Search

Your search keyword '"S Roth"' showing total 2,414 results
Start Over Author "S Roth" Language undetermined
2,414 results on '"S Roth"'

2. The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Katie E. Hebron, Xiaolin Wan, Jacob S. Roth, David J. Liewehr, Nancy E. Sealover, William J.E. Frye, Angela Kim, Stacey Stauffer, Olivia L. Perkins, Wenyue Sun, Kristine A. Isanogle, Christina M. Robinson, Amy James, Parirokh Awasthi, Priya Shankarappa, Xiaoling Luo, Haiyan Lei, Donna Butcher, Roberta Smith, Elijah F. Edmondson, Jin-Qiu Chen, Noemi Kedei, Cody J. Peer, Jack F. Shern, W. Douglas Figg, Lu Chen, Matthew D. Hall, Simone Difilippantonio, Frederic G. Barr, Robert L. Kortum, Robert W. Robey, Angelina V. Vaseva, Javed Khan, and Marielle E. Yohe

Subjects
Cancer Research, Oncology
Abstract

Purpose: PAX-fusion negative rhabdomyosarcoma (FN RMS) is driven by alterations in the RAS/MAP kinase pathway and is partially responsive to MEK inhibition. Overexpression of IGF1R and its ligands is also observed in FN RMS. Preclinical and clinical studies have suggested that IGF1R is itself an important target in FN RMS. Our previous studies revealed preclinical efficacy of the MEK1/2 inhibitor, trametinib, and an IGF1R inhibitor, BMS-754807, but this combination was not pursued clinically due to intolerability in preclinical murine models. Here, we sought to identify a combination of an MEK1/2 inhibitor and IGF1R inhibitor, which would be tolerated in murine models and effective in both cell line and patient-derived xenograft models of RAS-mutant FN RMS. Experimental Design: Using proliferation and apoptosis assays, we studied the factorial effects of trametinib and ganitumab (AMG 479), a mAb with specificity for human and murine IGF1R, in a panel of RAS-mutant FN RMS cell lines. The molecular mechanism of the observed synergy was determined using conventional and capillary immunoassays. The efficacy and tolerability of trametinib/ganitumab was assessed using a panel of RAS-mutated cell-line and patient-derived RMS xenograft models. Results: Treatment with trametinib and ganitumab resulted in synergistic cellular growth inhibition in all cell lines tested and inhibition of tumor growth in four of six models of RAS-mutant RMS. The combination had little effect on body weight and did not produce thrombocytopenia, neutropenia, or hyperinsulinemia in tumor-bearing SCID beige mice. Mechanistically, ganitumab treatment prevented the phosphorylation of AKT induced by MEK inhibition alone. Therapeutic response to the combination was observed in models without a mutation in the PI3K/PTEN axis. Conclusions: We demonstrate that combined trametinib and ganitumab is effective in a genomically diverse panel of RAS-mutated FN RMS preclinical models. Our data also show that the trametinib/ganitumab combination likely has a favorable tolerability profile. These data support testing this combination in a phase I/II clinical trial for pediatric patients with relapsed or refractory RAS-mutated FN RMS.

Published
2022

3. Bedeutung von intraoperativer Gefrierschnittanalyse und histopathologischen Ergebnissen von Wächterlymphknotenbiopsien: Vergleich von Z0011-Studie-geeigneten mit ungeeigneten Brustkrebspatientinnen

Author

Florian Reinhardt, Anna Fiedler, Felix Borgmeier, Petra Reinecke, Irene Esposito, Katalin Mattes-György, Mardjan Dabir, Verena Friebe, Natalia Krawczyk, Thomas Kaleta, Jürgen Hoffmann, Eugen Ruckhäberle, Tanja Fehm, Katrin S. Roth, and Svjetlana Mohrmann

