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Article: AXL Receptor Tyrosine Kinase as a Promising Therapeutic Target Directing Multiple Aspects of Cancer Progression and Metastasis.

Goyette, Marie-Anne / Côté, Jean-François

2022 Volume 14, Issue 3

Abstract: The receptor tyrosine kinase AXL is emerging as a key player in tumor progression and metastasis and its expression correlates with poor survival in a plethora of cancers. While studies have shown the benefits of AXL inhibition for the treatment of ... ...

Abstract	The receptor tyrosine kinase AXL is emerging as a key player in tumor progression and metastasis and its expression correlates with poor survival in a plethora of cancers. While studies have shown the benefits of AXL inhibition for the treatment of metastatic cancers, additional roles for AXL in cancer progression are still being explored. This review discusses recent advances in understanding AXL's functions in different tumor compartments including cancer, vascular, and immune cells. AXL is required at multiple steps of the metastatic cascade where its activation in cancer cells leads to EMT, invasion, survival, proliferation and therapy resistance. AXL activation in cancer cells and various stromal cells also results in tumor microenvironment deregulation, leading to modulation of angiogenesis, fibrosis, immune response and hypoxia. A better understanding of AXL's role in these processes could lead to new therapeutic approaches that would benefit patients suffering from metastatic diseases.
Language	English
Publishing date	2022-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14030466
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Article ; Online: Suspected medullary washout leading to severe polyuria following delayed cerebral ischemia: a case report.

Sene, Pape-Mamadou / Gebai, Ahmad / Kopel, Tal / Cailhier, Jean-François / Lafrance, Dominique / Côté, Jean-Maxime

BMC nephrology

2023 Volume 24, Issue 1, Page(s) 257

Abstract: Background: Delayed cerebral ischemia is a clinical entity commonly encountered in patients presenting with acute neurological injury and is often complicated by dysnatremias, such as the cerebral salt wasting syndrome. In this case report, we described ...

Abstract	Background: Delayed cerebral ischemia is a clinical entity commonly encountered in patients presenting with acute neurological injury and is often complicated by dysnatremias, such as the cerebral salt wasting syndrome. In this case report, we described an exceptional case of polyuria attributed to an initial cerebral salt wasting phenomenon and iatrogenic-induced medullary washout. Case presentation: A 53-year-old woman was admitted to our hospital for the management of a Modified Fisher scale grade 4 subarachnoid hemorrhage due to a ruptured posterior communicating aneurysm. She was initially managed with coil embolization and external ventricular drain due to secondary hydrocephalus. Throughout the course of her hospitalization, she developed severe polyuria reaching up to 40L per day. To keep up with the excessive urinary losses and maintain appropriate cerebral perfusion, fluid replacement therapy was adjusted every hour, reaching up to 1.3 L of crystalloid per hour in addition to aminergic support. An initial diagnosis of partial diabetes insipidus, followed by a cerebral salt wasting syndrome was suspected. While the urine output continued to increase, her serum urea concentration progressively decreased to a point of almost being undetectable on day 9. At that time, the presence of an interstitial medulla washout was hypothesized. Various pharmacological and non-pharmacological interventions were progressively introduced to regain normal renal homeostasis, including non-steroidal anti-inflammatory drugs, fludrocortisone, oral urea and high-protein intake. Medications were progressively weaned, and the patient was successfully discharged from the ICU. Conclusions: Cerebral salt wasting should be considered in the initial differential diagnosis of a patient presenting with polyuria in the context of acute neurological injury. Early recognition of this entity is critical to quickly implement proper management. However, as shown in this case report, the concomitance of delayed cerebral ischemia may complexify that management.
MeSH term(s)	Humans ; Female ; Middle Aged ; Polyuria/etiology ; Cerebral Infarction ; Kidney ; Anti-Inflammatory Agents, Non-Steroidal ; Blood Urea Nitrogen
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2041348-8
ISSN	1471-2369 ; 1471-2369
ISSN (online)	1471-2369
ISSN	1471-2369
DOI	10.1186/s12882-023-03281-4
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Article ; Online: Structural biology of DOCK-family guanine nucleotide exchange factors.

