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Article ; Online: First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b/2 trial.

Thibaudin, Marion / Fumet, Jean-David / Chibaudel, Benoist / Bennouna, Jaafar / Borg, Christophe / Martin-Babau, Jerome / Cohen, Romain / Fonck, Marianne / Taieb, Julien / Limagne, Emeric / Blanc, Julie / Ballot, Elise / Hampe, Léa / Bon, Marjorie / Daumoine, Susy / Peroz, Morgane / Mananet, Hugo / Derangère, Valentin / Boidot, Romain /

Michaud, Henri-Alexandre / Laheurte, Caroline / Adotevi, Olivier / Bertaut, Aurélie / Truntzer, Caroline / Ghiringhelli, François

Nature medicine

2023 Volume 29, Issue 8, Page(s) 2087–2098

Abstract: Although patients with microsatellite instable metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single-arm, ... ...

Abstract	Although patients with microsatellite instable metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single-arm, phase 1b/2 MEDITREME trial evaluated the safety and efficacy of durvalumab plus tremelimumab combined with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable metastatic CRC. Safety was the primary objective of phase Ib; no safety issue was observed. The phase 2 primary objective of efficacy in terms of 3-month progression-free survival (PFS) in patients with MSS tumors was met, with 3-month PFS of 90.7% (95% confidence interval (CI): 79.2-96%). For secondary objectives, response rate was 64.5%; median PFS was 8.2 months (95% CI: 5.9-8.6); and overall survival was not reached in patients with MSS tumors. We observed higher tumor mutational burden and lower genomic instability in responders. Integrated transcriptomic analysis underlined that high immune signature and low epithelial-mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor-specific T cell response associated with better PFS. The combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC. Clinicaltrials.gov identifier: NCT03202758 .
MeSH term(s)	Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology
Chemical Substances	durvalumab (28X28X9OKV) ; tremelimumab (QEN1X95CIX) ; Antibodies, Monoclonal
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Clinical Trial, Phase II ; Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-023-02497-z
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Article: Ecole Nationale Veterinaire Nantes

Peroz, David

Ecole Nationale Veterinaire Nantes, Thèses de doctorat vétérinaire 2004, [Elektronische Ressource], 2004

2004

Title variant	Induction of a specific colostrum immune response against rotavirus in goat and purification of the colostrum's immunoblobulins
Size	68 S
Document type	Article
Database	Special collection on veterinary medicine and general parasitology

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Article ; Online: Bidirectional Human-Swine Transmission of Seasonal Influenza A(H1N1)pdm09 Virus in Pig Herd, France, 2018.

Chastagner, Amélie / Enouf, Vincent / Peroz, David / Hervé, Séverine / Lucas, Pierrick / Quéguiner, Stéphane / Gorin, Stéphane / Beven, Véronique / Behillil, Sylvie / Leneveu, Philippe / Garin, Emmanuel / Blanchard, Yannick / van der Werf, Sylvie / Simon, Gaëlle

Emerging infectious diseases

2019 Volume 25, Issue 10, Page(s) 1940–1943

Abstract: In 2018, a veterinarian became sick shortly after swabbing sows exhibiting respiratory syndrome on a farm in France. Epidemiologic data and genetic analyses revealed consecutive human-to-swine and swine-to-human influenza A(H1N1)pdm09 virus transmission, ...

