Search

Your search keyword '"Karpowicz, Phillip A"' showing total 40 results
Start Over Author "Karpowicz, Phillip A"
40 results on '"Karpowicz, Phillip A"'

4. Designing a broad-spectrum integrative approach for cancer prevention and treatment

Author

Block, Keith I, Gyllenhaal, Charlotte, Lowe, Leroy, Amedei, Amedeo, Amin, ARM Ruhul, Amin, Amr, Aquilano, Katia, Arbiser, Jack, Arreola, Alexandra, Arzumanyan, Alla, Ashraf, S Salman, Azmi, Asfar S, Benencia, Fabian, Bhakta, Dipita, Bilsland, Alan, Bishayee, Anupam, Blain, Stacy W, Block, Penny B, Boosani, Chandra S, Carey, Thomas E, Carnero, Amancio, Carotenuto, Marianeve, Casey, Stephanie C, Chakrabarti, Mrinmay, Chaturvedi, Rupesh, Chen, Georgia Zhuo, Chen, Helen, Chen, Sophie, Chen, Yi Charlie, Choi, Beom K, Ciriolo, Maria Rosa, Coley, Helen M, Collins, Andrew R, Connell, Marisa, Crawford, Sarah, Curran, Colleen S, Dabrosin, Charlotta, Damia, Giovanna, Dasgupta, Santanu, DeBerardinis, Ralph J, Decker, William K, Dhawan, Punita, Diehl, Anna Mae E, Dong, Jin-Tang, Dou, Q Ping, Drew, Janice E, Elkord, Eyad, El-Rayes, Bassel, Feitelson, Mark A, Felsher, Dean W, Ferguson, Lynnette R, Fimognari, Carmela, Firestone, Gary L, Frezza, Christian, Fujii, Hiromasa, Fuster, Mark M, Generali, Daniele, Georgakilas, Alexandros G, Gieseler, Frank, Gilbertson, Michael, Green, Michelle F, Grue, Brendan, Guha, Gunjan, Halicka, Dorota, Helferich, William G, Heneberg, Petr, Hentosh, Patricia, Hirschey, Matthew D, Hofseth, Lorne J, Holcombe, Randall F, Honoki, Kanya, Hsu, Hsue-Yin, Huang, Gloria S, Jensen, Lasse D, Jiang, Wen G, Jones, Lee W, Karpowicz, Phillip A, Keith, W Nicol, Kerkar, Sid P, Khan, Gazala N, Khatami, Mahin, Ko, Young H, Kucuk, Omer, Kulathinal, Rob J, Kumar, Nagi B, Kwon, Byoung S, Le, Anne, Lea, Michael A, Lee, Ho-Young, Lichtor, Terry, Lin, Liang-Tzung, Locasale, Jason W, Lokeshwar, Bal L, Longo, Valter D, Lyssiotis, Costas A, MacKenzie, Karen L, Malhotra, Meenakshi, Marino, Maria, Martinez-Chantar, Maria L, and Matheu, Ander

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Rare Diseases, Precision Medicine, Aetiology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Good Health and Well Being, Antineoplastic Agents, Phytogenic, Drug Resistance, Neoplasm, Genetic Heterogeneity, Humans, Molecular Targeted Therapy, Neoplasms, Signal Transduction, Tumor Microenvironment, Multi-targeted, Cancer hallmarks, Phytochemicals, Targeted therapy, Integrative medicine, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.

Published
2015

13. BMAL1 Regulates the Daily Timing of Colitis

Author

Taleb, Zainab, primary, Carmona-Alcocer, Vania, additional, Stokes, Kyle, additional, Haireek, Marta, additional, Wang, Huaqing, additional, Collins, Stephen M., additional, Khan, Waliul I., additional, and Karpowicz, Phillip, additional

Published
2022
Full Text
View/download PDF

14. THE ROLE OF THE CLOCK GENE BMAL1 IN INFLAMMATORY BOWEL DISEASE

Author

Taleb, Zainab, Stokes, Kyle, Wang, Huaqing, Collins, Stephen, Khan, Waliul, and Karpowicz, Phillip

Subjects
digestive system diseases
Abstract

The circadian clock is a highly conserved molecular system that drives the oscillation of biological rhythms with a 24 hour period. Disruption of the circadian clock has been shown to cause an increased risk of Inflammatory Bowel Disease (IBD). Patients with IBD experience chronic inflammation along with impaired regeneration of intestinal epithelial cells. Inflammation and regeneration have been shown to be closely linked. Based on previous literature, we can hypothesize that disruption in the circadian clock leads to an increase in IBD severity. In this study, we compared the regenerative response of intestinal epithelial cells in BMAL1+/+ mice (with a functional clock) and BMAL1-/- mice (without a functional clock) who have been given IBD. Dextran Sulfate Sodium (DSS) was applied to induce acute colitis in mice, acting as an effective model for ulcerative colitis: one of the two categories of IBD. We observe a drastic decrease in the survival of mice lacking functional BMAL1 that were treated with 4% DSS over 7 days. Disease activity and cytokine analyses reveal time-dependent severity in inflammatory response that is worse in BMAL1-/- mice. To test the circadian rhythm of IBD, we performed a 24 hour analysis comparing epithelial cell proliferation, cell death, and inflammation in colon tissue. Our results indicate a significant rhythmic expression of mitosis throughout the day in BMAL1+/+ mice while mitosis in BMAL1-/- mice is arrhythmic and at lower levels. Based on these results, poor regeneration during IBD is in part attributed to decreased and arrhythmic regeneration. These data provides insight into how the core clock affects the inflammatory and regenerative abilities of intestinal epithelial cells.

