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Article: Effect of internal port on dose distribution in post-mastectomy radiotherapy for breast cancer patients after expander breast reconstruction.

Perrucci, Elisabetta / Marcantonini, Marta / Arena, Eleonora / Fulcheri, Christian / Reggioli, Valentina / Dipilato, Anna Concetta / Palumbo, Isabella / Saldi, Simonetta / Falcinelli, Lorenzo / Ingrosso, Gianluca / Bini, Vittorio / Aristei, Cynthia

Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology

2023 Volume 28, Issue 1, Page(s) 1–8

Abstract: Background: In patients with expander-based reconstruction a few dosimetric analyses detected radiation therapy dose perturbation due to the internal port of an expander, potentially leading to toxicity or loss of local control. This study aimed at ... ...

Abstract	Background: In patients with expander-based reconstruction a few dosimetric analyses detected radiation therapy dose perturbation due to the internal port of an expander, potentially leading to toxicity or loss of local control. This study aimed at adding data on this field. Materials and methods: A dosimetric analysis was conducted in 30 chest wall treatment planning without and with correction for port artifact. In plans with artifact correction density was overwritten as 1 g/cm Results: No significant differences emerged in the minimum, medium and maximum doses in the two plans, without and with correction for port artifacts. Conclusions: The port did not significantly affect dose distribution in patients who will receive post-mastectomy radiation therapy.
Language	English
Publishing date	2023-04-06
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2188087-6
ISSN	1507-1367
ISSN	1507-1367
DOI	10.5603/RPOR.a2023.0014
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Article: Unchain My Heart: Integrins at the Basis of iPSC Cardiomyocyte Differentiation.

Santoro, Rosaria / Perrucci, Gianluca Lorenzo / Gowran, Aoife / Pompilio, Giulio

Stem cells international

2019 Volume 2019, Page(s) 8203950

Abstract: The cellular response to the extracellular matrix (ECM) microenvironment mediated by integrin adhesion is of fundamental importance, in both developmental and pathological processes. In particular, mechanotransduction is of growing importance in ... ...

Abstract	The cellular response to the extracellular matrix (ECM) microenvironment mediated by integrin adhesion is of fundamental importance, in both developmental and pathological processes. In particular, mechanotransduction is of growing importance in groundbreaking cellular models such as induced pluripotent stem cells (iPSC), since this process may strongly influence cell fate and, thus, augment the precision of differentiation into specific cell types, e.g., cardiomyocytes. The decryption of the cellular machinery starting from ECM sensing to iPSC differentiation calls for new
Language	English
Publishing date	2019-02-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2573856-2
ISSN	1687-9678 ; 1687-966X
ISSN (online)	1687-9678
ISSN	1687-966X
DOI	10.1155/2019/8203950
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Article: Presence of SARS-CoV-2 Nucleoprotein in Cardiac Tissues of Donors with Negative COVID-19 Molecular Tests.

Perrucci, Gianluca Lorenzo / Sommariva, Elena / Ricci, Veronica / Songia, Paola / D'Alessandra, Yuri / Poggio, Paolo / Pompilio, Giulio / Polvani, Gianluca / Guarino, Anna

Diagnostics (Basel, Switzerland)

2021 Volume 11, Issue 4

Abstract: The 2019 Coronavirus disease (COVID-19) outbreak had detrimental effects on essential medical services such as organ and tissue donation. Lombardy, one of the most active Italian regions in organ/tissue procurement, has been strongly affected by the ... ...

Abstract	The 2019 Coronavirus disease (COVID-19) outbreak had detrimental effects on essential medical services such as organ and tissue donation. Lombardy, one of the most active Italian regions in organ/tissue procurement, has been strongly affected by the COVID-19 pandemic. To date, data concerning the risk of SARS-CoV-2 transmission after tissue transplantation are controversial. Here, we aimed to evaluate the presence/absence of SARS-CoV-2 in different cardiac tissues eligible for transplantation obtained from Lombard donors. We used cardiovascular tissues from eight donors potentially suitable for pulmonary valve transplantation. All donor subjects involved in the study returned negative results for the SARS-CoV-2 RNA molecular tests (quantitative real-time reverse-transcription PCR, qRT-PCR, and chip-based digital PCR) in nasopharyngeal swabs (NPS) or bronchoalveolar lavage (BAL). None of the eight donors included in this study revealed the presence of the SARS-CoV-2 viral genome. However, evaluation of the protein content of pulmonary vein wall (PVW) tissue revealed variable levels of SARS-CoV-2 nucleoprotein signal in all donors. Our study demonstrated for the first time, to the best of our knowledge, that viral nucleoprotein but not viral RNA was present in the examined tissue bank specimens, suggesting the need for caution and in-depth investigations on implantable tissue specimens collected during the COVID-19 pandemic period.
Language	English
Publishing date	2021-04-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics11040731
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Article: Cardiac fibrosis in regenerative medicine: destroy to rebuild.