Boland, Andreas / Côté, Jean-Francois / Barford, David

FEBS letters

2022 Volume 597, Issue 6, Page(s) 794–810

Abstract: DOCK proteins are a family of multi-domain guanine nucleotide exchange factors (GEFs) that activate the RHO GTPases CDC42 and RAC1, thereby regulating several RHO GTPase-dependent cellular processes. DOCK proteins are characterized by the catalytic DHR2 ... ...

Abstract	DOCK proteins are a family of multi-domain guanine nucleotide exchange factors (GEFs) that activate the RHO GTPases CDC42 and RAC1, thereby regulating several RHO GTPase-dependent cellular processes. DOCK proteins are characterized by the catalytic DHR2 domain (DOCK
MeSH term(s)	Guanine Nucleotide Exchange Factors/metabolism ; cdc42 GTP-Binding Protein/metabolism ; rho GTP-Binding Proteins/genetics ; Signal Transduction ; Nucleotides/metabolism ; Biology ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	Guanine Nucleotide Exchange Factors ; cdc42 GTP-Binding Protein (EC 3.6.5.2) ; rho GTP-Binding Proteins (EC 3.6.5.2) ; Nucleotides ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2022-11-04
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14523
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Article ; Online: Deep learning-enabled framework for automatic lens design starting point generation.

Côté, Geoffroi / Lalonde, Jean-François / Thibault, Simon

Optics express

2021 Volume 29, Issue 3, Page(s) 3841–3854

Abstract: We present a simple, highly modular deep neural network (DNN) framework to address the problem of automatically inferring lens design starting points tailored to the desired specifications. In contrast to previous work, our model can handle various and ... ...

Abstract	We present a simple, highly modular deep neural network (DNN) framework to address the problem of automatically inferring lens design starting points tailored to the desired specifications. In contrast to previous work, our model can handle various and complex lens structures suitable for real-world problems such as Cooke Triplets or Double Gauss lenses. Our successfully trained dynamic model can infer lens designs with realistic glass materials whose optical performance compares favorably to reference designs from the literature on 80 different lens structures. Using our trained model as a backbone, we make available to the community a web application that outputs a selection of varied, high-quality starting points directly from the desired specifications, which we believe will complement any lens designer's toolbox.
Language	English
Publishing date	2021-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1491859-6
ISSN	1094-4087 ; 1094-4087
ISSN (online)	1094-4087
ISSN	1094-4087
DOI	10.1364/OE.401590
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Article ; Online: Breast Cancer Metastatic Dormancy and Relapse: An Enigma of Microenvironment(s).

Elkholi, Islam E / Lalonde, Andréane / Park, Morag / Côté, Jean-François

Cancer research

2022 Volume 82, Issue 24, Page(s) 4497–4510

Abstract: Multiple factors act in concert to define the fate of disseminated tumor cells (DTC) to enter dormancy or develop overt metastases. Here, we review these factors in the context of three stages of the metastatic cascade that impact DTCs. First, cells can ... ...

Abstract	Multiple factors act in concert to define the fate of disseminated tumor cells (DTC) to enter dormancy or develop overt metastases. Here, we review these factors in the context of three stages of the metastatic cascade that impact DTCs. First, cells can be programmed within the primary tumor microenvironment to promote or inhibit dissemination, and the primary tumor can condition a premetastatic niche. Then, cancer cells from the primary tumor spread through hematogenous and lymphatic routes, and the primary tumor sends cues systematically to regulate the fate of DTCs. Finally, DTCs home to their metastatic site, where they are influenced by various organ-specific aspects of the new microenvironment. We discuss these factors in the context of breast cancer, where about one-third of patients develop metastatic relapse. Finally, we discuss how the standard-of-care options for breast cancer might affect the fate of DTCs.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/pathology ; Neoplasm Recurrence, Local/pathology ; Tumor Microenvironment
Language	English
Publishing date	2022-10-10
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-22-1902
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Article ; Online: Strength Through Unity

Rebecca Cusseddu / Amélie Robert / Jean-François Côté

Frontiers in Cell and Developmental Biology, Vol

The Power of the Mega-Scaffold MACF1

2021 Volume 9

Abstract: The tight coordination of diverse cytoskeleton elements is required to support several dynamic cellular processes involved in development and tissue homeostasis. The spectraplakin-family of proteins are composed of multiple domains that provide ... ...

