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Article: Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells.

bioRxiv : the preprint server for biology

2020

Abstract: ... cytokines G-CSF, M-CSF, IL-1α, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed ... Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein ... to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection ...

Abstract	COVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. In serum-deprived and stimulated cells treated with remdesivir and MEKi we observed correlations between pRB, pERK, and ACE2 expression further supporting role of proliferative state and MAPK pathway in ACE2 regulation. We show elevated cytokines in COVID-19-(+) patient plasma (N=9) versus control (N=11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1α, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed MEKi stimulation of NK-cell killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope infected human bronchial epithelial cells, small airway epithelial cells, or lung cancer cells and MEKi suppressed infectivity of the pseudovirus. We show a drug class-effect with MEKi to stimulate NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection to allow immune responses and antiviral agents to control disease progression.
Keywords	covid19
Language	English
Publishing date	2020-09-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.08.02.230839
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells

bioRxiv : the preprint server for biology

Abstract: ... in COVID-19- (+) patient plasma (N=9) versus control (N=11) TMPRSS2, inflammatory cytokines G-CSF, M- CSF ... S) protein on its envelope and used VSV-G lentivirus as a negative control Our results show ... of the SARS-CoV-2-S pseudovirus following infection We show a drug class-effect with MEKi to promote ...

Abstract	COVID-19 affects vulnerable populations including elderly individuals and patients with cancer Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells Chloroquine or hydroxychloroquine increase cleaved active SP-domain of TMPRSS2, and this is potentiated by MEKi In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi We show elevated cytokines in COVID-19- (+) patient plasma (N=9) versus control (N=11) TMPRSS2, inflammatory cytokines G-CSF, M- CSF, IL-1a, IL-6 and MCP-1 are suppressed by MEKi alone or in combination with remdesivir MEKi enhance NK cell (but not T-cell) killing of target-cells, without suppressing TRAIL-mediated cytotoxicity We generated a pseudotyped SARS-CoV-2 virus with a lentiviral core but with the SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope and used VSV-G lentivirus as a negative control Our results show infection of human bronchial epithelial cells or lung cancer cells and that MEKi suppress infectivity of the SARS-CoV-2-S pseudovirus following infection We show a drug class-effect with MEKi to promote immune responses involving NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells in a model system MEKi may attenuate coronavirus infection to allow immune responses and antiviral agents to control COVID-19 disease progression and severity
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #721062
Database	COVID19

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Article ; Online: Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells

bioRxiv

Abstract: ... M-CSF, IL-1alpha, IL-6 and MCP-1 are suppressed by MEKi alone or in combination with remdesivir ... or G614 SPIKE (S) protein on its envelope and used VSV-G lentivirus as a negative control ... infectivity of the SARS-CoV-2-S pseudovirus following infection. We show a drug class-effect with MEKi ...

Abstract	COVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. Chloroquine or hydroxychloroquine increase cleaved active SP-domain of TMPRSS2, and this is potentiated by MEKi. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. We show elevated cytokines in COVID-19-(+) patient plasma (N=9) versus control (N=11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1alpha, IL-6 and MCP-1 are suppressed by MEKi alone or in combination with remdesivir. MEKi enhance NK cell (but not T-cell) killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. We generated a pseudotyped SARS-CoV-2 virus with a lentiviral core but with the SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope and used VSV-G lentivirus as a negative control. Our results show infection of human bronchial epithelial cells or lung cancer cells and that MEKi suppress infectivity of the SARS-CoV-2-S pseudovirus following infection. We show a drug class-effect with MEKi to promote immune responses involving NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells in a model system. MEKi may attenuate coronavirus infection to allow immune responses and antiviral agents to control COVID-19 disease progression and severity.
Keywords	covid19
Language	English
Publishing date	2020-08-03
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.08.02.230839
Database	COVID19

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Article: Psychiatric diagnosis and the in-patient multidimensional psychiatric scale (I.M.P.S.).

Kerry, R J / Orme, J E

The British journal of psychiatry : the journal of mental science

1972 Volume 121, Issue 564, Page(s) 541–545

MeSH term(s)	Adjustment Disorders/diagnosis ; Anxiety/diagnosis ; Bipolar Disorder/diagnosis ; Depression/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Interview, Psychological ; Mental Disorders/diagnosis ; Neurotic Disorders/diagnosis ; Obsessive-Compulsive Disorder/diagnosis ; Psychiatric Status Rating Scales ; Schizophrenia/diagnosis ; Schizophrenia, Paranoid/diagnosis
Language	English
Publishing date	1972-11
Publishing country	England
Document type	Journal Article
ZDB-ID	218103-4
ISSN	1472-1465 ; 0007-1250
ISSN (online)	1472-1465
ISSN	0007-1250
DOI	10.1192/bjp.121.5.541
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Article: Designing, analyzing, and interpreting observational studies of physical activity and cancer outcomes from a clinical oncology perspective.

Courneya, Kerry S / Friedenreich, Christine M

Frontiers in oncology

2023 Volume 13, Page(s) 1098278

Abstract: Observational studies may play an important role in evaluating physical activity (PA) as a cancer treatment; however, few studies have been designed, analyzed, or interpreted from a clinical oncology perspective. The purpose of the present paper is to ... ...