Perrucci, Gianluca Lorenzo / Rurali, Erica / Pompilio, Giulio

Journal of thoracic disease

2018 Volume 10, Issue Suppl 20, Page(s) S2376–S2389

Abstract: The major limitations for cardiac regeneration in patients after myocardial infarction (MI) are the wide loss of cardiomyocytes and the adverse structural alterations of extracellular matrix (ECM). Cardiac fibroblast differentiation into myofibroblasts ( ... ...

Abstract	The major limitations for cardiac regeneration in patients after myocardial infarction (MI) are the wide loss of cardiomyocytes and the adverse structural alterations of extracellular matrix (ECM). Cardiac fibroblast differentiation into myofibroblasts (MFB) leads to a huge deposition of ECM and to the subsequent loss of ventricular structural integrity. All these molecular events depict the fundamental features at the basis of the post-MI fibrosis and deserve in depth cellular and molecular studies to fill the gap in the clinical practice. Indeed, to date, there are no effective therapeutic approaches to limit the post-MI massive fibrosis development. In this review we describe the involvement of integrins and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)/ADAMTS-like (ADAMTSL) proteins in cardiac reparative pro-fibrotic response after MI, proposing some of them as novel potential pharmacological tools.
Language	English
Publishing date	2018-08-13
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd.2018.03.82
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Article ; Online: Omics Analyses of Stromal Cells from ACM Patients Reveal Alterations in Chromatin Organization and Mitochondrial Homeostasis.

Lippi, Melania / Maione, Angela Serena / Chiesa, Mattia / Perrucci, Gianluca Lorenzo / Iengo, Lara / Sattin, Tommaso / Cencioni, Chiara / Savoia, Matteo / Zeiher, Andreas M / Tundo, Fabrizio / Tondo, Claudio / Pompilio, Giulio / Sommariva, Elena

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder characterized by ventricular arrhythmias, contractile dysfunctions and fibro-adipose replacement of myocardium. Cardiac mesenchymal stromal cells (CMSCs) participate in disease pathogenesis by ... ...

Abstract	Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder characterized by ventricular arrhythmias, contractile dysfunctions and fibro-adipose replacement of myocardium. Cardiac mesenchymal stromal cells (CMSCs) participate in disease pathogenesis by differentiating towards adipocytes and myofibroblasts. Some altered pathways in ACM are known, but many are yet to be discovered. We aimed to enrich the understanding of ACM pathogenesis by comparing epigenetic and gene expression profiles of ACM-CMSCs with healthy control (HC)-CMSCs. Methylome analysis identified 74 differentially methylated nucleotides, most of them located on the mitochondrial genome. Transcriptome analysis revealed 327 genes that were more expressed and 202 genes that were less expressed in ACM- vs. HC-CMSCs. Among these, genes implicated in mitochondrial respiration and in epithelial-to-mesenchymal transition were more expressed, and cell cycle genes were less expressed in ACM- vs. HC-CMSCs. Through enrichment and gene network analyses, we identified differentially regulated pathways, some of which never associated with ACM, including mitochondrial functioning and chromatin organization, both in line with methylome results. Functional validations confirmed that ACM-CMSCs exhibited higher amounts of active mitochondria and ROS production, a lower proliferation rate and a more pronounced epicardial-to-mesenchymal transition compared to the controls. In conclusion, ACM-CMSC-omics revealed some additional altered molecular pathways, relevant in disease pathogenesis, which may constitute novel targets for specific therapies.
MeSH term(s)	Humans ; Myocardium ; Mesenchymal Stem Cells/metabolism ; Adipocytes ; Homeostasis ; Chromatin/genetics ; Chromatin/metabolism
Chemical Substances	Chromatin
Language	English
Publishing date	2023-06-12
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/ijms241210017
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Article ; Online: Presence of SARS-CoV-2 Nucleoprotein in Cardiac Tissues of Donors with Negative COVID-19 Molecular Tests

Gianluca Lorenzo Perrucci / Elena Sommariva / Veronica Ricci / Paola Songia / Yuri D’Alessandra / Paolo Poggio / Giulio Pompilio / Gianluca Polvani / Anna Guarino

