Search

Your search keyword '"Rankin, Erinn B."' showing total 48 results
Start Over Author "Rankin, Erinn B." Publication Year Range Last 3 years
48 results on '"Rankin, Erinn B."'

1. Dosimetric calibration of an anatomically specific ultra-high dose rate electron irradiation platform for preclinical FLASH radiobiology experiments

Author

Wang, Jinghui, Melemenidis, Stavros, Manjappa, Rakesh, Viswanathan, Vignesh, Ashraf, Ramish M., Levy, Karen, Skinner, Lawrie, Soto, Luis A., Chow, Stephanie, Lau, Brianna, Ko, Ryan B., Graves, Edward E., Yu, Amy S., Bush, Karl K., Surucu, Murat, Rankin, Erinn B., Loo Jr, Billy W., Schüler, Emil, and Maxim, Peter G.

Subjects
Physics - Medical Physics
Abstract

We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate (UHDR) irradiation to mice and cell-culture FLASH radiobiology experiments. UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film at the entry surface of the mice. The setup for conventional (CONV) dose rate irradiation was similar but the source-to-surface distance was longer. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions. The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 MeV and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. Use of relay gating for pulse control initially led to a delivery failure rate of 20% ($+/-$ 1 pulse); adjustments to account for the linac latency improved this rate to <1/20. Beam field sizes for two anatomically specific mouse collimators (4x4 $cm^2$ for whole-abdomen and 1.5x1.5 $cm^2$ for unilateral lung irradiation) were accurate within <5% and had low radiation leakage (<4%). Normalizing the dose at the center of the mouse (~0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with >95% agreement. We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR applications., Comment: Jinghui Wang and Stavros Melemenidis are co-first authors, and Emil Sch\"uler and Peter G. Maxim are co-senior/co-corresponding authors

Published
2023

3. The controversial role and therapeutic development of the m6A demethylase FTO in renal cell carcinoma

Author

Zhang, Dalin, Wornow, Sarah, Peehl, Donna M, Rankin, Erinn B, and Brooks, James D

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Kidney Disease, Cancer, 2.1 Biological and endogenous factors, Aetiology, m(6)A RNA demethylase, FTO, Renal cell carcinoma, Cancer progression, Prognosis, Inhibitors, Biochemistry and Cell Biology, Clinical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Fat mass and obesity-associated (FTO) protein, the first m6A demethylase identified in 2011, regulates multiple aspects of RNA biology including splicing, localization, stability, and translation. Accumulating data show that FTO is involved in numerous physiological processes and is implicated in multiple cancers including renal cell carcinoma (RCC). However, the exact role of FTO in RCC remains controversial. Some studies demonstrated that decreased FTO expression was associated with aggressive clinical features and shorter overall survival in clear cell RCC (ccRCC) patients, while others found that FTO inhibition selectively reduced the growth and survival of VHL-deficient ccRCC cells in vitro and in vivo. Here, we review the evidence supporting either a promoting or suppressive role of FTO in kidney cancers, the mechanisms of action of FTO, and recent progress in developing FTO inhibitors.

Published
2022

5. 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
Full Text
View/download PDF

6. Supplementary Data from Neutralization of PD-L2 is Essential for Overcoming Immune Checkpoint Blockade Resistance in Ovarian Cancer

Author

Miao, Yu Rebecca, primary, Thakkar, Kaushik N., primary, Qian, Jin, primary, Kariolis, Mihalis S., primary, Huang, Wei, primary, Nandagopal, Saravanan, primary, Yang, Teddy Tat Chi, primary, Diep, Anh N., primary, Cherf, Gerald Maxwell, primary, Xu, Yu, primary, Moon, Eui Jung, primary, Xiao, Yiren, primary, Alemany, Haizea, primary, Li, Tiane, primary, Yu, Wenhua, primary, Wei, Bo, primary, Rankin, Erinn B., primary, and Giaccia, Amato J., primary

