8 results on '"R. Brooks Robey"'
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2. CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies
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William W. Feng, Owen Wilkins, Scott Bang, Matthew Ung, Jiaqi Li, Jennifer An, Carmen del Genio, Kaleigh Canfield, James DiRenzo, Wendy Wells, Arti Gaur, R. Brooks Robey, Jessie Yanxiang Guo, Ryan L. Powles, Christos Sotiriou, Lajos Pusztai, Maria Febbraio, Chao Cheng, William B. Kinlaw, and Manabu Kurokawa
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Biology (General) ,QH301-705.5 - Abstract
Summary: Although it is established that fatty acid (FA) synthesis supports anabolic growth in cancer, the role of exogenous FA uptake remains elusive. Here we show that, during acquisition of resistance to HER2 inhibition, metabolic rewiring of breast cancer cells favors reliance on exogenous FA uptake over de novo FA synthesis. Through cDNA microarray analysis, we identify the FA transporter CD36 as a critical gene upregulated in cells with acquired resistance to the HER2 inhibitor lapatinib. Accordingly, resistant cells exhibit increased exogenous FA uptake and metabolic plasticity. Genetic or pharmacological inhibition of CD36 suppresses the growth of lapatinib-resistant but not lapatinib-sensitive cells in vitro and in vivo. Deletion of Cd36 in mammary tissues of MMTV-neu mice significantly attenuates tumorigenesis. In breast cancer patients, CD36 expression increases following anti-HER2 therapy, which correlates with a poor prognosis. Our results define CD36-mediated metabolic rewiring as an essential survival mechanism in HER2-positive breast cancer. : The functional significance of lipid metabolism in cancer cells is not fully understood. Feng et al. show that the fatty acid transporter CD36 is essential for survival of breast cancer cells during anti-HER2 therapy, highlighting the role of lipid metabolism in acquired resistance to targeted therapy. Keywords: tyrosine kinase, HER2, FASN, drug resistance, lipid metabolism, AKT, ERK, MAPK
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- 2019
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3. Chronic Kidney Disease Progression and Cardiovascular Outcomes Following Cardiac Catheterization—A Population‐Controlled Study
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Jeremiah R. Brown, Richard J. Solomon, R. Brooks Robey, Meg E. Plomondon, Thomas M. Maddox, Emily J. Marshall, Elizabeth L. Nichols, Michael E. Matheny, Thomas T. Tsai, John S. Rumsfeld, Richard E. Lee, and Mark J. Sarnak
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angioplasty ,contrast media ,kidney ,morbidity ,survival ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundStudies of kidney disease associated with cardiac catheterization typically rely on billing records rather than laboratory data. We examined the associations between percutaneous coronary interventions, acute kidney injury, and chronic kidney disease progression using comprehensive Veterans Affairs clinical and laboratory databases. Methods and ResultsPatients undergoing percutaneous coronary interventions between 2005 and 2010 (N=24 405) were identified in the Veterans Affairs Clinical Assessment, Reporting, and Tracking registry and examined for associated acute kidney injury and chronic kidney disease development or progression relative to 24 405 matched population controls. Secondary outcomes analyzed included dialysis, acute myocardial infarction, and mortality. The incidence of chronic kidney disease progression following percutaneous coronary interventions complicated by acute kidney injury, following uncomplicated coronary interventions, and in matched controls were 28.66, 11.15, and 6.81 per 100 person‐years, respectively. Percutaneous coronary intervention also increased the likelihood of chronic kidney disease progression in both the presence and absence of acute injury relative to controls in adjusted analyses (hazard ratio [HR], 5.02 [95% CI, 4.68–5.39]; and HR, 1.76 [95% CI, 1.70–1.86]). Among patients with estimated glomerular filtration rate
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- 2016
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4. Perspectives from the Kidney Health Initiative on Advancing Technologies to Facilitate Remote Monitoring of Patient Self-Care in RRT
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Uptal D. Patel, Karen S. Rheuban, Susie Q. Lew, Robert Jarrin, Eric Wallace, Neal Sikka, Paul T. Conway, James A. Sloand, Patrick D. Brophy, R. Brooks Robey, Jennifer Ehrlich, and Mitchell H. Rosner
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Telemedicine ,Epidemiology ,education ,030232 urology & nephrology ,Hemodialysis, Home ,Review ,Telehealth ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,Nursing ,Cost Savings ,Multidisciplinary approach ,Humans ,Medicine ,030212 general & internal medicine ,Workgroup ,health care economics and organizations ,Monitoring, Physiologic ,Transplantation ,Government ,Cost–benefit analysis ,business.industry ,Patient Acceptance of Health Care ,Viewpoints ,Self Care ,Nephrology ,Insurance, Health, Reimbursement ,Kidney Failure, Chronic ,business ,Peritoneal Dialysis - Abstract
Telehealth and remote monitoring of a patient’s health status has become more commonplace in the last decade and has been applied to conditions such as heart failure, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease. Conversely, uptake of these technologies to help engender and support home RRTs has lagged. Although studies have looked at the role of telehealth in RRT, they are small and single-centered, and both outcome and cost-effectiveness data are needed to inform future decision making. Furthermore, alignment of payer and government (federal and state) regulations with telehealth procedures is needed along with a better understanding of the viewpoints of the various stakeholders in this process (patients, caregivers, clinicians, payers, dialysis organizations, and government regulators). Despite these barriers, telehealth has great potential to increase the acceptance of home dialysis, and improve outcomes and patient satisfaction while potentially decreasing costs. The Kidney Health Initiative convened a multidisciplinary workgroup to examine the current state of telehealth use in home RRTs as well as outline potential benefits and drawbacks, impediments to implementation, and key unanswered questions.