Abstract	Observational studies may play an important role in evaluating physical activity (PA) as a cancer treatment; however, few studies have been designed, analyzed, or interpreted from a clinical oncology perspective. The purpose of the present paper is to apply the Exercise as Cancer Treatment (EXACT) Framework to assess current observational studies of PA and cancer outcomes from a clinical oncology perspective and provide recommendations to improve their clinical utility. Recent systematic reviews and meta-analyses of over 130 observational studies have concluded that higher prediagnosis and postdiagnosis PA are associated with lower risks of cancer-specific and all-cause mortality. Most of these studies, however, have: (a) included cancer patients receiving heterogeneous treatment protocols, (b) provided minimal details about those cancer treatments, (c) assessed PA prediagnosis and/or postdiagnosis without reference to those cancer treatments, (d) reported mainly mortality outcomes, and (e) examined subgroups based on demographic and disease variables but not cancer treatments. As a result, current observational studies on PA and cancer outcomes have played a modest role in informing clinical exercise trials and clinical oncology practice. To improve their clinical utility, we recommend that future observational studies of PA and cancer outcomes: (a) recruit cancer patients receiving the same or similar first-line treatment protocols, (b) collect detailed data on all planned and unplanned cancer treatments beyond whether or not cancer treatments were received, (c) assess PA in relation to cancer treatments (i.e., before, during, between, after) rather than in relation to the cancer diagnosis (i.e., various time periods before and after diagnosis), (d) collect data on cancer-specific outcomes (e.g., disease response, progression, recurrence) in addition to mortality, (e) conduct subgroup analyses based on cancer treatments received in addition to demographic and disease variables, and (f) interpret mechanisms for any associations between PA and cancer-specific outcomes based on the clinical oncology scenario that is recapitulated rather than referencing generic mechanisms or discordant preclinical models. In conclusion, observational studies are well-suited to contribute important knowledge regarding the role of PA as a cancer treatment; however, modifications to study design and analysis are necessary if they are to inform clinical research and practice.
Language	English
Publishing date	2023-04-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1098278
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Article ; Online: Molecular Detection and Genetic Diversity of Cytomegaloviruses and Lymphocryptoviruses in Free-Roaming and Captive African Green Monkeys (

Mancuso, Diana M / Gainor, Kerry / Dore, Kerry M / Gallagher, Christa A / Beierschmitt, Amy / Malik, Yashpal S / Ghosh, Souvik

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: To date, limited information is available on cytomegalovirus (CMV) and lymphocryptovirus (LCV) ... ...

Abstract	To date, limited information is available on cytomegalovirus (CMV) and lymphocryptovirus (LCV) from
MeSH term(s)	Animals ; Chlorocebus aethiops ; Lymphocryptovirus/genetics ; Cytomegalovirus/genetics ; Phylogeny ; Herpesvirus 4, Human ; Glycoproteins/genetics ; Genetic Variation ; Cytomegalovirus Infections
Chemical Substances	Glycoproteins
Language	English
Publishing date	2024-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063272
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Book: A practical guide to cluster randomised trials in health services research

Eldridge, Sandra / Kerry, Sally M.

(Statistics in practice)

2012

Author's details	Sandra Eldridge ; Sally Kerry
Series title	Statistics in practice
Keywords	Health Services Research ; Randomized Controlled Trials as Topic ; Cluster Analysis
Language	English
Size	XX, 278 S. : Ill.
Publisher	Wiley
Publishing place	Chichester
Publishing country	Great Britain
Document type	Book
Note	Includes bibliographical references and index
HBZ-ID	HT017277281
ISBN	978-0-470-51047-6 ; 9781119966241 ; 9781119966258 ; 9781119966722 ; 9781119966739 ; 0-470-51047-1 ; 1119966248 ; 1119966256 ; 1119966728 ; 1119966736
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
2012 A 2843	order for loan	Magazin

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Article: Exercise as cancer treatment: A clinical oncology framework for exercise oncology research.

Courneya, Kerry S / Booth, Christopher M

Frontiers in oncology

2022 Volume 12, Page(s) 957135

Abstract: Exercise has been proposed as a possible cancer treatment; however, there are an infinite number of clinical oncology settings involving diverse cancer types and treatment protocols in which exercise could be tested as a cancer treatment. The primary ... ...