Abstract	The tight coordination of diverse cytoskeleton elements is required to support several dynamic cellular processes involved in development and tissue homeostasis. The spectraplakin-family of proteins are composed of multiple domains that provide versatility to connect different components of the cytoskeleton, including the actin microfilaments, microtubules and intermediates filaments. Spectraplakins act as orchestrators of precise cytoskeletal dynamic events. In this review, we focus on the prototypical spectraplakin MACF1, a protein scaffold of more than 700 kDa that coordinates the crosstalk between actin microfilaments and microtubules to support cell-cell connections, cell polarity, vesicular transport, proliferation, and cell migration. We will review over two decades of research aimed at understanding the molecular, physiological and pathological roles of MACF1, with a focus on its roles in developmental and cancer. A deeper understanding of MACF1 is currently limited by technical challenges associated to the study of such a large protein and we discuss ideas to advance the field.
Keywords	ACF7 ; spectraplakin ; signaling ; cancer ; cytoskeleton ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: A qPCR-based method to detect the eel parasitic nematode Anguillicola crassus in intermediate and final hosts.

Berger, Chloé Suzanne / Bougas, Bérénice / Côté, Guillaume / Dumont, Jean-François / Bernatchez, Louis

Parasitology research

2023 Volume 122, Issue 6, Page(s) 1435–1443

Abstract: Being able to systematically detect parasitic infection, even when no visual signs of infection are present, is crucial to the establishment of accurate conservation policies. The nematode Anguillicola crassus infects the swimbladder of anguillid species ...

Abstract	Being able to systematically detect parasitic infection, even when no visual signs of infection are present, is crucial to the establishment of accurate conservation policies. The nematode Anguillicola crassus infects the swimbladder of anguillid species and is a potential threat for eel populations. In North America, naïve hosts such as the American eel Anguilla rostrata are affected by this infection. The accidental introduction of A. crassus following restocking programs may contribute to the actual decline of the American eel in Canada. We present a quantitative real time PCR-based method to detect A. crassus infection in final and intermediate hosts. We tested two protocols on samples from different geographical origins in Canada: 1) a general detection of A. crassus DNA in pools of young final hosts (glass eels) or crustacean intermediate hosts 2) a detection at the individual scale by analyzing swim bladders from elvers, or from adult yellow and silver eels. The DNA of A. crassus was detected in one pool of zooplankton (intermediate host) from the Richelieu River (Montérégie-Québec), as well as in individual swim bladders of 13 elvers from Grande and Petite Trinité rivers (Côte-Nord-Québec). We suggest that our qPCR approach could be used in a quantitative way to estimate the parasitic burden in individual swim bladders of elvers. Our method, which goes beyond most of previous developed protocols that restricted the diagnosis of A. crassus to the moment when it was fully established in its final host, should help to detect early A. crassus infection in nature.
MeSH term(s)	Animals ; Fish Diseases/diagnosis ; Fish Diseases/parasitology ; Dracunculoidea ; Anguilla/parasitology ; Air Sacs/parasitology ; Geography
Language	English
Publishing date	2023-04-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-023-07843-1
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Article: Strength Through Unity: The Power of the Mega-Scaffold MACF1.

Cusseddu, Rebecca / Robert, Amélie / Côté, Jean-François

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 641727

Abstract	The tight coordination of diverse cytoskeleton elements is required to support several dynamic cellular processes involved in development and tissue homeostasis. The spectraplakin-family of proteins are composed of multiple domains that provide versatility to connect different components of the cytoskeleton, including the actin microfilaments, microtubules and intermediates filaments. Spectraplakins act as orchestrators of precise cytoskeletal dynamic events. In this review, we focus on the prototypical spectraplakin MACF1, a protein scaffold of more than 700 kDa that coordinates the crosstalk between actin microfilaments and microtubules to support cell-cell connections, cell polarity, vesicular transport, proliferation, and cell migration. We will review over two decades of research aimed at understanding the molecular, physiological and pathological roles of MACF1, with a focus on its roles in developmental and cancer. A deeper understanding of MACF1 is currently limited by technical challenges associated to the study of such a large protein and we discuss ideas to advance the field.
Language	English
Publishing date	2021-03-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.641727
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Article ; Online: Structural biology of DOCK‐family guanine nucleotide exchange factors

Boland, Andreas / Côté, Jean‐Francois / Barford, David

FEBS Letters. 2023 Mar., v. 597, no. 6 p.794-810

2023

Abstract: DOCK proteins are a family of multi‐domain guanine nucleotide exchange factors (GEFs) that activate the RHO GTPases CDC42 and RAC1, thereby regulating several RHO GTPase‐dependent cellular processes. DOCK proteins are characterized by the catalytic DHR2 ... ...

