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Article ; Online: Safety and efficacy of autologous cell vaccines in solid tumors: a systematic review and meta-analysis of randomized control trials.

Bastin, Donald J / Montroy, Joshua / Kennedy, Michael A / Martel, Andre B / Shorr, Risa / Ghiasi, Maryam / Boucher, Dominique M / Wong, Boaz / Gresham, Louise / Diallo, Jean-Simon / Fergusson, Dean A / Lalu, Manoj M / Kekre, Natasha / Auer, Rebecca C

Scientific reports

2023 Volume 13, Issue 1, Page(s) 3347

Abstract: We conducted a systematic review and meta-analysis of randomized control trials to formally assess the safety and efficacy of autologous whole cell vaccines as immunotherapies for solid tumors. Our primary safety outcome was number, and grade of adverse ... ...

Abstract	We conducted a systematic review and meta-analysis of randomized control trials to formally assess the safety and efficacy of autologous whole cell vaccines as immunotherapies for solid tumors. Our primary safety outcome was number, and grade of adverse events. Our primary efficacy outcome was clinical responses. Secondary outcomes included survival metrics and correlative immune assays. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published between 1946 and August 2020 using any autologous whole cell product in the treatment of any solid tumor. The Cochrane Randomized Controlled Trial risk of bias tool was used to assess risk of bias. Eighteen manuscripts were identified with a total of 714 patients enrolled in control and 808 in vaccine arms. In 698 patients receiving at least one dose of vaccine, treatment was well tolerated with a total of 5 grade III or higher adverse events. Clinical response was reported in a minority (n = 2, 14%) of studies. Autologous cell vaccines were associated with improved overall (HR 1.28, 95% CI 1.01-1.63) and disease-free survival (HR 1.33, 95% CI 1.05-1.67) over thirteen and ten trials respectively. Where reported, immune assays correlated well with clinical outcomes. Our results suggest that autologous whole cell vaccination is safe and efficacious in increasing survival in patients undergoing treatment for solid tumors.Registration: PROSPERO CRD42019140187.
MeSH term(s)	Humans ; Cancer Vaccines/adverse effects ; Immunotherapy ; Neoplasms/therapy
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2023-02-27
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-29630-9
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Article ; Online: Human Perivascular Adipose Tissue as a Regulator of the Vascular Microenvironment and Diseases of the Coronary Artery and Aorta.

Stieber, Caitlin / Malka, Kimberly / Boucher, Joshua M / Liaw, Lucy

Journal of cardiology and cardiovascular sciences

2019 Volume 3, Issue 4, Page(s) 10–15

Abstract: Perivascular adipose tissue (PVAT) is an adipose depot that surrounds blood vessels in the human body and exerts local paracrine signaling. Under physiologically healthy conditions, PVAT has an anti-contractile effect on vessels, but in obesity this ... ...

Abstract	Perivascular adipose tissue (PVAT) is an adipose depot that surrounds blood vessels in the human body and exerts local paracrine signaling. Under physiologically healthy conditions, PVAT has an anti-contractile effect on vessels, but in obesity this effect is lost. During metabolic disease, adiponectin secretion is dysregulated, influencing nitric oxide bioavailability and macrophage infiltration and inflammation, all of which mediate PVAT signaling. However, based on the location in the body, and the type of adipocyte present, PVAT has different relationships with risk factors for disease. Imaging studies in patients with cardiovascular disease have demonstrated important associations between PVAT structure and pathology, yet insight into molecular pathways regulating human PVAT function are still lacking. This review focuses on our current understanding of human PVAT and its secretory role in the vascular microenvironment. A current area of priority is defining molecular differences in the secretome between PVAT depots, as this could inform the treatment of diseases that occur in anatomically restricted locations. In addition, understanding progressive changes in PVAT structure and function during metabolic disease is required for effective targeted therapies.
Language	English
Publishing date	2019-08-13
Publishing country	United States
Document type	Journal Article
ISSN	2578-3025
ISSN (online)	2578-3025
DOI	10.29245/2578-3025/2019/4.1174
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Article ; Online: Antiangiogenic VEGF-A in peripheral artery disease.

Boucher, Joshua M / Bautch, Victoria L

Nature medicine

2014 Volume 20, Issue 12, Page(s) 1383–1385

Abstract: Vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic cytokine elevated in patients with peripheral artery disease (PAD). A new study links impaired vascular regrowth in PAD to increased expression of an antiangiogenic splice variant of ...