Subjects
General Medicine
Abstract

Zusammenfassung Hintergrund Nach der Veröffentlichung der American College of Surgeons Oncology Group Z0011-Studie (ACOSOG Z0011) ist die Analyse der intraoperativen Gefrierschnitte von Wächterlymphknoten zurückgegangen. Aber für Patientinnen, welche die ACOSOG Z0011-Kriterien nicht erfüllen, bleibt die Gefrierschnittanalyse ein wichtiges Instrument für die intraoperative Entscheidungsfindung im Hinblick auf eine Axilladissektion. Ziel dieser Studie war es, eine retrospektive Evaluierung der Vorteile und der diagnostischen Genauigkeit von Gefrierschnittanalysen bei Brustkrebspatientinnen durchzuführen, welche die Kriterien der Z0011-Studie erfüllten oder nicht erfüllten, und dabei mögliche prädiktive Faktoren für falsch negative Ergebnisse festzustellen. Methoden Zwischen 2008 und 2013 wurde eine intraoperative Gefrierschnittanalyse der Wächterlymphknoten bei 522 cT1-T3-Brustkrebspatientinnen durchgeführt. Die klinisch-pathologischen Merkmale wurden retrospektiv mithilfe der Krankenakten evaluiert. Ergebnisse Insgesamt betrug die Sensitivität und Spezifität für alle Gefrierschnittanalysen 67,8 % bzw. 100 %. Generell war die Sensitivität für Makrometastasen höher als für Mikrometastasen. Bei der Gruppe, welche die Kriterien der Z0011-Studie erfüllte, betrugen die Sensitivität und Spezifität 72,7 % bzw. 100 %, verglichen mit 62,1 % bzw. 100 % für die Gruppe, welche die Z0011-Kriterien nicht erfüllte. In der Gruppe, welche die Z0011-Kriterien erfüllte, wurde eine Untergruppenanalyse durchgeführt, und die Ergebnisse für ≤ 2 positiven Wächterlymphknoten wurden mit den Ergebnissen für > 2 verglichen. Bei beiden Untergruppen betrugen Spezifität und Sensitivität jeweils 100 %. In der Patientinnengruppe, welche die Z0011-Kriterien nicht erfüllte, waren mehrere klinisch-pathologische Faktoren mit einer höheren Rate an falsch positiven Ergebnissen assoziiert. Im Hinblick auf die intraoperative Entscheidungsfindung für eine Axilladissektion brachte die Durchführung einer intraoperativen Gefrierschnittanalyse Vorteile für 22,2 % der Patientinnen, welche die Z0011-Kriterien nicht erfüllten, aber nur für 0,6 % der Patientinnen, welche die Z0011-Kriterien erfüllten. Schlussfolgerungen Die Gefrierschnittanalyse ist besonders für die intraoperative Evaluierung von Wächterlymphknoten bei Patientinnen, welche die Z0011-Kriterien nicht erfüllen, vorteilhaft, da dadurch eine Zweitoperation zur Axilladissektion vermieden werden kann. Obwohl die Sensitivität der Gefrierschnittanalyse in der Gruppe, welche die Z0011-Kriterien erfüllte, insgesamt niedriger war, hat die Gefrierschnittanalyse in beiden Gruppen eine vergleichbar hohe Sensitivität und diagnostische Genauigkeit für Makrometastasen.

Published
2022

6. Supplementary Table from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Author

Nicolas Reynoird, Nima Mosammaparast, Pawel K. Mazur, Pierre Hainaut, Michiel Vermeulen, Yohann Couté, Pascal W.T.C. Jansen, Marianne Tardif, Rebecca Rodell, Jessica Vayr, Ana Morales Benitez, Florent Chuffart, Alexandre G. Casanova, Joshua R. Brickner, Ning Tsao, Tanveer Ahmad, Clement Oyeniran, Gael S. Roth, Simone Hausmann, and Valentina Lukinović

Abstract

Supplementary Table from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Published
2023

7. Data from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Author

Nicolas Reynoird, Nima Mosammaparast, Pawel K. Mazur, Pierre Hainaut, Michiel Vermeulen, Yohann Couté, Pascal W.T.C. Jansen, Marianne Tardif, Rebecca Rodell, Jessica Vayr, Ana Morales Benitez, Florent Chuffart, Alexandre G. Casanova, Joshua R. Brickner, Ning Tsao, Tanveer Ahmad, Clement Oyeniran, Gael S. Roth, Simone Hausmann, and Valentina Lukinović

