Search

Your search keyword '"Argueta, Christian"' showing total 125 results
Start Over Author "Argueta, Christian"
125 results on '"Argueta, Christian"'

2. Venetoclax response is enhanced by selective inhibitor of nuclear export compounds in hematologic malignancies

Author

Fischer, Melissa A., Friedlander, Sharon Y., Arrate, Maria P., Chang, Hua, Gorska, Agnieszka E., Fuller, Londa D., Ramsey, Haley E., Kashyap, Trinayan, Argueta, Christian, Debler, Sophie, Byrne, Michael, Villaume, Matthew T., Shaver, Aaron C., Senapedis, William, Landesman, Yosef, Baloglu, Erkan, Shacham, Sharon, and Savona, Michael R.

Published
2020
Full Text
View/download PDF

3. Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth

Author

Abu Aboud, Omran, Chen, Ching-Hsien, Senapedis, William, Baloglu, Erkan, Argueta, Christian, and Weiss, Robert H

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Cancer, Rare Diseases, Kidney Disease, Biotechnology, 5.1 Pharmaceuticals, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Acrylamides, Aminopyridines, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Apoptosis, Cell Cycle, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cell Survival, Disease Models, Animal, Humans, Kidney Neoplasms, Male, Mice, Molecular Targeted Therapy, NAD, Nicotinamide Phosphoribosyltransferase, Signal Transduction, Tumor Burden, Xenograft Model Antitumor Assays, beta Catenin, p21-Activated Kinases, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Kidney cancer (or renal cell carcinoma, RCC) is the sixth most common malignancy in the United States and one of the relatively few whose incidence is increasing. Because of the near universal resistance which occurs with the use of current treatment regimens, reprogrammed metabolic pathways are being investigated as potential targets for novel therapies of this disease. Borrowing from studies on other malignancies, we have identified the PAK4 and NAD biosynthetic pathways as being essential for RCC growth. We now show, using the dual PAK4/NAMPT inhibitor KPT-9274, that interference with these signaling pathways results in reduction of G2-M transit as well as induction of apoptosis and decrease in cell invasion and migration in several human RCC cell lines. Mechanistic studies demonstrate that inhibition of the PAK4 pathway by KPT-9274 attenuates nuclear β-catenin as well as the Wnt/β-catenin targets cyclin D1 and c-Myc. Furthermore, NAPRT1 downregulation, which we show occurs in all RCC cell lines tested, makes this tumor highly dependent on NAMPT for its NAD requirements, such that inhibition of NAMPT by KPT-9274 leads to decreased survival of these rapidly proliferating cells. When KPT-9274 was administered in vivo to a 786-O (VHL-mut) human RCC xenograft model, there was dose-dependent inhibition of tumor growth with no apparent toxicity; KPT-9274 demonstrated the expected on-target effects in this mouse model. KPT-9274 is being evaluated in a phase I human clinical trial in solid tumors and lymphomas, which will allow this data to be rapidly translated into the clinic for the treatment of RCC. Mol Cancer Ther; 15(9); 2119-29. ©2016 AACR.

Published
2016

4. Leukemogenic nucleophosmin mutation disrupts the transcription factor hub that regulates granulomonocytic fates

Author

Gu, Xiaorong, Ebrahem, Quteba, Mahfouz, Reda Z., Hasipek, Metis, Enane, Francis, Radivoyevitch, Tomas, Rapin, Nicolas, Przychodzen, Bartlomiej, Hu, Zhenbo, Balusu, Ramesh, Cotta, Claudiu V., Wald, David, Argueta, Christian, Landesman, Yosef, Martelli, Maria Paola, Falini, Brunangelo, Carraway, Hetty, Porse, Bo T., Maciejewski, Jaroslaw, Jha, Babal K., and Saunthararajah, Yogen

Subjects
Oncogenes -- Health aspects, Gene mutation -- Health aspects, Granulocytes -- Genetic aspects -- Health aspects, Transcription factors -- Health aspects, Gene expression -- Health aspects, Health care industry
Abstract