Abstract	Vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic cytokine elevated in patients with peripheral artery disease (PAD). A new study links impaired vascular regrowth in PAD to increased expression of an antiangiogenic splice variant of VEGF-A.
MeSH term(s)	Animals ; Humans ; Neovascularization, Physiologic/physiology ; Peripheral Arterial Disease/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2014-12
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.3767
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Article ; Online: On the Occurrence of Dangerous Problem Behavior during Functional Analysis: An Evaluation of 30 Applications.

Jessel, Joshua / Rosenthal, Debra / Hanley, Gregory P / Rymill, Lauren / Boucher, Megan B / Howard, Monica / Perrin, Jesse / Lemos, Felipe M

Behavior modification

2021 Volume 46, Issue 4, Page(s) 834–862

Abstract: Functional analyses are often conducted by behavior analysts to understand the environmental variables contributing to an individual's problem behavior to better inform treatment implementation. While functional analyses are integral for designing ... ...

Abstract	Functional analyses are often conducted by behavior analysts to understand the environmental variables contributing to an individual's problem behavior to better inform treatment implementation. While functional analyses are integral for designing function-based interventions, they often arrange contingencies to evoke and reinforce dangerous problem behavior. In Study 1 we reviewed 22 functional analyses with open-contingency classes including non-dangerous topographies of problem behavior and we found that participants were more likely to exhibit the non-dangerous behavior in 82% of the applications. We then conducted a single-subject comparison of closed and open-contingency classes with four additional participants in Study 2. Our results suggest that the functional analyses with the open-contingency class reduced the likelihood of observing dangerous problem behavior.
MeSH term(s)	Humans ; Probability ; Problem Behavior ; Reinforcement, Psychology
Language	English
Publishing date	2021-04-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	432229-0
ISSN	1552-4167 ; 0145-4455
ISSN (online)	1552-4167
ISSN	0145-4455
DOI	10.1177/01454455211010698
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Article: ARF6-dependent endocytic trafficking of the Interferon-γ receptor drives adaptive immune resistance in cancer.

Wee, Yinshen / Wang, Junhua / Wilson, Emily C / Rich, Coulson P / Rogers, Aaron / Tong, Zongzhong / DeGroot, Evelyn / Gopal, Y N Vashisht / Davies, Michael A / Ekiz, H Atakan / Tay, Joshua K H / Stubben, Chris / Boucher, Kenneth M / Oviedo, Juan M / Fairfax, Keke C / Williams, Matthew A / Holmen, Sheri L / Wolff, Roger K / Grossmann, Allie H

bioRxiv : the preprint server for biology

2023

Abstract: Adaptive immune resistance (AIR) is a protective process used by cancer to escape elimination by ... ...

Abstract	Adaptive immune resistance (AIR) is a protective process used by cancer to escape elimination by CD8
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.29.560199
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Article ; Online: Health psychology and behavioral medicine researchers in Canada: An environmental scan.

Ross, Kharah M / Hoggan, Ryan / Campbell, Tavis S / Gordon, Jennifer / Gosselin Boucher, Vincent / Kim, Eric / Lavoie, Kim / Linden, Wolfgang / Rash, Joshua A / Rouleau, Codie R / Stewart, Sherry H / Presseau, Justin

Journal of health psychology

2022 Volume 28, Issue 6, Page(s) 509–523

Abstract: The purpose of this study is to characterize contemporary Canadian health psychology through an environmental scan by identifying faculty, research productivity and strengths, and collaborator interconnectivity. Profiles at Canadian universities were ... ...

Abstract	The purpose of this study is to characterize contemporary Canadian health psychology through an environmental scan by identifying faculty, research productivity and strengths, and collaborator interconnectivity. Profiles at Canadian universities were reviewed for faculty with psychology doctorates and health psychology research programs. Publications were obtained through Google Scholar and PubMed (Jan/18-Mar/21). A total of 284 faculty were identified. Cancer, pain, and sleep were key research topics. The collaborator network analysis revealed that most were linked through a common network, with clusters organized around geography, topic, and trainee relationships. Canada is a unique and productive contributor to health psychology.
MeSH term(s)	Humans ; Behavioral Medicine ; Canada ; Faculty ; Efficiency ; Pain
Language	English
Publishing date	2022-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2021897-7
ISSN	1461-7277 ; 1359-1053
ISSN (online)	1461-7277
ISSN	1359-1053
DOI	10.1177/13591053221124748
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Article ; Online: Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells.

Scott, S Spencer / Yang, Xuehui / Robich, Michael / Liaw, Lucy / Boucher, Joshua M

Journal of visualized experiments : JoVE

2019 , Issue 145

Abstract: Adipose tissue is a rich source of multi-potent mesenchymal stem cells (MSC) capable of differentiating into osteogenic, adipogenic, and chondrogenic lineages. Adipogenic differentiation of progenitor cells is a major mechanism driving adipose tissue ... ...