Published
2020

19. Investigating the effect of circadian rhythm regulator Bmal1 on tumorigenesis in APCmin/- mice

Author

Zhou, Tina, Stokes, Kyle, Nunes, Malika, Curan, Colin, and Karpowicz, Phillip

Subjects
endocrine system
Abstract

Colorectal cancer is the second most commonly diagnosed cancer in Canada and among top three leading causes of cancer deaths. The rate of colorectal cancer is especially increased when the familial adenomatous polyposis coli (APC) gene is mutated. The APCmin/- mouse, which carries a heterozygous mutation of the Apc gene, is therefore a valuable model for studying colorectal cancer. The circadian rhythm contributes to a host of physiological activities in mammals, including sleep-wake cycle and immune response. It also plays an important role in numerous cellular processes, such as cell proliferation and differentiation. On a molecular level, the ‘rhythm’ is maintained by various negative feedback loops, leading to oscillating transcript and protein levels of several core clock genes, such as BMAL1, CLOCK, CRY 1-2 and PER 1-3. Recent studies show that dysfunction of circadian rhythm is strongly implicated in colorectal cancer. Abnormal levels of clock gene transcripts are found in more aggressive tumours and associated with worse disease prognosis. However, the precise mechanisms by which clock genes affect tumorigenesis are unclear. To investigate this correlation, we used Apcmin/-Bmal1-/- and Apcmin/-Bmal1+/+ mice and synchronized their clock activity, marked as time point 0 (ZT0). We then subjected the mice to a 12-hour light/12-hour dark rhythm, and collected intestinal samples at ZT4 and ZT12. Both genotypes of mice had significant polyp formations, as predicted given the Apc mutation. However, the Apcmin/-Bmal1-/- mice had twice as many tumours than the controls. This increase in tumorigenesis can be seen throughout the small intestine. There are many potential explanations for this result, including increase in cell proliferation, decrease in apoptosis, and dysregulation of cell differentiation. We are currently using cell staining methods to look for markers of these cellular activities to further understand the role of BMAL in tumorigenesis.

Published
2018

22. Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

Author

Amin, A.R.M. Ruhul, primary, Karpowicz, Phillip A., additional, Carey, Thomas E., additional, Arbiser, Jack, additional, Nahta, Rita, additional, Chen, Zhuo G., additional, Dong, Jin-Tang, additional, Kucuk, Omer, additional, Khan, Gazala N., additional, Huang, Gloria S., additional, Mi, Shijun, additional, Lee, Ho-Young, additional, Reichrath, Joerg, additional, Honoki, Kanya, additional, Georgakilas, Alexandros G., additional, Amedei, Amedeo, additional, Amin, Amr, additional, Helferich, Bill, additional, Boosani, Chandra S., additional, Ciriolo, Maria Rosa, additional, Chen, Sophie, additional, Mohammed, Sulma I., additional, Azmi, Asfar S., additional, Keith, W. Nicol, additional, Bhakta, Dipita, additional, Halicka, Dorota, additional, Niccolai, Elena, additional, Fujii, Hiromasa, additional, Aquilano, Katia, additional, Ashraf, S. Salman, additional, Nowsheen, Somaira, additional, Yang, Xujuan, additional, Bilsland, Alan, additional, and Shin, Dong M., additional

Published
2015
Full Text
View/download PDF

23. Surfaceome Profiling Reveals Regulators of Neural Stem Cell Function

Author

DeVeale, Brian, primary, Bausch-Fluck, Damaris, additional, Seaberg, Raewyn, additional, Runciman, Susan, additional, Akbarian, Vahe, additional, Karpowicz, Phillip, additional, Yoon, Charles, additional, Song, Hannah, additional, Leeder, Rachel, additional, Zandstra, Peter W., additional, Wollscheid, Bernd, additional, and Kooy, Derek, additional

Published
2014
Full Text
View/download PDF

25. A genome-scale shRNA resource for transgenic RNAi in Drosophila

Author

Ni, Jian-Quan, primary, Zhou, Rui, additional, Czech, Benjamin, additional, Liu, Lu-Ping, additional, Holderbaum, Laura, additional, Yang-Zhou, Donghui, additional, Shim, Hye-Seok, additional, Tao, Rong, additional, Handler, Dominik, additional, Karpowicz, Phillip, additional, Binari, Richard, additional, Booker, Matthew, additional, Brennecke, Julius, additional, Perkins, Lizabeth A, additional, Hannon, Gregory J, additional, and Perrimon, Norbert, additional

Published
2011
Full Text
View/download PDF

26. The Adult Mouse and Human Pancreas Contain Rare Multipotent Stem Cells that Express Insulin

Author

Smukler, Simon R., primary, Arntfield, Margot E., additional, Razavi, Rozita, additional, Bikopoulos, George, additional, Karpowicz, Phillip, additional, Seaberg, Raewyn, additional, Dai, Feihan, additional, Lee, Simon, additional, Ahrens, Rosemary, additional, Fraser, Paul E., additional, Wheeler, Michael B., additional, and van der Kooy, Derek, additional

Published
2011
Full Text
View/download PDF

35. Correction

Author

Karpowicz, Phillip, Morshead, Cindi, Kam, Angela, Jervis, Eric, Ramunas, John, Cheng, Vincent, and van der Kooy, Derek

Subjects
Correction, Corrections
Published
2005

36. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration.