Published
2024
Full Text
View/download PDF

7. Data from Neutralization of PD-L2 is Essential for Overcoming Immune Checkpoint Blockade Resistance in Ovarian Cancer

Author

Miao, Yu Rebecca, primary, Thakkar, Kaushik N., primary, Qian, Jin, primary, Kariolis, Mihalis S., primary, Huang, Wei, primary, Nandagopal, Saravanan, primary, Yang, Teddy Tat Chi, primary, Diep, Anh N., primary, Cherf, Gerald Maxwell, primary, Xu, Yu, primary, Moon, Eui Jung, primary, Xiao, Yiren, primary, Alemany, Haizea, primary, Li, Tiane, primary, Yu, Wenhua, primary, Wei, Bo, primary, Rankin, Erinn B., primary, and Giaccia, Amato J., primary

Published
2024
Full Text
View/download PDF

9. Data from Metabolic Profiling Reveals a Dependency of Human Metastatic Breast Cancer on Mitochondrial Serine and One-Carbon Unit Metabolism

Author

Li, Albert M., primary, Ducker, Gregory S., primary, Li, Yang, primary, Seoane, Jose A., primary, Xiao, Yiren, primary, Melemenidis, Stavros, primary, Zhou, Yiren, primary, Liu, Ling, primary, Vanharanta, Sakari, primary, Graves, Edward E., primary, Rankin, Erinn B., primary, Curtis, Christina, primary, Massagué, Joan, primary, Rabinowitz, Joshua D., primary, Thompson, Craig B., primary, and Ye, Jiangbin, primary

Published
2023
Full Text
View/download PDF

10. Supplementary Data from GAS6/AXL Inhibition Enhances Ovarian Cancer Sensitivity to Chemotherapy and PARP Inhibition through Increased DNA Damage and Enhanced Replication Stress

Author

Mullen, Mary M., primary, Lomonosova, Elena, primary, Toboni, Michael D., primary, Oplt, Alyssa, primary, Cybulla, Emily, primary, Blachut, Barbara, primary, Zhao, Peinan, primary, Noia, Hollie, primary, Wilke, Daniel, primary, Rankin, Erinn B., primary, Kuroki, Lindsay M., primary, Hagemann, Andrea R., primary, Hagemann, Ian S., primary, McCourt, Carolyn K., primary, Thaker, Premal H., primary, Mutch, David G., primary, Powell, Matthew A., primary, Mosammaparast, Nima, primary, Vindigni, Alessandro, primary, and Fuh, Katherine C., primary

Published
2023
Full Text
View/download PDF

11. Data from GAS6/AXL Inhibition Enhances Ovarian Cancer Sensitivity to Chemotherapy and PARP Inhibition through Increased DNA Damage and Enhanced Replication Stress

Author

Mullen, Mary M., primary, Lomonosova, Elena, primary, Toboni, Michael D., primary, Oplt, Alyssa, primary, Cybulla, Emily, primary, Blachut, Barbara, primary, Zhao, Peinan, primary, Noia, Hollie, primary, Wilke, Daniel, primary, Rankin, Erinn B., primary, Kuroki, Lindsay M., primary, Hagemann, Andrea R., primary, Hagemann, Ian S., primary, McCourt, Carolyn K., primary, Thaker, Premal H., primary, Mutch, David G., primary, Powell, Matthew A., primary, Mosammaparast, Nima, primary, Vindigni, Alessandro, primary, and Fuh, Katherine C., primary

Published
2023
Full Text
View/download PDF

12. Supplementary Data from Metabolic Profiling Reveals a Dependency of Human Metastatic Breast Cancer on Mitochondrial Serine and One-Carbon Unit Metabolism

