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1. Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer

Author

Park, Yeon Hee, Im, Seock-Ah, Park, Kyunghee, Wen, Ji, Lee, Kyung-Hun, Choi, Yoon-La, Lee, Won-Chul, Min, Ahrum, Bonato, Vinicius, Park, Seri, Ram, Sripad, Lee, Dae-Won, Kim, Ji-Yeon, Lee, Su Kyeong, Lee, Won-Woo, Lee, Jisook, Kim, Miso, Kim, Hyun Seon, Weinrich, Scott L., Ryu, Han Suk, Kim, Tae Yong, Dann, Stephen, Kim, Yu-Jin, Fernandez, Diane R., Koh, Jiwon, Wang, Shuoguo, Park, Song Yi, Deng, Shibing, Powell, Eric, Ravi, Rupesh Kanchi, Bienkowska, Jadwiga, Rejto, Paul A., Park, Woong-Yang, and Kan, Zhengyan

Published
2023
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2. Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib

Author

Zhu, Zhou, Turner, Nicholas C., Loi, Sherene, André, Fabrice, Martin, Miguel, Diéras, Véronique, Gelmon, Karen A., Harbeck, Nadia, Zhang, Cathy, Cao, Joan Q., Yan, Zhengming, Lu, Dongrui R., Wei, Ping, VanArsdale, Todd L., Rejto, Paul A., Huang, Xin, Rugo, Hope S., Loibl, Sibylle, Cristofanilli, Massimo, Finn, Richard S., and Liu, Yuan

Published
2022
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3. Preclinical Evaluation of 89Zr-Df-IAB22M2C PET as an Imaging Biomarker for the Development of the GUCY2C-CD3 Bispecific PF-07062119 as a T Cell Engaging Therapy

Author

Maresca, Kevin P., Chen, Jianqing, Mathur, Divya, Giddabasappa, Anand, Root, Adam, Narula, Jatin, King, Lindsay, Schaer, David, Golas, Jonathan, Kobylarz, Keith, Rosfjord, Edward, Keliher, Edmund, Chen, Laigao, Ram, Sripad, Pickering, Eve H., Hardwick, James S., Rejto, Paul A., Hussein, Amira, Ilovich, Ohad, Staton, Kevin, Wilson, Ian, and McCarthy, Timothy J.

Published
2021
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4. Pancreatic Cancer Action Network's SPARK: A Cloud-Based Patient Health Data and Analytics Platform for Pancreatic Cancer

Author

Abdilleh, Kawther, primary, Khalid, Omar, additional, Ladnier, Dennis, additional, Wan, Wenshuai, additional, Seepo, Sara, additional, Rupp, Garrett, additional, Corelj, Valentin, additional, Worman, Zelia F., additional, Sain, Divya, additional, DiGiovanna, Jack, additional, Press, Bruce, additional, Chandrashekhar, Satty, additional, Collisson, Eric, additional, Cui, Karen Y., additional, Maitra, Anirban, additional, Rejto, Paul A., additional, White, Kevin P., additional, Matrisian, Lynn, additional, and Doss, Sudheer, additional

Published
2024
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5. Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome

Author

Park, Yeon Hee, Lal, Samir, Lee, Jeong Eon, Choi, Yoon-La, Wen, Ji, Ram, Sripad, Ding, Ying, Lee, Soo-Hyeon, Powell, Eric, Lee, Se Kyung, Yu, Jong Han, Ching, Keith A., Nam, Jae-Yong, Kim, Seok Won, Nam, Seok Jin, Kim, Ji-Yeon, Cho, Soo Youn, Park, Seri, Kim, Jinho, Hwang, Soohyn, Kim, Yu Jin, Bonato, Vinicius, Fernandez, Diane, Deng, Shibing, Wang, Shuoguo, Shin, Hyuntae, Kang, Eun-Suk, Park, Woong-Yang, Rejto, Paul A., Bienkowska, Jadwiga, and Kan, Zhengyan

Published
2020
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8. Supplementary Table 4 from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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9. Data from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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10. Supplementary Figure 1 from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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11. Data from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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12. Supplementary Table 2 from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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13. Supplementary Table 2 from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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14. Supplementary Figure 2 from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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15. Supplementary Information from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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16. Supplementary Figure Legend from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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17. Supplementary Figure 3 from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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18. Supplementary Figure Legends 1-3, Table Legends 1-4 from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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19. Supplementary Material: DLDA Classifier IGF Signature from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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20. Supplementary Material: DLDA classifiers IGF Pathway Score from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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21. Supplementary Table 4 from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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22. Supplementary Figure 1 from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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23. Supplementary Table 3 from An Integrated Genomic Approach to Identify Predictive Biomarkers of Response to the Aurora Kinase Inhibitor PF-03814735