Author

Karpowicz, Phillip, Perez, Jessica, and Perrimon, Norbert

Subjects
*STEM cells, *HOMEOSTASIS, *CANCER, *DROSOPHILA, *CYTOKINES, *CARCINOGENESIS
Abstract

Identification of the signaling pathways that control the proliferation of stem cells (SCs), and whether they act in a cell or non-cell autonomous manner, is key to our understanding of tissue homeostasis and cancer. In the adult Drosophila midgut, the Jun N-Terminal Kinase (JNK) pathway is activated in damaged enterocyte cells (ECs) following injury. This leads to the production of Upd cytokines from ECs, which in turn activate the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) pathway in Intestinal SCs (ISCs), stimulating their proliferation. In addition, the Hippo pathway has been recently implicated in the regulation of Upd production from the ECs. Here, we show that the Hippo pathway target, Yorkie (Yki), also plays a crucial and cell-autonomous role in ISCs. Activation of Yki in ISCs is sufficient to increase ISC proliferation, a process involving Yki target genes that promote division, survival and the Upd cytokines. We further show that prior to injury, Yki activity is constitutively repressed by the upstream Hippo pathway members Fat and Dachsous (Ds). These findings demonstrate a cell-autonomous role for the Hippo pathway in SCs, and have implications for understanding the role of this pathway in tumorigenesis and cancer stem cells. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

37. Adhesion Is Prerequisite, But Alone Insufficient, to Elicit Stem Cell Pluripotency.

Author

Karpowicz, Phillip, Inoue, Tomoyuki, Runciman, Sue, Deveale, Brian, Seaberg, Raewyn, Gertsenstein, Marina, Byers, Lois, Yamanaka, Yojiro, Tondat, Sandra, Slevin, John, Hitoshi, Seiji, Rossant, Janet, and Van der Kooy, Derek

Subjects
*NEURAL stem cells, *EMBRYOLOGY, *STEM cells, *EMBRYONIC stem cells, *CADHERINS, *CELL communication
Abstract

Primitive mammalian neural stem cells (NSCs), arising during the earliest stages of embryogenesis, possess pluripotency in embryo chimera assays in contrast to definitive NSCs found in the adult. We hypothesized that adhesive differences determine the association of stem cells with embryonic cells in chimera assays and hence their ability to contribute to later tissues. We show that primitive NSCs and definitive NSCs possess adhesive differences, resulting from differential cadherin expression, that lead to a double dissociation in outcomes after introduction into the early-versus midgestation embryo. Primitive NSCs are able to sort with the cells of the inner cell mass and thus contribute to early embryogenesis, in contrast to definitive NSCs, which cannot. Conversely, primitive NSCs sort away from cells of the embryonic day 9.5 telencephalon and are unable to contribute to neural tissues at midembryogenesis, in contrast to definitive NSCs, which can. Overcoming these adhesive differences by E-cadherin overexpression allows some definitive NSCs to integrate into the inner cell mass but is insufficient to allow them to contribute to later development. These adhesive differences suggest an evolving compartmentalization in multipotent NSCs during development and serve to illustrate the importance of cell-cell association for revealing cellular contribution. [ABSTRACT FROM AUTHOR]

Published
2007
Full Text
View/download PDF

38. Support cor the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro.

Author

Karpowicz, Phillip, Morshead, Cindi, Kam, Angela, Jervis, Eric, Ramuns, John, Vincent Cheng, and van der Kooy, Derek

Subjects
*NEURAL stem cells, *STEM cells, *DNA, *CELL division, *THYMIDINE, *KARYOKINESIS
Abstract

The immortal strand hypothesis proposes that asymmetrically dividing stem cells (SCs) selectively segregate chromosomes that bear the oldest DNA templates. We investigated cosegregation in neural stem cells (NSCs). After exposure to the thymidine analogue 5-bromo-2-deoxyuridine (BrdU), which labels newly synthesized DNA, a subset of neural precursor cells were shown to retain BrdU signal. It was confirmed that some BrdU-retaining cells divided actively, and that these cells exhibited some characteristics of SCs. This asymmetric partitioning of DNA then was demonstrated during mitosis, and these results were further supported by real time imaging of SC clones, in which older and newly synthesized DNA templates were distributed asymmetrically after DNA synthesis. We demonstrate that NSCs are unique among precursor cells in the uneven partitioning of genetic material during cell divisions. [ABSTRACT FROM AUTHOR]

Published
2005
Full Text
View/download PDF

39. A genome-scale shRNA resource for transgenic RNAi in Drosophila.

Author

Jian-Quan Ni, Rui Zhou, Czech, Benjamin, Lu-Ping Liu, Holderbaum, Laura, Donghui Yang-Zhou, Hye-Seok Shim, Rong Tao, Handler, Dominik, Karpowicz, Phillip, Binari, Richard, Booker, Matthew, Brennecke, Julius, Perkins, Lizabeth A., Hannon, Gregory J., and Perrimon, Norbert

Subjects
RNA, DROSOPHILA melanogaster, GENOMES, GENETICS, MEDICAL research
Abstract

Existing transgenic RNAi resources in Drosophila melanogaster based on long double-stranded hairpin RNAs are powerful tools for functional studies, but they are ineffective in gene knockdown during oogenesis, an important model system for the study of many biological questions. We show that shRNAs, modeled on an endogenous microRNA, are extremely effective at silencing gene expression during oogenesis. We also describe our progress toward building a genome-wide shRNA resource. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