Abstract

Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining RNF113A E3 ligase activity, essential for its role in alkylation damage response. In turn, SMYD3 inhibition restores SCLC vulnerability to alkylating chemotherapy. Our study sheds light on a novel role of SMYD3 in cancer, uncovering this enzyme as a mediator of alkylation damage sensitivity and providing a rationale for small-molecule SMYD3 inhibition to improve responses to established chemotherapy.Significance:SCLC rapidly becomes resistant to conventional chemotherapy, leaving patients with no alternative treatment options. Our data demonstrate that SMYD3 upregulation and RNF113A methylation in SCLC are key mechanisms that control the alkylation damage response. Notably, SMYD3 inhibition sensitizes cells to alkylating agents and promotes sustained SCLC response to chemotherapy.This article is highlighted in the In This Issue feature, p. 2007

Published
2023

8. Supplementary Data from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Author

Nicolas Reynoird, Nima Mosammaparast, Pawel K. Mazur, Pierre Hainaut, Michiel Vermeulen, Yohann Couté, Pascal W.T.C. Jansen, Marianne Tardif, Rebecca Rodell, Jessica Vayr, Ana Morales Benitez, Florent Chuffart, Alexandre G. Casanova, Joshua R. Brickner, Ning Tsao, Tanveer Ahmad, Clement Oyeniran, Gael S. Roth, Simone Hausmann, and Valentina Lukinović

Abstract

Supplementary Data from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Published
2023

10. Supplementary Table S6 from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

Differentially expressed genes in NSD2 p.E1099K RCH-ACV cells with the change of H3K27me3 peaks

Published
2023

12. Supplementary Material and Method, Supplementary Tables 1-2, and Figure Legends from Efficacy of AKT Inhibitor ARQ 092 Compared with Sorafenib in a Cirrhotic Rat Model with Hepatocellular Carcinoma

Author

Thomas Decaens, Vincent Leroy, Patrice N. Marche, Benoit Busser, Yi Yu, Giovanni Abbadessa, Séyédéh Tayébéh Ahmad Pour, Keerthi Kurma, Ayca Zeybek Kuyucu, Zuzana Macek Jilkova, and Gaël S. Roth

Abstract

Supplementary Table 1: IC20 and IC50 values of ARQ 092 and sorafenib in Hep3B, Huh-7, HepG2, PLC/PRF/5 and HR4 cell lines after 48h of exposure; Supplementary Table 2: List of significantly different phospho-kinases from ARQ 092 treated rats compared to control group.

Published
2023

13. Supplementary Table S5 from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

List of genes bound and regulated by GR in NSD2 wild-type RCH-ACV and RMPI-8402 cells

Published
2023

15. Supplementary Table S4 from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

Combined RNA-Seq analysis of 4 ALL cell lines (RCH-ACV, SEM, RPMI-8402 and CEM) in response to dexamethasone treatment

Published
2023

16. Supplementary Methods and Figures from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

Supplementary Methods and Figures

Published
2023

18. Data from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

Mutations in epigenetic regulators are common in relapsed pediatric acute lymphoblastic leukemia (ALL). Here, we uncovered the mechanism underlying the relapse of ALL driven by an activating mutation of the NSD2 histone methyltransferase (p.E1099K). Using high-throughput drug screening, we found that NSD2-mutant cells were specifically resistant to glucocorticoids. Correction of this mutation restored glucocorticoid sensitivity. The transcriptional response to glucocorticoids was blocked in NSD2-mutant cells due to depressed glucocorticoid receptor (GR) levels and the failure of glucocorticoids to autoactivate GR expression. Although H3K27me3 was globally decreased by NSD2 p.E1099K, H3K27me3 accumulated at the NR3C1 (GR) promoter. Pretreatment of NSD2 p.E1099K cell lines and patient-derived xenograft samples with PRC2 inhibitors reversed glucocorticoid resistance in vitro and in vivo. PRC2 inhibitors restored NR3C1 autoactivation by glucocorticoids, increasing GR levels and allowing GR binding and activation of proapoptotic genes. These findings suggest a new therapeutic approach to relapsed ALL associated with NSD2 mutation.Significance:NSD2 histone methyltransferase mutations observed in relapsed pediatric ALL drove glucocorticoid resistance by repression of the GR and abrogation of GR gene autoactivation due to accumulation of K3K27me3 at its promoter. Pretreatment with PRC2 inhibitors reversed resistance, suggesting a new therapeutic approach to these patients with ALL.This article is highlighted in the In This Issue feature, p. 1

