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Article ; Online: The Role of Bacterial, Dentinal, Salivary, and Neutrophil Degradative Activity in Caries Pathogenesis.

Peled, Yuval / Stewart, Cameron A / Glogauer, Michael / Finer, Yoav

2023 Volume 11, Issue 9

Abstract: Until recently, it was widely accepted that bacteria participate in caries pathogenesis mainly through carbohydrate fermentation and acid production, which promote the dissolution of tooth components. Neutrophils, on the other hand, were considered white ...

Abstract	Until recently, it was widely accepted that bacteria participate in caries pathogenesis mainly through carbohydrate fermentation and acid production, which promote the dissolution of tooth components. Neutrophils, on the other hand, were considered white blood cells with no role in caries pathogenesis. Nevertheless, current literature suggests that both bacteria and neutrophils, among other factors, possess direct degradative activity towards both dentinal collagen type-1 and/or methacrylate resin-based restoratives and adhesives, the most common dental restoratives. Neutrophils are abundant leukocytes in the gingival sulcus, where they can readily reach adjacent tooth roots or gingival and cervical restorations and execute their degradative activity. In this review, we present the latest literature evidence for bacterial, dentinal, salivary, and neutrophil degradative action that may induce primary caries, secondary caries, and restoration failure.
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2681351-8
ISSN	2304-6767 ; 2304-6767
ISSN (online)	2304-6767
ISSN	2304-6767
DOI	10.3390/dj11090217
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Data on the identification of VRK2 as a mediator of PD-1 function.

Peled, Michael / Adam, Kieran / Mor, Adam

Data in brief

2021 Volume 37, Page(s) 107168

Abstract: Therapeutic programmed cell death protein 1 (PD-1) blockade ... ...

Abstract	Therapeutic programmed cell death protein 1 (PD-1) blockade enhances
Language	English
Publishing date	2021-05-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2021.107168
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Article: Data on the identification of VRK2 as a mediator of PD-1 function

Peled, Michael / Adam, Kieran / Mor, Adam

Data in Brief. 2021 Aug., v. 37

2021

Abstract: Therapeutic programmed cell death protein 1 (PD-1) blockade enhances T cell mediated anti-tumor immunity, but many patients do not respond, and a significant proportion develops inflammatory toxicities. To develop better therapeutics and to understand ... ...

Abstract	Therapeutic programmed cell death protein 1 (PD-1) blockade enhances T cell mediated anti-tumor immunity, but many patients do not respond, and a significant proportion develops inflammatory toxicities. To develop better therapeutics and to understand the signaling pathways downstream of PD-1 we performed phosphoproteomic interrogation of PD-1 to identify key mediators of PD-1 signaling. Hereby, supporting data of the research article “VRK2 inhibition synergizes with PD-1 blockade to improve T cell responses” are presented. In the primary publication, we proposed that VRK2 is a unique therapeutic target and that combination of VRK2 inhibitors with PD-1 blockade may improve cancer immunotherapy. Here, we provide data on the effect of other kinases on PD-1 signaling utilizing shRNA knockdown of the different kinases in Jurkat T cells. In addition, we used VRK2 inhibition by a pharmacologic approach in the MC38 tumor mouse model, to show the combined outcome of anti PD-1 treatment with VRK2 inhibition. These data provide additional targets downstream PD-1 and point toward methods of testing the effect of the inhibition of these targets on tumor progression in vivo.
Keywords	T-lymphocytes ; immunity ; immunotherapy ; mice ; neoplasm progression ; neoplasms ; phosphotransferases (kinases) ; programmed cell death
Language	English
Dates of publication	2021-08
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2021.107168
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Article ; Online: Data on the identification of VRK2 as a mediator of PD-1 function

Michael Peled / Kieran Adam / Adam Mor

Data in Brief, Vol 37, Iss , Pp 107168- (2021)

2021

Abstract	Therapeutic programmed cell death protein 1 (PD-1) blockade enhances T cell mediated anti-tumor immunity, but many patients do not respond, and a significant proportion develops inflammatory toxicities. To develop better therapeutics and to understand the signaling pathways downstream of PD-1 we performed phosphoproteomic interrogation of PD-1 to identify key mediators of PD-1 signaling. Hereby, supporting data of the research article “VRK2 inhibition synergizes with PD-1 blockade to improve T cell responses” are presented. In the primary publication, we proposed that VRK2 is a unique therapeutic target and that combination of VRK2 inhibitors with PD-1 blockade may improve cancer immunotherapy. Here, we provide data on the effect of other kinases on PD-1 signaling utilizing shRNA knockdown of the different kinases in Jurkat T cells. In addition, we used VRK2 inhibition by a pharmacologic approach in the MC38 tumor mouse model, to show the combined outcome of anti PD-1 treatment with VRK2 inhibition. These data provide additional targets downstream PD-1 and point toward methods of testing the effect of the inhibition of these targets on tumor progression in vivo.
Keywords	PD-1 ; T CELL ; TCR ; VRK2 ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
Subject code	572
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: VRK2 inhibition synergizes with PD-1 blockade to improve T cell responses.