40. Designing a broad-spectrum integrative approach for cancer prevention and treatment

Author

Chandra S. Boosani, William K. Decker, Punita Dhawan, Georgia Zhuo Chen, Mark E. Prince, Balakrishna L. Lokeshwar, Nagi B. Kumar, Michelle F. Green, Alan Bilsland, Michael P. Murphy, Dong M. Shin, H.P. Vasantha Rupasinghe, Paul Yaswen, Anupam Bishayee, Christian Frezza, John Stagg, Mahin Khatami, Lynnette R. Ferguson, R. Brooks Robeydf, Kanya Honoki, Alan K. Meeker, A.R.M. Ruhul Amin, Huanjie Yang, Eoin McDonnell, Virginia R. Parslow, Phuoc T. Tran, Patricia Hentosh, Frank Gieseler, Gloria S. Huang, Sulma I. Mohammed, Ho Young Lee, Giovanna Damia, Alexandra Arreola, Wamidh H. Talib, Mark A. Feitelson, Luigi Ricciardiello, Massimo Zollo, Sarallah Rezazadeh, Diana M. Stafforini, Katia Aquilano, Phillip Karpowicz, Markus D. Siegelin, Neetu Singh, Alexandros G. Georgakilas, Domenico Ribatti, Neeraj K. Saxena, Carl Smythe, Beom K. Choi, Mark M. Fuster, Gian Luigi Russo, Amedeo Amedei, Anna Mae Diehl, Terry Lichtor, D. James Morré, Charlotte Gyllenhaal, Vasundara Venkateswaran, Colleen S. Curran, Ramzi M. Mohammad, Jiyue Zhu, Anne Leb, Lizzia Raffaghello, Fabian Benencia, Sid P. Kerkar, Eddy S. Yang, Wen Guo Jiang, Jason W. Locasale, Alla Arzumanyan, W. Nicol Keith, Dorota Halicka, Gunjan Guhal, Xin Yin, Helen Chen, Irfana Muqbil, Gary L. Firestone, Panagiotis J. Vlachostergios, Maria Marino, Meenakshi Malhotra, Stacy W. Blain, Amancio Carnero, Liang Tzung Lin, Dass S. Vinay, Satya Prakash, Hsue-Yin Hsu, María L. Martínez-Chantar, Daniele Generali, Jeffrey C. Rathmell, Karen L. MacKenzie, Valter D. Longo, Dipita Bhakta, Ralph J. DeBerardinis, S. Salman Ashraf, Elena Niccolai, Hendrik Ungefroren, Carmela Fimognari, Mahya Mehrmohamadi, Zongwei Wang, Clement G. Yedjou, Costas A. Lyssiotis, Lasse Jensen, Jörg Reichrath, Sarah K. Thompson, Rita Nahta, David Sidransky, Q. Ping Dou, Brendan Grue, Isidro Sánchez-García, Brad Poore, Helen M. Coley, Bassel F. El-Rayes, Sophie Chen, Randall F. Holcombe, Dipali Sharma, Mrinmay Chakrabarti, Asfar S. Azmi, William G. Helferich, Gregory A. Michelotti, H. M. C. Shantha Kumara, Petr Heneberg, Rodney E. Shackelford, Andrew James Sanders, Daniel Sliva, Swapan K. Ray, Omer Kucuk, Christopher Maxwellx, Abbas Samadi, Leroy Lowe, Sarah Crawford, Daniele Santini, Andrew Collins, Yi Charlie Chen, Santanu Dasgupta, Kathryn E. Wellen, Richard L. Whelan, Janice E. Drewa, Ander Matheu, Sharanya Sivanand, Tetsuro Sasada, Xujuan Yang, Lee W. Jones, Byoung S. Kwon, Amr Amin, Francis Rodierdh, Ganji Purnachandra Nagaraju, Charlotta Dabrosin, Graham Pawelec, Rob J. Kulathinal, Elizabeth P. Ryan, Hiromasa Fujii, Thomas E. Carey, Somaira Nowsheen, Young Hee Ko, Deepak Poudyal, Eyad Elkord, Emanuela Signori, Rupesh Chaturvedi, Peter L. Pedersen, Carmela Spagnuolo, Keith I. Block, Marianeve Carotenuto, Vinayak Muralidharcq, Stephanie C. Casey, Kapil Mehta, Tabetha Sundin, Dean W. Felsheru, Matthew D. Hirschey, Matthew G. Vander Heiden, Lorne J. Hofseth, Francesco Pantano, Maria Rosa Ciriolo, Michael A. Leab, Carolina Panis, Marisa Connell, Gazala Khan, W. Kimryn Rathmell, Malancha Sarkar, Michael Gilbertson, Jack L. Arbiser, Penny B. Block, Pochi R. Subbarayan, Jin-Tang Dong, Frezza, Christian [0000-0002-3293-7397], Murphy, Mike [0000-0003-1115-9618], Apollo - University of Cambridge Repository, National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Andalucía, Associazione Italiana per la Ricerca sul Cancro, Avon Foundation for Women, Junta de Castilla y León, Ministerio de Ciencia e Innovación (España), Federal Ministry of Education and Research (Germany), Canadian Institutes of Health Research, Ikerbasque