Published
2023

19. Supplementary Table S1 from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

The full drug screen results

Published
2023

21. Supplementary Table S2 from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

ALL patients with NSD2 mutations

Published
2023

23. Supplementary Table S3 from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li

Abstract

Glucocorticoid response of PDX Cells with NSD2 mutations

Published
2023

25. Supplementary Figure S3 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Pharmacodynamic response to trametinib/ganitumab in xenograft models does not predict tumor shrinkage

Published
2023

26. Supplementary Data File S9 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Related to Figure 4

Published
2023

27. Data from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Purpose:PAX-fusion negative rhabdomyosarcoma (FN RMS) is driven by alterations in the RAS/MAP kinase pathway and is partially responsive to MEK inhibition. Overexpression of IGF1R and its ligands is also observed in FN RMS. Preclinical and clinical studies have suggested that IGF1R is itself an important target in FN RMS. Our previous studies revealed preclinical efficacy of the MEK1/2 inhibitor, trametinib, and an IGF1R inhibitor, BMS-754807, but this combination was not pursued clinically due to intolerability in preclinical murine models. Here, we sought to identify a combination of an MEK1/2 inhibitor and IGF1R inhibitor, which would be tolerated in murine models and effective in both cell line and patient-derived xenograft models of RAS-mutant FN RMS.Experimental Design:Using proliferation and apoptosis assays, we studied the factorial effects of trametinib and ganitumab (AMG 479), a mAb with specificity for human and murine IGF1R, in a panel of RAS-mutant FN RMS cell lines. The molecular mechanism of the observed synergy was determined using conventional and capillary immunoassays. The efficacy and tolerability of trametinib/ganitumab was assessed using a panel of RAS-mutated cell-line and patient-derived RMS xenograft models.Results:Treatment with trametinib and ganitumab resulted in synergistic cellular growth inhibition in all cell lines tested and inhibition of tumor growth in four of six models of RAS-mutant RMS. The combination had little effect on body weight and did not produce thrombocytopenia, neutropenia, or hyperinsulinemia in tumor-bearing SCID beige mice. Mechanistically, ganitumab treatment prevented the phosphorylation of AKT induced by MEK inhibition alone. Therapeutic response to the combination was observed in models without a mutation in the PI3K/PTEN axis.Conclusions:We demonstrate that combined trametinib and ganitumab is effective in a genomically diverse panel of RAS-mutated FN RMS preclinical models. Our data also show that the trametinib/ganitumab combination likely has a favorable tolerability profile. These data support testing this combination in a phase I/II clinical trial for pediatric patients with relapsed or refractory RAS-mutated FN RMS.

Published
2023

28. Supplementary Data File S4 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Sample Sizes

Published
2023

29. Supplementary Data File S2 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Related to Figure 1B

Published
2023

30. Supplementary Figure S2 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

The combination of trametinib and ganitumab does not induce hyperinsulinemia or hematologic adverse events in SCID beige mice

Published
2023

31. Supplementary Figure S4 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Effect of trametinib and ganitumab in additional cell culture models of RAS-mutated RMS

Published
2023

32. Supplementary Data File S1 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Copy Number

Published
2023

33. Supplementary Data File S6 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Related to Figure 2 - SMS-CTR

Published
2023

34. Supplementary Data File S8 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Related to Figure 3

Published
2023

35. Supplementary Figure S5 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Mechanism of decreased PTEN expression in RD

