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  1. Article: The Role of the Tumor Suppressor Gene Protein Tyrosine Phosphatase Gamma in Cancer.

    Boni, Christian / Sorio, Claudio

    Frontiers in cell and developmental biology

    2022  Volume 9, Page(s) 768969

    Abstract: Members of the Protein Tyrosine Phosphatase (PTPs) family are associated with growth regulation and cancer development. Acting as natural counterpart of tyrosine kinases (TKs), mainly involved in crucial signaling pathways such as regulation of cell ... ...

    Abstract Members of the Protein Tyrosine Phosphatase (PTPs) family are associated with growth regulation and cancer development. Acting as natural counterpart of tyrosine kinases (TKs), mainly involved in crucial signaling pathways such as regulation of cell cycle, proliferation, invasion and angiogenesis, they represent key parts of complex physiological homeostatic mechanisms. Protein tyrosine phosphatase gamma (PTPRG) is classified as a R5 of the receptor type (RPTPs) subfamily and is broadly expressed in various isoforms in different tissues.
    Language English
    Publishing date 2022-01-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2021.768969
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Current Views on the Interplay between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia.

    Boni, Christian / Sorio, Claudio

    Cancers

    2021  Volume 13, Issue 10

    Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by BCR-ABL1 oncogene expression. This dysregulated protein-tyrosine kinase (PTK) is known as the principal driver of the disease and is targeted by tyrosine kinase inhibitors ( ... ...

    Abstract Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by BCR-ABL1 oncogene expression. This dysregulated protein-tyrosine kinase (PTK) is known as the principal driver of the disease and is targeted by tyrosine kinase inhibitors (TKIs). Extensive documentation has elucidated how the transformation of malignant cells is characterized by multiple genetic/epigenetic changes leading to the loss of tumor-suppressor genes function or proto-oncogenes expression. The impairment of adequate levels of substrates phosphorylation, thus affecting the balance PTKs and protein phosphatases (PPs), represents a well-established cellular mechanism to escape from self-limiting signals. In this review, we focus our attention on the characterization of and interactions between PTKs and PPs, emphasizing their biological roles in disease expansion, the regulation of LSCs and TKI resistance. We decided to separate those PPs that have been validated in primary cell models or leukemia mouse models from those whose studies have been performed only in cell lines (and, thus, require validation), as there may be differences in the manner that the associated pathways are modified under these two conditions. This review summarizes the roles of diverse PPs, with hope that better knowledge of the interplay among phosphatases and kinases will eventually result in a better understanding of this disease and contribute to its eradication.
    Language English
    Publishing date 2021-05-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13102311
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: How the latent geometry of a biological network provides information on its dynamics: the case of the gene network of chronic myeloid leukaemia.

    Lecca, Paola / Lombardi, Giulia / Latorre, Roberta Valeria / Sorio, Claudio

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1235116

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2023-11-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1235116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Crosslink between SARS-CoV-2 replication and cystic fibrosis hallmarks.

    Lotti, Virginia / Lagni, Anna / Diani, Erica / Sorio, Claudio / Gibellini, Davide

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1162470

    Abstract: SARS-CoV-2, the etiological cause of the COVID-19 pandemic, can cause severe illness in certain at-risk populations, including people with cystic fibrosis (pwCF). Nevertheless, several studies indicated that pwCF do not have higher risks of SARS-CoV-2 ... ...

    Abstract SARS-CoV-2, the etiological cause of the COVID-19 pandemic, can cause severe illness in certain at-risk populations, including people with cystic fibrosis (pwCF). Nevertheless, several studies indicated that pwCF do not have higher risks of SARS-CoV-2 infection nor do they demonstrate worse clinical outcomes than those of the general population. Recent
    Language English
    Publishing date 2023-05-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1162470
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Organoid Technology and Its Role for Theratyping Applications in Cystic Fibrosis.

    Conti, Jessica / Sorio, Claudio / Melotti, Paola

    Children (Basel, Switzerland)

    2022  Volume 10, Issue 1

    Abstract: Cystic fibrosis (CF) is a autosomal recessive, multisystemic disease caused by different mutations in the CFTR gene encoding CF transmembrane conductance regulator. Although symptom management is important to avoid complications, the approval of CFTR ... ...

    Abstract Cystic fibrosis (CF) is a autosomal recessive, multisystemic disease caused by different mutations in the CFTR gene encoding CF transmembrane conductance regulator. Although symptom management is important to avoid complications, the approval of CFTR modulator drugs in the clinic has demonstrated significant improvements by targeting the primary molecular defect of CF and thereby preventing problems related to CFTR deficiency or dysfunction. CFTR modulator therapies have positively changed the patients' quality of life, especially for those who start their use at the onset of the disease. Due to early diagnosis with the implementation of newborn screening programs and considerable progress in the treatment options, nowadays pediatric mortality was dramatically reduced. In any case, the main obstacle to treat CF is to predict the drug response of patients due to genetic complexity and heterogeneity. Advances in 3D culture systems have led to the extrapolation of disease modeling and individual drug response in vitro by producing mini organs called "organoids" easily obtained from nasal and rectal mucosa biopsies. In this review, we focus primarily on patient-derived intestinal organoids used as in vitro model for CF disease. Organoids combine high-validity of outcomes with a high throughput, thus enabling CF disease classification, drug development and treatment optimization in a personalized manner.
    Language English
    Publishing date 2022-12-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2732685-8
    ISSN 2227-9067
    ISSN 2227-9067
    DOI 10.3390/children10010004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A Comprehensive Review of Receptor-Type Tyrosine-Protein Phosphatase Gamma (PTPRG) Role in Health and Non-Neoplastic Disease.