Basque Foundation for Science, American Cancer Society, European Commission, Swedish Research Council, University of Glasgow, Block, Keith I, Gyllenhaal, Charlotte, Lowe, Leroy, Amedei, Amedeo, Amin, A. R. M. Ruhul, Amin, Amr, Aquilano, Katia, Arbiser, Jack, Arreola, Alexandra, Arzumanyan, Alla, Ashraf, S. Salman, Azmi, Asfar S, Benencia, Fabian, Bhakta, Dipita, Bilsland, Alan, Bishayee, Anupam, Blain, Stacy W, Block, Penny B, Boosani, Chandra S, Carey, Thomas E, Carnero, Amancio, Carotenuto, Marianeve, Casey, Stephanie C, Chakrabarti, Mrinmay, Chaturvedi, Rupesh, Chen, Georgia Zhuo, Chen, Helen, Chen, Sophie, Chen, Yi Charlie, Choi, Beom K, Ciriolo, Maria Rosa, Coley, Helen M, Collins, Andrew R, Connell, Marisa, Crawford, Sarah, Curran, Colleen S, Dabrosin, Charlotta, Damia, Giovanna, Dasgupta, Santanu, Deberardinis, Ralph J, Decker, William K, Dhawan, Punita, Diehl, Anna Mae E, Dong, Jin Tang, Dou, Q. Ping, Drew, Janice E, Elkord, Eyad, El Rayes, Bassel, Feitelson, Mark A, Felsher, Dean W, Ferguson, Lynnette R, Fimognari, Carmela, Firestone, Gary L, Frezza, Christian, Fujii, Hiromasa, Fuster, Mark M, Generali, Daniele, Georgakilas, Alexandros G, Gieseler, Frank, Gilbertson, Michael, Green, Michelle F, Grue, Brendan, Guha, Gunjan, Halicka, Dorota, Helferich, William G, Heneberg, Petr, Hentosh, Patricia, Hirschey, Matthew D, Hofseth, Lorne J, Holcombe, Randall F, Honoki, Kanya, Hsu, Hsue Yin, Huang, Gloria S, Jensen, Lasse D, Jiang, Wen G, Jones, Lee W, Karpowicz, Phillip A, Keith, W. Nicol, Kerkar, Sid P, Khan, Gazala N, Khatami, Mahin, Ko, Young H, Kucuk, Omer, Kulathinal, Rob J, Kumar, Nagi B, Kwon, Byoung S, Le, Anne, Lea, Michael A, Lee, Ho Young, Lichtor, Terry, Lin, Liang Tzung, Locasale, Jason W, Lokeshwar, Bal L, Longo, Valter D, Lyssiotis, Costas A, Mackenzie, Karen L, Malhotra, Meenakshi, Marino, Maria, Martinez Chantar, Maria L, Matheu, Ander, Maxwell, Christopher, Mcdonnell, Eoin, Meeker, Alan K, Mehrmohamadi, Mahya, Mehta, Kapil, Michelotti, Gregory A, Mohammad, Ramzi M, Mohammed, Sulma I, Morre, D. Jame, Muralidhar, Vinayak, Muqbil, Irfana, Murphy, Michael P, Nagaraju, Ganji Purnachandra, Nahta, Rita, Niccolai, Elena, Nowsheen, Somaira, Panis, Carolina, Pantano, Francesco, Parslow, Virginia R, Pawelec, Graham, Pedersen, Peter L, Poore, Brad, Poudyal, Deepak, Prakash, Satya, Prince, Mark, Raffaghello, Lizzia, Rathmell, Jeffrey C, Rathmell, W. Kimryn, Ray, Swapan K, Reichrath, Jörg, Rezazadeh, Sarallah, Ribatti, Domenico, Ricciardiello, Luigi, Robey, R. Brook, Rodier, Franci, Rupasinghe, H. P. Vasantha, Russo, Gian Luigi, Ryan, Elizabeth P, Samadi, Abbas K, Sanchez Garcia, Isidro, Sanders, Andrew J, Santini, Daniele, Sarkar, Malancha, Sasada, Tetsuro, Saxena, Neeraj K, Shackelford, Rodney E, Shantha Kumara, H. M. C, Sharma, Dipali, Shin, Dong M, Sidransky, David, Siegelin, Markus David, Signori, Emanuela, Singh, Neetu, Sivanand, Sharanya, Sliva, Daniel, Smythe, Carl, Spagnuolo, Carmela, Stafforini, Diana M, Stagg, John, Subbarayan, Pochi R, Sundin, Tabetha, Talib, Wamidh H, Thompson, Sarah K, Tran, Phuoc T, Ungefroren, Hendrik, Vander Heiden, Matthew G, Venkateswaran, Vasundara, Vinay, Dass S, Vlachostergios, Panagiotis J, Wang, Zongwei, Wellen, Kathryn E, Whelan, Richard L, Yang, Eddy S, Yang, Huanjie, Yang, Xujuan, Yaswen, Paul, Yedjou, Clement, Yin, Xin, Zhu, Jiyue, Zollo, Massimo, Amin, A R M Ruhul, Ashraf, S Salman, Dong, Jin-Tang, Dou, Q Ping, El-Rayes, Bassel, Hsu, Hsue-Yin, Keith, W Nicol, Lee, Ho-Young, Lin, Liang-Tzung, Martinez-Chantar, Maria L, Morre, D Jame, Rathmell, W Kimryn, Robey, R Brook, Rupasinghe, H P Vasantha, Sanchez-Garcia, Isidro, Shantha Kumara, H M