Published
2023

36. Supplemental Data File S3 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Related to Figure 1D

Published
2023

37. Supplementary Figure S6 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Schematic depicting the impact of PTEN loss on sensitivity to MEK inhibition

Published
2023

38. Supplementary Figure S1 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Combining ganitumab with trametinib inhibits tumor growth and increases fibrosis in SMS-CTR but not RD xenografts

Published
2023

39. Supplementary Data File S7 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Related to Figure 2 - RD

Published
2023

40. Supplementary Data File S5 from The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author

Marielle E. Yohe, Javed Khan, Angelina V. Vaseva, Robert W. Robey, Robert L. Kortum, Frederic G. Barr, Simone Difilippantonio, Matthew D. Hall, Lu Chen, W. Douglas Figg, Jack F. Shern, Cody J. Peer, Noemi Kedei, Jin-Qiu Chen, Elijah F. Edmondson, Roberta Smith, Donna Butcher, Haiyan Lei, Xiaoling Luo, Priya Shankarappa, Parirokh Awasthi, Amy James, Christina M. Robinson, Kristine A. Isanogle, Wenyue Sun, Olivia L. Perkins, Stacey Stauffer, Angela Kim, William J.E. Frye, Nancy E. Sealover, David J. Liewehr, Jacob S. Roth, Xiaolin Wan, and Katie E. Hebron

Abstract

Baseline Statistics

Published
2023

41. Who gets caught by the emotion? Attentional biases toward emotional facial expressions and their link to social anxiety and autistic traits

Author

Julia Folz, Tom S. Roth, Milica Nikolić, and Mariska E. Kret

Subjects
General Psychology
Abstract

The emotional facial expressions of other individuals are a valuable information source in adapting behaviour to situational demands, and have been found to receive prioritized attention. Yet, enhanced attentional biases, such as a bias to social threat in Social Anxiety Disorder (SAD), or blunted attention to emotional information, as assumed in Autism Spectrum Disorder (ASD), can easily become maladaptive in daily life. In order to investigate individual differences in attentional biases toward different emotional expressions (angry, happy, sad, and fearful versus neutral) and their links to social anxiety and autistic traits, we tested 104 healthy participants with an emotional dot-probe paradigm on a touch screen, and measured clinical trait levels associated with ASD and SAD. While confirming the presence of attentional biases toward all emotional expressions, we did not find robust evidence for systematic links between these biases and either clinical trait dimension. Only an exploratory Bayesian analysis pointed to a less pronounced bias towards happy facial expressions with higher autistic trait levels. Moreover, a closer examination of the attentional bias towards angry facial expressions suggested that alterations in this bias might depend on a complex interplay between both trait dimensions. Novel approaches in the assessment of attentional biases might yield the potential to describe disorder-specific biases in attention to emotions more validly.

Published
2023

43. Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

Author

Manuel Gentiluomo, M. Piccardi, S. Bertoncini, E. Costello, L. Morelli, S. Landi, A. Milanetto, B. Schöttker, G. Di Franco, S. Ermini, A. Scarpa, J. Izbicki, R. Pezzilli, F. Uzunoglu, R. Talar-Wojnarowska, M. Goetz, R. Lawlor, M. Aoki, B. Bueno-de-Mesquita, O. Busch, R. Chammas, F. Tavano, H. van Laarhoven, G. Cavestro, H. Stocker, F. Bazzocchi, C. Pasquali, X. Chen, M. Puzzono, R. Ponz de Leon Pisani, C. Sperti, M. Lovecek, B. Erőss, D. Basso, J. Kupcinskas, T. Vanagas, D. Janciauskas, L. Poskiene, M. Tacelli, B. Mohelnikova Duchonova, F. Perri, A. Latiano, A. Mambrini, E. Maiello, P. Hegyi, A. Szentesi, S. Bunduc, T. Hussein, P. Arcidiacono, U. Boggi, T. Hackert, P. Soucek, M. Lucchesi, L. Ginocchi, M. Gazouli, A. Zerbi, S. Roth, K. Jamroziak, S. Carrara, V. Hlavac, M. Oliverius, J. Neoptolemos, G. Theodoropoulos, C. van Eijck, M. Dannemann, F. Canzian, S. Tofanelli, and D. Campa