Nucleophosmin (NPM1) is among the most frequently mutated genes in acute myeloid leukemia (AML). It is not known, however, how the resulting oncoprotein mutant NPM1 is leukemogenic. To reveal the cellular machinery in which NPM1 participates in myeloid cells, we analyzed the endogenous NPM1 protein interactome by mass spectrometry and discovered abundant amounts of the master transcription factor driver of monocyte lineage differentiation PU.1 (also known as SPI1). Mutant NPM1, which aberrantly accumulates in cytoplasm, dislocated PU.1 into cytoplasm with it. CEBPA and RUNX1, the master transcription factors that collaborate with PU.1 to activate granulomonocytic lineage fates, remained nuclear; but without PU.1, their coregulator interactions were toggled from coactivators to corepressors, repressing instead of activating more than 500 granulocyte and monocyte terminal differentiation genes. An inhibitor of nuclear export, selinexor, by locking mutant NPM1/PU.1 in the nucleus, activated terminal monocytic fates. Direct depletion of the corepressor DNA methyltransferase 1 (DNMT1) from the CEBPA/RUNX1 protein interactome using the clinical drug decitabine activated terminal granulocytic fates. Together, these noncytotoxic treatments extended survival by more than 160 days versus vehicle in a patient-derived xenotransplant model of NPM1/FLT3-mutated AML. In sum, mutant NPM1 represses monocyte and granulocyte terminal differentiation by disrupting PU.1/CEBPA/RUNX1 collaboration, a transforming action that can be reversed by pharmacodynamically directed dosing of clinical small molecules., Introduction Nucleophosmin (NPM1) is one of the most frequently mutated genes in de novo acute myeloid leukemia (AML) (~30% of cases) (1). Only approximately 50% of patients with NPM1-mutated AML [...]

Published
2018
Full Text
View/download PDF

8. Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma

Author

Fulciniti, Mariateresa, Martinez-Lopez, Joaquin, Senapedis, William, Oliva, Stefania, Lakshmi Bandi, Rajya, Amodio, Nicola, Xu, Yan, Szalat, Raphael, Gulla, Annamaria, Samur, Mehmet K., Roccaro, Aldo, Linares, Maria, Cea, Michele, Baloglu, Erkan, Argueta, Christian, Landesman, Yosef, Shacham, Sharon, Liu, Siyuan, Schenone, Monica, Wu, Shiaw-Lin, Karger, Barry, Prabhala, Rao, Anderson, Kenneth C., and Munshi, Nikhil C.

Published
2017
Full Text
View/download PDF

9. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer

Author

Wu, Di, Hu, Di, Chen, Hao, Shi, Guoming, Fetahu, Irfete S., Wu, Feizhen, Rabidou, Kimberlie, Fang, Rui, Tan, Li, Xu, Shuyun, Liu, Hang, Argueta, Christian, Zhang, Lei, Mao, Fei, Yan, Guoquan, Chen, Jiajia, Dong, Zhaoru, Lv, Ruitu, Xu, Yufei, Wang, Mei, Ye, Yong, Zhang, Shike, Duquette, Danielle, Geng, Songmei, Yin, Clark, Lian, Christine Guo, Murphy, George F., Adler, Gail K., Garg, Rajesh, Lynch, Lydia, Yang, Pengyuan, Li, Yiming, Lan, Fei, Fan, Jia, Shi, Yang, and Shi, Yujiang Geno

Published
2018
Full Text
View/download PDF

12. RKIP localizes to the nucleus through a bipartite nuclear localization signal and interaction with importin a to regulate mitotic progression.

Author

Argueta, Christian E., Figy, Christopher, Bouali, Sawssen, Guo, Anna, Yeung, Kam C., and Fenteany, Gabriel

Subjects
*BIOLOGICAL transport, *PROTEIN kinase inhibitors, *NUCLEAR fusion, *DELETION mutation, *CANCER cells
Abstract