Abstract	In 2018, a veterinarian became sick shortly after swabbing sows exhibiting respiratory syndrome on a farm in France. Epidemiologic data and genetic analyses revealed consecutive human-to-swine and swine-to-human influenza A(H1N1)pdm09 virus transmission, which occurred despite some biosecurity measures. Providing pig industry workers the annual influenza vaccine might reduce transmission risk.
MeSH term(s)	Animals ; Disease Outbreaks/statistics & numerical data ; Disease Outbreaks/veterinary ; Female ; France/epidemiology ; Humans ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza, Human/epidemiology ; Influenza, Human/transmission ; Orthomyxoviridae Infections/epidemiology ; Orthomyxoviridae Infections/transmission ; Phylogeny ; Swine ; Swine Diseases/epidemiology ; Swine Diseases/transmission ; Zoonoses/epidemiology ; Zoonoses/transmission ; Zoonoses/virology
Language	English
Publishing date	2019-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2510.190068
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Article ; Online: Bidirectional Human–Swine Transmission of Seasonal Influenza A(H1N1)pdm09 Virus in Pig Herd, France, 2018

Amélie Chastagner / Vincent Enouf / David Peroz / Séverine Hervé / Pierrick Lucas / Stéphane Quéguiner / Stéphane Gorin / Véronique Beven / Sylvie Behillil / Philippe Leneveu / Emmanuel Garin / Yannick Blanchard / Sylvie van der Werf / Gaëlle Simon

Emerging Infectious Diseases, Vol 25, Iss 10, Pp 1940-

2019 Volume 1943

Abstract	In 2018, a veterinarian became sick shortly after swabbing sows exhibiting respiratory syndrome on a farm in France. Epidemiologic data and genetic analyses revealed consecutive human-to-swine and swine-to-human influenza A(H1N1)pdm09 virus transmission, which occurred despite some biosecurity measures. Providing pig industry workers the annual influenza vaccine might reduce transmission risk.
Keywords	influenza ; A(H1N1)pdm09 ; interspecies transmission ; pandemic ; zoonotic disease ; reverse zoonosis ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
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Article: LQT1-associated mutations increase KCNQ1 proteasomal degradation independently of Derlin-1.

Peroz, David / Dahimène, Shehrazade / Baró, Isabelle / Loussouarn, Gildas / Mérot, Jean

The Journal of biological chemistry

2008 Volume 284, Issue 8, Page(s) 5250–5256

Abstract: Mutations in the potassium channel KCNQ1 that determine retention of the mutated proteins in the endoplasmic reticulum (ER) are associated with the autosomal dominant negative Romano-Ward LQT1 cardiac syndrome. In the present study, we have analyzed the ... ...

Abstract	Mutations in the potassium channel KCNQ1 that determine retention of the mutated proteins in the endoplasmic reticulum (ER) are associated with the autosomal dominant negative Romano-Ward LQT1 cardiac syndrome. In the present study, we have analyzed the consequences and the potential molecular mechanisms involved in the ER retention of three Romano-Ward mutations located in KCNQ1 N terminus (Y111C, L114P, and P117L). We showed that the mutant KCNQ1 proteins exhibited reduced expression levels with respect to wild-type (WT)-KCNQ1. Radiolabeling pulse-chase experiments revealed that the lower expression levels did not result from reduced rate of synthesis. Instead, using a combination of Western blot and pulse-chase experiments, we showed that the mutant channel Y111C-KCNQ1, used as a model, was ubiquitinated and degraded in the proteasome more rapidly (t((1/2)) = 82 min) than WT-KCNQ1 channel (t((1/2)) = 113 min). On the other hand, KCNQ1 degradation did not appear to involve the GTP-dependent pathway. We also showed that KCNE1 stabilized both wild-type and Y111C proteins. To identify potential actors involved in KCNQ1 degradation, we studied the implication of the ER-resident protein Derlin-1 in KCNQ1 degradation. We showed that although KCNQ1 and Derlin-1 share the same molecular complex and co-immunoprecipitate when co-expressed in HEK293FT cells, Derlin-1 did not affect KCNQ1 steady state expression and degradation. These data were confirmed in T84 cells that express endogenous KCNQ1 and Derlin-1. Small interfering RNA knock-down of Derlin-1 did not modify KCNQ1 expression level, and no interaction between endogenous KCNQ1 and Derlin-1 could be detected.
MeSH term(s)	Amino Acid Substitution ; Cell Line ; Endoplasmic Reticulum/genetics ; Endoplasmic Reticulum/metabolism ; Gene Expression Regulation/genetics ; Guanosine Triphosphate/metabolism ; Humans ; KCNQ1 Potassium Channel/genetics ; KCNQ1 Potassium Channel/metabolism ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mutation, Missense ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; RNA, Small Interfering ; Romano-Ward Syndrome/genetics ; Romano-Ward Syndrome/metabolism ; Ubiquitination/genetics
Chemical Substances	DERL1 protein, human ; KCNQ1 Potassium Channel ; KCNQ1 protein, human ; Membrane Proteins ; RNA, Small Interfering ; Guanosine Triphosphate (86-01-1) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2008-12-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M806459200
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Article: LQT1-associated Mutations Increase KCNQ1 Proteasomal Degradation Independently of Derlin-1

