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Article ; Online: Targeting network circuitry in glioma.

Robbins, Stephen M / Senger, Donna L

Nature cancer

2023 Volume 4, Issue 10, Page(s) 1406–1407

MeSH term(s)	Humans ; Glioma/therapy ; Brain Neoplasms/therapy
Language	English
Publishing date	2023-10-25
Publishing country	England
Document type	Journal Article
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00640-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: To promote or inhibit glioma progression, that is the question for IL-33.

Robbins, Stephen M / Senger, Donna L

Cell stress

2020 Volume 5, Issue 1, Page(s) 19–22

Abstract: IL-33, a member of the IL-1 cytokine family has been shown to play a dual role within the body. First IL-33, similar to other IL-1 family members, is a secreted cytokine that binds to the cell surface receptor ST2 to induce a number of cell signaling ... ...

Abstract	IL-33, a member of the IL-1 cytokine family has been shown to play a dual role within the body. First IL-33, similar to other IL-1 family members, is a secreted cytokine that binds to the cell surface receptor ST2 to induce a number of cell signaling pathways. Second, IL-33 enters the nucleus where it binds chromatin and directs transcriptional control of an array of growth factors and cytokines. Consistent with its complex cellular regulation, IL-33 mediates an array of biological functions by acting on a wide range of innate and adaptive immune cells. Recently, we found that IL-33 is expressed in a large number of human glioma patient specimens where its expression within the tumor correlates with the increased presence of Iba+ cells that include both resident microglia and recruited monocyte and macrophages. Strikingly, glioma derived expression of IL-33 correlates with a dramatic decrease in overall survival of tumor-bearing animals and thus supports its role as an influential factor in gliomagenesis. Notably however, when the nuclear localization function of IL-33 is crippled, the tumor microenvironment is programmed to be anti-tumorigenic and results in prolonged overall survival suggesting that when educated appropriately this could represent a novel therapeutic strategy for glioma (De Boeck
Language	English
Publishing date	2020-12-03
Publishing country	Austria
Document type	Journal Article ; Comment
ISSN	2523-0204
ISSN (online)	2523-0204
DOI	10.15698/cst2021.01.240
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Article ; Online: Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19).

Somayaji, Ranjani / Luke, David R / Lau, Arthur / Guner, Rahmet / Tabak, Ŏ Fehmi / Hepokoski, Mark / Gardetto, Nancy / Conrad, Steven A / Kumar, Sunil D / Ghosh, Kalyan / Robbins, Stephen M / Senger, Donna L / Sun, Daisy / Lim, Rachel K S / Liu, Jonathan / Eser, Fatma / Karaali, Ridvan / Tremblay, Alain / Muruve, Daniel

BMJ open

2024 Volume 14, Issue 3, Page(s) e076142

Abstract: Objective: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed ...

Abstract	Objective: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. Design: Phase 2a randomised, placebo-controlled, double-blinded, trial. Setting: Hospitals in Canada, Turkey and the USA. Participants: A total of 61 subjects with moderate-to-severe COVID-19. Interventions: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measures: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. Results: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O Conclusion: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration number: NCT04402957.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Proof of Concept Study ; Double-Blind Method ; Respiratory Insufficiency ; Respiratory Distress Syndrome/prevention & control ; Acute Kidney Injury/prevention & control ; Treatment Outcome
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Randomized Controlled Trial ; Multicenter Study ; Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-076142
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Article ; Online: The Canadian Path from Discovery to Implementation of Personalized Medicine Approaches.

Richer, Étienne / Syme, Rachel / Robbins, Stephen M / Lasko, Paul

Biomedicine hub

2017 Volume 2, Issue Suppl 1, Page(s) 41–43

Abstract: Personalized (or precision) medicine approaches are currently being introduced in healthcare delivery following the development of new technologies and of novel ways to integrate and analyze various data sources. This editorial describes the efforts ... ...

Abstract	Personalized (or precision) medicine approaches are currently being introduced in healthcare delivery following the development of new technologies and of novel ways to integrate and analyze various data sources. This editorial describes the efforts invested since 2012 by the Canadian Institutes of Health Research (CIHR) to foster the development and implementation of personalized medicine in Canada. Success stories from past investments as well as future developments are presented from a Canadian perspective.
Language	English
Publishing date	2017-11-21
Publishing country	Switzerland
Document type	Journal Article
ISSN	2296-6870
ISSN (online)	2296-6870
DOI	10.1159/000479487
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Article ; Online: Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury.

Lau, Arthur / Rahn, Jennifer J / Chappellaz, Mona / Chung, Hyunjae / Benediktsson, Hallgrimur / Bihan, Dominique / von Mässenhausen, Anne / Linkermann, Andreas / Jenne, Craig N / Robbins, Stephen M / Senger, Donna L / Lewis, Ian A / Chun, Justin / Muruve, Daniel A

Science advances

2022 Volume 8, Issue 5, Page(s) eabm0142

Abstract: The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia ... ...

