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Your search keyword '"Ian D. Waddell"' showing total 8 results
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8 results on '"Ian D. Waddell"'

1. Figure S7 from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Supplementary Fig S7 describes western blot and RTPCR of PARG in modified shPARG cells.

Published
2023
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2. Data from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have an average survival of less than 1 year, underscoring the importance of evaluating novel targets with matched targeted agents. We recently identified that poly (ADP) ribose glycohydrolase (PARG) is a strong candidate target due to its dependence on the pro-oncogenic mRNA stability factor HuR (ELAVL1). Here, we evaluated PARG as a target in PDAC models using both genetic silencing of PARG and established small-molecule PARG inhibitors (PARGi), PDDX-01/04. Homologous repair–deficient cells compared with homologous repair–proficient cells were more sensitive to PARGi in vitro. In vivo, silencing of PARG significantly decreased tumor growth. PARGi synergized with DNA-damaging agents (i.e., oxaliplatin and 5-fluorouracil), but not with PARPi therapy. Mechanistically, combined PARGi and oxaliplatin treatment led to persistence of detrimental PARylation, increased expression of cleaved caspase-3, and increased γH2AX foci. In summary, these data validate PARG as a relevant target in PDAC and establish current therapies that synergize with PARGi.Significance:PARG is a potential target in pancreatic cancer as a single-agent anticancer therapy or in combination with current standard of care.

Published
2023
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3. Figure S3 from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Supplementary Figure S3 describes synthetic lethality of olaparib with siDDR in PDAC.

Published
2023
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4. Figure S2 from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Supplementary Fig S2 describes protein expression of PARG across PDAC cell models and drug sensitivity of PDAC, KPC, DLD and RKO cells to olaparib and/or PDDX-001.

Published
2023
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5. Figure S5 from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Supplementary Figure S5 describes PARG ELISA.

Published
2023
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6. Table 1 from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Supplementary Table 1 describes BRCA and KRAS status of PDX models and IC50 of PDDX-001 and olaparib in PDAC/PDX lines

Published
2023
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7. Figure S4 from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Supplementary Fig S4 describes synergy plots in Hs 766T cells.

Published
2023
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8. Figure S1 from Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer

Author

Jonathan R. Brody, Allan M. Jordan, Dominic I. James, Donald Ogilvie, Michael J. Pishvaian, Talia Golan, Kenneth P. Olive, Jordan M. Winter, Charles J. Yeo, Dikla Atias, Yulia Glick Gorman, Chani Stossel, Maria Raitses-Gurevich, Ian D. Waddell, Kate M. Smith, Cinthya Yabar Lowder, Christopher W. Schultz, Joseph Cozzitorto, Avinoam Nevler, AnnJosette Ramirez, Saswati N. Chand, Grace A. McCarthy, Lebaron C. Agostini, and Aditi Jain

Abstract

Supplementary Figure S1 describes mRNA and protein expression of PARG in shPARG models and in vitro sensitivity to oxaliplatin.

Published
2023
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