Raf kinase inhibitor protein (RKIP) is a multifunctional modulator of intracellular signal transduction. Although most of its functions have been considered cytosolic, we show here that the localization of RKIP is primarily nuclear in both growing and quiescent Madin-Darby canine kidney epithelial cells and in Cal-51 and BT-20 human breast cancer cells. We have identified a putative bipartite nuclear localization signal (NLS) in RKIP that maps to the surface of the protein surrounding a known regulatory region. Like classical NLS sequences, the putative NLS of RKIP is rich in arginine and lysine residues. Deletion of and point mutations in the putative NLS lead to decreased nuclear localization. Point mutation of all the basic residues in the putative NLS of RKIP particularly strongly reduces nuclear localization. We found consistent results in reexpression experiments with wildtype or mutant RKIP in RKIP-silenced cells. A fusion construct of the putative NLS of RKIP alone to a heterologous reporter protein leads to nuclear localization of the fusion protein, demonstrating that this sequence alone is sufficient for import into the nucleus. We found that RKIP interacts with the nuclear transport factor importin a in BT-20 and MDA-MB-231 human breast cancer cells, suggesting importin-mediated active nuclear translocation. Evaluating the biological function of nuclear localization of RKIP, we found that the presence of the putative NLS is important for the role of RKIP in mitotic checkpoint regulation in MCF-7 human breast cancer cells. Taken together, these findings suggest that a bipartite NLS in RKIP interacts with importin a for active transport of RKIP into the nucleus and that this process may be involved in the regulation of mitotic progression. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

13. Small Molecule Inhibitors of Nuclear Export and the Amelioration of Lupus by Modulation of Plasma Cell Generation and Survival

Author

Rangel‐Moreno, Javier, primary, Garcia‐Hernandez, Maria de la Luz, additional, Owen, Teresa, additional, Barnard, Jennifer, additional, Becerril‐Villanueva, Enrique, additional, Kashyap, Trinayan, additional, Argueta, Christian, additional, Gamboa‐Dominguez, Armando, additional, Tamir, Sharon, additional, Landesman, Yosef, additional, Goldman, Bruce I., additional, Ritchlin, Christopher T., additional, and Anolik, Jennifer H., additional

Published
2022
Full Text
View/download PDF

16. Tumour suppressor TET2 safeguards enhancers from aberrant DNA methylation and epigenetic reprogramming in ERα-positive breast cancer cells.

Author

Lyu, Ruitu, Zhu, Xuguo, Shen, Yinghui, Xiong, Lijun, Liu, Lu, Liu, Hang, Wu, Feizhen, Argueta, Christian, and Tan, Li

Subjects
DNA methylation, BREAST cancer, METHYLATION, CANCER cells, BRCA genes, GENE enhancers, EPIGENETICS, DNA methyltransferases
Abstract

Aberrant DNA methylation is an epigenetic hallmark of malignant tumours. The DNA methylation level is regulated by not only DNA methyltransferases (DNMTs) but also Ten-Eleven Translocation (TET) family proteins. However, the exact role of TET genes in breast cancer remains controversial. Here, we uncover that the ERα-positive breast cancer patients with high TET2 mRNA expression had better overall survival rates. Consistently, knockout of TET2 promotes the tumorigenesis of ERα-positive MCF7 breast cancer cells. Mechanistically, TET2 loss leads to aberrant DNA methylation (gain of 5mC) at a large proportion of enhancers, accompanied by significant reduction in H3K4me1 and H3K27ac enrichment. By analysing the epigenetically reprogrammed enhancers, we identify oestrogen responsive element (ERE) as one of the enriched motifs of transcriptional factors. Importantly, TET2 loss impairs 17beta-oestradiol (E2)-induced transcription of the epigenetically reprogrammed EREs-associated genes through attenuating the binding of ERα. Taken together, these findings shed light on our understanding of the epigenetic mechanisms underlying the enhancer reprogramming during breast cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

17. Risk factors for mortality in patients with acute bacterial cholangitis: type 2 diabetes is a significant clinical predictor

Author

Jiménez Castillo, Raúl Alberto, primary, Jáquez-Quintana, Joel Omar, additional, Reyna-Aréchiga, Ariadnee Irma, additional, López-Alejandro, Yessica Guadalupe, additional, Juárez-Hernández, Sayra Nallely, additional, Del Ángel-Argueta, Christian Devanny, additional, Benavides-Salgado, Daniel Eduardo, additional, and Maldonado-Garza, Héctor Jesús, additional