Peroz, David / Dahimène, Shehrazade / Baró, Isabelle / Loussouarn, Gildas / Mérot, Jean

Journal of biological chemistry. 2009 Feb. 20, v. 284, no. 8

2009

Abstract	Mutations in the potassium channel KCNQ1 that determine retention of the mutated proteins in the endoplasmic reticulum (ER) are associated with the autosomal dominant negative Romano-Ward LQT1 cardiac syndrome. In the present study, we have analyzed the consequences and the potential molecular mechanisms involved in the ER retention of three Romano-Ward mutations located in KCNQ1 N terminus (Y111C, L114P, and P117L). We showed that the mutant KCNQ1 proteins exhibited reduced expression levels with respect to wild-type (WT)-KCNQ1. Radiolabeling pulse-chase experiments revealed that the lower expression levels did not result from reduced rate of synthesis. Instead, using a combination of Western blot and pulse-chase experiments, we showed that the mutant channel Y111C-KCNQ1, used as a model, was ubiquitinated and degraded in the proteasome more rapidly (t[fraction one₋half] = 82 min) than WT-KCNQ1 channel (t[fraction one₋half] = 113 min). On the other hand, KCNQ1 degradation did not appear to involve the GTP-dependent pathway. We also showed that KCNE1 stabilized both wild-type and Y111C proteins. To identify potential actors involved in KCNQ1 degradation, we studied the implication of the ER-resident protein Derlin-1 in KCNQ1 degradation. We showed that although KCNQ1 and Derlin-1 share the same molecular complex and co-immunoprecipitate when co-expressed in HEK293FT cells, Derlin-1 did not affect KCNQ1 steady state expression and degradation. These data were confirmed in T84 cells that express endogenous KCNQ1 and Derlin-1. Small interfering RNA knock-down of Derlin-1 did not modify KCNQ1 expression level, and no interaction between endogenous KCNQ1 and Derlin-1 could be detected.
Language	English
Dates of publication	2009-0220
Size	p. 5250-5256.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Article ; Online: Kv7.1 (KCNQ1) properties and channelopathies.

Peroz, David / Rodriguez, Nicolas / Choveau, Frank / Baró, Isabelle / Mérot, Jean / Loussouarn, Gildas

The Journal of physiology

2008 Volume 586, Issue 7, Page(s) 1785–1789

Abstract: KCNQ1 is the pore-forming subunit of a channel complex whose expression and function have been rather well characterized in the heart. Almost 300 mutations of KCNQ1 have been identified in patients and a vast majority of the described mutations are ... ...