Author

Li, Albert M., primary, Ducker, Gregory S., primary, Li, Yang, primary, Seoane, Jose A., primary, Xiao, Yiren, primary, Melemenidis, Stavros, primary, Zhou, Yiren, primary, Liu, Ling, primary, Vanharanta, Sakari, primary, Graves, Edward E., primary, Rankin, Erinn B., primary, Curtis, Christina, primary, Massagué, Joan, primary, Rabinowitz, Joshua D., primary, Thompson, Craig B., primary, and Ye, Jiangbin, primary

Published
2023
Full Text
View/download PDF

13. Supplementary Methods from Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

Author

Natarajan, Suchitra, primary, Foreman, Kaitlyn M., primary, Soriano, Michaela I., primary, Rossen, Ninna S., primary, Shehade, Hussein, primary, Fregoso, Daniel R., primary, Eggold, Joshua T., primary, Krishnan, Venkatesh, primary, Dorigo, Oliver, primary, Krieg, Adam J., primary, Heilshorn, Sarah C., primary, Sinha, Subarna, primary, Fuh, Katherine C., primary, and Rankin, Erinn B., primary

Published
2023
Full Text
View/download PDF

14. Supplementary Figures and Legends from Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

Author

Natarajan, Suchitra, primary, Foreman, Kaitlyn M., primary, Soriano, Michaela I., primary, Rossen, Ninna S., primary, Shehade, Hussein, primary, Fregoso, Daniel R., primary, Eggold, Joshua T., primary, Krishnan, Venkatesh, primary, Dorigo, Oliver, primary, Krieg, Adam J., primary, Heilshorn, Sarah C., primary, Sinha, Subarna, primary, Fuh, Katherine C., primary, and Rankin, Erinn B., primary

Published
2023
Full Text
View/download PDF

15. Supplemental Table 2 from Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma

Author

Jiang, Haowen, primary, Greathouse, Rachel L., primary, Tiche, Sarah Jane, primary, Zhao, Man, primary, He, Bo, primary, Li, Yang, primary, Li, Albert M., primary, Forgo, Balint, primary, Yip, Michaela, primary, Li, Allison, primary, Shih, Moriah, primary, Banuelos, Selene, primary, Zhou, Meng-Ning, primary, Gruber, Joshua J., primary, Rankin, Erinn B., primary, Hu, Zhen, primary, Shimada, Hiroyuki, primary, Chiu, Bill, primary, and Ye, Jiangbin, primary

Published
2023
Full Text
View/download PDF

16. Supplementary Table S1 from Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

Author

Natarajan, Suchitra, primary, Foreman, Kaitlyn M., primary, Soriano, Michaela I., primary, Rossen, Ninna S., primary, Shehade, Hussein, primary, Fregoso, Daniel R., primary, Eggold, Joshua T., primary, Krishnan, Venkatesh, primary, Dorigo, Oliver, primary, Krieg, Adam J., primary, Heilshorn, Sarah C., primary, Sinha, Subarna, primary, Fuh, Katherine C., primary, and Rankin, Erinn B., primary

Published
2023
Full Text
View/download PDF

17. Supplementary Data from Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma

Author

Jiang, Haowen, primary, Greathouse, Rachel L., primary, Tiche, Sarah Jane, primary, Zhao, Man, primary, He, Bo, primary, Li, Yang, primary, Li, Albert M., primary, Forgo, Balint, primary, Yip, Michaela, primary, Li, Allison, primary, Shih, Moriah, primary, Banuelos, Selene, primary, Zhou, Meng-Ning, primary, Gruber, Joshua J., primary, Rankin, Erinn B., primary, Hu, Zhen, primary, Shimada, Hiroyuki, primary, Chiu, Bill, primary, and Ye, Jiangbin, primary

Published
2023
Full Text
View/download PDF

18. Data from Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

Author

Natarajan, Suchitra, primary, Foreman, Kaitlyn M., primary, Soriano, Michaela I., primary, Rossen, Ninna S., primary, Shehade, Hussein, primary, Fregoso, Daniel R., primary, Eggold, Joshua T., primary, Krishnan, Venkatesh, primary, Dorigo, Oliver, primary, Krieg, Adam J., primary, Heilshorn, Sarah C., primary, Sinha, Subarna, primary, Fuh, Katherine C., primary, and Rankin, Erinn B., primary