Peled, Michael / Tocheva, Anna S / Adam, Kieran / Mor, Adam

Immunology letters

2021 Volume 233, Page(s) 42–47

Abstract: Therapeutic programmed cell death protein 1 (PD-1) blockade enhances T cell mediated anti-tumor immunity but many patients do not respond and a significant proportion develops inflammatory toxicities. To develop better therapeutics and to understand the ... ...

Abstract	Therapeutic programmed cell death protein 1 (PD-1) blockade enhances T cell mediated anti-tumor immunity but many patients do not respond and a significant proportion develops inflammatory toxicities. To develop better therapeutics and to understand the signaling pathways downstream of PD-1 we performed phosphoproteomic analysis of PD-1 and identified vaccinia related kinase 2 (VRK2) as a key mediator of PD-1 signaling. Using genetic and pharmacological approaches, we discovered that VRK2 is required for PD-1-induced phosphorylation of the protein p21 activated kinase 2 (PAK2), and for the inhibition of IL-2, IL-8, and IFN-γ secretion. Moving into in vivo syngeneic tumor models, pharmacologic inhibition of VRK2 in combination with PD-1 blockade enhanced tumor clearance through T cell activation. This study suggests that VRK2 is a unique therapeutic target and that combination of VRK2 inhibitors with PD-1 blockade may improve cancer immunotherapy.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cytokines/biosynthesis ; Drug Synergism ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immunity, Cellular ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/immunology ; Mice ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	Antineoplastic Agents ; Cytokines ; Immune Checkpoint Inhibitors ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; VRK2 protein, human (EC 2.7.11.1)
Language	English
Publishing date	2021-03-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	445150-8
ISSN	1879-0542 ; 0165-2478
ISSN (online)	1879-0542
ISSN	0165-2478
DOI	10.1016/j.imlet.2021.03.007
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Article ; Online: Referral rates and barriers to lung transplantation based on pulmonary function criteria in interstitial lung diseases: a retrospective cohort study.

Deri, Ofir / Ovadia, David / Huszti, Ella / Peled, Michael / Saute, Milton / Hod, Tammy / Onn, Amir / Seluk, Lior / Furie, Nadav / Shafran, Inbal / Mass, Ronen / Chatterji, Sumit / Levy, Liran

Therapeutic advances in respiratory disease

2024 Volume 18, Page(s) 17534666231221750

Abstract: Background: Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with ...

Abstract	Background: Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with significant morbidity and mortality. Among other criteria, patients with ILD should be considered for LTx if forced vital capacity (FVC) is less than 80% or diffusion capacity for carbon monoxide (DLCO) is less than 40%. However, data on referral rates are lacking. Objectives: To evaluate referral rates for LTx based on pulmonary function tests (PFTs) and identify barriers associated with non-referral. Design: A single-center retrospective cohort study. Methods: The study consisted of ILD patients who performed PFT between 2014 and 2020. Patients with FVC < 80% or a DLCO < 40% were included in the study. Patients with absolute contraindications to LTx were excluded. Referral rates were computed, and a comparison was made between referred and non-referred subjects. Results: Out of 114 ILD patients meeting criteria for referral to LTx, 35 were referred (30.7%), and 7 proceeded to undergo LTx. Median time from PFT to referral for assessment was 255 days [interquartile range (IQR) 35-1077]. Median time from referral to LTx was 89 days (IQR 59-143). Referred patients were younger ( Conclusion: There is under-referral of ILD patients who are eligible for LTx, which is associated with severe disease and missed opportunities for LTx. Further research is required to validate these findings.
MeSH term(s)	Humans ; Retrospective Studies ; Quality of Life ; Lung ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/surgery ; Lung Transplantation/adverse effects ; Referral and Consultation
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2476459-0
ISSN	1753-4666 ; 1753-4658
ISSN (online)	1753-4666
ISSN	1753-4658
DOI	10.1177/17534666231221750
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Zs.A 6753: Show issues

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Article: Weaning of Severe COVID-19 Mechanically Ventilated Patients: Experience within a Dedicated Unit in Israel.

Ovadya, David / Bachar, Keren / Peled, Michael / Skudowitz, Maya / Wollner, Arie

The Israel Medical Association journal : IMAJ

2020 Volume 22, Issue 12, Page(s) 733–735

Abstract: Background: Patients diagnosed with coronavirus disease-19 (COVID-19) who deteriorate to respiratory failure and require mechanical ventilation may later need to be weaned from the ventilator and undergo a rehabilitation process. The rate of weaning ... ...