Abstract	The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia reperfusion injury (IRI) induces robust neutrophil and monocyte recruitment and causes acute kidney injury (AKI). Renal inflammation and the AKI phenotype were attenuated in
MeSH term(s)	Acute Kidney Injury/etiology ; Animals ; Dipeptidases/metabolism ; Female ; GPI-Linked Proteins/metabolism ; Humans ; Inflammation/complications ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury
Chemical Substances	GPI-Linked Proteins ; Dipeptidases (EC 3.4.13.-) ; dipeptidase (EC 3.4.13.18) ; dipeptidase 1 (EC 3.4.13.19)
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abm0142
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Article: The Eph receptor/ephrin system: an emerging player in the invasion game.

Campbell, Tessa N / Robbins, Stephen M

Current issues in molecular biology

2008 Volume 10, Issue 1-2, Page(s) 61–66

Abstract: Eph receptor tyrosine kinases (Ephs) and their membrane-anchored ligands (ephrins) form a vital cell communication system capable of bi-directional signaling. This Eph receptor/ephrin system has classically been demonstrated to play a role in development. ...

Abstract	Eph receptor tyrosine kinases (Ephs) and their membrane-anchored ligands (ephrins) form a vital cell communication system capable of bi-directional signaling. This Eph receptor/ephrin system has classically been demonstrated to play a role in development. However, emerging evidence has revealed differential expression of Ephs and ephrins in numerous cancers. Recent studies suggest that this system influences invasive behaviour, promoting a more aggressive and metastatic phenotype. Hence, this minireview summarizes the current understanding of the contribution of both Eph receptors and their ephrin ligands to invasiveness in cancer, as well as their use as potential therapeutic targets.
MeSH term(s)	Animals ; Ephrins/metabolism ; Humans ; Neoplasm Invasiveness ; Neoplasms/metabolism ; Neoplasms/therapy ; Receptor, EphA1/metabolism
Chemical Substances	Ephrins ; Receptor, EphA1 (EC 2.7.10.1)
Language	English
Publishing date	2008-05-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2000024-8
ISSN	1467-3037
ISSN	1467-3037
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Article: The Canadian Path from Discovery to Implementation of Personalized Medicine Approaches

Richer, Étienne / Syme, Rachel / Robbins, Stephen M. / Lasko, Paul

Biomedicine Hub

2017 Volume 2, Issue 1

Institution	CIHR Institute of Genetics, Montreal, QC, and CIHR Institute of Cancer Research, Calgary, AB, Canada
Abstract	Personalized (or precision) medicine approaches are currently being introduced in healthcare delivery following the development of new technologies and of novel ways to integrate and analyze various data sources. This editorial describes the efforts invested since 2012 by the Canadian Institutes of Health Research (CIHR) to foster the development and implementation of personalized medicine in Canada. Success stories from past investments as well as future developments are presented from a Canadian perspective.
Keywords	Canada ; Implementation ; Personalized medicine
Language	English
Publishing date	2017-11-21
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Commentary ; This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
ISBN	978-3-318-06127-7 ; 3-318-06127-1
ISSN	2296-6870
ISSN (online)	2296-6870
DOI	10.1159/000479487
Database	Karger publisher's database

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Article ; Online: Characterization of the C. elegans erlin homologue

Hoegg Maja B / Robbins Stephen M / McGhee James D

BMC Cell Biology, Vol 13, Iss 1, p

2012 Volume 2

Abstract: Abstract Background Erlins are highly conserved proteins associated with lipid rafts within the endoplasmic reticulum (ER). Biochemical studies in mammalian cell lines have shown that erlins are required for ER associated protein degradation (ERAD) of ... ...

Abstract	Abstract Background Erlins are highly conserved proteins associated with lipid rafts within the endoplasmic reticulum (ER). Biochemical studies in mammalian cell lines have shown that erlins are required for ER associated protein degradation (ERAD) of activated inositol-1,4,5-trisphosphate receptors (IP3Rs), implying that erlin proteins might negatively regulate IP3R signalling. In humans, loss of erlin function appears to cause progressive intellectual disability, motor dysfunction and joint contractures. However, it is unknown if defects in IP3R ERAD are the underlying cause of this disease phenotype, whether ERAD of activated IP3Rs is the only function of erlin proteins, and what role ERAD plays in regulating IP3R-dependent processes in the context of an intact animal or embryo. In this study, we characterize the erlin homologue of the nematode Caenorhabditis elegans and examine erlin function in vivo . We specifically set out to test whether C. elegans erlin modulates IP3R-dependent processes, such as egg laying, embryonic development and defecation rates. We also explore the possibility that erlin might play a more general role in the ERAD pathway of C. elegans . Results We first show that the C. elegans erlin homologue, ERL-1, is highly similar to mammalian erlins with respect to amino acid sequence, domain structure, biochemical properties and subcellular location. ERL-1 is present throughout the C. elegans embryo; in adult worms, ERL-1 appears restricted to the germline. The expression pattern of ERL-1 thus only partially overlaps with that of ITR-1, eliminating the possibility of ERL-1 being a ubiquitous and necessary regulator of ITR-1. We show that loss of ERL-1 does not affect overall phenotype, or alter brood size, embryonic development or defecation cycle length in either wild type or sensitized itr-1 mutant animals. Moreover we show that ERL-1 deficient worms respond normally to ER stress conditions, suggesting that ERL-1 is not an essential component of the general ERAD pathway. Conclusions Although loss of erlin function apparently causes a strong phenotype in humans, no such effect is seen in C. elegans . C. elegans erlin does not appear to be a ubiquitous major modulator of IP3 receptor activity nor does erlin appear to play a major role in ERAD.
Keywords	Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Cytology ; QH573-671
Subject code	571
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of a peptide-based delivery platform for targeting malignant brain tumors.