Published
2021
Full Text
View/download PDF

23. CONSEJO NACIONAL DE CIENCIA Y TECNOLOGÌA -CONCYT SECRETARÌA NACIONAL DE CIENCIA Y TECNOLOGÌA-SENACYT FONDO NACIONAL DE CIENCIA Y TECNOLOGÌA -FONACYT UNIVERSIDAD DE SAN CARLOS DE GUATEMALA-USAC FACULTAD DE INGENIERÌA INFORME FINAL TECNOLOGÍA INNOVADORA EN MANEJO DE LODOS RESIDUALES Y POLÍTICAS MEJORADAS. PROYECTO FINDECYT/FODECYT No. 07-2018

Author

Iván, Jorge, Cifuentes, Jorge, Cifuentes, Jorge Ivan, Pineda, Moris, Paiz, Jennyfer, Barrera, Andrea, Argueta, Christian, and Martinez, Alan Josué

Published
2020
Full Text
View/download PDF

25. Characterization of Synergistic Selinexor Combinations of Dexamethasone, Pomalidomide, Elotuzumab and Daratumumab in Primary MM Samples Ex Vivo

Author

Shain, Kenneth H., primary, Renatino-Canevarolo, Rafael, additional, Meads, Mark B., additional, Sudalagunta, Praneeth Reddy, additional, Coelho Siqueira Silva, Maria D, additional, Cubitt, Christopher, additional, De Avila, Gabriel, additional, Alugubelli, Raghunandan Reddy, additional, Kulkarni, Amit, additional, Zhang, Qi, additional, Hampton, Oliver, additional, Logothetis, Constantine, additional, Argueta, Christian, additional, Landesman, Yosef, additional, and Siqueira Silva, Ariosto, additional

Published
2020
Full Text
View/download PDF

26. Selinexor Sensitizes TRAIL-R2-Positive TNBC Cells to the Activity of TRAIL-R2xCD3 Bispecific Antibody

Author

Martini, Silvia, primary, Figini, Mariangela, additional, Croce, Aurora, additional, Frigerio, Barbara, additional, Pennati, Marzia, additional, Gianni, Alessandro Massimo, additional, De Marco, Cinzia, additional, Daidone, Maria Grazia, additional, Argueta, Christian, additional, Landesman, Yosef, additional, Zaffaroni, Nadia, additional, and Satta, Alessandro, additional

Published
2020
Full Text
View/download PDF

27. Correction: Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer

Author

Gravina, Giovanni Luca, primary, Mancini, Andrea, additional, Colapietro, Alessandro, additional, Marampon, Francesco, additional, Sferra, Roberta, additional, Pompili, Simona, additional, Biordi, Leda Assunta, additional, Iorio, Roberto, additional, Flati, Vincenzo, additional, Argueta, Christian, additional, Landesman, Yosef, additional, Kauffman, Michael, additional, Shacham, Sharon, additional, and Festuccia, Claudio, additional

Published
2019
Full Text
View/download PDF

29. An open label, multicenter, phase 1b/2 study of rebastinib (DCC-2036) in combination with carboplatin to assess safety, tolerability, and pharmacokinetics in patients with advanced or metastatic solid tumors.

Author

Tolcher, Anthony W., primary, Munster, Pamela N., additional, Rosen, Lee S., additional, Murphy, Curran, additional, Argueta, Christian, additional, Kuida, Keisuke, additional, Ruiz-Soto, Rodrigo, additional, and Janku, Filip, additional

Published
2019
Full Text
View/download PDF

30. Down-regulation of AR splice variants through XPO1 suppression contributes to the inhibition of prostate cancer progression

Author

Aboukameel, Amro, primary, Muqbil, Irfana, additional, Baloglu, Erkan, additional, Senapedis, William, additional, Landesman, Yosef, additional, Argueta, Christian, additional, Kauffman, Michael, additional, Chang, Hua, additional, Kashyap, Trinayan, additional, Shacham, Sharon, additional, Neggers, Jasper E., additional, Daelemans, Dirk, additional, Heath, Elisabeth I., additional, and Azmi, Asfar S., additional

Published
2018
Full Text
View/download PDF

31. Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer

Author

Gravina, Giovanni Luca, Mancini, Andrea, Colapietro, Alessandro, Marampon, Francesco, Sferra, Roberta, Pompili, Simona, Biordi, Leda Assunta, Iorio, Roberto, Flati, Vincenzo, Argueta, Christian, Landesman, Yosef, Kauffman, Michael, Shacham, Sharon, Festuccia, Claudio, and Biordi, ASSUNTA LEDA