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- 2017
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5. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
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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
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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.
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- 2015
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6. Metabolic Dysregulation in Environmental Carcinogenesis and Toxicology
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R. Brooks Robey
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Toxicology ,Cancer metabolism ,Environmental Carcinogenesis ,Cancer biology ,Biology - Published
- 2017
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7. Metabolic reprogramming and dysregulated metabolism: Cause, consequence and/or enabler of environmental carcinogenesis?
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Stefano Forte, Arthur Berg, Graeme Williams, Ferdinando Chiaradonna, Francis Martin, Monica Vaccari, Annamaria Colacci, Dustin G. Brown, Amedeo Amedei, Judith Weisz, Roslida Abd Hamid, R. Brooks Robey, Jordan Woodrick, Nancy B. Kuemmerle, Rabeah Al-Temaimi, William H. Bisson, Lorenzo Memeo, Roberta Palorini, Hosni Salem, Neetu Singh, Joel N. Meyer, Jayadev Raju, A. Ivana Scovassi, Chiara Mondello, Laura L. Kubik, Rabindra Roy, Fahd Al-Mulla, Elizabeth P. Ryan, Leroy Lowe, Anna C. Salzberg, Brooks Robey, R, Weisz, J, Kuemmerle, N, Salzberg, A, Berg, A, Brown, D, Kubik, L, Palorini, R, Al Mulla, F, Al Temaimi, R, Colacci, A, Mondello, C, Raju, J, Woodrick, J, Ivana Scovassi, A, Singh, N, Vaccari, M, Roy, R, Forte, S, Memeo, L, Salem, H, Amedei, A, Hamid, R, Williams, G, Lowe, L, Meyer, J, Martin, F, Bisson, W, Chiaradonna, F, and Ryan, E
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Cancer Research ,Carcinogenesis ,Metabolic reprogramming ,Computational biology ,Review ,Pharmacology ,Biology ,medicine.disease_cause ,Neoplasms ,medicine ,Animals ,Humans ,Carcinogenesi ,Environmental risk assessment ,Animal ,General Medicine ,Environmental exposure ,Environmental Exposure ,BIO/10 - BIOCHIMICA ,Carcinogens, Environmental ,Enabling ,Cancer metabolism ,Environmental Carcinogenesis ,Neoplasm ,Cancer development ,Human - Abstract
Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested.
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- 2015
8. A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis.
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Blaha CS, Ramakrishnan G, Jeon SM, Nogueira V, Rho H, Kang S, Bhaskar P, Terry AR, Aissa AF, Frolov MV, Patra KC, Brooks Robey R, and Hay N
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- A Kinase Anchor Proteins metabolism, A549 Cells, Animals, CHO Cells, Carcinogenesis pathology, Cell Line, Tumor, Cricetulus, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit metabolism, Deoxyglucose pharmacology, Epithelial-Mesenchymal Transition physiology, Female, Glycogen Synthase Kinase 3 beta antagonists & inhibitors, Glycosylation, HCT116 Cells, HEK293 Cells, Hexokinase genetics, Humans, Mice, Mice, Inbred BALB C, Myeloid Cell Leukemia Sequence 1 Protein metabolism, NF-E2-Related Factor 2 metabolism, Neoplasm Metastasis pathology, Phosphorylation drug effects, Rats, Snail Family Transcription Factors metabolism, Glucose metabolism, Glycogen Synthase Kinase 3 beta metabolism, Hexokinase metabolism, Neoplasms pathology
- Abstract
Hexokinase 2 (HK2), which catalyzes the first committed step in glucose metabolism, is induced in cancer cells. HK2's role in tumorigenesis has been attributed to its glucose kinase activity. Here, we describe a kinase independent HK2 activity, which contributes to metastasis. HK2 binds and sequesters glycogen synthase kinase 3 (GSK3) and acts as a scaffold forming a ternary complex with the regulatory subunit of protein kinase A (PRKAR1a) and GSK3β to facilitate GSK3β phosphorylation and inhibition by PKA. Thus, HK2 functions as an A-kinase anchoring protein (AKAP). Phosphorylation by GSK3β targets proteins for degradation. Consistently, HK2 increases the level and stability of GSK3 targets, MCL1, NRF2, and particularly SNAIL. In addition to GSK3 inhibition, HK2 kinase activity mediates SNAIL glycosylation, which prohibits its phosphorylation by GSK3. Finally, in mouse models of breast cancer metastasis, HK2 deficiency decreases SNAIL protein levels and inhibits SNAIL-mediated epithelial mesenchymal transition and metastasis., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2022
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