Abstract	KCNQ1 is the pore-forming subunit of a channel complex whose expression and function have been rather well characterized in the heart. Almost 300 mutations of KCNQ1 have been identified in patients and a vast majority of the described mutations are linked to the long QT syndrome. Only a few mutations are linked to other pathologies such as atrial fibrillation and the short QT syndrome. However, a considerable amount of work remains to be done to get a clear picture of the molecular mechanisms responsible for the pathogenesis related to each mutation. The present review gives three examples of recent studies towards this goal and illustrates the diversity of the molecular mechanisms involved.
MeSH term(s)	Atrial Fibrillation/genetics ; Humans ; KCNQ1 Potassium Channel/chemistry ; KCNQ1 Potassium Channel/genetics ; KCNQ1 Potassium Channel/metabolism ; Long QT Syndrome/genetics ; Mutation/genetics ; Myocytes, Cardiac/metabolism ; Patch-Clamp Techniques ; Phosphatidylinositol 4,5-Diphosphate/metabolism
Chemical Substances	KCNQ1 Potassium Channel ; Phosphatidylinositol 4,5-Diphosphate
Language	English
Publishing date	2008-04-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2007.148254
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Article ; Online: 14-3-3 is a regulator of the cardiac voltage-gated sodium channel Nav1.5.

Allouis, Marie / Le Bouffant, Françoise / Wilders, Ronald / Péroz, David / Schott, Jean-Jacques / Noireaud, Jacques / Le Marec, Hervé / Mérot, Jean / Escande, Denis / Baró, Isabelle

Circulation research

2006 Volume 98, Issue 12, Page(s) 1538–1546

Abstract: The voltage-sensitive Na(+) channel Na(v)1.5 plays a crucial role in generating and propagating the cardiac action potential and its dysfunction promotes cardiac arrhythmias. The channel takes part into a large molecular complex containing regulatory ... ...

Abstract	The voltage-sensitive Na(+) channel Na(v)1.5 plays a crucial role in generating and propagating the cardiac action potential and its dysfunction promotes cardiac arrhythmias. The channel takes part into a large molecular complex containing regulatory proteins. Thus, factors that modulate its biosynthesis, localization, activity, and/or degradation are of great interest from both a physiological and pathological standpoint. Using a yeast 2-hybrid screen, we unveiled a novel partner, 14-3-3eta, interacting with the Na(v)1.5 cytoplasmic I interdomain. The interaction was confirmed by coimmunoprecipitation of 14-3-3 and full-length Na(v)1.5 both in COS-7 cells expressing recombinant Na(v)1.5 and in mouse cardiac myocytes. Using immunocytochemistry, we also found that 14-3-3 and Na(v)1.5 colocalized at the intercalated discs. We tested the functional link between Na(v)1.5 and 14-3-3eta using the whole-cell patch-clamp configuration. Coexpressing Na(v)1.5, the beta1 subunit and 14-3-3eta induced a negative shift in the inactivation curve of the Na(+) current, a delayed recovery from inactivation, but no changes in the activation curve or in the current density. The negative shift was reversed, and the recovery from inactivation was normalized by overexpressing the Na(v)1.5 cytoplasmic I interdomain interacting with 14-3-3eta. Reversal was also obtained with the dominant negative R56,60A 14-3-3eta mutant, suggesting that dimerization of 14-3-3 is needed for current regulation. Computer simulations suggest that the absence of 14-3-3 could exert proarrhythmic effects on cardiac electrical restitution properties. Based on these findings, we propose that the 14-3-3 protein is a novel component of the cardiac Na(+) channel acting as a cofactor for the regulation of the cardiac Na(+) current.
MeSH term(s)	14-3-3 Proteins/chemistry ; 14-3-3 Proteins/physiology ; Action Potentials/physiology ; Animals ; COS Cells ; Cercopithecus aethiops ; Computer Simulation ; Dimerization ; Electric Conductivity ; Electrophysiology ; Heart/physiology ; Humans ; Intracellular Membranes/metabolism ; Models, Cardiovascular ; Muscle Proteins/genetics ; Muscle Proteins/metabolism ; Muscle Proteins/physiology ; Myocardium/metabolism ; NAV1.5 Voltage-Gated Sodium Channel ; Protein Isoforms/physiology ; Protein Structure, Tertiary ; Recombinant Proteins/metabolism ; Sodium Channels/genetics ; Sodium Channels/metabolism ; Sodium Channels/physiology ; Transfection
Chemical Substances	14-3-3 Proteins ; Muscle Proteins ; NAV1.5 Voltage-Gated Sodium Channel ; Protein Isoforms ; Recombinant Proteins ; SCN5A protein, human ; Scn5a protein, mouse ; Sodium Channels
Language	English
Publishing date	2006-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/01.RES.0000229244.97497.2c
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Article ; Online: Evolution of nasal carriage of methicillin-resistant coagulase-negative staphylococci in a remote population.