Published
2023
Full Text
View/download PDF

19. Supplemental Table 4 from Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma

Author

Jiang, Haowen, primary, Greathouse, Rachel L., primary, Tiche, Sarah Jane, primary, Zhao, Man, primary, He, Bo, primary, Li, Yang, primary, Li, Albert M., primary, Forgo, Balint, primary, Yip, Michaela, primary, Li, Allison, primary, Shih, Moriah, primary, Banuelos, Selene, primary, Zhou, Meng-Ning, primary, Gruber, Joshua J., primary, Rankin, Erinn B., primary, Hu, Zhen, primary, Shimada, Hiroyuki, primary, Chiu, Bill, primary, and Ye, Jiangbin, primary

Published
2023
Full Text
View/download PDF

20. Data from S100A10 Is a Critical Mediator of GAS6/AXL–Induced Angiogenesis in Renal Cell Carcinoma

Author

Xiao, Yiren, primary, Zhao, Hongjuan, primary, Tian, Lei, primary, Nolley, Rosalie, primary, Diep, Anh N., primary, Ernst, Anne, primary, Fuh, Katherine C., primary, Miao, Yu Rebecca, primary, von Eyben, Rie, primary, Leppert, John T., primary, Brooks, James D., primary, Peehl, Donna M., primary, Giaccia, Amato J., primary, and Rankin, Erinn B., primary

Published
2023
Full Text
View/download PDF

21. Supplemental Table 3 from Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma

Author

Jiang, Haowen, primary, Greathouse, Rachel L., primary, Tiche, Sarah Jane, primary, Zhao, Man, primary, He, Bo, primary, Li, Yang, primary, Li, Albert M., primary, Forgo, Balint, primary, Yip, Michaela, primary, Li, Allison, primary, Shih, Moriah, primary, Banuelos, Selene, primary, Zhou, Meng-Ning, primary, Gruber, Joshua J., primary, Rankin, Erinn B., primary, Hu, Zhen, primary, Shimada, Hiroyuki, primary, Chiu, Bill, primary, and Ye, Jiangbin, primary

Published
2023
Full Text
View/download PDF

22. Supplemental Table 1 from Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma

Author

Jiang, Haowen, primary, Greathouse, Rachel L., primary, Tiche, Sarah Jane, primary, Zhao, Man, primary, He, Bo, primary, Li, Yang, primary, Li, Albert M., primary, Forgo, Balint, primary, Yip, Michaela, primary, Li, Allison, primary, Shih, Moriah, primary, Banuelos, Selene, primary, Zhou, Meng-Ning, primary, Gruber, Joshua J., primary, Rankin, Erinn B., primary, Hu, Zhen, primary, Shimada, Hiroyuki, primary, Chiu, Bill, primary, and Ye, Jiangbin, primary

Published
2023
Full Text
View/download PDF

23. Figure S5 from S100A10 Is a Critical Mediator of GAS6/AXL–Induced Angiogenesis in Renal Cell Carcinoma

Author

Xiao, Yiren, primary, Zhao, Hongjuan, primary, Tian, Lei, primary, Nolley, Rosalie, primary, Diep, Anh N., primary, Ernst, Anne, primary, Fuh, Katherine C., primary, Miao, Yu Rebecca, primary, von Eyben, Rie, primary, Leppert, John T., primary, Brooks, James D., primary, Peehl, Donna M., primary, Giaccia, Amato J., primary, and Rankin, Erinn B., primary

Published
2023
Full Text
View/download PDF

24. Supplementary Data from Induced Tumor Heterogeneity Reveals Factors Informing Radiation and Immunotherapy Combinations