Abstract	Background: Patients diagnosed with coronavirus disease-19 (COVID-19) who deteriorate to respiratory failure and require mechanical ventilation may later need to be weaned from the ventilator and undergo a rehabilitation process. The rate of weaning COVID-19 patients from mechanical ventilation is unknown. Objectives: To present our experience with ventilator weaning of COVID-19 patients in a dedicated facility. Methods: A retrospective cohort study was conducted of 18 patients hospitalized in a COVID-19 dedicated ventilator weaning unit. Results: Eighteen patients were hospitalized in the dedicated unit between 6 April and 19 May 2020. Of these, 88% (16/18) were weaned and underwent decannulation, while two patients deteriorated and were re-admitted to the intensive care unit. The average number of days spent in our department was 12. There was no statistically significant correlation between patient characteristics and time to weaning from ventilation or with the time to decannulation. Conclusions: Despite the high mortality of COVID-19 patients who require mechanical ventilation, most of the patients in our cohort were weaned in a relatively short period of time. Further large-scale studies are necessary to assess the cost effectiveness of dedicated COVID-19 departments for ventilator weaning.
MeSH term(s)	Adult ; Aged ; COVID-19/epidemiology ; COVID-19/therapy ; Female ; Follow-Up Studies ; Humans ; Intensive Care Units ; Israel/epidemiology ; Length of Stay/trends ; Male ; Middle Aged ; Pandemics ; Prognosis ; Respiration, Artificial/methods ; Retrospective Studies ; SARS-CoV-2 ; Ventilator Weaning/methods ; Young Adult
Language	English
Publishing date	2020-12-30
Publishing country	Israel
Document type	Journal Article
ZDB-ID	2008291-5
ISSN	1565-1088 ; 0021-2180
ISSN	1565-1088 ; 0021-2180
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Zs.A 5470: Show issues

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Article ; Online: Transmembrane adaptor protein PAG is a mediator of PD-1 inhibitory signaling in human T cells.

Strazza, Marianne / Azoulay-Alfaguter, Inbar / Peled, Michael / Adam, Kieran / Mor, Adam

Communications biology

2021 Volume 4, Issue 1, Page(s) 672

Abstract: The inhibitory receptor PD-1 is expressed on T cells to inhibit select functions when ligated. The complete signaling mechanism downstream of PD-1 has yet to be uncovered. Here, we discovered phosphoprotein associated with glycosphingolipid-enriched ... ...

Abstract	The inhibitory receptor PD-1 is expressed on T cells to inhibit select functions when ligated. The complete signaling mechanism downstream of PD-1 has yet to be uncovered. Here, we discovered phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG) is phosphorylated following PD-1 ligation and associate this with inhibitory T cell function. Clinical cohort analysis correlates low PAG expression with increased survival from numerous tumor types. PAG knockdown in T cells prevents PD-1-mediated inhibition of cytokine secretion, cell adhesion, CD69 expression, and ERK
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Antigens, CD/metabolism ; Antigens, Differentiation, T-Lymphocyte/metabolism ; Cell Line, Tumor ; Cells, Cultured ; Cytokines/metabolism ; Humans ; Lectins, C-Type/metabolism ; Lymphocyte Activation ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Phosphorylation ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/metabolism ; Signal Transduction ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Mice
Chemical Substances	Adaptor Proteins, Signal Transducing ; Antigens, CD ; Antigens, Differentiation, T-Lymphocyte ; CD69 antigen ; Cytokines ; Lectins, C-Type ; Membrane Proteins ; PAG1 protein, human ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2021-06-03
Publishing country	England
Document type	Journal Article
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-02225-8
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Article: High-dose alectinib for

Dziadziuszko, Rafal / Peled, Nir / Mok, Tony / Peters, Solange / Aix, Santiago Ponce / Alatorre-Alexander, Jorge / Vicuna, Brian D / Maclennan, Margaret / Bhagawati-Prasad, Vijay / Shagan, Sarah M / Schleifman, Erica / Ruf, Thorsten / Mathisen, Michael S / Gadgeel, Shirish M

Contemporary oncology (Poznan, Poland)

2024 Volume 27, Issue 4, Page(s) 217–223

Abstract: Introduction: This paper presents results from Cohort B (rearranged during transfection [: Material and methods: Adults with advanced : Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable ... ...

Abstract	Introduction: This paper presents results from Cohort B (rearranged during transfection [ Material and methods: Adults with advanced Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients. Conclusions: Alectinib showed limited activity in advanced
Language	English
Publishing date	2024-01-30
Publishing country	Poland
Document type	Clinical Trial
ISSN	1428-2526
ISSN	1428-2526
DOI	10.5114/wo.2023.135246
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Article: Tumor-Infiltrating Lymphocytes-Location for Prognostic Evaluation.

Peled, Michael / Onn, Amir / Herbst, Roy S

Clinical cancer research : an official journal of the American Association for Cancer Research

2018 Volume 25, Issue 5, Page(s) 1449–1451

Abstract: Tumor-infiltrating lymphocytes (TIL) are crucial for the success of immunotherapy, and their density can predict prognosis. It has now been shown that computer-based analysis of the spatial organization of TILs adds prognostic value in early-stage non- ... ...

Abstract	Tumor-infiltrating lymphocytes (TIL) are crucial for the success of immunotherapy, and their density can predict prognosis. It has now been shown that computer-based analysis of the spatial organization of TILs adds prognostic value in early-stage non-small cell lung cancer, possibly improving the treatment algorithm to prevent recurrence.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms ; Lymphocytes, Tumor-Infiltrating ; Neoplasm Recurrence, Local ; Prognosis
Language	English
Publishing date	2018-12-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-18-3803
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