Abstract	Exercise has been proposed as a possible cancer treatment; however, there are an infinite number of clinical oncology settings involving diverse cancer types and treatment protocols in which exercise could be tested as a cancer treatment. The primary purpose of this paper is to propose a conceptual framework to organize and guide research on exercise as a cancer treatment across distinct clinical oncology settings. A secondary purpose is to provide an overview of existing exercise research using the proposed framework. The Exercise as Cancer Treatment (EXACT) framework proposes nine distinct clinical oncology scenarios based on tumor/disease status and treatment status at the time of the proposed exercise treatment. In terms of tumor/disease status, the primary tumor has either been surgically removed (primary goal to treat micrometastases), not surgically removed (primary goal to treat the primary tumor), or metastatic disease is present (primary goal to treat metastatic disease). In terms of treatment status, the extant disease has either not been treated yet (treatment naïve), is currently being treated (active treatment), or has previously been treated. These two key clinical oncology variables-tumor/disease status and treatment status-result in nine distinct clinical oncology scenarios in which exercise could be tested as a new cancer treatment: (a) treatment naïve micrometastases, (b) actively treated micrometastases, (c) previously treated micrometastases, (d) treatment naïve primary tumors, (e) actively treated primary tumors, (f) previously treated primary tumors, (g) treatment naïve metastatic disease, (h) actively treated metastatic disease, and (i) previously treated metastatic disease. To date, most preclinical animal studies have examined the effects of exercise on treatment naïve and actively treated primary tumors. Conversely, most observational human studies have examined the associations between exercise and cancer recurrence/survival in patients actively treated or previously treated for micrometastases. Few clinical trials have been conducted in any of these scenarios. For exercise to be integrated into clinical oncology practice as a cancer treatment, it will need to demonstrate benefit in a specific clinical setting. The EXACT framework provides a simple taxonomy for systematically evaluating exercise as a potential cancer treatment across a diverse range of cancer types and treatment protocols.
Language	English
Publishing date	2022-09-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.957135
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Article: Incorporation of Sea Spaghetti (

Głuchowski, Artur / Crofton, Emily / Inguglia, Elena S / O'Sullivan, Maurice G / Kerry, Joe P / Hamill, Ruth M

Foods (Basel, Switzerland)

2024 Volume 13, Issue 8

Abstract: Seaweed is a naturally rich source of nutrients and exhibits techno-functional properties that are under study for their potential as ingredients in meat products. However, seaweed is associated with a particular flavor profile, and optimization of the ... ...

Abstract	Seaweed is a naturally rich source of nutrients and exhibits techno-functional properties that are under study for their potential as ingredients in meat products. However, seaweed is associated with a particular flavor profile, and optimization of the sensory profile should be conducted alongside technical performance. This study investigated the feasibility of the application of sea spaghetti (
Language	English
Publishing date	2024-04-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704223-6
ISSN	2304-8158
ISSN	2304-8158
DOI	10.3390/foods13081197
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Article ; Online: Analysis of Incidentally Found Proliferative Lesions in Oncoplastic and Macromastia Breast Reductions.

Morrison, Kerry A / Choi, Mihye / Karp, Nolan S

Plastic and reconstructive surgery

2023 Volume 152, Issue 4, Page(s) 559e–565e

Abstract: ... in 342 patients. Mean age was 43.9 ± 15.9 years, mean body mass index was 29.2 ± 5.7 kg/m 2 , and mean ...

Abstract	Background: Reduction mammaplasty pathologic specimens can reveal incidentally found proliferative lesions. However, there is a lack of data investigating the comparative incidences and risk factors for such lesions. Methods: A retrospective review was conducted of all consecutively performed reduction mammaplasty cases at a single large academic medical institution in a metropolitan city by two plastic surgeons over a 2-year period. All reduction mammaplasties, symmetrizing reductions, and oncoplastic reductions performed were included. There were no exclusion criteria. Results: A total of 632 breasts were analyzed-502 reduction mammaplasties, 85 symmetrizing reductions, and 45 oncoplastic reductions-in 342 patients. Mean age was 43.9 ± 15.9 years, mean body mass index was 29.2 ± 5.7 kg/m 2 , and mean reduction weight was 610.0 ± 313.1 g. Patients who underwent reduction mammaplasty for benign macromastia had a significantly lower incidence (3.6%) of incidentally found breast cancers and proliferative lesions compared with patients with oncoplastic reductions (13.3%) and symmetrizing reductions (17.6%) ( P < 0.001). On univariate analysis, personal history of breast cancer ( P < 0.001), first-degree family history of breast cancer ( P = 0.008), age ( P < 0.001), and tobacco use ( P = 0.033) were all statistically significant risk factors. Using a backward elimination stepwise reduced multivariable logistic regression model for risk factors associated with breast cancer or proliferative lesions, age ( P < 0.001) was the only retained significant risk factor. Conclusions: Proliferative lesions and carcinomas of the breast found in reduction mammaplasty pathologic specimens may be more common than previously reported. The incidence of newly found proliferative lesions was significantly lower in cases of benign macromastia compared with oncoplastic and symmetrizing reductions. Clinical question/level of evidence: Risk, II.
MeSH term(s)	Female ; Humans ; Adult ; Middle Aged ; Breast/surgery ; Breast/pathology ; Mammaplasty/adverse effects ; Breast Neoplasms/epidemiology ; Breast Neoplasms/surgery ; Breast Neoplasms/pathology ; Carcinoma, Intraductal, Noninfiltrating/surgery ; Retrospective Studies
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	208012-6
ISSN	1529-4242 ; 0032-1052 ; 0096-8501
ISSN (online)	1529-4242
ISSN	0032-1052 ; 0096-8501
DOI	10.1097/PRS.0000000000010341
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