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2. Intercellular pathways of cancer treatment-related cardiotoxicity and their therapeutic implications: the paradigm of radiotherapy

Author

Logotheti, Stella, Pavlopoulou, Athanasia, Rudsari, Hamid Khoshfekr, Galow, Anne-Marie, Kafalı, Yağmur, Kyrodimos, Efthymios, Giotakis, Aris I., Marquardt, Stephan, Velalopoulou, Anastasia, Verginadis, Ioannis I., Koumenis, Constantinos, Stiewe, Thorsten, Zoidakis, Jerome, Balasingham, Ilangko, David, Robert, and Georgakilas, Alexandros G.

Published
2024
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3. FLASH Proton Radiation Therapy Mitigates Inflammatory and Fibrotic Pathways and Preserves Cardiac Function in a Preclinical Mouse Model of Radiation-Induced Heart Disease

Author

Kim, Kyle, Kim, Michele M., Skoufos, Giorgos, Diffenderfer, Eric S., Motlagh, Seyyedeh Azar Oliaei, Kokkorakis, Michail, Koliaki, Ilektra, Morcos, George, Shoniyozov, Khayrullo, Griffin, Joanna, Hatzigeorgiou, Artemis G., Metz, James M., Lin, Alexander, Feigenberg, Steven J., Cengel, Keith A., Ky, Bonnie, Koumenis, Constantinos, and Verginadis, Ioannis I.

Published
2024
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5. Figure S3 from Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer

Author

Chowdhury, Priyanka, primary, Velalopoulou, Anastasia, primary, Verginadis, Ioannis I., primary, Morcos, George, primary, Loo, Phoebe E., primary, Kim, Michele M., primary, Motlagh, Seyyedeh Azar Oliaei, primary, Shoniyozov, Khayrullo, primary, Diffenderfer, Eric S., primary, Ocampo, Emilio A., primary, Putt, Mary, primary, Assenmacher, Charles-Antoine, primary, Radaelli, Enrico, primary, Lu, Jiawei, primary, Qin, Ling, primary, Liu, Hengxi, primary, Leli, Nektaria Maria, primary, Girdhani, Swati, primary, Denef, Nicolas, primary, Vander Stappen, Francois, primary, Cengel, Keith A., primary, Busch, Theresa M., primary, Metz, James M., primary, Dong, Lei, primary, Lin, Alexander, primary, and Koumenis, Constantinos, primary

Published
2024
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6. Data from Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer

Author

Chowdhury, Priyanka, primary, Velalopoulou, Anastasia, primary, Verginadis, Ioannis I., primary, Morcos, George, primary, Loo, Phoebe E., primary, Kim, Michele M., primary, Motlagh, Seyyedeh Azar Oliaei, primary, Shoniyozov, Khayrullo, primary, Diffenderfer, Eric S., primary, Ocampo, Emilio A., primary, Putt, Mary, primary, Assenmacher, Charles-Antoine, primary, Radaelli, Enrico, primary, Lu, Jiawei, primary, Qin, Ling, primary, Liu, Hengxi, primary, Leli, Nektaria Maria, primary, Girdhani, Swati, primary, Denef, Nicolas, primary, Vander Stappen, Francois, primary, Cengel, Keith A., primary, Busch, Theresa M., primary, Metz, James M., primary, Dong, Lei, primary, Lin, Alexander, primary, and Koumenis, Constantinos, primary

Published
2024
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7. Supplementary Table 2 from Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer

Author

Chowdhury, Priyanka, primary, Velalopoulou, Anastasia, primary, Verginadis, Ioannis I., primary, Morcos, George, primary, Loo, Phoebe E., primary, Kim, Michele M., primary, Motlagh, Seyyedeh Azar Oliaei, primary, Shoniyozov, Khayrullo, primary, Diffenderfer, Eric S., primary, Ocampo, Emilio A., primary, Putt, Mary, primary, Assenmacher, Charles-Antoine, primary, Radaelli, Enrico, primary, Lu, Jiawei, primary, Qin, Ling, primary, Liu, Hengxi, primary, Leli, Nektaria Maria, primary, Girdhani, Swati, primary, Denef, Nicolas, primary, Vander Stappen, Francois, primary, Cengel, Keith A., primary, Busch, Theresa M., primary, Metz, James M., primary, Dong, Lei, primary, Lin, Alexander, primary, and Koumenis, Constantinos, primary