Subjects
0301 basic medicine, Exportin-1 (XPO-1), Cell cycle checkpoint, Pharmacology, Selective inhibitors of nuclear export (SINE), 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, DU145, Survivin, medicine, Castration resistant prostate cancer (CrPCa), Chromosome region maintenance (CRM-1), Docetaxel (DTX), Oncology, Nuclear export signal, business.industry, Cancer, Correction, medicine.disease, 030104 developmental biology, Docetaxel, Apoptosis, 030220 oncology & carcinogenesis, business, medicine.drug, Research Paper
Abstract

// Giovanni Luca Gravina 1, 2 , Andrea Mancini 1 , Alessandro Colapietro 1 , Francesco Marampon 1 , Roberta Sferra 3 , Simona Pompili 3 , Leda Assunta Biordi 4 , Roberto Iorio 5 , Vincenzo Flati 4 , Christian Argueta 6 , Yosef Landesman 6 , Michael Kauffman 6 , Sharon Shacham 6 and Claudio Festuccia 1 1 Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L’Aquila, L’Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, Division of Radiotherapy, University of L’Aquila, L’Aquila, Italy 3 Department of Biotechnological and Applied Clinical Sciences, Division of Human Anatomy, University of L’Aquila, L’Aquila, Italy 4 Department of Biotechnological and Applied Clinical Sciences, Division of Molecular Pathology, University of L’Aquila, L’Aquila, Italy 5 Department of Biotechnological and Applied Clinical Sciences, Division of Applied Biology, University of L’Aquila, L’Aquila, Italy 6 Karyopharm Therapeutics, Newton, MA, USA Correspondence to: Claudio Festuccia, email: claudio.festuccia@univaq.it Keywords: castration resistant prostate cancer (CrPCa); chromosome region maintenance (CRM-1); exportin-1 (XPO-1); selective inhibitors of nuclear export (SINE); docetaxel (DTX) Received: June 29, 2017 Accepted: November 13, 2017 Published: November 30, 2017 ABSTRACT Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX resistant derivatives. Results and conclusions: We show that DTX resistance may involve overexpression of β-III tubulin (TUBB3) and P-glycoprotein as well as increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also observed in DTX resistant cells suggesting that SINE compounds may modulate DTX effectiveness in sensitive cells as well as restore the sensitivity to DTX in resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX through increased tumor shrinkage and apoptosis by preventing DTX-induced cell cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear accumulation increasing the expression of FOXO-responsive genes including p21, p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin supporting apoptosis. βdown-regulated Cyclin D1, c-myc, Nuclear sequestration of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged γ expression. Selinexor treatment increased DTX-mediated double strand breaks (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and Topo2A. Our results provide supportive evidence for the therapeutic use of SINE compounds in combination with DTX suggesting their clinical use in mCRPC patients.

Published
2017

32. Selinexor reduces the expression of DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents

Author

Kashyap, Trinayan, primary, Argueta, Christian, additional, Unger, Thaddeus, additional, Klebanov, Boris, additional, Debler, Sophia, additional, Senapedis, William, additional, Crochiere, Marsha L., additional, Lee, Margaret S., additional, Kauffman, Michael, additional, Shacham, Sharon, additional, and Landesman, Yosef, additional

Published
2018
Full Text
View/download PDF

33. Abstract 2492: Down-regulation of AR splice variants through XPO1 suppression contributes to the inhibition of prostate cancer progression

Author

Muqbil, Irfana, primary, Li, Yiwei, additional, Baloglu, Erkan, additional, Senapedis, William, additional, Landesman, Yosef, additional, Argueta, Christian, additional, Kauffman, Michael, additional, Friedlander, Sharon, additional, Chang, Hua, additional, Shacham, Sharon, additional, Heath, Elisabeth, additional, and Azmi, Asfar S., additional

Published
2018
Full Text
View/download PDF

34. Abstract 1877: Selective inhibitor of nuclear export (SINE) compound, eltanexor (KPT-8602), synergizes with venetoclax (ABT-199) to eliminate leukemia cells and extend survival in an in vivo model of acute myeloid leukemia