Abstract	Adipose tissue is a rich source of multi-potent mesenchymal stem cells (MSC) capable of differentiating into osteogenic, adipogenic, and chondrogenic lineages. Adipogenic differentiation of progenitor cells is a major mechanism driving adipose tissue expansion and dysfunction in response to obesity. Understanding changes to perivascular adipose tissue (PVAT) is thus clinically relevant in metabolic disease. However, previous studies have been predominately performed in the mouse and other animal models. This protocol uses human thoracic PVAT samples collected from patients undergoing coronary artery bypass graft surgery. Adipose tissue from the ascending aorta was collected and used for explantation of the stromal vascular fraction. We previously confirmed the presence of adipose progenitor cells in human PVAT with the capacity to differentiate into lipid-containing adipocytes. In this study, we further analyzed the differentiation potential of cells from the stromal vascular fraction, presumably containing multi-potent progenitor cells. We compared PVAT-derived cells to human bone marrow MSC for differentiation into adipogenic, osteogenic, and chondrogenic lineages. Following 14 days of differentiation, specific stains were utilized to detect lipid accumulation in adipocytes (Oil red O), calcific deposits in osteogenic cells (Alizarin Red), or glycosaminoglycans and collagen in chondrogenic cells (Masson's Trichrome). While bone marrow MSC efficiently differentiated into all three lineages, PVAT-derived cells had adipogenic and chondrogenic potential, but lacked robust osteogenic potential.
MeSH term(s)	Adipocytes/cytology ; Adipogenesis ; Adipose Tissue/blood supply ; Adipose Tissue/cytology ; Animals ; Aorta/cytology ; Cell Differentiation ; Cell Shape ; Cells, Cultured ; Chondrogenesis ; Humans ; Mesenchymal Stem Cells/cytology ; Osteogenesis ; Stromal Cells/cytology
Language	English
Publishing date	2019-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/59337
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Article: Differentiation capacity of human aortic perivascular adipose progenitor cells

Scott, S. Spencer / Yang, Xuehui / Robich, Michael / Liaw, Lucy / Boucher, Joshua M

Journal of visualized experiments. 2019 Mar. 05, , no. 145

2019

Abstract	Adipose tissue is a rich source of multi-potent mesenchymal stem cells (MSC) capable of differentiating into osteogenic, adipogenic, and chondrogenic lineages. Adipogenic differentiation of progenitor cells is a major mechanism driving adipose tissue expansion and dysfunction in response to obesity. Understanding changes to perivascular adipose tissue (PVAT) is thus clinically relevant in metabolic disease. However, previous studies have been predominately performed in the mouse and other animal models. This protocol uses human thoracic PVAT samples collected from patients undergoing coronary artery bypass graft surgery. Adipose tissue from the ascending aorta was collected and used for explantation of the stromal vascular fraction. We previously confirmed the presence of adipose progenitor cells in human PVAT with the capacity to differentiate into lipid-containing adipocytes. In this study, we further analyzed the differentiation potential of cells from the stromal vascular fraction, presumably containing multi-potent progenitor cells. We compared PVAT-derived cells to human bone marrow MSC for differentiation into adipogenic, osteogenic, and chondrogenic lineages. Following 14 days of differentiation, specific stains were utilized to detect lipid accumulation in adipocytes (Oil red O), calcific deposits in osteogenic cells (Alizarin Red), or glycosaminoglycans and collagen in chondrogenic cells (Masson’s Trichrome). While bone marrow MSC efficiently differentiated into all three lineages, PVAT-derived cells had adipogenic and chondrogenic potential, but lacked robust osteogenic potential.
Keywords	adipocytes ; adipogenesis ; adipose tissue ; alizarin ; animal models ; aorta ; bone formation ; bone marrow ; collagen ; coronary vessels ; glycosaminoglycans ; humans ; lipids ; mesenchymal stromal cells ; metabolic diseases ; mice ; obesity ; patients ; stem cells ; surgery
Language	English
Dates of publication	2019-0305
Size	p. e59337.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/59337
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Article ; Online: Comprehensive evaluation and efficient classification of BRCA1 RING domain missense substitutions.

Clark, Kathleen A / Paquette, Andrew / Tao, Kayoko / Bell, Russell / Boyle, Julie L / Rosenthal, Judith / Snow, Angela K / Stark, Alex W / Thompson, Bryony A / Unger, Joshua / Gertz, Jason / Varley, Katherine E / Boucher, Kenneth M / Goldgar, David E / Foulkes, William D / Thomas, Alun / Tavtigian, Sean V

American journal of human genetics

2022 Volume 109, Issue 6, Page(s) 1153–1174

Abstract: BRCA1 is a high-risk susceptibility gene for breast and ovarian cancer. Pathogenic protein-truncating variants are scattered across the open reading frame, but all known missense substitutions that are pathogenic because of missense dysfunction are ... ...