Published
2024
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8. Supplementary Table 1 from Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer

Author

Chowdhury, Priyanka, primary, Velalopoulou, Anastasia, primary, Verginadis, Ioannis I., primary, Morcos, George, primary, Loo, Phoebe E., primary, Kim, Michele M., primary, Motlagh, Seyyedeh Azar Oliaei, primary, Shoniyozov, Khayrullo, primary, Diffenderfer, Eric S., primary, Ocampo, Emilio A., primary, Putt, Mary, primary, Assenmacher, Charles-Antoine, primary, Radaelli, Enrico, primary, Lu, Jiawei, primary, Qin, Ling, primary, Liu, Hengxi, primary, Leli, Nektaria Maria, primary, Girdhani, Swati, primary, Denef, Nicolas, primary, Vander Stappen, Francois, primary, Cengel, Keith A., primary, Busch, Theresa M., primary, Metz, James M., primary, Dong, Lei, primary, Lin, Alexander, primary, and Koumenis, Constantinos, primary

Published
2024
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9. A stromal Integrated Stress Response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumour progression

Author

Verginadis, Ioannis I., Avgousti, Harris, Monslow, James, Skoufos, Giorgos, Chinga, Frank, Kim, Kyle, Leli, Nektaria Maria, Karagounis, Ilias V., Bell, Brett I., Velalopoulou, Anastasia, Salinas, Carlo Salas, Wu, Victoria S., Li, Yang, Ye, Jiangbin, Scott, David A., Osterman, Andrei L., Sengupta, Arjun, Weljie, Aalim, Huang, Menggui, Zhang, Duo, Fan, Yi, Radaelli, Enrico, Tobias, John W., Rambow, Florian, Karras, Panagiotis, Marine, Jean-Christophe, Xu, Xiaowei, Hatzigeorgiou, Artemis G., Ryeom, Sandra, Diehl, J. Alan, Fuchs, Serge Y., Puré, Ellen, and Koumenis, Constantinos

Published
2022
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10. ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression

Author

Tameire, Feven, Verginadis, Ioannis I, Leli, Nektaria Maria, Polte, Christine, Conn, Crystal S, Ojha, Rani, Salas Salinas, Carlo, Chinga, Frank, Monroy, Alexandra M, Fu, Weixuan, Wang, Paul, Kossenkov, Andrew, Ye, Jiangbin, Amaravadi, Ravi K, Ignatova, Zoya, Fuchs, Serge Y, Diehl, J Alan, Ruggero, Davide, and Koumenis, Constantinos

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Aetiology, 2.1 Biological and endogenous factors, Cancer, Activating Transcription Factor 4, Adaptor Proteins, Signal Transducing, Animals, Cell Cycle Proteins, Endoplasmic Reticulum Stress, Genes, myc, Humans, Mechanistic Target of Rapamycin Complex 1, Mice, Transgenic, Phosphoproteins, Phosphorylation, Protein Biosynthesis, TOR Serine-Threonine Kinases, Transcriptional Activation, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

The c-Myc oncogene drives malignant progression and induces robust anabolic and proliferative programmes leading to intrinsic stress. The mechanisms enabling adaptation to MYC-induced stress are not fully understood. Here we reveal an essential role for activating transcription factor 4 (ATF4) in survival following MYC activation. MYC upregulates ATF4 by activating general control nonderepressible 2 (GCN2) kinase through uncharged transfer RNAs. Subsequently, ATF4 co-occupies promoter regions of over 30 MYC-target genes, primarily those regulating amino acid and protein synthesis, including eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), a negative regulator of translation. 4E-BP1 relieves MYC-induced proteotoxic stress and is essential to balance protein synthesis. 4E-BP1 activity is negatively regulated by mammalian target of rapamycin complex 1 (mTORC1)-dependent phosphorylation and inhibition of mTORC1 signalling rescues ATF4-deficient cells from MYC-induced endoplasmic reticulum stress. Acute deletion of ATF4 significantly delays MYC-driven tumour progression and increases survival in mouse models. Our results establish ATF4 as a cellular rheostat of MYC activity, which ensures that enhanced translation rates are compatible with survival and tumour progression.