Author

Hook, Kenneth E., primary, Garza, Scott J., primary, Lira, Maruja E., primary, Ching, Keith A., primary, Lee, Nathan V., primary, Cao, Joan, primary, Yuan, Jing, primary, Ye, Jingjing, primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, Christensen, James G., primary, and Pavlicek, Adam, primary

Published
2023
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24. Supplementary Table 1 from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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25. Supplementary Table 3 from Molecular Predictors of Sensitivity to the Insulin-like Growth Factor 1 Receptor Inhibitor Figitumumab (CP-751,871)

Author

Pavlicek, Adam, primary, Lira, Maruja E., primary, Lee, Nathan V., primary, Ching, Keith A., primary, Ye, Jingjing, primary, Cao, Joan, primary, Garza, Scott J., primary, Hook, Kenneth E., primary, Ozeck, Mark, primary, Shi, Stephanie T., primary, Yuan, Jing, primary, Zheng, Xianxian, primary, Rejto, Paul A., primary, Kan, Julie L.C., primary, and Christensen, James G., primary

Published
2023
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26. Supplementary Figures 1-13 from PEST Domain Mutations in Notch Receptors Comprise an Oncogenic Driver Segment in Triple-Negative Breast Cancer Sensitive to a γ-Secretase Inhibitor

Author

Wang, Kai, primary, Zhang, Qin, primary, Li, Danan, primary, Ching, Keith, primary, Zhang, Cathy, primary, Zheng, Xianxian, primary, Ozeck, Mark, primary, Shi, Stephanie, primary, Li, Xiaorong, primary, Wang, Hui, primary, Rejto, Paul, primary, Christensen, James, primary, and Olson, Peter, primary

Published
2023
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27. Supplemental Materials and Methods from PEST Domain Mutations in Notch Receptors Comprise an Oncogenic Driver Segment in Triple-Negative Breast Cancer Sensitive to a γ-Secretase Inhibitor

Author

Wang, Kai, primary, Zhang, Qin, primary, Li, Danan, primary, Ching, Keith, primary, Zhang, Cathy, primary, Zheng, Xianxian, primary, Ozeck, Mark, primary, Shi, Stephanie, primary, Li, Xiaorong, primary, Wang, Hui, primary, Rejto, Paul, primary, Christensen, James, primary, and Olson, Peter, primary

Published
2023
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28. Supplementary Methods from Biomarker and Pharmacologic Evaluation of the γ-Secretase Inhibitor PF-03084014 in Breast Cancer Models

Author

Zhang, Cathy C., primary, Pavlicek, Adam, primary, Zhang, Qin, primary, Lira, Maruja E., primary, Painter, Cory L., primary, Yan, Zhengming, primary, Zheng, Xianxian, primary, Lee, Nathan V., primary, Ozeck, Mark, primary, Qiu, Ming, primary, Zong, Qing, primary, Lappin, Patrick B., primary, Wong, Anthony, primary, Rejto, Paul A., primary, Smeal, Tod, primary, and Christensen, James G., primary

Published
2023
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29. Supplementary Figures 1 - 5 from Biomarker and Pharmacologic Evaluation of the γ-Secretase Inhibitor PF-03084014 in Breast Cancer Models

Author

Zhang, Cathy C., primary, Pavlicek, Adam, primary, Zhang, Qin, primary, Lira, Maruja E., primary, Painter, Cory L., primary, Yan, Zhengming, primary, Zheng, Xianxian, primary, Lee, Nathan V., primary, Ozeck, Mark, primary, Qiu, Ming, primary, Zong, Qing, primary, Lappin, Patrick B., primary, Wong, Anthony, primary, Rejto, Paul A., primary, Smeal, Tod, primary, and Christensen, James G., primary

Published
2023
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32. Abstract A008: PanCAN SPARK: A cloud-based health data integration platform for pancreatic cancer data

Author

Abdilleh, Kawther, primary, Khalid, Omar, additional, Ladnier, Dennis, additional, Wan, Wenshuai, additional, Seepo, Sara, additional, Rupp, Garrett, additional, Corelj, Valentin, additional, Worman, Zelia F., additional, Press, Bruce, additional, DiGiovanna, Jack, additional, Chandrashekhar, Satty, additional, Collisson, Eric, additional, Cui, Karen, additional, Maitra, Anirban, additional, Rejto, Paul A., additional, White, Kevin, additional, Matrisian, Lynn, additional, and Doss, Sudheer, additional