Author

Aguilera, Todd A., primary, Elghonaimy, Eslam A., primary, Shehade, Hussein, primary, Rafat, Marjan, primary, Castellini, Laura, primary, Jiang, Dadi, primary, Kariolis, Mihalis, primary, Koong, Albert C., primary, Le, Quynh-Thu, primary, Ellies, Lesley G., primary, Rankin, Erinn B., primary, Graves, Edward E., primary, and Giaccia, Amato J., primary

Published
2023
Full Text
View/download PDF

25. Table from Induced Tumor Heterogeneity Reveals Factors Informing Radiation and Immunotherapy Combinations

Author

Aguilera, Todd A., primary, Elghonaimy, Eslam A., primary, Shehade, Hussein, primary, Rafat, Marjan, primary, Castellini, Laura, primary, Jiang, Dadi, primary, Kariolis, Mihalis, primary, Koong, Albert C., primary, Le, Quynh-Thu, primary, Ellies, Lesley G., primary, Rankin, Erinn B., primary, Graves, Edward E., primary, and Giaccia, Amato J., primary

Published
2023
Full Text
View/download PDF

26. Supplementary Tables from S100A10 Is a Critical Mediator of GAS6/AXL–Induced Angiogenesis in Renal Cell Carcinoma

Author

Xiao, Yiren, primary, Zhao, Hongjuan, primary, Tian, Lei, primary, Nolley, Rosalie, primary, Diep, Anh N., primary, Ernst, Anne, primary, Fuh, Katherine C., primary, Miao, Yu Rebecca, primary, von Eyben, Rie, primary, Leppert, John T., primary, Brooks, James D., primary, Peehl, Donna M., primary, Giaccia, Amato J., primary, and Rankin, Erinn B., primary

Published
2023
Full Text
View/download PDF

38. Serine starvation silences estrogen receptor signaling through histone hypoacetylation.

Author

Li, Albert M., Bo He, Karagiannis, Dimitris, Yang Li, Haowen Jiang, Srinivasan, Preethi, Ramirez, Yaniel, Meng-Ning Zhou, Curtis, Christina, Gruber, Joshua J., Chao Lu, Rankin, Erinn B., and Jiangbin Ye

Subjects
ESTROGEN receptors, SERINE, HISTONE acetylation, STARVATION, METABOLIC regulation
Abstract

Loss of estrogen receptor (ER) pathway activity promotes breast cancer progression, yet how this occurs remains poorly understood. Here, we show that serine starvation, a metabolic stress often found in breast cancer, represses estrogen receptor alpha (ERa) signaling by reprogramming glucose metabolism and epigenetics. Using isotope tracing and time-resolved metabolomic analyses, we demonstrate that serine is required to maintain glucose flux through glycolysis and the TCA cycle to support acetyl-CoA generation for histone acetylation. Consequently, limiting serine depletes histone H3 lysine 27 acetylation (H3K27ac), particularly at the promoter region of ER pathway genes including the gene encoding ERα, ESR1. Mechanistically, serine starvation impairs acetyl-CoA-dependent gene expression by inhibiting the entry of glycolytic carbon into the TCA cycle and down-regulating the mitochondrial citrate exporter SLC25A1, a critical enzyme in the production of nucleocytosolic acetyl-CoA from glucose. Consistent with this model, total H3K27ac and ERα expression are suppressed by SLC25A1 inhibition and restored by acetate, an alternate source of acetyl-CoA, in serine-free conditions. We thus uncover an unexpected role for serine in sustaining ER signaling through the regulation of acetyl-CoA metabolism. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

39. Correction: Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma

Author

Jiang, Haowen, primary, Greathouse, Rachel L., additional, Tiche, Sarah Jane, additional, Zhao, Man, additional, He, Bo, additional, Li, Yang, additional, Li, Albert M., additional, Forgo, Balint, additional, Yip, Michaela, additional, Li, Allison, additional, Shih, Moriah, additional, Banuelos, Selene, additional, Zhou, Meng-Ning, additional, Gruber, Joshua J., additional, Rankin, Erinn B., additional, Hu, Zhen, additional, Shimada, Hiroyuki, additional, Chiu, Bill, additional, and Ye, Jiangbin, additional