Published
2019

11. Proton FLASH radiotherapy ameliorates radiation-induced salivary gland dysfunction and oral mucositis and increases survival in a mouse model of head and neck cancer

Author

Chowdhury, Priyanka, primary, Velalopoulou, Anastasia, additional, Verginadis, Ioannis I., additional, Morcos, George, additional, Loo, Phoebe E., additional, Kim, Michele M., additional, Motlagh, Seyyedeh Azar Oliaei, additional, Shoniyozov, Khayrullo, additional, Diffenderfer, Eric S., additional, Ocampo, Emilio A., additional, Putt, Mary, additional, Assenmacher, Charles-Antoine, additional, Radaelli, Enrico, additional, Lu, Jiawei, additional, Qin, Ling, additional, Liu, Hengxi, additional, Leli, Nektaria Maria, additional, Girdhani, Swati, additional, Denef, Nicolas, additional, Vander Stappen, Francois, additional, Cengel, Keith A., additional, Busch, Theresa M., additional, Metz, James M., additional, Dong, Lei, additional, Lin, Alexander, additional, and Koumenis, Constantinos, additional

Published
2024
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12. Proton radiation boosts the efficacy of mesothelin-targeting chimeric antigen receptor T cell therapy in pancreatic cancer.

Author

Amit, Uri, Uslu, Ugur, Verginadis, Ioannis I., Kim, Michele M., Oliaei Motlagh, Seyyedeh Azar, Diffenderfer, Eric S., Assenmacher, Charles-Antoine, Bicher, Sandra, Atoche, Sebastian J., Ben-Josef, Edgar, Young, Regina M., June, Carl H., and Koumenis, Constantinos

Subjects
MYELOID-derived suppressor cells, CHIMERIC antigen receptors, T cells, PANCREATIC duct, RADIOTHERAPY
Abstract

Pancreatic ductal adenocarcinoma (PDAC) represents a challenge in oncology, with limited treatment options for advanced-stage patients. Chimeric antigen receptor T cell (CAR T) therapy targeting mesothelin (MSLN) shows promise, but challenges such as the hostile immunosuppressive tumor microenvironment (TME) hinder its efficacy. This study explores the synergistic potential of combining proton radiation therapy (RT) with MSLN-targeting CAR T therapy in a syngeneic PDAC model. Proton RT significantly increased MSLN expression in tumor cells and caused a significant increase in CAR T cell infiltration into tumors. The combination therapy reshaped the immunosuppressive TME, promoting antitumorigenic M1 polarized macrophages and reducing myeloid-derived suppressor cells (MDSC). In a flank PDAC model, the combination therapy demonstrated superior attenuation of tumor growth and improved survival compared to individual treatments alone. In an orthotopic PDAC model treated with image-guided proton RT, tumor growth was significantly reduced in the combination group compared to the RT treatment alone. Further, the combination therapy induced an abscopal effect in a dual-flank tumor model, with increased serum interferon-γ levels and enhanced proliferation of extratumoral CAR T cells. In conclusion, combining proton RT with MSLN-targeting CAR T therapy proves effective in modulating the TME, enhancing CAR T cell trafficking, and exerting systemic antitumor effects. Thus, this combinatorial approach could present a promising strategy for improving outcomes in unresectable PDAC. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Navigating the Critical Translational Questions for Implementing FLASH in the Clinic.

Author

Loo, Billy W., Verginadis, Ioannis I., Sørensen, Brita Singers, Mascia, Anthony E., Perentesis, John P., Koong, Albert C., Schüler, Emil, Rankin, Erinn B., Maxim, Peter G., Limoli, Charles L., and Vozenin, Marie-Catherine

Abstract

The "FLASH effect" is an increased therapeutic index, that is, reduced normal tissue toxicity for a given degree of anti-cancer efficacy, produced by ultra-rapid irradiation delivered on time scales orders of magnitude shorter than currently conventional in the clinic for the same doses. This phenomenon has been observed in numerous preclinical in vivo tumor and normal tissue models. While the underlying biological mechanism(s) remain to be elucidated, a path to clinical implementation of FLASH can be paved by addressing several critical translational questions. Technological questions pertinent to each beam type (eg , electron, proton, photon) also dictate the logical progression of experimentation required to move forward in safe and decisive clinical trials. Here we review the available preclinical data pertaining to these questions and how they may inform strategies for FLASH cancer therapy clinical trials. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System

Author

Diffenderfer, Eric S., Verginadis, Ioannis I., Kim, Michele M., Shoniyozov, Khayrullo, Velalopoulou, Anastasia, Goia, Denisa, Putt, Mary, Hagan, Sarah, Avery, Stephen, Teo, Kevin, Zou, Wei, Lin, Alexander, Swisher-McClure, Samuel, Koch, Cameron, Kennedy, Ann R., Minn, Andy, Maity, Amit, Busch, Theresa M., Dong, Lei, Koumenis, Costas, Metz, James, and Cengel, Keith A.