Lebeaux, David / Barbier, François / Angebault, Cécile / Benmahdi, Lahcene / Ruppé, Etienne / Felix, Benjamin / Gaillard, Kevin / Djossou, Félix / Epelboin, Loïc / Dupont, Claire / Renard, Magaly / Peroz, Gilles / Vandenesch, François / Wolff, Michel / Andremont, Antoine / Ruimy, Raymond

Antimicrobial agents and chemotherapy

2011 Volume 56, Issue 1, Page(s) 315–323

Abstract: Nasal carriage of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) is highly prevalent in community subjects, but its dynamic has been little investigated. Nasal swabbing was performed in 2006 and 2008 in 154 Amerindians living isolated ... ...

Abstract	Nasal carriage of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) is highly prevalent in community subjects, but its dynamic has been little investigated. Nasal swabbing was performed in 2006 and 2008 in 154 Amerindians living isolated in French Guiana. MR-CoNS strains were identified and characterized by non-β-lactam susceptibility testing and staphylococcal cassette chromosome mec element (SCCmec) typing, characterizing the associations of ccr and mec gene complex allotypes, and for MR Staphylococcus epidermidis (MRSE), multilocus variable number of tandem repeats analysis (MLVA) was used. The impact of sociodemographic and medical characteristics on the persistence of MR-CoNS carriage was assessed by bivariate analysis. Prevalence of MR-CoNS carriage was 50.6% in 2006 and 46.8% in 2008. The 274 MR-CoNS isolates, including S. epidermidis (n = 89, 62 MLVA patterns), Staphylococcus haemolyticus (n = 78), and Staphylococcus hominis (n = 72), exhibited 41 distinct ccr and mec gene complex associations. Persistent carriage (in 2006 and 2008), intermittent carriage (either in 2006 or 2008), and noncarriage were documented in 25.3, 47.4, and 27.3% of the participants, respectively. Persistent carriage of a given MRSE isolate was rarely observed (n = 8 isolates). Furthermore, no epidemiological factor, including antibiotic exposure, was associated with persistent carriage. The high diversity of MRSE clones and their ccr and mec gene complex associations contrasted with the high carriage rates in this isolated community, which might reflect the occurrence of SCCmec rearrangement and the generation of new MR-CoNS strains.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/therapeutic use ; Bacterial Typing Techniques ; Carrier State ; Chromosomes, Bacterial ; Coagulase/deficiency ; Coagulase/genetics ; Female ; French Guiana/epidemiology ; Genes, Bacterial ; Genetic Linkage ; Genetic Variation ; Humans ; Male ; Methicillin Resistance/drug effects ; Methicillin Resistance/genetics ; Middle Aged ; Nose/microbiology ; Polymerase Chain Reaction ; Prevalence ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/epidemiology ; Staphylococcal Infections/microbiology ; Staphylococcus epidermidis/drug effects ; Staphylococcus epidermidis/genetics ; Staphylococcus epidermidis/isolation & purification ; Staphylococcus haemolyticus/drug effects ; Staphylococcus haemolyticus/genetics ; Staphylococcus haemolyticus/isolation & purification ; Staphylococcus hominis/drug effects ; Staphylococcus hominis/genetics ; Staphylococcus hominis/isolation & purification
Chemical Substances	Anti-Bacterial Agents ; Coagulase
Language	English
Publishing date	2011-11-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00547-11
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