C, Block, Ki, Gyllenhaal, C, Lowe, L, Amedei, A, Amin, Ar, Amin, A, Aquilano, K, Arbiser, J, Arreola, A, Arzumanyan, A, Ashraf, S, Azmi, A, Benencia, F, Bhakta, D, Bilsland, A, Bishayee, A, Blain, Sw, Block, Pb, Boosani, C, Carey, Te, Carnero, A, Casey, Sc, Chakrabarti, M, Chaturvedi, R, Chen, Gz, Chen, H, Chen, S, Chen, Yc, Choi, Bk, Ciriolo, Mr, Coley, Hm, Collins, Ar, Connell, M, Crawford, S, Curran, C, Dabrosin, C, Damia, G, Dasgupta, S, Deberardinis, Rj, Decker, Wk, Dhawan, P, Diehl, Am, Dong, Jt, Dou, Qp, Drew, Je, Elkord, E, El Rayes, B, Feitelson, Ma, Felsher, Dw, Ferguson, Lr, Fimognari, C, Firestone, Gl, Frezza, C, Fujii, H, Fuster, Mm, Generali, D, Georgakilas, Ag, Gieseler, F, Gilbertson, M, Green, Mf, Grue, B, Guha, G, Halicka, D, Helferich, Wg, Heneberg, P, Hentosh, P, Hirschey, Md, Hofseth, Lj, Holcombe, Rf, Honoki, K, Hsu, Hy, Huang, G, Jensen, Ld, Jiang, Wg, Jones, Lw, Karpowicz, Pa, Keith, Wn, Kerkar, Sp, Khan, Gn, Khatami, M, Ko, Yh, Kucuk, O, Kulathinal, Rj, Kumar, Nb, Kwon, B, Le, A, Lea, Ma, Lee, Hy, Lichtor, T, Lin, Lt, Locasale, Jw, Lokeshwar, Bl, Longo, Vd, Lyssiotis, Ca, Mackenzie, Kl, Malhotra, M, Marino, M, Martinez Chantar, Ml, Matheu, A, Maxwell, C, Mcdonnell, E, Meeker, Ak, Mehrmohamadi, M, Mehta, K, Michelotti, Ga, Mohammad, Rm, Mohammed, Si, Morre, Dj, Muralidhar, V, Muqbil, I, Murphy, Mp, Nagaraju, Gp, Nahta, R, Niccolai, E, Nowsheen, S, Panis, C, Pantano, F, Parslow, Vr, Pawelec, G, Pedersen, Pl, Poore, B, Poudyal, D, Prakash, S, Prince, M, Raffaghello, L, Rathmell, Jc, Rathmell, Wk, Ray, Sk, Reichrath, J, Rezazadeh, S, Ribatti, D, Ricciardiello, L, Robey, Rb, Rodier, F, Rupasinghe, Hp, Russo, Gl, Ryan, Ep, Samadi, Ak, Sanchez Garcia, I, Sanders, Aj, Santini, D, Sarkar, M, Sasada, T, Saxena, Nk, Shackelford, Re, Shantha Kumara, Hm, Sharma, D, Shin, Dm, Sidransky, D, Siegelin, Md, Signori, E, Singh, N, Sivanand, S, Sliva, D, Smythe, C, Spagnuolo, C, Stafforini, Dm, Stagg, J, Subbarayan, Pr, Sundin, T, Talib, Wh, Thompson, Sk, Tran, Pt, Ungefroren, H, Vander Heiden, Mg, Venkateswaran, V, Vinay, D, Vlachostergios, Pj, Wang, Z, Wellen, Ke, Whelan, Rl, Yang, E, Yang, H, Yang, X, Yaswen, P, Yedjou, C, Yin, X, Zhu, J, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G., Ruhul Amin, A. R. M., Salman Ashraf, S., Azmi, Asfar S., Blain, Stacy W., Block, Penny B., Boosani, Chandra S., Carey, Thomas E., Casey, Stephanie C., Choi, Beom K., Coley, Helen M., Collins, Andrew R., Curran, Colleen S., Deberardinis, Ralph J., Decker, William K., Diehl, Anna Mae E., Drewa, Janice E., Feitelson, Mark A., Felsheru, Dean W., Ferguson, Lynnette R., Firestone, Gary L., Fuster, Mark M., Georgakilas, Alexandros G., Green, Michelle F., Guhal, Gunjan, Helferich, William G., Hirschey, Matthew D., Hofseth, Lorne J., Holcombe, Randall F., Huang, Gloria S., Jensen, Lasse D., Jiang, Wen G., Jones, Lee W., Karpowicz, Phillip A., Kerkar, Sid P., Khan, Gazala N., Ko, Young H., Kulathinal, Rob J., Kumar, Nagi B., Kwon, Byoung S., Leb, Anne, Leab, Michael A., Locasale, Jason W., Lokeshwar, Bal L., Longo, Valter D., Lyssiotis, Costas A., Maxwellx, Christopher, Meeker, Alan K., Michelotti, Gregory A., Mohammad, Ramzi M., Mohammed, Sulma I., Muralidharcq, Vinayak, Murphy, Michael P., Parslow, Virginia R., Pedersen, Peter L., Rathmell, Jeffrey C., Ray, Swapan K., Robeydf, R. Brook, Rodierdh, Franci, Ryan, Elizabeth P., Samadi, Abbas K., Sanders, Andrew J., Saxena, Neeraj K., Shackelford, Rodney E., Shantha Kumara, H. M. C., Shin, Dong M., Stafforini, Diana M., Subbarayan, Pochi R., Talib, Wamidh H., Thompson, Sarah K., Tran, Phuoc T., Vinay, Dass S., Vlachostergios, Panagiotis J., Wellen, Kathryn E., Whelan, Richard L., and Yang, Eddy S.

