallés, Daniel, Beaulieu, Marie-Eve, Swigart, Lamorna B, Mc Gee, Margaret M, Somma, Maria Patrizia, Nasi, Sergio, Seoane, Joan, Evan, Gerard I, and Soucek, Laura
- Subjects
Protein Tyrosine Phosphatase, Non-Receptor Type 1 ,Brain Neoplasms ,Mitosis ,Apoptosis ,Mice, Transgenic ,Glioma ,Ubiquitin-Activating Enzymes ,Astrocytoma ,3. Good health ,Proto-Oncogene Proteins c-myc ,Disease Models, Animal ,Mice ,Cell Line, Tumor ,Animals ,Heterografts ,Humans ,Glioblastoma ,Cell Proliferation - Abstract
Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.
40. The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets
- Author
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Marie-Eve Beaulieu, Laura Soucek, Jonathan Whitfield, Mariano F. Zacarias-Fluck, Íñigo González-Larreategui, Génesis Martín-Fernández, Jastrinjan Kaur, Daniel Massó-Vallés, Sandra Martínez-Martín, Lamorna Brown-Swigart, David M. Virshup, Erika Serrano del Pozo, Toni Jauset, Sílvia Casacuberta-Serra, Babita Madan, Sergio López-Estévez, Gerard I. Evan, Zacarías-Fluck, Mariano F [0000-0002-7171-4268], Martínez-Martín, Sandra [0000-0003-4443-0697], Kaur, Jastrinjan [0000-0002-4474-5093], Casacuberta-Serra, Sílvia [0000-0002-2595-1115], Massó-Vallés, Daniel [0000-0003-4231-0456], González-Larreategui, Íñigo [0000-0002-0959-8497], López-Estévez, Sergio [0000-0001-5355-8073], Brown-Swigart, Lamorna [0000-0003-2076-5177], Beaulieu, Marie-Eve [0000-0001-5224-8436], Whitfield, Jonathan R [0000-0002-4925-7283], Virshup, David M [0000-0001-6976-850X], Evan, Gerard I [0000-0003-0412-1216], Soucek, Laura [0000-0002-4750-7971], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Male ,Carcinogenesis ,Health, Toxicology and Mutagenesis ,Genes, myc ,Plant Science ,medicine.disease_cause ,Mice ,0302 clinical medicine ,Cell Movement ,Gene expression ,2.1 Biological and endogenous factors ,Aetiology ,Receptor ,Wnt Signaling Pathway ,beta Catenin ,Research Articles ,Cancer ,Ecology ,Effector ,Wnt signaling pathway ,myc ,Adenoma, Islet Cell ,Islet Cell ,Cell biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Research Article ,Adenoma ,Biology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,03 medical and health sciences ,Pancreatic Cancer ,Islets of Langerhans ,Rare Diseases ,medicine ,Genetics ,Animals ,Insulinoma ,Cell Proliferation ,Cell growth ,Pancreatic islets ,medicine.disease ,Frizzled Receptors ,030104 developmental biology ,Genes ,Digestive Diseases - Abstract
Zacarías-Fluck, et al identify and validate the Wnt receptor Fzd9 as a key effector of Myc-Wnt signaling cross-talk in a mouse model of Myc-driven pancreatic insulinomas., The huge cadre of genes regulated by Myc has obstructed the identification of critical effectors that are essential for Myc-driven tumorigenesis. Here, we describe how only the lack of the receptor Fzd9, previously identified as a Myc transcriptional target, impairs sustained tumor expansion and β-cell dedifferentiation in a mouse model of Myc-driven insulinoma, allows pancreatic islets to maintain their physiological structure and affects Myc-related global gene expression. Importantly, Wnt signaling inhibition in Fzd9-competent mice largely recapitulates the suppression of proliferation caused by Fzd9 deficiency upon Myc activation. Together, our results indicate that the Wnt signaling receptor Fzd9 is essential for Myc-induced tumorigenesis in pancreatic islets.