Published
2023
Full Text
View/download PDF

40. Human enteroids as a tool to study conventional and ultra-high dose rate radiation

Author

Klett, Katarina C, primary, Martin-Villa, Briana C, additional, Villarreal, Victoria S, additional, Melemenidis, Stavros, additional, Viswanathan, Vignesh, additional, Manjappa, Rakesh, additional, Ashraf, M Ramish, additional, Soto, Luis, additional, Lau, Brianna, additional, Dutt, Suparna, additional, Rankin, Erinn B, additional, Loo, Billy W, additional, and Heilshorn, Sarah C, additional

Published
2023
Full Text
View/download PDF

41. Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma

Author

Jiang, Haowen, primary, Greathouse, Rachel L., additional, Tiche, Sarah Jane, additional, Zhao, Man, additional, He, Bo, additional, Li, Yang, additional, Li, Albert M., additional, Forgo, Balint, additional, Yip, Michaela, additional, Li, Allison, additional, Shih, Moriah, additional, Banuelos, Selene, additional, Zhou, Meng-Ning, additional, Gruber, Joshua J., additional, Rankin, Erinn B., additional, Hu, Zhen, additional, Shimada, Hiroyuki, additional, Chiu, Bill, additional, and Ye, Jiangbin, additional

Published
2022
Full Text
View/download PDF

45. GAS6/AXL Inhibition Enhances Ovarian Cancer Sensitivity to Chemotherapy and PARP Inhibition through Increased DNA Damage and Enhanced Replication Stress

Author

Mullen, Mary M., primary, Lomonosova, Elena, additional, Toboni, Michael D., additional, Oplt, Alyssa, additional, Cybulla, Emily, additional, Blachut, Barbara, additional, Zhao, Peinan, additional, Noia, Hollie, additional, Wilke, Daniel, additional, Rankin, Erinn B., additional, Kuroki, Lindsay M., additional, Hagemann, Andrea R., additional, Hagemann, Ian S., additional, McCourt, Carolyn K., additional, Thaker, Premal H., additional, Mutch, David G., additional, Powell, Matthew A., additional, Mosammaparast, Nima, additional, Vindigni, Alessandro, additional, and Fuh, Katherine C., additional

Published
2022
Full Text
View/download PDF

46. Abdominopelvic FLASH Irradiation Improves PD-1 Immune Checkpoint Inhibition in Preclinical Models of Ovarian Cancer

Author

Eggold, Joshua T., primary, Chow, Stephanie, additional, Melemenidis, Stavros, additional, Wang, Jinghui, additional, Natarajan, Suchitra, additional, Loo, Phoebe E., additional, Manjappa, Rakesh, additional, Viswanathan, Vignesh, additional, Kidd, Elizabeth A., additional, Engleman, Edgar, additional, Dorigo, Oliver, additional, Loo, Billy W., additional, and Rankin, Erinn B., additional

Published
2022
Full Text
View/download PDF

47. Dosimetric calibration of anatomy‐specific ultra‐high dose rate electron irradiation platform for preclinical FLASH radiobiology experiments.

Author

Wang, Jinghui, Melemenidis, Stavros, Manjappa, Rakesh, Viswanathan, Vignesh, Ashraf, Ramish M., Levy, Karen, Skinner, Lawrie B., Soto, Luis A., Chow, Stephanie, Lau, Brianna, Ko, Ryan B., Graves, Edward E., Yu, Amy S., Bush, Karl K., Surucu, Murat, Rankin, Erinn B., Loo, Billy W. Jr., Schüler, Emil, and Maxim, Peter G.