Author

Fischer, Melissa A., primary, Arrate, Pia M., additional, Chang, Hua, additional, Gorska, Agnieszka E., additional, Fuller, Londa S., additional, Ramsey, Haley E., additional, Kashyap, Trinayan, additional, Argueta, Christian, additional, Senapedis, William, additional, Baloglu, Erkan, additional, Landesman, Yosef, additional, Shacham, Sharon, additional, and Savona, Michael R., additional

Published
2018
Full Text
View/download PDF

35. Targeting the XPO1-dependent nuclear export of E2F7 reverses anthracycline resistance in head and neck squamous cell carcinomas

Author

Saenz-Ponce, Natalia, primary, Pillay, Rachael, additional, de Long, Lilia Merida, additional, Kashyap, Trinayan, additional, Argueta, Christian, additional, Landesman, Yosef, additional, Hazar-Rethinam, Mehlika, additional, Boros, Samuel, additional, Panizza, Benedict, additional, Jacquemyn, Maarten, additional, Daelemans, Dirk, additional, Gannon, Orla M., additional, and Saunders, Nicholas A., additional

Published
2018
Full Text
View/download PDF

37. Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma

Author

Jardin, Fabrice, Pujals, Anais, Pelletier, Laura, Bohers, Elodie, Camus, Vincent, Mareschal, Sylvain, Dubois, Sydney, Sola, Brigitte, Ochmann, Marlène, Lemonnier, François, Viailly, Pierre-Julien, Bertrand, Philippe, Maingonnat, Catherine, Traverse-Glehen, Alexandra, Gaulard, Philippe, Damotte, Diane, Delarue, Richard, Haioun, Corinne, Argueta, Christian, Landesman, Yosef, Salles, Gilles, Jais, Jean-Philippe, Figeac, Martin, Copie-Bergman, Christiane, Molina, Thierry Jo, Picquenot, Jean Michel, Cornic, Marie, Fest, Thierry, Milpied, Noel, Lemasle, Emilie, Stamatoullas, Aspasia, Moeller, Peter, Dyer, Martin J S, Sundström, Christer, Bastard, Christian, Tilly, Hervé, Leroy, Karen, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany, University of Leicester, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Service hématologie Poitiers, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), The authors thank Dr. Lin Chook for her critical review and for providing the molecular data on the conformation of XPO1/CRM1 protein residues., Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5), Centre hospitalier universitaire de Nantes (CHU Nantes), Universität Ulm - Ulm University [Ulm, Allemagne], Uppsala University, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chard-Hutchinson, Xavier, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institute of Human Genetics, University of Ulm

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, Lymphoma, B-Cell, Adolescent, Active Transport, Cell Nucleus, Receptors, Cytoplasmic and Nuclear, [SDV.CAN]Life Sciences [q-bio]/Cancer, Karyopherins, Mediastinal Neoplasms, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Humans, Aged, Clinical Laboratory Medicine, Gene Expression Profiling, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Sequence Analysis, DNA, Middle Aged, Triazoles, Hodgkin Disease, Klinisk laboratoriemedicin, Hydrazines, Acrylates, Mutation, Female, Biomarkers
Abstract

Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016

38. Abstract 329: Selinexor or KPT-8602 mediated XPO1 inhibition synergizes with dexamethasone to repress convergent pathways in the mTORC1 signaling network and drive cell death in multiple myeloma

Author

Argueta, Christian, primary, Kashyap, Trinayan, additional, Klebanov, Boris, additional, Chang, Hua, additional, Friedlander, Sharon, additional, Baloglu, Erkan, additional, Landesman, Yosef, additional, Lee, Margaret, additional, Gardner, Humphrey, additional, Shacham, Sharon, additional, and Senapedis, William, additional

Published
2017
Full Text
View/download PDF

39. Abstract 1587: Disruption of nuclear export with selinexor or KPT-8602 reduces androgen receptor expression and leads to potent anti-tumor activity in preclinical models of androgen-independent prostate cancer