    Boni, Christian / Laudanna, Carlo / Sorio, Claudio

    Biomolecules

    2022  Volume 12, Issue 1

    Abstract: Protein tyrosine phosphatase receptor gamma (PTPRG) is known to interact with and regulate several tyrosine kinases, exerting a tumor suppressor role in several type of cancers. Its wide expression in human tissues compared to the other component of ... ...

    Abstract Protein tyrosine phosphatase receptor gamma (PTPRG) is known to interact with and regulate several tyrosine kinases, exerting a tumor suppressor role in several type of cancers. Its wide expression in human tissues compared to the other component of group 5 of receptor phosphatases, PTPRZ expressed as a chondroitin sulfate proteoglycan in the central nervous system, has raised interest in its role as a possible regulatory switch of cell signaling processes. Indeed, a carbonic anhydrase-like domain (CAH) and a fibronectin type III domain are present in the N-terminal portion and were found to be associated with its role as [HCO
    MeSH term(s) Biomarkers/metabolism ; Cell Adhesion ; Humans ; Organ Specificity ; Receptor-Like Protein Tyrosine Phosphatases, Class 5/genetics ; Receptor-Like Protein Tyrosine Phosphatases, Class 5/metabolism ; Signal Transduction ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
    Chemical Substances Biomarkers ; Tumor Suppressor Proteins ; PTPRG protein, human (EC 3.1.3.48) ; Receptor-Like Protein Tyrosine Phosphatases, Class 5 (EC 3.1.3.48)
    Language English
    Publishing date 2022-01-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12010084
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Protein Tyrosine Phosphatase Receptor Gamma as Potential Therapeutic Target for Chronic Myeloid Leukemia Patients.

    Ismail, Mohamed A / Sorio, Claudio / Al-Dewik, Nader

    Cancer control : journal of the Moffitt Cancer Center

    2022  Volume 29, Page(s) 10732748221140201

    Abstract: The worldwide CML incidence expects 100,000 patients every year thus representing a substantial health burden. A year 2000 is notable year, where Tyrosine kinase inhibitors (TKIs) had been introduced to the CML treatment plan. However, despite the ... ...

    Abstract The worldwide CML incidence expects 100,000 patients every year thus representing a substantial health burden. A year 2000 is notable year, where Tyrosine kinase inhibitors (TKIs) had been introduced to the CML treatment plan. However, despite the dramatically reduce in mortality rate of CML patients due to TKIs, still over 25% of CML patients need to switch TKIs at least once during treatment timeline for many reasons. On the other hand,
    MeSH term(s) Humans ; Fusion Proteins, bcr-abl/genetics ; Fusion Proteins, bcr-abl/metabolism ; Fusion Proteins, bcr-abl/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Down-Regulation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Protein Kinase Inhibitors
    Language English
    Publishing date 2022-11-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1328503-8
    ISSN 1526-2359 ; 1073-2748
    ISSN (online) 1526-2359
    ISSN 1073-2748
    DOI 10.1177/10732748221140201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Jg. 1995 - 2021: Lesesall (2.OG)
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  8. Article ; Online: CFTR Inhibitors Display In Vitro Antiviral Activity against SARS-CoV-2.

    Lagni, Anna / Lotti, Virginia / Diani, Erica / Rossini, Giada / Concia, Ercole / Sorio, Claudio / Gibellini, Davide

    Cells

    2023  Volume 12, Issue 5

    Abstract: Several reports have indicated that SARS-CoV-2 infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting that CFTR expression and function may be involved in the SARS-CoV-2 life cycle. To evaluate the ... ...

    Abstract Several reports have indicated that SARS-CoV-2 infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting that CFTR expression and function may be involved in the SARS-CoV-2 life cycle. To evaluate the possible association of CFTR activity with SARS-CoV-2 replication, we tested the antiviral activity of two well-known CFTR inhibitors (IOWH-032 and PPQ-102) in wild type (WT)-CFTR bronchial cells. SARS-CoV-2 replication was inhibited by IOWH-032 treatment, with an IC
    MeSH term(s) Humans ; SARS-CoV-2/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Antiviral Agents ; COVID-19
    Chemical Substances Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Antiviral Agents ; IOWH-032 (8Y3GDT6YWV) ; CFTR protein, human
    Language English
    Publishing date 2023-02-28
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12050776
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Revisiting the Role of Leukocytes in Cystic Fibrosis.