Abstract	BRCA1 is a high-risk susceptibility gene for breast and ovarian cancer. Pathogenic protein-truncating variants are scattered across the open reading frame, but all known missense substitutions that are pathogenic because of missense dysfunction are located in either the amino-terminal RING domain or the carboxy-terminal BRCT domain. Heterodimerization of the BRCA1 and BARD1 RING domains is a molecularly defined obligate activity. Hence, we tested every BRCA1 RING domain missense substitution that can be created by a single nucleotide change for heterodimerization with BARD1 in a mammalian two-hybrid assay. Downstream of the laboratory assay, we addressed three additional challenges: assay calibration, validation thereof, and integration of the calibrated results with other available data, such as computational evidence and patient/population observational data to achieve clinically applicable classification. Overall, we found that 15%-20% of BRCA1 RING domain missense substitutions are pathogenic. Using a Bayesian point system for data integration and variant classification, we achieved clinical classification of 89% of observed missense substitutions. Moreover, among missense substitutions not present in the human observational data used here, we find an additional 45 with concordant computational and functional assay evidence in favor of pathogenicity plus 223 with concordant evidence in favor of benignity; these are particularly likely to be classified as likely pathogenic and likely benign, respectively, once human observational data become available.
MeSH term(s)	Animals ; BRCA1 Protein/genetics ; Bayes Theorem ; Breast Neoplasms/genetics ; Female ; Humans ; Mammals ; Mutation, Missense/genetics ; Ovarian Neoplasms/genetics ; Protein Domains
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human
Language	English
Publishing date	2022-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2022.05.004
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Article ; Online: Neurodegeneration in a novel invertebrate model system: Failed microtubule-mediated cell adhesion and unraveling of macroglia.

Fabian-Fine, Ruth / Aiken, Anna M / Aug, Julia R / Boucher, Jason D / Butler, Danielle C / Clancy, Liam J / Clem, Shaun A / Crotty, Samantha C / Dalpe, Abigail M / Donzello-Jewett, Elizabeth J / Galgay, Taylor M / Gillis, Bonnie K / Heinrich, Brigid W / Hines, Kai R / Kimmel, Jordan E / McGrath, Joseph M / Miles, Marissa M / Morey, Jordyn A / Ortiz, Isaiah A /

Pham, Kevin Q / Quinn, Liam C / Radican, Colin J / Speidel, Nolan T / Thomas, Bailey J / Troisi, Angela R / Weiss, Joshua L / Wentzheimer, Kayne V / Weaver, Adam L

The Journal of comparative neurology

2023 Volume 531, Issue 5, Page(s) 618–638

Abstract: Neurodegenerative diseases are among the main causes of death in the United States, leading to irreversible disintegration of neurons. Despite intense international research efforts, cellular mechanisms that initiate neurodegeneration remain elusive, ... ...

Abstract	Neurodegenerative diseases are among the main causes of death in the United States, leading to irreversible disintegration of neurons. Despite intense international research efforts, cellular mechanisms that initiate neurodegeneration remain elusive, thus inhibiting the development of effective preventative and early onset medical treatment. To identify underlying cellular mechanisms that initiate neuron degeneration, it is critical to identify histological and cellular hallmarks that can be linked to underlying biochemical processes. Due to the poor tissue preservation of degenerating mammalian brain tissue, our knowledge regarding histopathological hallmarks of early to late degenerative stages is only fragmentary. Here, we introduce a novel model organism to study histological hallmarks of neurodegeneration, the spider Cupiennius salei. We utilized toluidine blue-stained 0.9-μm serial semithin and 50-nm ultrathin sections of young and old spider nervous tissue. Our findings suggest that the initial stages of neurodegeneration in spiders may be triggered by (1) dissociation of neuron- and glia-derived microtubules, and (2) the weakening of microtubule-associated desmosomal junctions that lead to the unraveling of neuron-insulating macroglia, compromising the structural integrity of affected neurons. The involvement of macroglia in the disposal of neuronal debris described here-although different in the proposed transport mechanisms-shows resemblance to the mammalian glymphatic system. We propose that this model system is highly suitable to investigate invertebrate neurodegenerative processes from early onset to scar formation and that this knowledge may be useful for the study of neurodegeneration in mammalian tissue.
MeSH term(s)	Animals ; Cell Adhesion ; Neurons/metabolism ; Brain ; Microtubules ; Invertebrates ; Spiders ; Mammals
Language	English
Publishing date	2023-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.25450
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