- Published
- 2021
41. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
- Author
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Dustin G. Brown, Tove Hultman, Judith Weisz, H. Kim Lyerly, Paola A. Marignani, Ann-Karin Olsen, Rabindra Roy, Kim Moorwood, Masoud H. Manjili, Monica Vaccari, Jesse Roman, Hasiah Ab Hamid, Kalan R. Prudhomme, Periyadan K. Krishnakumar, Chenfang Dong, Tiziana Guarnieri, Leandro S. D'Abronzo, Gloria M. Calaf, Amelia K Charles, Emanuela Corsini, Yunus A. Luqmani, Graeme Williams, Louis Vermeulen, Pankaj Vadgama, Sarah N Bay, Véronique Maguer-Satta, Sabine A. S. Langie, Christian C. Naus, Le Jian, Gladys N. Nangami, Lorenzo Memeo, Stephanie C. Casey, Thomas Sanderson, Takemi Otsuki, Nichola Cruickshanks, William H. Bisson, Sudjit Luanpitpong, Jonathan Whitfield, Ahmed Lasfar, Yon Rojanasakul, A. Ivana Scovassi, Shelley A. Harris, Ferdinando Chiaradonna, Richard Ponce-Cusi, Gregory T. Wolf, Valérian Dormoy, Roslida Abd Hamid, Hyun Ho Park, Matilde E. Lleonart, William K. Decker, Maria Romano, Leroy Lowe, Fabio Marongiu, Jan Vondráček, Chiara Mondello, Luc Leyns, Josiah Ochieng, Pratima Nangia-Makker, Edward A. Ratovitski, Zhiwei Hu, Jayadev Raju, Hemad Yasaei, Rafaela Andrade-Vieira, Jordan Woodrick, Hideko Sone, Harini Krishnan, W. Kimryn Rathmell, Andrew Collins, Luoping Zhang, Barry J. Barclay, Amaya Azqueta, Laura Soucek, Marc A. Williams, David O. Carpenter, Roberta Palorini, Rita Nahta, Juan Fernando Martinez-Leal, Firouz Darroudi, Rita Dornetshuber-Fleiss, James E. Klaunig, Elizabeth P. Ryan, Qiang Shawn Cheng, Arthur Berg, Andrew Ward, Gudrun Koppen, Tao Chen, Petr Heneberg, Michael Gilbertson, Amedeo Amedei, Sakina E. Eltom, Ezio Laconi, Joseph Christopher, Hiroshi Kondoh, Neetu Singh, Danielle J Carlin, Marion Chapellier, Michalis V. Karamouzis, Rekha Mehta, Tae-Jin Lee, Annamaria Colacci, Venkata S. Sabbisetti, Mark Wade, Micheline Kirsch-Volders, Patricia Ostrosky-Wegman, Isabelle R. Miousse, Patricia A. Thompson, Philippa D. Darbre, Frederik J. van Schooten, Sofia Pavanello, Igor Koturbash, Binhua P. Zhou, Ranjeet Kumar Sinha, Anna C. Salzberg, Mahara Valverde, Fahd Al-Mulla, Julia Kravchenko, Nicole Kleinstreuer, Carolyn J. Baglole, Menghang Xia, Samira A. Brooks, Amancio Carnero, Gunnar Brunborg, Sandra S. Wise, Daniel C. Koch, John Pierce Wise, Rabeah Al-Temaimi, Laetitia Gonzalez, Lisa J. McCawley, R. Brooks Robey, Gary S. Goldberg, Thierry Massfelder, Linda S M Gulliver, Olugbemiga Ogunkua, Emilio Rojas, Eun-Yi Moon, Lin Li, Silvana Papagerakis, Nik van Larebeke, Adela Lopez de Cerain Salsamendi, Staffan Eriksson, Simona Romano, Dean W. Felsher, Paramita M. Ghosh, Karine A. Cohen-Solal, Paul Dent, Jun Sun, Carmen Blanco-Aparicio, Riccardo Di Fiore, Chia-Wen Hsu, Mahin Khatami, Kannan Badri Narayanan, Francis Martin, Colleen S. Curran, Dale W. Laird, William H. Goodson, Abdul Manaf Ali, Valerie Odero-Marah, Michael J. Gonzalez, Renza Vento, Liang Tzung Lin, Clement G. Yedjou, Hosni Salem, Hsue-Yin Hsu, Zhenbang Chen, Nuzhat Ahmed, Gerard Wagemaker, Sandra Ryeom, Stefano Forte, Debasish Roy, Nancy B. Kuemmerle, Robert C. Castellino, Po Sing Leung, Wilhelm Engström, National Institute of Environmental Health Sciences (US), Research Council of Norway, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Cáncer (España), European Commission, Junta de Andalucía, Ministerio de Educación y Ciencia (España), Ministero dell'Istruzione, dell'Università e della Ricerca, University of Oslo, Regione Emilia Romagna, National Institutes of Health (US), Consejo Nacional de Ciencia y Tecnología (México), Associazione Italiana per la Ricerca sul Cancro, National Research Foundation of Korea, Ministry of Education, Science and Technology (South Korea), Fondo Nacional de Desarrollo Científico y Tecnológico (Chile), Ministry of Education, Culture, Sports, Science and Technology (Japan), Japan Science and Technology Agency, Ministry of Science and Technology (Taiwan), Arkansas Biosciences Institute, Czech Science Foundation, Fundación Fero, Swim Across America, American Cancer Society, Research Foundation - Flanders, Austrian Science Fund, Institut National de la Santé et de la Recherche Médicale (France), Natural Sciences and Engineering Research Council of Canada, Farmacologie en Toxicologie, RS: NUTRIM - R4 - Gene-environment interaction, Goodson, William H, Lowe, Leroy, Carpenter, David O, Gilbertson, Michael, Manaf Ali, Abdul, Lopez de Cerain Salsamendi, Adela, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, Amelia K, Collins, Andrew R, Ward, Andrew, Salzberg, Anna C, Colacci, Annamaria, Olsen, Ann Karin, Berg, Arthur, Barclay, Barry J, Zhou, Binhua P, Blanco Aparicio, Carmen, Baglole, Carolyn J, Dong, Chenfang, Mondello, Chiara, Hsu, Chia Wen, Naus, Christian C, Yedjou, Clement, Curran, Colleen S, Laird, Dale W, Koch, Daniel C, Carlin, Danielle J, Felsher, Dean W, Roy, Debasish, Brown, Dustin G, Ratovitski, Edward, Ryan, Elizabeth P, Corsini, Emanuela, Rojas, Emilio, Moon, Eun