Diagnostics, Vol 11, Iss 731, p

2021 Volume 731

Abstract	The 2019 Coronavirus disease (COVID-19) outbreak had detrimental effects on essential medical services such as organ and tissue donation. Lombardy, one of the most active Italian regions in organ/tissue procurement, has been strongly affected by the COVID-19 pandemic. To date, data concerning the risk of SARS-CoV-2 transmission after tissue transplantation are controversial. Here, we aimed to evaluate the presence/absence of SARS-CoV-2 in different cardiac tissues eligible for transplantation obtained from Lombard donors. We used cardiovascular tissues from eight donors potentially suitable for pulmonary valve transplantation. All donor subjects involved in the study returned negative results for the SARS-CoV-2 RNA molecular tests (quantitative real-time reverse-transcription PCR, qRT-PCR, and chip-based digital PCR) in nasopharyngeal swabs (NPS) or bronchoalveolar lavage (BAL). None of the eight donors included in this study revealed the presence of the SARS-CoV-2 viral genome. However, evaluation of the protein content of pulmonary vein wall (PVW) tissue revealed variable levels of SARS-CoV-2 nucleoprotein signal in all donors. Our study demonstrated for the first time, to the best of our knowledge, that viral nucleoprotein but not viral RNA was present in the examined tissue bank specimens, suggesting the need for caution and in-depth investigations on implantable tissue specimens collected during the COVID-19 pandemic period.
Keywords	SARS-CoV-2 nucleoprotein ; tissue donor transplantation ; pulmonary vein wall ; cardiac tissue ; diagnosis ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unchain My Heart

Rosaria Santoro / Gianluca Lorenzo Perrucci / Aoife Gowran / Giulio Pompilio

Stem Cells International, Vol

Integrins at the Basis of iPSC Cardiomyocyte Differentiation

2019 Volume 2019

Abstract	The cellular response to the extracellular matrix (ECM) microenvironment mediated by integrin adhesion is of fundamental importance, in both developmental and pathological processes. In particular, mechanotransduction is of growing importance in groundbreaking cellular models such as induced pluripotent stem cells (iPSC), since this process may strongly influence cell fate and, thus, augment the precision of differentiation into specific cell types, e.g., cardiomyocytes. The decryption of the cellular machinery starting from ECM sensing to iPSC differentiation calls for new in vitro methods. Conveniently, engineered biomaterials activating controlled integrin-mediated responses through chemical, physical, and geometrical designs are key to resolving this issue and could foster clinical translation of optimized iPSC-based technology. This review introduces the main integrin-dependent mechanisms and signalling pathways involved in mechanotransduction. Special consideration is given to the integrin-iPSC linkage signalling chain in the cardiovascular field, focusing on biomaterial-based in vitro models to evaluate the relevance of this process in iPSC differentiation into cardiomyocytes.
Keywords	Internal medicine ; RC31-1245
Subject code	571
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Omics Analyses of Stromal Cells from ACM Patients Reveal Alterations in Chromatin Organization and Mitochondrial Homeostasis

Melania Lippi / Angela Serena Maione / Mattia Chiesa / Gianluca Lorenzo Perrucci / Lara Iengo / Tommaso Sattin / Chiara Cencioni / Matteo Savoia / Andreas M. Zeiher / Fabrizio Tundo / Claudio Tondo / Giulio Pompilio / Elena Sommariva

International Journal of Molecular Sciences, Vol 24, Iss 10017, p

2023 Volume 10017

Abstract	Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder characterized by ventricular arrhythmias, contractile dysfunctions and fibro-adipose replacement of myocardium. Cardiac mesenchymal stromal cells (CMSCs) participate in disease pathogenesis by differentiating towards adipocytes and myofibroblasts. Some altered pathways in ACM are known, but many are yet to be discovered. We aimed to enrich the understanding of ACM pathogenesis by comparing epigenetic and gene expression profiles of ACM-CMSCs with healthy control (HC)-CMSCs. Methylome analysis identified 74 differentially methylated nucleotides, most of them located on the mitochondrial genome. Transcriptome analysis revealed 327 genes that were more expressed and 202 genes that were less expressed in ACM- vs. HC-CMSCs. Among these, genes implicated in mitochondrial respiration and in epithelial-to-mesenchymal transition were more expressed, and cell cycle genes were less expressed in ACM- vs. HC-CMSCs. Through enrichment and gene network analyses, we identified differentially regulated pathways, some of which never associated with ACM, including mitochondrial functioning and chromatin organization, both in line with methylome results. Functional validations confirmed that ACM-CMSCs exhibited higher amounts of active mitochondria and ROS production, a lower proliferation rate and a more pronounced epicardial-to-mesenchymal transition compared to the controls. In conclusion, ACM-CMSC-omics revealed some additional altered molecular pathways, relevant in disease pathogenesis, which may constitute novel targets for specific therapies.
Keywords	arrhythmogenic cardiomyopathy ; cardiac mesenchymal stromal cells ; omics ; methylome ; transcriptome ; mitochondria ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570 ; 610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy.