Author

Argueta, Christian, primary, Klebanov, Boris, additional, Kashyap, Trinayan, additional, Chang, Hua, additional, Friedlander, Sharon, additional, Baloglu, Erkan, additional, Lee, Margaret, additional, Gardner, Humphrey, additional, Shacham, Sharon, additional, and Senapedis, William, additional

Published
2017
Full Text
View/download PDF

42. Abstract 1089: Anti-tumor activity of selinexor is enhanced by palbociclib in preclinical models of HER2+ breast cancer

Author

Chang, Hua, primary, Friedlander, Sharon, additional, Kashyap, Trinayan, additional, Klebanov, Boris, additional, Argueta, Christian, additional, Gonzalez, Oscar A., additional, Baloglu, Erkan, additional, Landesman, Yosef, additional, Shacham, Sharon, additional, Lee, Margaret, additional, and Senapedis, William, additional

Published
2017
Full Text
View/download PDF

43. Synergistic Anti-Tumor Effect of KPT-8602, a Second Generation Selective Inhibitor of Nuclear Export (SINE) Compound, and Panobinostat, a Pan-Histone Deacetylase (HDAC) Inhibitor in Multiple Myeloma

Author

Argueta, Christian, primary, Chang, Hua, additional, Kashyap, Trinayan, additional, Elloul, Sivan, additional, Friedlander, Sharon, additional, Lee, Margaret S., additional, Kauffman, Michael, additional, Shacham, Sharon, additional, Senapedis, William, additional, and Baloglu, Erkan, additional

Published
2016
Full Text
View/download PDF

44. Combination of Selective Inhibitor of Nuclear Export (SINE) Compounds, Selinexor and KPT-8602, with Venetoclax (ABT-199) Displays Enhanced Activity in Leukemia and Large Cell Lymphoma

Author

Fischer, Melissa A., primary, Friedlander, Sharon, additional, Hogdal, Leah, additional, Arrate, Pia, additional, Chang, Hua, additional, Kashyap, Trinayan, additional, Argueta, Christian, additional, Klebanov, Boris, additional, Senapedis, William, additional, Baloglu, Erkan, additional, Lee, Margaret S., additional, Shacham, Sharon, additional, and Savona, Michael R., additional

Published
2016
Full Text
View/download PDF

46. Selinexor, a Selective Inhibitor of Nuclear Export (SINE) compound, acts through NF-κB deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death

Author

Kashyap, Trinayan, primary, Argueta, Christian, additional, Aboukameel, Amro, additional, Unger, Thaddeus John, additional, Klebanov, Boris, additional, Mohammad, Ramzi M., additional, Muqbil, Irfana, additional, Azmi, Asfar S., additional, Drolen, Claire, additional, Senapedis, William, additional, Lee, Margaret, additional, Kauffman, Michael, additional, Shacham, Sharon, additional, and Landesman, Yosef, additional

Published
2016
Full Text
View/download PDF

50. Recurrent Mutations of the Exportin 1 Gene (XPO1) in Primary Mediastinal B-Cell Lymphoma: A Lysa Study

Author

Jardin, Fabrice, primary, Pujals, Anais, additional, Pelletier, Laura, additional, Bohers, Elodie, additional, Camus, Vincent, additional, Mareschal, Sylvain, additional, Dubois, Sydney, additional, Ochman, Marlène, additional, Lemonnier, Francois, additional, Viailly, Pierre-Julien, additional, Bertrand, Philippe, additional, Maingonnat, Catherine, additional, Traverse-Glehen, Alexandra, additional, Gaulard, Philippe, additional, Damotte, Diane, additional, Delarue, Richard, additional, Haioun, Corinne, additional, Landesman, Yosef, additional, Senapedis, William, additional, Argueta, Christian, additional, Salles, Gilles Andre, additional, Jais, Jean-Philippe, additional, Figeac, Martin, additional, Copie-Bergman, Christiane, additional, Molina, Thierry, additional, Picquenot, Jean-Michel, additional, Cornic, Marie, additional, Fest, Thierry, additional, Milpied, Noel, additional, Lemasle, Emilie, additional, Stamatoullas, Aspasia, additional, Moeller, Peter, additional, Dyer, Martin JS, additional, Sundstrom, Christer, additional, Bastard, Christian, additional, Tilly, Hervé, additional, and Leroy, Karen, additional

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results