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Your search keyword '"Pierre Olivier Frappart"' showing total 11 results
Start Over Author "Pierre Olivier Frappart" Publisher american association for cancer research (aacr)
11 results on '"Pierre Olivier Frappart"'

1. Supplementary Data from RINT1 Regulates SUMOylation and the DNA Damage Response to Preserve Cellular Homeostasis in Pancreatic Cancer

Author

Alexander Kleger, Pierre-Olivier Frappart, Thomas Seufferlein, Peter Möller, Hans A. Kestler, Sebastian Wiese, Volker Rasche, Konstantin M.J. Sparrer, Ewa K. Kaminska, Axel Fürstberger, Li Hao, Ninel Azoitei, Thomas J. Ettrich, André Lechel, Caterina Prelli Bozzo, Jeanette Scheible, Karolin Walter, Lukas Perkhofer, Elodie Roger, Stephanie E. Weissinger, Heike Wiese, Johann Gout, and Frank Arnold

Abstract

Contains a more detailed method section as well as all additional supplementary figures S1 to S8

Published
2023
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2. Figure S5 Tumour growth upon ATRi and Gemcitabine Treatment in Allografts model from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

Tumour growth upon ATRi and Gemcitabine Treatment in Allografts model

Published
2023
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3. Figure S2 from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

Tumour growth upon Olaparib and Gemcitabine Treatment in Allografts model

Published
2023
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4. Figure S4 Tumour growth upon ATRi and Gemcitabine Treatment in Allografts model from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

Tumour growth upon ATRi and Gemcitabine Treatment in Allografts model

Published
2023
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5. Data from RINT1 Regulates SUMOylation and the DNA Damage Response to Preserve Cellular Homeostasis in Pancreatic Cancer

Author

Alexander Kleger, Pierre-Olivier Frappart, Thomas Seufferlein, Peter Möller, Hans A. Kestler, Sebastian Wiese, Volker Rasche, Konstantin M.J. Sparrer, Ewa K. Kaminska, Axel Fürstberger, Li Hao, Ninel Azoitei, Thomas J. Ettrich, André Lechel, Caterina Prelli Bozzo, Jeanette Scheible, Karolin Walter, Lukas Perkhofer, Elodie Roger, Stephanie E. Weissinger, Heike Wiese, Johann Gout, and Frank Arnold

Abstract

Pancreatic ductal adenocarcinoma (PDAC) still presents with a dismal prognosis despite intense research. Better understanding of cellular homeostasis could identify druggable targets to improve therapy. Here we propose RAD50-interacting protein 1 (RINT1) as an essential mediator of cellular homeostasis in PDAC. In a cohort of resected PDAC, low RINT1 protein expression correlated significantly with better survival. Accordingly, RINT1 depletion caused severe growth defects in vitro associated with accumulation of DNA double-strand breaks (DSB), G2 cell cycle arrest, disruption of Golgi–endoplasmic reticulum homeostasis, and cell death. Time-resolved transcriptomics corroborated by quantitative proteome and interactome analyses pointed toward defective SUMOylation after RINT1 loss, impairing nucleocytoplasmic transport and DSB response. Subcutaneous xenografts confirmed tumor response by RINT1 depletion, also resulting in a survival benefit when transferred to an orthotopic model. Primary human PDAC organoids licensed RINT1 relevance for cell viability. Taken together, our data indicate that RINT1 loss affects PDAC cell fate by disturbing SUMOylation pathways. Therefore, a RINT1 interference strategy may represent a new putative therapeutic approach.Significance:These findings provide new insights into the aggressive behavior of PDAC, showing that RINT1 directly correlates with survival in patients with PDAC by disturbing the SUMOylation process, a crucial modification in carcinogenesis.

Published
2023
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6. Data from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial–mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576–90. ©2017 AACR.

Published
2023
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7. Table S2 from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

Description of the genomic alterations in KC and AKC PDAC cell lines

Published
2023
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8. Figure S1 GSEA Analysis from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

GSEA Analysis

Published
2023
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9. Figure S3 Tumour growth upon Olaparib and Gemcitabine Treatment in Allografts model from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

Tumour growth upon Olaparib and Gemcitabine Treatment in Allografts model

Published
2023
Full Text
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10. Table S1 from ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Alexander Kleger, Pierre-Olivier Frappart, Hans Christian Reinhardt, Thomas Seufferlein, Bence Sipos, Lisa Wiesmüller, Martin Wagner, Jochen Gaedcke, Evelin Schröck, Laura Gieldon, Hana Algül, Marina Lesina, Hanibal Bohnenberger, Meike Hohwieler, Stefan Liebau, Qiong Lin, Ninel Azoitei, André Lechel, Ronan Russell, Elisabeth Hessmann, Dietrich Alexander Ruess, Stephanie Hampp, Michaela Ihle, Maria Carolina Romero Carrasco, Anna Schmitt, and Lukas Perkhofer

Abstract

DNA Repair gene set

Published
2023
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11. ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

Author

Hans Christian Reinhardt, Stefan Liebau, Marina Lesina, Dietrich A. Ruess, Pierre Olivier Frappart, Stephanie Hampp, Thomas Seufferlein, André Lechel, Jochen Gaedcke, Lisa Wiesmüller, Qiong Lin, Bence Sipos, Laura Gieldon, Michaela Ihle, Ninel Azoitei, Hanibal Bohnenberger, Alexander Kleger, Martin Wagner, Hana Algül, Anna Schmitt, Evelin Schröck, Ronan Russell, Maria Carolina Romero Carrasco, Elisabeth Hessmann, Lukas Perkhofer, and Meike Hohwieler

Subjects
Male, 0301 basic medicine, Genome instability, Cancer Research, endocrine system diseases, DNA damage, Poly ADP ribose polymerase, Gene Expression, Ataxia Telangiectasia Mutated Proteins, Mice, SCID, Synthetic lethality, Biology, medicine.disease_cause, Deoxycytidine, Genomic Instability, Piperazines, Olaparib, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Humans, Cancer, medicine.disease, Immunohistochemistry, Gemcitabine, Molecular biology, digestive system diseases, 3. Good health, Pancreatic Neoplasms, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, PARP inhibitor, Cancer research, Phthalazines, Fluorouracil, Carcinogenesis, Carcinoma, Pancreatic Ductal, DNA Damage
Abstract

Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial–mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576–90. ©2017 AACR.

Published
2017
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