Maione, Angela Serena / Stadiotti, Ilaria / Pilato, Chiara Assunta / Perrucci, Gianluca Lorenzo / Saverio, Valentina / Catto, Valentina / Vettor, Giulia / Casella, Michela / Guarino, Anna / Polvani, Gianluca / Pompilio, Giulio / Sommariva, Elena

International journal of molecular sciences

2021 Volume 22, Issue 5

Abstract: Arrhythmogenic Cardiomyopathy (ACM) is characterized by the replacement of the myocardium with fibrotic or fibro-fatty tissue and inflammatory infiltrates in the heart. To date, while ACM adipogenesis is a well-investigated differentiation program, ACM- ... ...

Abstract	Arrhythmogenic Cardiomyopathy (ACM) is characterized by the replacement of the myocardium with fibrotic or fibro-fatty tissue and inflammatory infiltrates in the heart. To date, while ACM adipogenesis is a well-investigated differentiation program, ACM-related fibrosis remains a scientific gap of knowledge. In this study, we analyze the fibrotic process occurring during ACM pathogenesis focusing on the role of cardiac mesenchymal stromal cells (C-MSC) as a source of myofibroblasts. We performed the ex vivo studies on plasma and right ventricular endomyocardial bioptic samples collected from ACM patients and healthy control donors (HC). In vitro studies were performed on C-MSC isolated from endomyocardial biopsies of both groups. Our results revealed that circulating TGF-β1 levels are significantly higher in the ACM cohort than in HC. Accordingly, fibrotic markers are increased in ACM patient-derived cardiac biopsies compared to HC ones. This difference is not evident in isolated C-MSC. Nevertheless, ACM C-MSC are more responsive than HC ones to TGF-β1 treatment, in terms of pro-fibrotic differentiation and higher activation of the SMAD2/3 signaling pathway. These results provide the novel evidence that C-MSC are a source of myofibroblasts and participate in ACM fibrotic remodeling, being highly responsive to ACM-characteristic excess TGF-β1.
MeSH term(s)	Adult ; Arrhythmogenic Right Ventricular Dysplasia/blood ; Arrhythmogenic Right Ventricular Dysplasia/pathology ; Arrhythmogenic Right Ventricular Dysplasia/physiopathology ; Cell Differentiation ; Endocardium/metabolism ; Endocardium/pathology ; Female ; Fibrosis ; Humans ; Male ; Mesenchymal Stem Cells/metabolism ; Mesenchymal Stem Cells/pathology ; Middle Aged ; Myofibroblasts/pathology ; RNA, Messenger/biosynthesis ; Signal Transduction/physiology ; Smad2 Protein/physiology ; Smad3 Protein/physiology ; Transforming Growth Factor beta1/blood ; Transforming Growth Factor beta1/physiology
Chemical Substances	RNA, Messenger ; SMAD2 protein, human ; SMAD3 protein, human ; Smad2 Protein ; Smad3 Protein ; Transforming Growth Factor beta1
Language	English
Publishing date	2021-03-06
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/ijms22052673
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Article ; Online: Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy

Angela Serena Maione / Ilaria Stadiotti / Chiara Assunta Pilato / Gianluca Lorenzo Perrucci / Valentina Saverio / Valentina Catto / Giulia Vettor / Michela Casella / Anna Guarino / Gianluca Polvani / Giulio Pompilio / Elena Sommariva

International Journal of Molecular Sciences, Vol 22, Iss 5, p

2021 Volume 2673

Abstract	Arrhythmogenic Cardiomyopathy (ACM) is characterized by the replacement of the myocardium with fibrotic or fibro-fatty tissue and inflammatory infiltrates in the heart. To date, while ACM adipogenesis is a well-investigated differentiation program, ACM-related fibrosis remains a scientific gap of knowledge. In this study, we analyze the fibrotic process occurring during ACM pathogenesis focusing on the role of cardiac mesenchymal stromal cells (C-MSC) as a source of myofibroblasts. We performed the ex vivo studies on plasma and right ventricular endomyocardial bioptic samples collected from ACM patients and healthy control donors (HC). In vitro studies were performed on C-MSC isolated from endomyocardial biopsies of both groups. Our results revealed that circulating TGF-β1 levels are significantly higher in the ACM cohort than in HC. Accordingly, fibrotic markers are increased in ACM patient-derived cardiac biopsies compared to HC ones. This difference is not evident in isolated C-MSC. Nevertheless, ACM C-MSC are more responsive than HC ones to TGF-β1 treatment, in terms of pro-fibrotic differentiation and higher activation of the SMAD2/3 signaling pathway. These results provide the novel evidence that C-MSC are a source of myofibroblasts and participate in ACM fibrotic remodeling, being highly responsive to ACM-characteristic excess TGF-β1.
Keywords	arrhythmogenic cardiomyopathy ; cardiac-mesenchymal stromal cells ; fibrosis ; TGF-β1 ; cardiac remodeling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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