    Averna, Monica / Melotti, Paola / Sorio, Claudio

    Cells

    2021  Volume 10, Issue 12

    Abstract: Cystic fibrosis in characterized by pulmonary bacterial colonization and hyperinflammation. Lymphocytes, monocytes/macrophages, neutrophils, and dendritic cells of patients with CF express functional CFTR and are directly affected by altered CFTR ... ...

    Abstract Cystic fibrosis in characterized by pulmonary bacterial colonization and hyperinflammation. Lymphocytes, monocytes/macrophages, neutrophils, and dendritic cells of patients with CF express functional CFTR and are directly affected by altered CFTR expression/function, impairing their ability to resolve infections and inflammation. However, the mechanism behind and the contribution of leukocytes in the pathogenesis of CF are still poorly characterized. The recent clinical introduction of specific CFTR modulators added an important tool not only for the clinical management of the disease but also to the investigation of the pathophysiological mechanisms related to CFTR dysfunction and dysregulated immunity. These drugs treat the basic defect in cystic fibrosis (CF) by increasing CFTR function with improvement of lung function and quality of life, and may improve clinical outcomes also by correcting the dysregulated immune function that characterizes CF. Measure of CFTR function, protein expression profiling and several omics methods were used to identify molecular changes in freshly isolated leukocytes of CF patients, highlighting two roles of leukocytes in CF: one more generally related to the mechanism(s) causing immune dysregulation in CF and unresolved inflammation, and another more applicative role, which identifies in myeloid cells, an important tool predictive of the therapeutic response of CF patients. In this review we will summarize available data on CFTR expression and function in leukocyte populations and will discuss potential clinical applications based on available data.
    MeSH term(s) Animals ; Clinical Trials as Topic ; Cystic Fibrosis/pathology ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Humans ; Leukocytes/pathology ; Models, Biological
    Chemical Substances Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
    Language English
    Publishing date 2021-12-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10123380
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Functional rescue of CFTR in rectal organoids from patients carrying R334W variant by CFTR modulators and PDE4 inhibitor Roflumilast.

    Latorre, Roberta Valeria / Calicchia, Martina / Bigliardi, Martina / Conti, Jessica / Kleinfelder, Karina / Melotti, Paola / Sorio, Claudio

    Respiratory investigation

    2024  Volume 62, Issue 3, Page(s) 455–461

    Abstract: Background: Many disease-causing variants in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene remain uncharacterized and untreated. Restoring the function of the impaired CFTR protein is the goal of personalized medicine, particularly ...

    Abstract Background: Many disease-causing variants in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene remain uncharacterized and untreated. Restoring the function of the impaired CFTR protein is the goal of personalized medicine, particularly in patients carrying rare CFTR variants. In this study, functional defects related to the rare R334W variant were evaluated after treatment with CFTR modulators or Roflumilast, a phosphodiesterase-4 inhibitor (PDE4i).
    Methods: Rectal organoids from subjects with R334W/2184insA and R334W/2183AA > G genotypes were used to perform the Forskolin-induced swelling (FIS) assay. Organoids were left drug-untreated or treated with modulators VX-770 (I), VX-445 (E), and VX-661 (T) mixed, and their combination (ETI). Roflumilast (R) was used alone or as a combination of I + R.
    Results: Our data show a significant increase in FIS rate following treatment with I alone. The combined use of modulators, such as ETI, did not increase further swelling than I alone, nor in protein maturation. Treatment with R shows an increase in FIS response similar to those of I, and the combination R + I significantly increases the rescue of CFTR activity.
    Conclusions: Equivalent I and ETI treatment efficacy was observed for both genotypes. Furthermore, significant organoid swelling was observed with combined I + R used that supports the recently published data describing a potentiating effect of only I in patients carrying the variant R334W and, at the same time, corroborating the role of strategies that include PDE4 inhibitors further to potentiate the effect of I for this variant.
    MeSH term(s) Humans ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/pharmacology ; Cystic Fibrosis/genetics ; Cystic Fibrosis/metabolism ; Phosphodiesterase 4 Inhibitors/pharmacology ; Phosphodiesterase 4 Inhibitors/metabolism ; Colforsin/metabolism ; Colforsin/pharmacology ; Organoids/metabolism ; Mutation ; Aminopyridines ; Benzamides ; Cyclopropanes
    Chemical Substances Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Phosphodiesterase 4 Inhibitors ; Roflumilast (0P6C6ZOP5U) ; Colforsin (1F7A44V6OU) ; CFTR protein, human ; Aminopyridines ; Benzamides ; Cyclopropanes
    Language English
    Publishing date 2024-03-27
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2660821-2
    ISSN 2212-5353 ; 2212-5345
    ISSN (online) 2212-5353
    ISSN 2212-5345
    DOI 10.1016/j.resinv.2024.03.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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