Yi, Laconi, Ezio, Marongiu, Fabio, Al Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L, Van Schooten, Frederik J, Goldberg, Gary S, Wagemaker, Gerard, Nangami, Gladys N, Calaf, Gloria M, Williams, Graeme, Wolf, Gregory T, Koppen, Gudrun, Brunborg, Gunnar, Lyerly, H. Kim, Krishnan, Harini, Ab Hamid, Hasiah, Yasaei, Hemad, Sone, Hideko, Kondoh, Hiroshi, Salem, Hosni K, Hsu, Hsue Yin, Park, Hyun Ho, Koturbash, Igor, Miousse, Isabelle R, Scovassi, A. Ivana, Klaunig, James E, Vondráček, Jan, Raju, Jayadev, Roman, Jesse, Wise, John Pierce, Whitfield, Jonathan R, Woodrick, Jordan, Christopher, Joseph A, Ochieng, Josiah, Martinez Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Sun, Jun, Prudhomme, Kalan R, Narayanan, Kannan Badri, Cohen Solal, Karine A, Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D'Abronzo, Leandro S, Lin, Liang Tzung, Li, Lin, Gulliver, Linda, Mccawley, Lisa J, Memeo, Lorenzo, Vermeulen, Loui, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, MARIA FIAMMETTA, Chapellier, Marion, Williams, Marc A, Wade, Mark, Manjili, Masoud H, Lleonart, Matilde E, Xia, Menghang, Gonzalez, Michael J, Karamouzis, Michalis V, Kirsch Volders, Micheline, Vaccari, Monica, Kuemmerle, Nancy B, Singh, Neetu, Cruickshanks, Nichola, Kleinstreuer, Nicole, van Larebeke, Nik, Ahmed, Nuzhat, Ogunkua, Olugbemiga, Krishnakumar, P. K, Vadgama, Pankaj, Marignani, Paola A, Ghosh, Paramita M, Ostrosky Wegman, Patricia, Thompson, Patricia A, Dent, Paul, Heneberg, Petr, Darbre, Philippa, Sing Leung, Po, Nangia Makker, Pratima, Cheng, Qiang Shawn, Robey, R. Brook, Al Temaimi, Rabeah, Roy, Rabindra, Andrade Vieira, Rafaela, Sinha, Ranjeet K, Mehta, Rekha, Vento, Renza, Di Fiore, Riccardo, Ponce Cusi, Richard, Dornetshuber Fleiss, Rita, Nahta, Rita, Castellino, Robert C, Palorini, Roberta, Abd Hamid, Roslida, Langie, Sabine A. S, Eltom, Sakina E, Brooks, Samira A, Ryeom, Sandra, Wise, Sandra S, Bay, Sarah N, Harris, Shelley A, Papagerakis, Silvana, Romano, Simona, Pavanello, Sofia, Eriksson, Staffan, Forte, Stefano, Casey, Stephanie C, Luanpitpong, Sudjit, Lee, Tae Jin, Otsuki, Takemi, Chen, Tao, Massfelder, Thierry, Sanderson, Thoma, Guarnieri, Tiziana, Hultman, Tove, Dormoy, Valérian, Odero Marah, Valerie, Sabbisetti, Venkata, Maguer Satta, Veronique, Rathmell, W. Kimryn, Engström, Wilhelm, Decker, William K, Bisson, William H, Rojanasakul, Yon, Luqmani, Yunu, Chen, Zhenbang, Hu, Zhiwei, Goodson, W., Lowe, L., Carpenter, D., Gilbertson, M., Ali, A., de Cerain Salsamendi, A., Lasfar, A., Carnero, A., Azqueta, A., Amedei, A., Charles, A., Collins, A., Ward, A., Salzberg, A., Colacci, A., Olsen, A., Berg, A., Barclay, B., Zhou, B., Blanco-Aparicio, C., Baglole, C., Dong, C., Mondello, C., Hsu, C., Naus, C., Yedjou, C., Curran, C., Laird, D., Koch, D., Carlin, D., Felsher, D., Roy, D., Brown, D., Ratovitski, E., Ryan, E., Corsini, E., Rojas, E., Moon, E., Laconi, E., Marongiu, F., Al-Mulla, F., Chiaradonna, F., Darroudi, F., Martin, F., Van Schooten, F., Goldberg, G., Wagemaker, G., Nangami, G., Calaf, G., Williams, G., Wolf, G., Koppen, G., Brunborg, G., Kim Lyerly, H., Krishnan, H., Hamid, H., Yasaei, H., Sone, H., Kondoh, H., Salem, H., Hsu, H., Park, H., Koturbash, I., Miousse, I., Ivana Scovassi, A., Klaunig, J., Vondráček, J., Raju, J., Roman, J., Wise, J., Whitfield, J., Woodrick, J., Christopher, J., Ochieng, J., Martinez-Leal, J., Weisz, J., Kravchenko, J., Sun, J., Prudhomme, K., Narayanan, K., Cohen-Solal, K., Moorwood, K., Gonzalez, L., Soucek, L., Jian, L., D'Abronzo, L., Lin, L., Li, L., Gulliver, L., Mccawley, L., Memeo, L., Vermeulen, L., Leyns, L., Zhang, L., Valverde, M., Khatami, M., Romano, M., Chapellier, M., Williams, M., Wade, M., Manjili, M., Lleonart, M., Xia, M., Gonzalez, M., Karamouzis, M., Kirsch-Volders, M., Vaccari, M., Kuemmerle, N., Singh, N., Cruickshanks, N., Kleinstreuer, N., Van Larebeke, N., Ahmed, N., Ogunkua, O., Krishnakumar, P., Vadgama, P., Marignani, P., Ghosh, P., Ostrosky-Wegman, P., Thompson, P., Dent, P., Heneberg, P., Darbre, P., Leung, P., Nangia-Makker, P., Cheng, Q., Brooks Robey, R., Al-Temaimi, R., Roy, R., Andrade-Vieira, R., Sinha, R., Mehta, R., Vento, R., Di Fiore, R., Ponce-Cusi, R., Dornetshuber-Fleiss, R., Nahta, R., Castellino, R., Palorini, R., Hamid, R., Langie, S., Eltom, S., Brooks, S., Ryeom, S., Wise, S., Bay, S., Harris, S., Papagerakis, S., Romano, S., Pavanello, S., Eriksson, S., Forte, S., Casey, S., Luanpitpong, S., Lee, T., Otsuki, T., Chen, T., Massfelder, T., Sanderson, T., Guarnieri, T., Hultman, T., Dormoy, V., Odero-Marah, V., Sabbisetti, V., Maguer-Satta, V., Kimryn Rathmell, W., Engström, W., Decker, W., Bisson, W., Rojanasakul, Y., Luqmani, Y., Chen, Z., Hu, Z., Goodson, W.H., Carpenter, D.O., Ali, A.M., de Cerain Salsamendi, A.L., Charles, A.K., Collins, A.R., Salzberg, A.C., Olsen, A.-K., Barclay, B.J., Zhou, B.P., Baglole, C.J., Hsu, C.-W., Naus, C.C., Curran, C.S., Laird, D.W., Koch, D.C., Carlin, D.J., Felsher, D.W., Brown, D.G., Ryan, E.P., Moon, E.