Published
2020
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15. FLASH proton radiotherapy mitigates inflammatory and fibrotic pathways and preserves cardiac function in a preclinical mouse model of radiation-induced heart disease

Author

Kim, Kyle, primary, Kim, Michele M., additional, Skoufos, Giorgos, additional, Diffenderfer, Eric S., additional, Motlagh, Seyyedeh Azar Oliaei, additional, Kokkorakis, Michail, additional, Koliaki, Ilektra, additional, Morcos, George, additional, Shoniyozov, Khayrullo, additional, Griffin, Joanna, additional, Hatzigeorgiou, Artemis G., additional, Metz, James M., additional, Lin, Alexander, additional, Feigenberg, Steven J., additional, Cengel, Keith A., additional, Ky, Bonnie, additional, Koumenis, Constantinos, additional, and Verginadis, Ioannis I., additional

Published
2024
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19. Data from ER Translocation of the MAPK Pathway Drives Therapy Resistance in BRAF-Mutant Melanoma

Author

Ojha, Rani, primary, Leli, Nektaria M., primary, Onorati, Angelique, primary, Piao, Shengfu, primary, Verginadis, Ioannis I., primary, Tameire, Feven, primary, Rebecca, Vito W., primary, Chude, Cynthia I., primary, Murugan, Sengottuvelan, primary, Fennelly, Colin, primary, Noguera-Ortega, Estela, primary, Chu, Charleen T., primary, Liu, Shujing, primary, Xu, Xiaowei, primary, Krepler, Clemens, primary, Xiao, Min, primary, Xu, Wei, primary, Wei, Zhi, primary, Frederick, Dennie T., primary, Boland, Genevieve, primary, Mitchell, Tara C., primary, Karakousis, Giorgos C., primary, Schuchter, Lynn M., primary, Flaherty, Keith T., primary, Zhang, Gao, primary, Herlyn, Meenhard, primary, Koumenis, Constantinos, primary, and Amaravadi, Ravi K., primary

Published
2023
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20. Supplementary Figures from ER Translocation of the MAPK Pathway Drives Therapy Resistance in BRAF-Mutant Melanoma

Author

Ojha, Rani, primary, Leli, Nektaria M., primary, Onorati, Angelique, primary, Piao, Shengfu, primary, Verginadis, Ioannis I., primary, Tameire, Feven, primary, Rebecca, Vito W., primary, Chude, Cynthia I., primary, Murugan, Sengottuvelan, primary, Fennelly, Colin, primary, Noguera-Ortega, Estela, primary, Chu, Charleen T., primary, Liu, Shujing, primary, Xu, Xiaowei, primary, Krepler, Clemens, primary, Xiao, Min, primary, Xu, Wei, primary, Wei, Zhi, primary, Frederick, Dennie T., primary, Boland, Genevieve, primary, Mitchell, Tara C., primary, Karakousis, Giorgos C., primary, Schuchter, Lynn M., primary, Flaherty, Keith T., primary, Zhang, Gao, primary, Herlyn, Meenhard, primary, Koumenis, Constantinos, primary, and Amaravadi, Ravi K., primary

Published
2023
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21. Supplementary Movie 1 from ER Translocation of the MAPK Pathway Drives Therapy Resistance in BRAF-Mutant Melanoma

Author

Ojha, Rani, primary, Leli, Nektaria M., primary, Onorati, Angelique, primary, Piao, Shengfu, primary, Verginadis, Ioannis I., primary, Tameire, Feven, primary, Rebecca, Vito W., primary, Chude, Cynthia I., primary, Murugan, Sengottuvelan, primary, Fennelly, Colin, primary, Noguera-Ortega, Estela, primary, Chu, Charleen T., primary, Liu, Shujing, primary, Xu, Xiaowei, primary, Krepler, Clemens, primary, Xiao, Min, primary, Xu, Wei, primary, Wei, Zhi, primary, Frederick, Dennie T., primary, Boland, Genevieve, primary, Mitchell, Tara C., primary, Karakousis, Giorgos C., primary, Schuchter, Lynn M., primary, Flaherty, Keith T., primary, Zhang, Gao, primary, Herlyn, Meenhard, primary, Koumenis, Constantinos, primary, and Amaravadi, Ravi K., primary