Published
2022
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35. Additional file 6 of Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer

Author

Park, Yeon Hee, Im, Seock-Ah, Park, Kyunghee, Wen, Ji, Lee, Kyung-Hun, Choi, Yoon-La, Lee, Won-Chul, Min, Ahrum, Bonato, Vinicius, Park, Seri, Ram, Sripad, Lee, Dae-Won, Kim, Ji-Yeon, Lee, Su Kyeong, Lee, Won-Woo, Lee, Jisook, Kim, Miso, Kim, Hyun Seon, Weinrich, Scott L., Ryu, Han Suk, Kim, Tae Yong, Dann, Stephen, Kim, Yu-Jin, Fernandez, Diane R., Koh, Jiwon, Wang, Shuoguo, Park, Song Yi, Deng, Shibing, Powell, Eric, Ravi, Rupesh Kanchi, Bienkowska, Jadwiga, Rejto, Paul A., Park, Woong-Yang, and Kan, Zhengyan

Abstract

Additional file 6. Fig. S1. Kaplan-Meier plots of poor prognostic biomarkers. Fig. S2. Characteristics of the HRD-high cluster. Fig. S3. Characteristics of HRD-high tumors co-occurring with TP53 mutation. Fig. S4. Kaplan-Meier plots of expression-based prognosis markers. Fig. S5. Proliferative cluster enriched in poor prognostic markers. Fig. S6. Integrative analysis identified distinct prognostic clusters. Fig. S7. Molecular characteristics of integrative clusters. Fig. S8. Subtype switching driven by changes in PAM50 score composition. Fig. S9. Increased tumor growth and proliferation at PD. Fig. S10. IHC analysis of cell cycle markers. Fig. S11. Landscape of PD-specific genomic alterations. Fig. S12. RB1 LOF associated with increased APOBEC signature at PD. Fig. S13. APOBEC signature enriched in PD-specific tumor subclones.

Published
2023
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36. Abstract PD2-08: Serial genomic profiling reveals molecular mechanisms of breast cancer resistance to palbociclib

Author

Kan, Zhengyan, primary, Im, Seock-Ah, additional, Park, Kyunghee, additional, Wen, Ji, additional, Lee, Kyung-Hun, additional, Choi, Yoon-La, additional, Lee, Won-Chul, additional, Min, Ahrum, additional, Bonato, Vinicius, additional, Park, Seri, additional, Ram, Sripad, additional, Lee, Dae-Won, additional, Kim, Ji-Yeon, additional, Lee, Su Kyeong, additional, Lee, Won-Woo, additional, Lee, Jisook, additional, Kim, Miso, additional, Weinrich, Scott L., additional, Ryu, Han Suk, additional, Kim, Tae Yong, additional, Dann, Stephen, additional, Fernandez, Diane, additional, Koh, Jiwon, additional, Park, Song Yi, additional, Deng, Shibing, additional, Powell, Eric, additional, Ravi, Rupesh Kanchi, additional, Bienkowska, Jadwiga, additional, Rejto, Paul A., additional, Park, Woong-Yang, additional, and Park, Yeon Hee, additional

Published
2022
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41. MOESM2 of Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors

Author

Wenyan Zhong, Myers, Jeremy, Wang, Fang, Wang, Kai, Lucas, Justin, Rosfjord, Edward, Lucas, Judy, Hooper, Andrea, Yang, Sharon, Lemon, Lu, Guffroy, Magali, May, Chad, Bienkowska, Jadwiga, and Rejto, Paul

Abstract

Additional file 2: Figure S1. Mutation landscape of syngeneic models and types of somatic variants for each model. Figure S2. A. Ratio of Ts (Transition) to Tv (Transversion) substitution mutation in each syngeneic model; dashed lines represent maximum, median and minimum of median Ts/Tv from each human tumor types (data from (Alexandrov et al. 2013)) respectively. B. Single nucleotide mutation changes in each syngeneic model. Figure S3. E-cadherin and vimentin stain in syngeneic models. Figure S4. A. Correlation of neoantigen with mutational load in syngeneic models. B. Correlation of neoantigen with cytolytic activity in syngeneic models. The correlation was calculated using spearman method in R. numMutation: number of missense mutation. Figure S5. Response of syngeneic tumor models to anti-CTLA4, or anti PD-1. All mice were dosed intravenously. Individual tumor volumes are shown for 10 mice treated with PBS (black) or 10 mg/kg anti-CTLA4 (9H10) (red trace), or 10 mg/kg anti-PD-1 (RMP 1–14) (blue trace). All 10 mice bearing CT26 tumors dosed with anti-CTLA4 had no measurable tumor from study day 25 until measurements ended on study day 238. Comparison of mean tumor volumes was analyzed using log-transformed ANOVA. P-values are shown if there was a statistical difference between vehicle and antibody-treated groups. n.s. not significant. Figure S6. A. Expression of Gzma and Prf1 in syngeneic model grown in vitro (Cell) and in vivo (Tissue) across models based on protein expression. B. Cytolytic activity of syngeneic models. Cytolytic activity (CYT) is defined as the log-average (geometric mean) of Gzma and Prf1 protein expression. C. Protein expression of Gzma in soluble fraction. LFQ: label free quantitation. Figure S7. Gene expression of β-catenin, β-catenin target genes (gene list from (Spranger et al. 2015)) and epigenetic modulators (Ezh2, Dnmt1) across syngeneic models. Figure S8. CTLA4 expression in syngeneic in vivo tumor samples.