Abstract	DOCK proteins are a family of multi‐domain guanine nucleotide exchange factors (GEFs) that activate the RHO GTPases CDC42 and RAC1, thereby regulating several RHO GTPase‐dependent cellular processes. DOCK proteins are characterized by the catalytic DHR2 domain (DOCKᴰᴴᴿ²), and a phosphatidylinositol(3,4,5)P₃‐binding DHR1 domain (DOCKᴰᴴᴿ¹) that targets DOCK proteins to plasma membranes. DOCK‐family GEFs are divided into four subfamilies (A to D) differing in their specificities for CDC42 and RAC1, and the composition of accessory signalling domains. Additionally, the DOCK‐A and DOCK‐B subfamilies are constitutively associated with ELMO proteins that auto‐inhibit DOCK GEF activity. We review structural studies that have provided mechanistic insights into DOCK‐protein functions. These studies revealed how a conserved nucleotide sensor in DOCKᴰᴴᴿ² catalyses nucleotide exchange, the basis for how different DOCK proteins activate specifically CDC42 and RAC1, and sometimes both, and how up‐stream regulators relieve the ELMO‐mediated auto‐inhibition. We conclude by presenting a model for full‐length DOCK9 of the DOCK‐D subfamily. The involvement of DOCK GEFs in a range of diseases highlights the importance of gaining structural insights into these proteins to better understand and specifically target them.
Keywords	guanosinetriphosphatase ; models ; structural biology
Language	English
Dates of publication	2023-03
Size	p. 794-810.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	REVIEW
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14523
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Article ; Online: Risk of acute kidney injury associated with anti-pseudomonal and anti-MRSA antibiotic strategies in critically ill patients.

Jean-Maxime Côté / Michaël Desjardins / Jean-François Cailhier / Patrick T Murray / William Beaubien Souligny

PLoS ONE, Vol 17, Iss 3, p e

2022 Volume 0264281

Abstract: Background An increased risk of acute kidney injury (AKI) with the widely prescribed piperacillin-tazobactam(PTZ)-vancomycin combination in hospitalized patients has recently been reported, but evidence in ICU patients remain uncertain. This study ... ...

Abstract	Background An increased risk of acute kidney injury (AKI) with the widely prescribed piperacillin-tazobactam(PTZ)-vancomycin combination in hospitalized patients has recently been reported, but evidence in ICU patients remain uncertain. This study evaluates the association between the exposure of various broad-spectrum antibiotic regimens with Pseudomonas and/or methicillin-resistance Staphylococcus aureus (MRSA) coverage and the risk of AKI in critically ill patients. Methods and findings A retrospective cohort study based on the publicly available MIMIC-III database reporting hospitalization data from ICU patients from a large academic medical center between 2001 and 2012. Adult patients receiving an anti-pseudomonal or an anti-MRSA agent in the ICU for more than 24-hours were included. Non-PTZ anti-pseudomonal agents were compared to PTZ; non-vancomycin agents covering MRSA were compared to vancomycin; and their combinations were compared to the PTZ-vancomycin combination. The primary outcome was defined as new or worsening AKI within 7 days of the antibiotic exposure using an adjusted binomial generalized estimating equation. Overall, 18 510 admissions from 15 673 individual patients, cumulating 169 966 days of antibiotherapy were included. When compared to PTZ, exposure to another anti-pseudomonal agent was associated with lower AKI risk (OR, 0.85; 95% CI, 0.80-0.91; p < .001). When compared to vancomycin, exposure to another anti-MRSA was also associated with lower AKI risk (OR, 0.71; 95% CI, 0.64-0.80; p < .001). Finally, when compared to the PTZ-vancomycin combination, exposure to another regimen with a similar coverage was associated with an even lower risk (OR, 0.63; 95% CI; 0.54-0.73; p < .001). A sensitivity analysis of patients with high illness severity showed similar results. Conclusions These results suggest that the risk of AKI in ICU patients requiring antibiotherapy may be partially mitigated by the choice of antibiotics administered. Further clinical trials are required to confirm ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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