Subjects
*IONIZATION chambers, *MONTE Carlo method, *LINEAR accelerators, *CHARGE measurement, *MEDICAL dosimetry
Abstract

Background Purpose Methods Results Conclusion FLASH radiation therapy (RT) offers a promising avenue for the broadening of the therapeutic index. However, to leverage the full potential of FLASH in the clinical setting, an improved understanding of the biological principles involved is critical. This requires the availability of specialized equipment optimized for the delivery of conventional (CONV) and ultra‐high dose rate (UHDR) irradiation for preclinical studies. One method to conduct such preclinical radiobiological research involves adapting a clinical linear accelerator configured to deliver both CONV and UHDR irradiation.We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra‐high dose rate irradiation to two anatomic sites in mice and for cell‐culture FLASH radiobiology experiments.Delivered doses of UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We also produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film measurements at the entry surface of the mice. The setup for conventional dose rate irradiation utilized the same collimation system but at increased source‐to‐surface distance. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions.The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. The use of relay gating for pulse control initially led to a delivery failure rate of 20% (± 1 pulse); adjustments to account for the linac latency improved this rate to < 1/20. Beam field sizes for two anatomically specific mouse collimators (4 × 4 cm2 for whole‐abdomen and 1.5 × 1.5 cm2 for unilateral lung irradiation) were accurate within < 5% and had low radiation leakage (< 4%). Normalizing the dose at the center of the mouse (∼0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with > 95% agreement.We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR irradiation applications. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

48. Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma.

Author

Jiang H, Greathouse RL, Tiche SJ, Zhao M, He B, Li Y, Li AM, Forgo B, Yip M, Li A, Shih M, Banuelos S, Zhou MN, Gruber JJ, Rankin EB, Hu Z, Shimada H, Chiu B, and Ye J

Subjects
Animals, Mice, beta Catenin genetics, Cell Line, Tumor, Ethanolamine pharmacology, Ethanolamine therapeutic use, Ethanolamines therapeutic use, Hypoxia drug therapy, Niclosamide pharmacology, Mitochondria drug effects, Mitochondria physiology, Cell Differentiation genetics, Epigenome genetics, Epigenome physiology, Neuroblastoma genetics, Neuroblastoma pathology, Warburg Effect, Oncologic drug effects
Abstract

The Warburg effect is the major metabolic hallmark of cancer. According to Warburg himself, the consequence of the Warburg effect is cell dedifferentiation. Therefore, reversing the Warburg effect might be an approach to restore cell differentiation in cancer. In this study, we used a mitochondrial uncoupler, niclosamide ethanolamine (NEN), to activate mitochondrial respiration, which induced neural differentiation in neuroblastoma cells. NEN treatment increased the NAD+/NADH and pyruvate/lactate ratios and also the α-ketoglutarate/2-hydroxyglutarate (2-HG) ratio. Consequently, NEN treatment induced promoter CpG island demethylation and epigenetic landscape remodeling, activating the neural differentiation program. In addition, NEN treatment upregulated p53 but downregulated N-Myc and β-catenin signaling in neuroblastoma cells. Importantly, even under hypoxia, NEN treatment remained effective in inhibiting 2-HG generation, promoting DNA demethylation, and suppressing hypoxia-inducible factor signaling. Dietary NEN intervention reduced tumor growth rate, 2-HG levels, and expression of N-Myc and β-catenin in tumors in an orthotopic neuroblastoma mouse model. Integrative analysis indicated that NEN treatment upregulated favorable prognosis genes and downregulated unfavorable prognosis genes, which were defined using multiple neuroblastoma patient datasets. Altogether, these results suggest that mitochondrial uncoupling is an effective metabolic and epigenetic therapy for reversing the Warburg effect and inducing differentiation in neuroblastoma., Significance: Targeting cancer metabolism using the mitochondrial uncoupler niclosamide ethanolamine leads to methylome reprogramming and differentiation in neuroblastoma, providing a therapeutic opportunity to reverse the Warburg effect and suppress tumor growth. See related commentary by Byrne and Bell, p.167., (©2022 American Association for Cancer Research.)

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results