-Y., Martin, F.L., Van Schooten, F.J., Goldberg, G.S., Calaf, G.M., Wolf, G.T., Hamid, H.A., Salem, H.K., Hsu, H.-Y., Park, H.H., Miousse, I.R., Klaunig, J.E., Vondracek, J., Wise, J.P., Whitfield, J.R., Christopher, J.A., Martinez-Leal, J.F., Prudhomme, K.R., Narayanan, K.B., Cohen-Solal, K.A., D'Abronzo, L.S., Lin, L.-T., Mccawley, L.J., Romano, M.F., Williams, M.A., Manjili, M.H., Gonzalez, M.J., Karamouzis, M.V., Kuemmerle, N.B., Krishnakumar, P.K., Marignani, P.A., Ghosh, P.M., Leung, P.S., Cheng, Q.S., Sinha, R.K., Castellino, R.C., Hamid, R.A., Langie, S.A.S., Brooks, S.A., Wise, S.S., Bay, S.N., Harris, S.A., Casey, S.C., Lee, T.-J., Engstrom, W., Decker, W.K., Bisson, W.H., sans affiliation, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), We gratefully acknowledge the support of the National Institute of Health-National Institute of Environmental Health Sciences (NIEHS) conference grant travel support (R13ES023276), Glenn Rice, Office of Research and Development, United States Environmental Protection Agency, Cincinnati, OH, USA also deserves thanks for his thoughtful feedback and inputs on the manuscript, William H.Goodson III was supported by the California Breast Cancer Research Program, Clarence Heller Foundation and California Pacific Medical Center Foundation, Abdul M.Ali would like to acknowledge the financial support of the University of Sultan Zainal Abidin, Malaysia, Ahmed Lasfar was supported by an award from the Rutgers Cancer Institute of New Jersey, Ann-Karin Olsen and Gunnar Brunborg were supported by the Research Council of Norway (RCN) through its Centres of Excellence funding scheme (223268/F50), Amancio Carnero’s lab was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0306-2012), Matilde E. Lleonart was supported by a trienal project grant PI12/01104 and by project CP03/00101 for personal support. Amaya Azqueta would like to thank the Ministerio de Educacion y Ciencia (‘Juande la Cierva’ programme, 2009) of the Spanish Government for personal support, Amedeo Amedei was supported by the Italian Ministry of University and Research (2009FZZ4XM_002), and the University of Florence (ex60%2012), Andrew R.Collins was supported by the University of Oslo, Annamaria Colacci was supported by the Emilia-Romagna Region - Project ‘Supersite’ in Italy, Carolyn Baglole was supported by a salary award from the Fonds de recherche du Quebec-Sante (FRQ-S), Chiara Mondello’s laboratory is supported by Fondazione Cariplo in Milan, Italy (grant n. 2011-0370), Christian C.Naus holds a Canada Research Chair, Clement Yedjou was supported by a grant from the National Institutes of Health (NIH-NIMHD grant no. G12MD007581), Daniel C.Koch is supported by the Burroughs Wellcome Fund Postdoctoral Enrichment Award and the Tumor Biology Training grant: NIH T32CA09151, Dean W. Felsher would like to acknowledge the support of United States Department of Health and Human Services, NIH grants (R01 CA170378 PQ22, R01 CA184384, U54 CA149145, U54 CA151459, P50 CA114747 and R21 CA169964), Emilio Rojas would like to thank CONACyT support 152473, Ezio Laconi was supported by AIRC (Italian Association for Cancer Research, grant no. IG 14640) and by the Sardinian Regional Government (RAS), Eun-Yi Moon was supported by grants from the Public Problem-Solving Program (NRF-015M3C8A6A06014500) and Nuclear R&D Program (#2013M2B2A9A03051296 and 2010-0018545) through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science and Technology (MEST) in Korea, Fahd Al-Mulla was supported by the Kuwait Foundation for the Advancement of Sciences (2011-1302-06), Ferdinando Chiaradonna is supported by SysBioNet, a grant for the Italian Roadmap of European Strategy Forum on Research Infrastructures (ESFRI) and by AIRC (Associazione Italiana Ricerca sul Cancro, IG 15364), Francis L.Martin acknowledges funding from Rosemere Cancer Foundation, he also thanks Lancashire Teaching Hospitals NHS trust and the patients who have facilitated the studies he has undertaken over the course of the last 10 years, Gary S.Goldberg would like to acknowledge the support of the New Jersey Health Foundation, Gloria M.Calaf was supported by Fondo Nacional de Ciencia y Tecnología (FONDECYT), Ministerio de Educación de Chile (MINEDUC), Universidad de Tarapacá (UTA), Gudrun Koppen was supported by the Flemish Institute for Technological Research (VITO), Belgium, Hemad Yasaei was supported from a triennial project grant (Strategic Award) from the National Centre for the Replacement, Refinement and Reduction (NC3Rs) of animals in research (NC.K500045.1 and G0800697), Hiroshi Kondoh was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Science and Technology Agency and by JST, CREST, Hsue-Yin Hsu was supported by the Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 and NSC94-2314-B-320-002), Hyun Ho Park was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (2012R1A2A2A01010870) and a grant from the Korea Healthcare Technology R&D project, Ministry of Health and Welfare, Republic of