Published
2023
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22. Supplementary Movie 2 from ER Translocation of the MAPK Pathway Drives Therapy Resistance in BRAF-Mutant Melanoma

Author

Ojha, Rani, primary, Leli, Nektaria M., primary, Onorati, Angelique, primary, Piao, Shengfu, primary, Verginadis, Ioannis I., primary, Tameire, Feven, primary, Rebecca, Vito W., primary, Chude, Cynthia I., primary, Murugan, Sengottuvelan, primary, Fennelly, Colin, primary, Noguera-Ortega, Estela, primary, Chu, Charleen T., primary, Liu, Shujing, primary, Xu, Xiaowei, primary, Krepler, Clemens, primary, Xiao, Min, primary, Xu, Wei, primary, Wei, Zhi, primary, Frederick, Dennie T., primary, Boland, Genevieve, primary, Mitchell, Tara C., primary, Karakousis, Giorgos C., primary, Schuchter, Lynn M., primary, Flaherty, Keith T., primary, Zhang, Gao, primary, Herlyn, Meenhard, primary, Koumenis, Constantinos, primary, and Amaravadi, Ravi K., primary

Published
2023
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23. Supplementary tables from ER Translocation of the MAPK Pathway Drives Therapy Resistance in BRAF-Mutant Melanoma

Author

Ojha, Rani, primary, Leli, Nektaria M., primary, Onorati, Angelique, primary, Piao, Shengfu, primary, Verginadis, Ioannis I., primary, Tameire, Feven, primary, Rebecca, Vito W., primary, Chude, Cynthia I., primary, Murugan, Sengottuvelan, primary, Fennelly, Colin, primary, Noguera-Ortega, Estela, primary, Chu, Charleen T., primary, Liu, Shujing, primary, Xu, Xiaowei, primary, Krepler, Clemens, primary, Xiao, Min, primary, Xu, Wei, primary, Wei, Zhi, primary, Frederick, Dennie T., primary, Boland, Genevieve, primary, Mitchell, Tara C., primary, Karakousis, Giorgos C., primary, Schuchter, Lynn M., primary, Flaherty, Keith T., primary, Zhang, Gao, primary, Herlyn, Meenhard, primary, Koumenis, Constantinos, primary, and Amaravadi, Ravi K., primary

Published
2023
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31. Supplementary Data from A Novel Mouse Model of Radiation-Induced Cardiac Injury Reveals Biological and Radiological Biomarkers of Cardiac Dysfunction with Potential Clinical Relevance

Author

Dreyfuss, Alexandra D., primary, Goia, Denisa, primary, Shoniyozov, Khayrullo, primary, Shewale, Swapnil V., primary, Velalopoulou, Anastasia, primary, Mazzoni, Susan, primary, Avgousti, Harris, primary, Metzler, Scott D., primary, Bravo, Paco E., primary, Feigenberg, Steven J., primary, Ky, Bonnie, primary, Verginadis, Ioannis I., primary, and Koumenis, Constantinos, primary

Published
2023
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32. Figure SF6 from FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response

Author

Velalopoulou, Anastasia, primary, Karagounis, Ilias V., primary, Cramer, Gwendolyn M., primary, Kim, Michele M., primary, Skoufos, Giorgos, primary, Goia, Denisa, primary, Hagan, Sarah, primary, Verginadis, Ioannis I., primary, Shoniyozov, Khayrullo, primary, Chiango, June, primary, Cerullo, Michelle, primary, Varner, Kelley, primary, Yao, Lutian, primary, Qin, Ling, primary, Hatzigeorgiou, Artemis G., primary, Minn, Andy J., primary, Putt, Mary, primary, Lanza, Matthew, primary, Assenmacher, Charles-Antoine, primary, Radaelli, Enrico, primary, Huck, Jennifer, primary, Diffenderfer, Eric, primary, Dong, Lei, primary, Metz, James, primary, Koumenis, Constantinos, primary, Cengel, Keith A., primary, Maity, Amit, primary, and Busch, Theresa M., primary

Published
2023
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33. Table ST1 from FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response