Published
2020
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43. Preclinical Evaluation of 89Zr-Df-IAB22M2C PET as an Imaging Biomarker for the Development of the GUCY2C-CD3 Bispecific PF-07062119 as a T Cell Engaging Therapy.

Author

Maresca, Kevin P., Chen, Jianqing, Mathur, Divya, Giddabasappa, Anand, Root, Adam, Narula, Jatin, King, Lindsay, Schaer, David, Golas, Jonathan, Kobylarz, Keith, Rosfjord, Edward, Keliher, Edmund, Chen, Laigao, Ram, Sripad, Pickering, Eve H., Hardwick, James S., Rejto, Paul A., Hussein, Amira, Ilovich, Ohad, and Staton, Kevin

Subjects
POSITRON emission tomography, T cells, COMPUTED tomography, BISPECIFIC antibodies, CELLULAR therapy, COLORECTAL cancer
Abstract

Purpose: A sensitive and specific imaging biomarker to monitor immune activation and quantify pharmacodynamic responses would be useful for development of immunomodulating anti-cancer agents. PF-07062119 is a T cell engaging bispecific antibody that binds to CD3 and guanylyl cyclase C, a protein that is over-expressed by colorectal cancers. Here, we used 89Zr-Df-IAB22M2C (89Zr-Df-Crefmirlimab), a human CD8-specific minibody to monitor CD8+ T cell infiltration into tumors by positron emission tomography. We investigated the ability of 89Zr-Df-IAB22M2C to track anti-tumor activity induced by PF-07062119 in a human CRC adoptive transfer mouse model (with injected activated/expanded human T cells), as well as the correlation of tumor radiotracer uptake with CD8+ immunohistochemical staining. Procedures: NOD SCID gamma mice bearing human CRC LS1034 tumors were treated with four different doses of PF-07062119, or a non-targeted CD3 BsAb control, and imaged with 89Zr-Df-IAB22M2C PET at days 4 and 9. Following PET/CT imaging, mice were euthanized and dissected for ex vivo distribution analysis of 89Zr-Df-IAB22M2C in tissues on days 4 and 9, with additional data collected on day 6 (supplementary). Data were analyzed and reported as standard uptake value and %ID/g for in vivo imaging and ex vivo tissue distribution. In addition, tumor tissues were evaluated by immunohistochemistry for CD8+ T cells. Results: The results demonstrated substantial mean uptake of 89Zr-Df-IAB22M2C (%ID/g) in PF-07062119-treated tumors, with significant increases in comparison to non-targeted BsAb-treated controls, as well as PF-07062119 dose-dependent responses over time of treatment. A moderate correlation was observed between tumor tissue radioactivity uptake and CD8+ cell density, demonstrating the value of the imaging agent for non-invasive assessment of intra-tumoral CD8+ T cells and the mechanism of action for PF-07062119. Conclusion: Immune-imaging technologies for quantitative cellular measures would be a valuable biomarker in immunotherapeutic clinical development. We demonstrated a qualification of 89Zr-IAB22M2C PET to evaluate PD responses (mice) to a novel immunotherapeutic. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Monte Carlo simulations of HIV-1 protease binding dynamics and thermodynamics with ensembles of protein conformations: Incorporating protein flexibility in deciphering mechanisms of molecular recognition

Author

Verkhivker, Gennady M., primary, Bouzida, Djamal, additional, Gehlhaar, Daniel K., additional, Rejto, Paul A., additional, Schaffer, Lana, additional, Arthurs, Sandra, additional, Colson, Anthony B., additional, Freer, Stephan T., additional, Larson, Veda, additional, Luty, Brock A., additional, Marrone, Tami, additional, and Rose, Peter W., additional

Published
2001
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