Korea (HI13C1449), Igor Koturbash is supported by the UAMS/NIH Clinical and Translational Science Award (UL1TR000039 and KL2TR000063) and the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000, Jan Vondráček acknowledges funding from the Czech Science Foundation (13-07711S), Jesse Roman thanks the NIH for their support (CA116812), John Pierce Wise Sr. and Sandra S.Wise were supported by National Institute of Environmental Health Sciences (ES016893 to J.P.W.) and the Maine Center for Toxicology and Environmental Health, Jonathan Whitfield acknowledges support from the FERO Foundation in Barcelona, Spain, Joseph Christopher is funded by Cancer Research UK and the International Journal of Experimental Pathology, Julia Kravchenko is supported by a philanthropic donation by Fred and Alice Stanback, Jun Sun is supported by a Swim Across America Cancer Research Award, Karine A.Cohen-Solal is supported by a research scholar grant from the American Cancer Society (116683-RSG-09-087-01-TBE), Laetitia Gonzalez received a postdoctoral fellowship from the Fund for Scientific Research–Flanders (FWO-Vlaanderen) and support by an InterUniversity Attraction Pole grant (IAP-P7-07), Laura Soucek is supported by grant #CP10/00656 from the Miguel Servet Research Contract Program and acknowledges support from the FERO Foundation in Barcelona, Spain, Liang-Tzung Lin was supported by funding from the Taipei Medical University (TMU101-AE3-Y19), Linda Gulliver is supported by a Genesis Oncology Trust (NZ) Professional Development Grant, and the Faculty of Medicine, University of Otago, Dunedin, New Zealand, Louis Vermeulen is supported by a Fellowship of the Dutch Cancer Society (KWF, UVA2011-4969) and a grant from the AICR (14–1164), Mahara Valverde would like to thank CONACyT support 153781, Masoud H. Manjili was supported by the office of the Assistant Secretary of Defense for Health Affairs (USA) through the Breast Cancer Research Program under Award No. W81XWH-14-1-0087 Neetu Singh was supported by grant #SR/FT/LS-063/2008 from the Department of Science and Technology, Government of India, Nicole Kleinstreuer is supported by NIEHS contracts (N01-ES 35504 and HHSN27320140003C), P.K. Krishnakumar is supported by the Funding (No. T.K. 11-0629) of King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia, Paola A.Marignani is supported by the Dalhousie Medical Research Foundation, The Beatrice Hunter Cancer Institute and CIHR and the Nova Scotia Lung Association, Paul Dent is the holder of the Universal Inc.Chair in Signal Transduction Research and is supported with funds from PHS grants from the NIH (R01-CA141704, R01-CA150214, R01-DK52825 and R01-CA61774), Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, and by the Czech Science Foundation projects P301/12/1686 and 15-03834Y, Po Sing Leung was supported by the Health and Medical Research Fund of Food and Health Bureau, Hong Kong Special Administrative Region, Ref. No: 10110021, Qiang Cheng was supported in part by grant NSF IIS-1218712, R. Brooks Robey is supported by the United States Department of Veterans Affairs, Rabindra Roy was supported by United States Public Health Service Grants (RO1 CA92306, RO1 CA92306-S1 and RO1 CA113447), Rafaela Andrade-Vieira is supported by the Beatrice Hunter Cancer Research Institute and the Nova Scotia Health Research Foundation, Renza Vento was partially funded by European Regional Development Fund, European Territorial Cooperation 2007–13 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007–13) and grants from the Italian Ministry of Education, University and Research (MIUR) ex-60%, 2007, Riccardo Di Fiore was a recipient of fellowship granted by European Regional Development Fund, European Territorial Cooperation 2007–2013 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007–2013), Rita Dornetshuber-Fleiss was supported by the Austrian Science Fund (FWF, project number T 451-B18) and the Johanna Mahlke, geb.-Obermann-Stiftung, Roberta Palorini is supported by a SysBioNet fellowship, Roslida Abd Hamid is supported by the Ministry of Education, Malaysia-Exploratory Research Grant Scheme-Project no: ERGS/1-2013/5527165, Sabine A.S.Langie is the beneficiary of a postdoctoral grant from the AXA Research Fund and the Cefic-LRI Innovative Science Award 2013, Sakina Eltom is supported by NIH grant SC1CA153326, Samira A.Brooks was supported by National Research Service Award (T32 ES007126) from the National Institute of Environmental Health Sciences and the HHMI Translational Medicine Fellowship, Sandra Ryeom was supported by The Garrett B. Smith Foundation and the TedDriven Foundation, Thierry Massfelder was supported by the Institut National de la Santé et de la Recherche Médicale INSERM and Université de Strasbourg, Thomas Sanderson is supported by the Canadian Institutes of Health Research (CIHR, MOP-115019), the Natural Sciences and Engineering Council of Canada (NSERC, 313313) and the California Breast Cancer Research Program (CBCRP, 