Author

Velalopoulou, Anastasia, primary, Karagounis, Ilias V., primary, Cramer, Gwendolyn M., primary, Kim, Michele M., primary, Skoufos, Giorgos, primary, Goia, Denisa, primary, Hagan, Sarah, primary, Verginadis, Ioannis I., primary, Shoniyozov, Khayrullo, primary, Chiango, June, primary, Cerullo, Michelle, primary, Varner, Kelley, primary, Yao, Lutian, primary, Qin, Ling, primary, Hatzigeorgiou, Artemis G., primary, Minn, Andy J., primary, Putt, Mary, primary, Lanza, Matthew, primary, Assenmacher, Charles-Antoine, primary, Radaelli, Enrico, primary, Huck, Jennifer, primary, Diffenderfer, Eric, primary, Dong, Lei, primary, Metz, James, primary, Koumenis, Constantinos, primary, Cengel, Keith A., primary, Maity, Amit, primary, and Busch, Theresa M., primary

Published
2023
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34. Supplemental Methods from FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response

Author

Velalopoulou, Anastasia, primary, Karagounis, Ilias V., primary, Cramer, Gwendolyn M., primary, Kim, Michele M., primary, Skoufos, Giorgos, primary, Goia, Denisa, primary, Hagan, Sarah, primary, Verginadis, Ioannis I., primary, Shoniyozov, Khayrullo, primary, Chiango, June, primary, Cerullo, Michelle, primary, Varner, Kelley, primary, Yao, Lutian, primary, Qin, Ling, primary, Hatzigeorgiou, Artemis G., primary, Minn, Andy J., primary, Putt, Mary, primary, Lanza, Matthew, primary, Assenmacher, Charles-Antoine, primary, Radaelli, Enrico, primary, Huck, Jennifer, primary, Diffenderfer, Eric, primary, Dong, Lei, primary, Metz, James, primary, Koumenis, Constantinos, primary, Cengel, Keith A., primary, Maity, Amit, primary, and Busch, Theresa M., primary

Published
2023
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35. Regulation of intercellular biomolecule transfer-driven tumor angiogenesis and responses to anticancer therapies

Author

Lu, Zhen, Ortiz, Angelica, Verginadis, Ioannis I., Peck, Amy R., Zahedi, Farima, Cho, Christina, Yu, Pengfei, DeRita, Rachel M., Zhang, Hongru, Kubanoff, Ryan, Sun, Yunguang, Yaspan, Andrew T., Krespan, Elise, Beiting, Daniel P., Radaelli, Enrico, Ryeom, Sandra W., Diehl, J. Alan, Rui, Hallgeir, Koumenis, Constantinos, and Fuchs, Serge Y.

Subjects
Biological transport -- Genetic aspects, Neovascularization -- Health aspects -- Genetic aspects, Carcinogenesis -- Genetic aspects, Cancer -- Care and treatment, Health care industry
Abstract

Intercellular biomolecule transfer (ICBT) between malignant and benign cells is a major driver of tumor growth, resistance to anticancer therapies, and therapy-triggered metastatic disease. Here we characterized cholesterol 25-hydroxylase (CH25H) as a key genetic suppressor of ICBT between malignant and endothelial cells (ECs) and of ICBT-driven angiopoietin-2-dependent activation of ECs, stimulation of intratumoral angiogenesis, and tumor growth. Human CH25H was downregulated in the ECs from patients with colorectal cancer and the low levels of stromal CH25H were associated with a poor disease outcome. Knockout of endothelial CH25H stimulated angiogenesis and tumor growth in mice. Pharmacologic inhibition of ICBT by reserpine compensated for CH25H loss, elicited angiostatic effects (alone or combined with sunitinib), augmented the therapeutic effect of radio-/chemotherapy, and prevented metastatic disease induced by these regimens. We propose inhibiting ICBT to improve the overall efficacy of anticancer therapies and limit their prometastatic side effects., Introduction Within a multicellular organism, the horizontal exchange of biomolecules such as nucleic acids, polypeptides, lipids, and others between cells has emerged as an important mode of communication that encourages [...]