Subjects
Cancer Research, medicine.medical_treatment, Phytochemicals, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Pharmacology, Bioinformatics, Targeted therapy, Broad spectrum, 0302 clinical medicine, Cancer hallmark, Neoplasms, Tumor Microenvironment, Molecular Targeted Therapy, Precision Medicine, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Cancer hallmarks, Integrative medicine, Multi-targeted, 1. No poverty, Life Sciences, 3. Good health, 030220 oncology & carcinogenesis, Signal Transduction, Phytochemical, Article, RC0254, 03 medical and health sciences, Therapeutic approach, Genetic Heterogeneity, medicine, Humans, Settore BIO/10, Biology, 030304 developmental biology, Tumor microenvironment, Cancer och onkologi, Cancer prevention, business.industry, Cancer, Precision medicine, medicine.disease, Antineoplastic Agents, Phytogenic, Drug Resistance, Neoplasm, Data_GENERAL, Cancer and Oncology, business
Abstract

Under a Creative Commons license.-- Review.-- et al., Targeted therapies and the consequent adoption of >personalized> oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity >broad-spectrum> therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered., Amr Amin was funded by Terry Fox Foundation Grant # TF-13-20 and UAEU Program for Advanced Research (UPAR) #31S118; Jack Arbiser was funded by NIHAR47901; Alexandra Arreola was funded by NIH NRSA Grant F31CA154080; Alla Arzumanyan was funded by NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer (AI076535); Work in the lab of Asfar S. Azmi is supported by NIH R21CA188818 as well as from Sky Foundation Inc. Michigan; Fabian Benencia was supported by NIH Grant R15 CA137499-01; Alan Bilsland was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Amancio Carnero 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-6844 and CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012). His work on this project has also been made possible thanks to the Grant PIE13/0004 co-funded by the ISCIII and FEDER funds; Stephanie C. Casey was supported by NIH Grant F32CA177139; Mrinmay Chakrabarti was supported by the United Soybean Board; Rupesh Chaturvedi was supported by an NIH NCCAM Grant (K01AT007324); Georgia Zhuo Chen was supported by an NIH NCI Grant (R33 CA161873-02); Helen Chen acknowledges financial support from the Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Sophie Chen acknowledges financial support from the Ovarian and Prostate Cancer Research Trust, UK; Yi Charlie Chen acknowledges financial support from the West Virginia Higher Education Policy Commission/Division of Science Research, his research was also supported by NIH grants (P20RR016477 and P20GM103434) from the National Institutes of Health awarded to the West Virginia IDeA Network of Biomedical Research Excellence; Maria Rosa Ciriolo was partially supported by the Italian Association for Cancer Research (AIRC) Grants #IG10636 and #15403; Helen M. Coley acknowledges financial support from the GRACE Charity, UK and the Breast Cancer Campaign, UK; Marisa Connell was supported by a Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Sarah Crawford was supported by a research grant from Connecticut State University; Charlotta Dabrosin acknowledges financial support from the Swedish Research Council and the Swedish Research Society; Giovanna Damia gratefully acknowledges the generous contributions of The Italian Association for Cancer Research (IG14536 to G.D.), Santanu Dasgupta gratefully acknowledges the support of the University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; William K. Decker was supported in part by CPRIT, the Cancer Prevention and Research Institute of Texas; Anna Mae E. Diehl was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA), Gilead and Shire Pharmaceuticals; Q. Ping Dou was partially supported by NIH/NCI (1R01CA20009, 5R01CA127258-05 and R21CA184788), and NIH P30 CA22453 (to Karmanos Cancer Institute); Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division; Eyad Elkord thanks the National Research Foundation, United Arab Emirates University and the Terry Fox Foundation for supporting research projects in his lab; Bassel El-Rayes was supported by Novartis Pharmaceutical, Aveo Pharmaceutical, Roche, Bristol Myers Squibb, Bayer Pharmaceutical, Pfizer, and Kyowa Kirin; Mark A. Feitelson was supported by NIH/NIAID Grant AI076535, Dean W. Felsher was supported by NIH grants (R01CA170378, U54CA149145, and U54CA143907); Lynnette R Ferguson was financially supported by the Auckland Cancer Society and the Cancer Society of New Zealand; Gary L. Firestone was supported by NIH Public Service Grant CA164095 awarded from the National Cancer Institute; Christian Frezza “would like to acknowledge funding from a Medical Research Council CCU-Program Grant on cancer metabolism, and a unique applicant AICR project grant”; Mark M. Fuster was supported by NIH Grant R01-HL107652; Alexandros G. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program ‘Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES (Grant number MIS 379346) and COST Action CM1201 ‘Biomimetic Radical Chemistry’; Michelle F. Green was supported by a Duke University Molecular Cancer Biology T32 Training Grant; Brendan Grue was supported by a National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Dorota Halicka was supported by by NIH NCI grant NCI RO1 28704; Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, by the Czech Science Foundation projects 15-03834Y and P301/12/1686, by the Czech Health Research Council AZV project 15-32432A, and by the Internal Grant Agency of the Ministry of Health of the Czech Republic project NT13663-3/2012; Matthew D. Hirschey wishes to acknowledge Duke University Institutional Support, the Duke Pepper Older Americans Independence Center (OAIC) Program in Aging Research supported by the National Institute of Aging (P30AG028716-01) and NIH/NCI training grants to Duke University (T32-CA059365-19 and 5T32-CA059365), Lorne J. Hofseth was supported by NIH grants (1R01CA151304, 1R03CA1711326, and 1P01AT003961); Kanya Honoki was supported in part by the grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 24590493); Hsue-Yin Hsu was supported in part by grants from the Ministry of Health and Welfare (CCMP101-RD-031 and CCMP102-RD-112) and Tzu-Chi University (61040055-10) of Taiwan; Lasse D. Jensen was supported by Svenska Sallskapet for Medicinsk Forskning, Gosta Fraenkels Stiftelse, Ak.e Wibergs Stiftelse, Ollie och Elof Ericssons Stiftelse, Linkopings Universitet and the Karolinska Institute, Sweden; Wen G. Jiang wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Lee W. Jones was supported in part by grants from the NIH NCI; W Nicol Keith was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Sid P. Kerkar was supported by the NIH Intramural Research Program; Rob J. Kulathinal was