17UB-8703), Tiziana Guarnieri is supported by a grant from Fundamental Oriented Research (RFO) to the Alma Mater Studiorum University of Bologna, Bologna, Italy and thanks the Fondazione Cassa di Risparmio di Bologna and the Fondazione Banca del Monte di Bologna e Ravenna for supporting the Center for Applied Biomedical Research, S.Orsola-Malpighi University Hospital, Bologna, Italy, W.Kimryn Rathmell is supported by the V Foundation for Cancer Research and the American Cancer Society, William K.Decker was supported in part by grant RP110545 from the Cancer Prevention Research Institute of Texas, William H.Bisson was supported with funding from the NIH P30 ES000210, Yon Rojanasakul was supported with NIH grant R01-ES022968, Zhenbang Chen is supported by NIH grants (MD004038, CA163069 and MD007593), Zhiwei Hu is grateful for the grant support from an institutional start-up fund from The Ohio State University College of Medicine and The OSU James Comprehensive Cancer Center (OSUCCC) and a Seed Award from the OSUCCC Translational Therapeutics Program., Sans affiliation, Courcelles, Michel, Goodson, W, Lowe, L, Carpenter, D, Gilbertson, M, Ali, A, de Cerain Salsamendi, A, Lasfar, A, Carnero, A, Azqueta, A, Amedei, A, Charles, A, Collins, A, Ward, A, Salzberg, A, Colacci, A, Olsen, A, Berg, A, Barclay, B, Zhou, B, Blanco Aparicio, C, Baglole, C, Dong, C, Mondello, C, Hsu, C, Naus, C, Yedjou, C, Curran, C, Laird, D, Koch, D, Carlin, D, Felsher, D, Roy, D, Brown, D, Ratovitski, E, Ryan, E, Corsini, E, Rojas, E, Moon, E, Laconi, E, Marongiu, F, Al Mulla, F, Chiaradonna, F, Darroudi, F, Martin, F, Van Schooten, F, Goldberg, G, Wagemaker, G, Nangami, G, Calaf, G, Williams, G, Wolf, G, Koppen, G, Brunborg, G, Kim Lyerly, H, Krishnan, H, Hamid, H, Yasaei, H, Sone, H, Kondoh, H, Salem, H, Hsu, H, Park, H, Koturbash, I, Miousse, I, Ivana Scovassi, A, Klaunig, J, Vondráček, J, Raju, J, Roman, J, Wise, J, Whitfield, J, Woodrick, J, Christopher, J, Ochieng, J, Martinez Leal, J, Weisz, J, Kravchenko, J, Sun, J, Prudhomme, K, Narayanan, K, Cohen Solal, K, Moorwood, K, Gonzalez, L, Soucek, L, Jian, L, D'Abronzo, L, Lin, L, Li, L, Gulliver, L, Mccawley, L, Memeo, L, Vermeulen, L, Leyns, L, Zhang, L, Valverde, M, Khatami, M, Romano, M, Chapellier, M, Williams, M, Wade, M, Manjili, M, Lleonart, M, Xia, M, Gonzalez, M, Karamouzis, M, Kirsch Volders, M, Vaccari, M, Kuemmerle, N, Singh, N, Cruickshanks, N, Kleinstreuer, N, Van Larebeke, N, Ahmed, N, Ogunkua, O, Krishnakumar, P, Vadgama, P, Marignani, P, Ghosh, P, Ostrosky Wegman, P, Thompson, P, Dent, P, Heneberg, P, Darbre, P, Leung, P, Nangia Makker, P, Cheng, Q, Brooks Robey, R, Al Temaimi, R, Roy, R, Andrade Vieira, R, Sinha, R, Mehta, R, Vento, R, Di Fiore, R, Ponce Cusi, R, Dornetshuber Fleiss, R, Nahta, R, Castellino, R, Palorini, R, Hamid, R, Langie, S, Eltom, S, Brooks, S, Ryeom, S, Wise, S, Bay, S, Harris, S, Papagerakis, S, Romano, S, Pavanello, S, Eriksson, S, Forte, S, Casey, S, Luanpitpong, S, Lee, T, Otsuki, T, Chen, T, Massfelder, T, Sanderson, T, Guarnieri, T, Hultman, T, Dormoy, V, Odero Marah, V, Sabbisetti, V, Maguer Satta, V, Kimryn Rathmell, W, Engström, W, Decker, W, Bisson, W, Rojanasakul, Y, Luqmani, Y, Chen, Z, and Hu, Z
- Subjects
Cancer Research ,Carcinogenesis ,[SDV]Life Sciences [q-bio] ,METHOXYCHLOR-INDUCED ALTERATIONS ,Review ,Pharmacology ,MESH: Carcinogens, Environmental ,Carcinogenic synergies ,Chemical mixtures ,Neoplasms ,MESH: Animals ,MESH: Neoplasms ,Carcinogenesi ,Risk assessment ,Cancer ,ACTIVATED PROTEIN-KINASES ,Medicine (all) ,Low dose ,1. No poverty ,Cumulative effects ,BREAST-CANCER CELLS ,General Medicine ,Environmental exposure ,MESH: Carcinogenesis ,BIO/10 - BIOCHIMICA ,EPITHELIAL-MESENCHYMAL TRANSITION ,3. Good health ,[SDV] Life Sciences [q-bio] ,Environmental Carcinogenesis ,ESTROGEN-RECEPTOR-ALPHA ,Human ,MESH: Environmental Exposure ,ENDOCRINE-DISRUPTING CHEMICALS ,TARGETING TISSUE FACTOR ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Prototypical chemical disruptors ,Exposure ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Environmental health ,medicine ,[SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health ,Carcinogen ,Environmental carcinogenesis ,[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health ,MESH: Humans ,Animal ,POLYBROMINATED DIPHENYL ETHERS ,Environmental Exposure ,medicine.disease ,MESH: Hazardous Substances ,Carcinogens, Environmental ,MIGRATION INHIBITORY FACTOR ,VASCULAR ENDOTHELIAL-CELLS ,Hazardous Substance ,Neoplasm - Abstract
