scholarly journals Metformin Induces Apoptosis and Inhibits Notch1 in Malignant Pleural Mesothelioma Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Marika Rossini ◽  
Fernanda Martini ◽  
Elena Torreggiani ◽  
Francesca Fortini ◽  
Giorgio Aquila ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Notch Pathway ◽  
Cell Communication ◽  
Mesothelial Cells ◽  
Pleural Mesothelioma ◽  
Proliferative Effect ◽  
Pleural Mesothelial Cells ◽  
Different Types ◽  
Line Drug

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related cancer arising from the mesothelial cells lining the pleural cavity. MPM is characterized by a silent clinical progression and a highly resistance to conventional chemo/radio-therapies. MPM patients die in a few months/years from diagnosis. Notch signaling is a well-conserved cell communication system, which regulates many biological processes. In humans, the dysregulation of Notch pathway potentially contributes to cancer onset/progression, including MPM. Metformin is the first-line drug used to treat type 2 diabetes mellitus. Metformin is proven to be an effective antitumor drug in preclinical models of different types of cancer. To date, clinical efficacy is being studied in many clinical trials. In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated. MPM cells showed high levels of Notch1 activation compared to normal pleural mesothelial cells. Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.

scholarly journals Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

2020 ◽  
Vol 21 (15) ◽  
pp. 5432 ◽  
Author(s):  
Stefano Burgio ◽  
Leila Noori ◽  
Antonella Marino Gammazza ◽  
Claudia Campanella ◽  
Mariantonia Logozzi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Delivery System ◽  
Malignant Pleural Mesothelioma ◽  
Cell Communication ◽  
Cell Types ◽  
Delivery Systems ◽  
Pleural Mesothelioma ◽  
Potential Use

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

Taurolidine and povidone-iodine induce different types of cell death in malignant pleural mesothelioma

Lung Cancer ◽  
2007 ◽  
Vol 56 (3) ◽  
pp. 327-336 ◽  
Author(s):  
I. Opitz ◽  
B. Sigrist ◽  
S. Hillinger ◽  
D. Lardinois ◽  
R. Stahel ◽  
...  
Keyword(s):  
Cell Death ◽  
Malignant Pleural Mesothelioma ◽  
Povidone Iodine ◽  
Pleural Mesothelioma ◽  
Different Types

scholarly journals Metabolic rewiring and redox alterations in malignant pleural mesothelioma

2019 ◽  
Vol 122 (1) ◽  
pp. 52-61 ◽  
Author(s):  
Loredana Urso ◽  
Ilaria Cavallari ◽  
Evgeniya Sharova ◽  
Francesco Ciccarese ◽  
Giulia Pasello ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Malignant Pleural Mesothelioma ◽  
Tumour Progression ◽  
Mesothelial Cells ◽  
Polyamine Metabolism ◽  
Aetiological Factor ◽  
Pleural Mesothelioma ◽  
Loss Of Function ◽  
Control Of Gene Expression ◽  
Dismal Prognosis

AbstractMalignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in 18F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.

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