Subjects
Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology
Published
2022

45. PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author

Crissandra Piper, Matthew D. Hall, Marta Kulis, Richard L. Bennett, Alok Swaroop, Min Shen, Richard B. Lock, Jonathan H. Shrimp, Jon A. Oyer, Christine Will, Alberto Riva, Heidi L. Casellas Roman, Duohui Jing, Jianping Li, Catalina Troche, Adolfo A. Ferrando, Jacob S. Roth, Daphné Dupéré-Richer, Jonathan D. Licht, and Julia Cathryn Hlavka-Zhang

Subjects
Mutation, biology, business.industry, medicine.disease_cause, Glucocorticoid receptor, Glucocorticoid Sensitivity, Oncology, In vivo, Cell culture, Histone methyltransferase, medicine, Cancer research, biology.protein, Epigenetics, PRC2, business, hormones, hormone substitutes, and hormone antagonists
Abstract

Mutations in epigenetic regulators are common in relapsed pediatric acute lymphoblastic leukemia (ALL). Here, we uncovered the mechanism underlying the relapse of ALL driven by an activating mutation of the NSD2 histone methyltransferase (p.E1099K). Using high-throughput drug screening, we found that NSD2-mutant cells were specifically resistant to glucocorticoids. Correction of this mutation restored glucocorticoid sensitivity. The transcriptional response to glucocorticoids was blocked in NSD2-mutant cells due to depressed glucocorticoid receptor (GR) levels and the failure of glucocorticoids to autoactivate GR expression. Although H3K27me3 was globally decreased by NSD2 p.E1099K, H3K27me3 accumulated at the NR3C1 (GR) promoter. Pretreatment of NSD2 p.E1099K cell lines and patient-derived xenograft samples with PRC2 inhibitors reversed glucocorticoid resistance in vitro and in vivo. PRC2 inhibitors restored NR3C1 autoactivation by glucocorticoids, increasing GR levels and allowing GR binding and activation of proapoptotic genes. These findings suggest a new therapeutic approach to relapsed ALL associated with NSD2 mutation. Significance: NSD2 histone methyltransferase mutations observed in relapsed pediatric ALL drove glucocorticoid resistance by repression of the GR and abrogation of GR gene autoactivation due to accumulation of K3K27me3 at its promoter. Pretreatment with PRC2 inhibitors reversed resistance, suggesting a new therapeutic approach to these patients with ALL. This article is highlighted in the In This Issue feature, p. 1

Published
2022

49. Immunotherapy in hepatocellular carcinoma: How does underlying liver disease influence therapeutic strategy and outcomes?

Author

Gael S. Roth, François Villeret, Thomas Decaens, Philippe Merle, and Pierre Nahon

Subjects
Hepatology
Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with up to 90% of HCC cases occurring in the setting of underlying cirrhosis. Therapeutic landscape for advanced HCC has dramatically changed in recent years with the advent of immunotherapy, including several combinations. Data suggest that the surrounding liver milieu may influence tumour response. In addition, different aetiologies of HCC and their effects on the host liver may impact response to immunotherapy. However, to date, guidelines do not take into account this parameter to guide therapeutic selection, and phase III trials are likewise performed in patients irrespective of HCC aetiology. Moreover, most clinical trial data are collected in highly selected patients with preserved liver function (defined as Child-Pugh class A) and controlled portal hypertension, which does not accurately reflect routine clinical practice. In this review, we discuss the influence of liver disease aetiology on the response to immunotherapy in patients with advanced HCC. We also discuss the safety and efficacy of various immunotherapeutic agents in Child-Pugh B patients to determine if these treatments are beneficial in this vulnerable patient population.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results