Goodson, William H. et al., © The Author 2015. Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology., We gratefully acknowledge the support of the National Institute of Health-National Institute of Environmental Health Sciences (NIEHS) conference grant travel support (R13ES023276); Glenn Rice, Office of Research and Development, United States Environmental Protection Agency, Cincinnati, OH, USA also deserves thanks for his thoughtful feedback and inputs on the manuscript; William H.Goodson III was supported by the California Breast Cancer Research Program, Clarence Heller Foundation and California Pacific Medical Center Foundation; Abdul M.Ali would like to acknowledge the financial support of the University of Sultan Zainal Abidin, Malaysia; Ahmed Lasfar was supported by an award from the Rutgers Cancer Institute of New Jersey; Ann-Karin Olsen and Gunnar Brunborg were supported by the Research Council of Norway (RCN) through its Centres of Excellence funding scheme (223268/F50), Amancio Carnero’s lab was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0306-2012); Matilde E. Lleonart was supported by a trienal project grant PI12/01104 and by project CP03/00101 for personal support. Amaya Azqueta would like to thank the Ministerio de Educacion y Ciencia (‘Juande la Cierva’ programme, 2009) of the Spanish Government for personal support; Amedeo Amedei was supported by the Italian Ministry of University and Research (2009FZZ4XM_002), and the University of Florence (ex60%2012); Andrew R.Collins was supported by the University of Oslo; Annamaria Colacci was supported by the Emilia-Romagna Region - Project ‘Supersite’ in Italy; Carolyn Baglole was supported by a salary award from the Fonds de recherche du Quebec-Sante (FRQ-S); Chiara Mondello’s laboratory is supported by Fondazione Cariplo in Milan, Italy (grant n. 2011-0370); Christian C.Naus holds a Canada Research Chair; Clement Yedjou was supported by a grant from the National Institutes of Health (NIH-NIMHD grant no. G12MD007581); Daniel C.Koch is supported by the Burroughs Wellcome Fund Postdoctoral Enrichment Award and the Tumor Biology Training grant: NIH T32CA09151; Dean W. Felsher would like to acknowledge the support of United States Department of Health and Human Services, NIH grants (R01 CA170378 PQ22, R01 CA184384, U54 CA149145, U54 CA151459, P50 CA114747 and R21 CA169964); Emilio Rojas would like to thank CONACyT support 152473, Ezio Laconi was supported by AIRC (Italian Association for Cancer Research, grant no. IG 14640) and by the Sardinian Regional Government (RAS); Eun-Yi Moon was supported by grants from the Public Problem-Solving Program (NRF-015M3C8A6A06014500) and Nuclear R&D Program (#2013M2B2A9A03051296 and 2010-0018545) through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science and Technology (MEST) in Korea; Fahd Al-Mulla was supported by the Kuwait Foundation for the Advancement of Sciences (2011-1302-06); Ferdinando Chiaradonna is supported by SysBioNet, a grant for the Italian Roadmap of European Strategy Forum on Research Infrastructures (ESFRI) and by AIRC (Associazione Italiana Ricerca sul Cancro; IG 15364); Francis L.Martin acknowledges funding from Rosemere Cancer Foundation; he also thanks Lancashire Teaching Hospitals NHS trust and the patients who have facilitated the studies he has undertaken over the course of the last 10 years; Gary S.Goldberg would like to acknowledge the support of the New Jersey Health Foundation; Gloria M.Calaf was supported by Fondo Nacional de Ciencia y Tecnología (FONDECYT), Ministerio de Educación de Chile (MINEDUC), Universidad de Tarapacá (UTA); Gudrun Koppen was supported by the Flemish Institute for Technological Research (VITO), Belgium; Hemad Yasaei was supported from a triennial project grant (Strategic Award) from the National Centre for the Replacement, Refinement and Reduction (NC3Rs) of animals in research (NC.K500045.1 and G0800697); Hiroshi Kondoh was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Science and Technology Agency and by JST, CREST; Hsue-Yin Hsu was supported by the Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 and NSC94-2314-B-320-002); Hyun Ho Park was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (2012R1A2A2A01010870) and a grant from the Korea Healthcare Technology R&D project, Ministry of Health and Welfare, Republic of Korea (HI13C1449); Igor Koturbash is supported by the UAMS/NIH Clinical and Translational Science Award (UL1TR000039 and KL2TR000063) and the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000; Jan Vondráček acknowledges funding from the Czech Science Foundation (13-07711S); Jesse Roman thanks the NIH for their support (CA116812), John Pierce Wise Sr. and Sandra S.Wise were supported by National Institute of Environmental Health Sciences (ES016893 to J.P.W.) and the Maine Center for Toxicology and Environmental Health; Jonathan Whitfield acknowledges support from the FERO Foundation in Barcelona, Spain; Joseph Christopher is funded by Cancer Research UK and the International Journal of Experimental Pathology; Julia Kravchenko is supported by a philanthropic donation by Fred and Alice Stanback; Jun Sun is supported by a Swim Across America Cancer Research Award; Karine A.Cohen-Solal is supported by a research scholar grant from the American Cancer Society (116683-RSG-09-087-01-TBE); Laetitia Gonzalez received a postdoctoral fellowship from the Fund for Scientific Research–Flanders (FWO-Vlaanderen) and support