Published
2021
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36. The Radiogenomic and Spatiogenomic Landscapes of Glioblastoma, and their Relationship to Oncogenic Drivers

Author

Kazerooni, Anahita Fathi, primary, Akbari, Hamed, additional, Hu, Xiaoju, additional, Bommineni, Vikas, additional, Grigoriadis, Dimitris, additional, Toorens, Erik, additional, Sako, Chiharu, additional, Mamourian, Elizabeth, additional, Ballinger, Dominique, additional, Sussman, Robyn, additional, Singh, Ashish, additional, Verginadis, Ioannis I., additional, Dahmane, Nadia, additional, Koumenis, Constantinos, additional, Binder, Zev A., additional, Bagley, Stephen J., additional, Mohan, Suyash, additional, Hatzigeorgiou, Artemis, additional, O’Rourke, Donald M., additional, Ganguly, Tapan, additional, De, Subhajyoti, additional, Bakas, Spyridon, additional, Nasrallah, MacLean P., additional, and Davatzikos, Christos, additional

Published
2022
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38. Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities

Author

Lu, Zhen, primary, Bae, Eun-Ah, additional, Verginadis, Ioannis I., additional, Zhang, Hongru, additional, Cho, Christina, additional, McBrearty, Noreen, additional, George, Subin S., additional, Diehl, J. Alan, additional, Koumenis, Constantinos, additional, Bradley, Linda M., additional, and Fuchs, Serge Y., additional

Published
2022
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39. Abstract 3178: A stromal integrated stress response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumor progression

Author

Verginadis, Ioannis I., primary, Avgousti, Harris, additional, Kim, Kyle, additional, Skoufos, Giorgos, additional, Chinga, Frank, additional, Leli, Nektaria Maria, additional, Karagounis, Ilias V., additional, Bell, Brett I., additional, Velalopoulou, Anastasia, additional, Wu, Victoria S., additional, Li, Yang, additional, Ye, Jiangbin, additional, Scott, David A., additional, Osterman, Andrei L., additional, Sengupta, Arjun, additional, Weljie, Aalim, additional, Hatzigeorgiou, Artemis G., additional, Ryeom, Sandra, additional, Diehl, Alan J., additional, Fuchs, Serge Y., additional, Puré, Ellen, additional, and Koumenis, Constantinos, additional

Published
2022
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40. Abstract 3320: Single-cell RNA sequencing analysis and transgenic mouse models reveal differential effects of flash vs. standard proton radiotherapy on gastrointestinal tissues and tumors

Author

Verginadis, Ioannis I., primary, Martinez, Clara Morral, additional, Lim, Tristan, additional, Chowdhury, Priyanka, additional, Skoufos, Giorgos, additional, Kim, Michele M., additional, Velalopoulou, Anastasia, additional, Goia, Denisa, additional, Luo, Leo, additional, Foley, Caitlin J., additional, Reitman, Zachary J., additional, Daniel, Andrea R., additional, Diffenderfer, Eric, additional, Dong, Lei, additional, Metz, James, additional, Kirsch, David G., additional, Minn, Andy, additional, and Koumenis, Constantinos, additional

Published
2022
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42. Abstract 3304: Gene expression profiling of full-thickness skin after FLASH proton radiotherapy

Author

Velalopoulou, Anastasia, primary, Karagounis, Ilias V., additional, Skoufos, Giorgos, additional, Verginadis, Ioannis I., additional, Kim, Michele, additional, Shoniyozov, Khayrullo, additional, Hatzigeorgiou, Artemis G., additional, Diffenderfer, Eric, additional, Dong, Lei, additional, Metz, James, additional, Koumenis, Constantinos, additional, Cengel, Keith A., additional, Maity, Amit, additional, and Busch, Theresa M., additional

Published
2022
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44. Author Correction: ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression

Author

Tameire, Feven, Verginadis, Ioannis I., Leli, Nektaria Maria, Polte, Christine, Conn, Crystal S., Ojha, Rani, Salinas, Carlo Salas, Chinga, Frank, Monroy, Alexandra. M., Fu, Weixuan, Wang, Paul, Kossenkov, Andrew, Ye, Jiangbin, Amaravadi, Ravi K., Ignatova, Zoya, Fuchs, Serge Y., Diehl, J. Alan, Ruggero, Davide, and Koumenis, Constantinos

Published
2019
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47. Loss of p19Arf promotes fibroblast survival during leucine deprivation

Author

Roby, Kerry C., primary, Lieberman, Allyson, additional, Kim, Bang-Jin, additional, Rodríguez, Nicole Zaragoza, additional, Posimo, Jessica M., additional, Tsang, Tiffany, additional, Verginadis, Ioannis I., additional, Puré, Ellen, additional, Brady, Donita C., additional, Koumenis, Constantinos, additional, and Ryeom, Sandra, additional

Published
2022
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