supported by the National Science Foundation, and the American Cancer Society; Byoung S. Kwon was supported in part by National Cancer Center (NCC-1310430-2) and National Research Foundation (NRF-2005-0093837); Anne Le was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, a Lustgarten Fund Grant 90049125 and Grant NIHR21CA169757 (to Anne Le); Michael A. Lea was funded by the The Alma Toorock Memorial for Cancer Research; Ho-Young Lee., This work was supported by grants from the National Research Foundation of Korea (NRF), the Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea (Nos. 2011-0017639 and 2011-0030001) and by a NIH Grant R01 CA100816; Liang-Tzung Lin was supported in part by a grant from the Ministry of Education of Taiwan (TMUTOP103005-4); Jason W. Locasale acknowledges support from NIH awards (CA168997 and AI110613) and the International Life Sciences Institute; Bal L. Lokeshwar was supported in part by United States’ Public Health Services Grants: NIH R01CA156776 and VA-BLR&D Merit Review Grant No. 5I01-BX001517-02; Valter D. Longo acknowledges support from NIH awards (P01AG034906 and R01AG020642) and from the V Foundation; Costas A. Lyssiotis was funded in part by the Pancreatic Cancer Action Network as a Pathway to Leadership Fellow and through a Dale F. Frey Breakthrough award from the Damon Runyon Cancer Research Foundation; Karen L. MacKenzie wishes to acknowledge the support from the Children's Cancer Institute Australia (affiliated with the University of New South Wales, Australia and the Sydney Children's Hospital Network); Maria Marino was supported by grant from University Roma Tre to M.M. (CLA 2013) and by the Italian Association for Cancer Research (AIRC-Grant #IG15221), Ander Matheu is funded by Carlos III Health Institute (AM: CP10/00539), Basque Foundation for Science (IKERBASQUE) and Marie Curie CIG Grant (AM: 2012/712404); Christopher Maxwell was supported by funding from the Canadian Institutes of Health Research, in partnership with the Avon Foundation for Women (OBC-134038) and the Canadian Institutes of Health Research New Investigator Salary Award (MSH-136647); Eoin McDonnell received Duke University Institutional Support; Kapil Mehta was supported by Bayer Healthcare System G4T (Grants4Targets); Gregory A. Michelotti received support from NIH NIDDK, NIH NIAAA, and Shire Pharmaceuticals; Vinayak Muralidhar was supported by the Harvard-MIT Health Sciences and Technology Research Assistantship Award; Elena Niccolai was supported by the Italian Ministry of University and the University of Italy; Virginia R. Parslow gratefully acknowledges the financial support of the Auckland Cancer Society Research Centre (ACSRC); Graham Pawelec was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) Grant number 16SV5536K, and by the European Commission (FP7 259679 “IDEAL”); Peter L. Pedersen was supported by NIH Grant CA-10951; Brad Poore was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, the Lustgarten Fund Grant 90049125, and Grant NIHR21CA169757 (to Anne Le); Satya Prakash was supported by a Canadian Institutes of Health Research Grant (MOP 64308); Lizzia Raffaghello was supported by an NIH Grant (P01AG034906-01A1) and Cinque per Mille dell’IRPEF–Finanziamento della Ricerca Sanitaria; Jeffrey C. Rathmell was supported by an NIH Grant (R01HL108006); Swapan K. Ray was supported by the United Soybean Board; Domenico Ribatti received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under Grant agreement n°278570; Luigi Ricciardiello was supported by the AIRC Investigator Grants 10216 and 13837, and the European Community's Seventh Framework Program FP7/2007–2013 under Grant agreement 311876; Francis Rodier acknowledges the support of the Canadian Institute for Health Research (FR: MOP114962, MOP125857), Fonds de Recherche Québec Santé (FR: 22624), and the Terry Fox Research Institute (FR: 1030), Gian Luigi Russo contributed to this effort while participating in the Fulbright Research Scholar Program 2013–14; Isidro Sanchez-Garcia is partially supported by FEDER and by MICINN (SAF2012-32810), by NIH Grant (R01 CA109335-04A1), by Junta de Castilla y León (BIO/SA06/13) and by the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program). Isidro Sanchez-Garcia's lab is also a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program; Andrew J. Sanders wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Neeraj K. Saxena was supported by grant funding from NIH NIDDK (K01DK077137, R03DK089130); Dipali Sharma was partially funded by NIH NCI grants (R01CA131294, R21 CA155686), the Avon Foundation and a Breast Cancer Research Foundation Grant (90047965); Markus David Siegelin received funding from National Institute of Health, NINDS Grant K08NS083732, and the 2013 AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research, Grant Number 13-20-23-SIEG; Neetu Singh was supported by funds from the Department of Science and Technology (SR/FT/LS-063/2008), New Delhi, India; Carl Smythe was supported by Yorkshire Cancer Research and The Wellcome Trust, UK; Carmela Spagnuolo was supported by funding from Project C.I.S.I.A., act n. 191/2009 from the Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region 2007/2013, objectives 2.1, 2.2; Diana M. Stafforini was supported by grants from the National Cancer Institute (5P01CA073992), IDEA Award W81XWH-12-1-0515 from the Department of Defense, and by the Huntsman Cancer Foundation; John Stagg was supported by the Canadian Institutes of Health Research; Pochi R. Subbarayan was supported by the University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant (CTSI-2013-P03) and SEEDS You Choose Awards; Phuoc T. Tran was funded by the DoD (W81XWH-11-1-0272 and W81XWH-13-1-0182), a Kimmel Translational Science Award (SKF-13-021), an ACS Scholar award (122688-RSG-12-196-01-TBG) and the NIH (R01CA166348); Kathryn E. Wellen receives funding from the National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts, American Diabetes Association, and Elsa U. Pardee Foundation; Huanjie Yang was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011), Paul Yaswen was supported by funding from the United States National Institutes of Health (ES019458) and the California Breast Cancer Research Program (17UB-8708); Clement Yedjou was supported by a grant from the National Institutes of Health (Grant # G1200MD007581), through the RCMI-Center for Environmental Health; Xin Yin was supported by NIH/National Heart, Lung, and Blood Institute Training Grant T32HL098062.; Jiyue Zhu was supported by NIH Grant R01GM071725; Massimo Zollo was supported by the European FP7-TuMIC HEALTH-F2-2008-201662, the Italian Association for Cancer research (AIRC) Grant IG # 11963 and the Regione Campania L.R:N.5, the European National Funds PON01-02388/1 2007-2013.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results