by an InterUniversity Attraction Pole grant (IAP-P7-07); Laura Soucek is supported by grant #CP10/00656 from the Miguel Servet Research Contract Program and acknowledges support from the FERO Foundation in Barcelona, Spain; Liang-Tzung Lin was supported by funding from the Taipei Medical University (TMU101-AE3-Y19); Linda Gulliver is supported by a Genesis Oncology Trust (NZ) Professional Development Grant, and the Faculty of Medicine, University of Otago, Dunedin, New Zealand; Louis Vermeulen is supported by a Fellowship of the Dutch Cancer Society (KWF, UVA2011-4969) and a grant from the AICR (14–1164); Mahara Valverde would like to thank CONACyT support 153781; Masoud H. Manjili was supported by the office of the Assistant Secretary of Defense for Health Affairs (USA) through the Breast Cancer Research Program under Award No. W81XWH-14-1-0087 Neetu Singh was supported by grant #SR/FT/LS-063/2008 from the Department of Science and Technology, Government of India; Nicole Kleinstreuer is supported by NIEHS contracts (N01-ES 35504 and HHSN27320140003C); P.K. Krishnakumar is supported by the Funding (No. T.K. 11-0629) of King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia; Paola A.Marignani is supported by the Dalhousie Medical Research Foundation, The Beatrice Hunter Cancer Institute and CIHR and the Nova Scotia Lung Association; Paul Dent is the holder of the Universal Inc.Chair in Signal Transduction Research and is supported with funds from PHS grants from the NIH (R01-CA141704, R01-CA150214, R01-DK52825 and R01-CA61774); Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, and by the Czech Science Foundation projects P301/12/1686 and 15-03834Y; Po Sing Leung was supported by the Health and Medical Research Fund of Food and Health Bureau, Hong Kong Special Administrative Region, Ref. No: 10110021; Qiang Cheng was supported in part by grant NSF IIS-1218712; R. Brooks Robey is supported by the United States Department of Veterans Affairs; Rabindra Roy was supported by United States Public Health Service Grants (RO1 CA92306, RO1 CA92306-S1 and RO1 CA113447); Rafaela Andrade-Vieira is supported by the Beatrice Hunter Cancer Research Institute and the Nova Scotia Health Research Foundation, Renza Vento was partially funded by European Regional Development Fund, European Territorial Cooperation 2007–13 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007–13) and grants from the Italian Ministry of Education, University and Research (MIUR) ex-60%, 2007; Riccardo Di Fiore was a recipient of fellowship granted by European Regional Development Fund, European Territorial Cooperation 2007–2013 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007–2013); Rita Dornetshuber-Fleiss was supported by the Austrian Science Fund (FWF, project number T 451-B18) and the Johanna Mahlke, geb.-Obermann-Stiftung; Roberta Palorini is supported by a SysBioNet fellowship; Roslida Abd Hamid is supported by the Ministry of Education, Malaysia-Exploratory Research Grant Scheme-Project no: ERGS/1-2013/5527165; Sabine A.S.Langie is the beneficiary of a postdoctoral grant from the AXA Research Fund and the Cefic-LRI Innovative Science Award 2013; Sakina Eltom is supported by NIH grant SC1CA153326; Samira A.Brooks was supported by National Research Service Award (T32 ES007126) from the National Institute of Environmental Health Sciences and the HHMI Translational Medicine Fellowship; Sandra Ryeom was supported by The Garrett B. Smith Foundation and the TedDriven Foundation; Thierry Massfelder was supported by the Institut National de la Santé et de la Recherche Médicale INSERM and Université de Strasbourg; Thomas Sanderson is supported by the Canadian Institutes of Health Research (CIHR; MOP-115019), the Natural Sciences and Engineering Council of Canada (NSERC; 313313) and the California Breast Cancer Research Program (CBCRP; 17UB-8703); Tiziana Guarnieri is supported by a grant from Fundamental Oriented Research (RFO) to the Alma Mater Studiorum University of Bologna, Bologna, Italy and thanks the Fondazione Cassa di Risparmio di Bologna and the Fondazione Banca del Monte di Bologna e Ravenna for supporting the Center for Applied Biomedical Research, S.Orsola-Malpighi University Hospital, Bologna, Italy; W.Kimryn Rathmell is supported by the V Foundation for Cancer Research and the American Cancer Society; William K.Decker was supported in part by grant RP110545 from the Cancer Prevention Research Institute of Texas; William H.Bisson was supported with funding from the NIH P30 ES000210; Yon Rojanasakul was supported with NIH grant R01-ES022968; Zhenbang Chen is supported by NIH grants (MD004038, CA163069 and MD007593); Zhiwei Hu is grateful for the grant support from an institutional start-up fund from The Ohio State University College of Medicine and The OSU James Comprehensive Cancer Center (OSUCCC) and a Seed Award from the OSUCCC Translational Therapeutics Program.
- Published
- 2015
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