Rahn, Jennifer J / Lun, Xueqing / Jorch, Selina K / Hao, Xiaoguang / Venugopal, Chitra / Vora, Parvez / Ahn, Bo Young / Babes, Liane / Alshehri, Mana M / Cairncross, J Gregory / Singh, Sheila K / Kubes, Paul / Senger, Donna L / Robbins, Stephen M

Biomaterials

2020 Volume 252, Page(s) 120105

Abstract: Despite extensive molecular characterization, human glioblastoma remains a fatal disease with survival rates measured in months. Little improvement is seen with standard surgery, radiotherapy and chemotherapy. Clinical progress is hampered by the ... ...

Abstract	Despite extensive molecular characterization, human glioblastoma remains a fatal disease with survival rates measured in months. Little improvement is seen with standard surgery, radiotherapy and chemotherapy. Clinical progress is hampered by the inability to detect and target glioblastoma disease reservoirs based on a diffuse invasive pattern and the presence of molecular and phenotypic heterogeneity. The goal of this study was to target the invasive and stem-like glioblastoma cells that evade first-line treatments using agents capable of delivering imaging enhancers or biotherapeutic cargo. To accomplish this, a combinatorial phage display library was biopanned against glioblastoma cell model systems that accurately recapitulate the intra- and inter-tumor heterogeneity and infiltrative nature of the disease. Candidate peptides were screened for specificity and ability to target glioblastoma cells in vivo. Cargo-conjugated peptides delivered contrast-enhancing agents to highly infiltrative tumor populations in intracranial xenograft models without the obvious need for blood brain barrier disruption. Simultaneous use of five independent targeting peptides provided greater coverage of this complex tumor and selected peptides have the capacity to deliver a therapeutic cargo (oncolytic virus VSVΔM51) to the tumor cells in vivo. Herein, we have identified a series of peptides with utility as an innovative platform to assist in targeting glioblastoma for the purpose of diagnostic or prognostic imaging, image-guided surgery, and/or improved delivery of therapeutic agents to glioblastoma cells implicated in disease relapse.
MeSH term(s)	Animals ; Brain Neoplasms ; Cell Line, Tumor ; Glioblastoma/drug therapy ; Humans ; Oncolytic Viruses ; Peptides
Chemical Substances	Peptides
Language	English
Publishing date	2020-05-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2020.120105
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Article: Development of a peptide-based delivery platform for targeting malignant brain tumors

Rahn, Jennifer J / Lun, Xueqing / Jorch, Selina K / Hao, Xiaoguang / Venugopal, Chitra / Vora, Parvez / Ahn, Bo Young / Babes, Liane / Alshehri, Mana M / Cairncross, J. Gregory / Singh, Sheila K / Kubes, Paul / Senger, Donna L / Robbins, Stephen M

Biomaterials. 2020 Sept., v. 252

2020

Abstract	Despite extensive molecular characterization, human glioblastoma remains a fatal disease with survival rates measured in months. Little improvement is seen with standard surgery, radiotherapy and chemotherapy. Clinical progress is hampered by the inability to detect and target glioblastoma disease reservoirs based on a diffuse invasive pattern and the presence of molecular and phenotypic heterogeneity. The goal of this study was to target the invasive and stem-like glioblastoma cells that evade first-line treatments using agents capable of delivering imaging enhancers or biotherapeutic cargo. To accomplish this, a combinatorial phage display library was biopanned against glioblastoma cell model systems that accurately recapitulate the intra- and inter-tumor heterogeneity and infiltrative nature of the disease. Candidate peptides were screened for specificity and ability to target glioblastoma cells in vivo. Cargo-conjugated peptides delivered contrast-enhancing agents to highly infiltrative tumor populations in intracranial xenograft models without the obvious need for blood brain barrier disruption. Simultaneous use of five independent targeting peptides provided greater coverage of this complex tumor and selected peptides have the capacity to deliver a therapeutic cargo (oncolytic virus VSVΔM51) to the tumor cells in vivo. Herein, we have identified a series of peptides with utility as an innovative platform to assist in targeting glioblastoma for the purpose of diagnostic or prognostic imaging, image-guided surgery, and/or improved delivery of therapeutic agents to glioblastoma cells implicated in disease relapse.
Keywords	bacteriophages ; biocompatible materials ; blood-brain barrier ; brain ; drug therapy ; glioblastoma ; humans ; peptides ; phenotypic variation ; radiotherapy ; relapse ; xenotransplantation
Language	English
Dates of publication	2020-09
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2020.120105
Database	NAL-Catalogue (AGRICOLA)

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