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  1. Article: Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path.

    Iessi, Elisabetta / Vona, Rosa / Cittadini, Camilla / Matarrese, Paola

    Biomedicines

    2021  Volume 9, Issue 12

    Abstract: In cancer cells, metabolic adaptations are often observed in terms of nutrient absorption, biosynthesis of macromolecules, and production of energy necessary to meet the needs of the tumor cell such as uncontrolled proliferation, dissemination, and ... ...

    Abstract In cancer cells, metabolic adaptations are often observed in terms of nutrient absorption, biosynthesis of macromolecules, and production of energy necessary to meet the needs of the tumor cell such as uncontrolled proliferation, dissemination, and acquisition of resistance to death processes induced by both unfavorable environmental conditions and therapeutic drugs. Many oncogenes and tumor suppressor genes have a significant effect on cellular metabolism, as there is a close relationship between the pathways activated by these genes and the various metabolic options. The metabolic adaptations observed in cancer cells not only promote their proliferation and invasion, but also their survival by inducing intrinsic and acquired resistance to various anticancer agents and to various forms of cell death, such as apoptosis, necroptosis, autophagy, and ferroptosis. In this review we analyze the main metabolic differences between cancer and non-cancer cells and how these can affect the various cell death pathways, effectively determining the susceptibility of cancer cells to therapy-induced death. Targeting the metabolic peculiarities of cancer could represent in the near future an innovative therapeutic strategy for the treatment of those tumors whose metabolic characteristics are known.
    Language English
    Publishing date 2021-12-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines9121942
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  2. Article: Role of Cholesterol and Lipid Rafts in Cancer Signaling: A Promising Therapeutic Opportunity?

    Vona, Rosa / Iessi, Elisabetta / Matarrese, Paola

    Frontiers in cell and developmental biology

    2021  Volume 9, Page(s) 622908

    Abstract: Cholesterol is a lipid molecule that plays an essential role in a number of biological processes, both physiological and pathological. It is an essential structural constituent of cell membranes, and it is fundamental for biosynthesis, integrity, and ... ...

    Abstract Cholesterol is a lipid molecule that plays an essential role in a number of biological processes, both physiological and pathological. It is an essential structural constituent of cell membranes, and it is fundamental for biosynthesis, integrity, and functions of biological membranes, including membrane trafficking and signaling. Moreover, cholesterol is the major lipid component of lipid rafts, a sort of lipid-based structures that regulate the assembly and functioning of numerous cell signaling pathways, including those related to cancer, such as tumor cell growth, adhesion, migration, invasion, and apoptosis. Considering the importance of cholesterol metabolism, its homeostasis is strictly regulated at every stage: import, synthesis, export, metabolism, and storage. The alterations of this homeostatic balance are known to be associated with cardiovascular diseases and atherosclerosis, but mounting evidence also connects these behaviors to increased cancer risks. Although there is conflicting evidence on the role of cholesterol in cancer development, most of the studies consistently suggest that a dysregulation of cholesterol homeostasis could lead to cancer development. This review aims to discuss the current understanding of cholesterol homeostasis in normal and cancerous cells, summarizing key findings from recent preclinical and clinical studies that have investigated the role of major players in cholesterol regulation and the organization of lipid rafts, which could represent promising therapeutic targets.
    Language English
    Publishing date 2021-03-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2021.622908
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  3. Article ; Online: Role of Cholesterol and Lipid Rafts in Cancer Signaling

    Rosa Vona / Elisabetta Iessi / Paola Matarrese

    Frontiers in Cell and Developmental Biology, Vol

    A Promising Therapeutic Opportunity?

    2021  Volume 9

    Abstract: Cholesterol is a lipid molecule that plays an essential role in a number of biological processes, both physiological and pathological. It is an essential structural constituent of cell membranes, and it is fundamental for biosynthesis, integrity, and ... ...

    Abstract Cholesterol is a lipid molecule that plays an essential role in a number of biological processes, both physiological and pathological. It is an essential structural constituent of cell membranes, and it is fundamental for biosynthesis, integrity, and functions of biological membranes, including membrane trafficking and signaling. Moreover, cholesterol is the major lipid component of lipid rafts, a sort of lipid-based structures that regulate the assembly and functioning of numerous cell signaling pathways, including those related to cancer, such as tumor cell growth, adhesion, migration, invasion, and apoptosis. Considering the importance of cholesterol metabolism, its homeostasis is strictly regulated at every stage: import, synthesis, export, metabolism, and storage. The alterations of this homeostatic balance are known to be associated with cardiovascular diseases and atherosclerosis, but mounting evidence also connects these behaviors to increased cancer risks. Although there is conflicting evidence on the role of cholesterol in cancer development, most of the studies consistently suggest that a dysregulation of cholesterol homeostasis could lead to cancer development. This review aims to discuss the current understanding of cholesterol homeostasis in normal and cancerous cells, summarizing key findings from recent preclinical and clinical studies that have investigated the role of major players in cholesterol regulation and the organization of lipid rafts, which could represent promising therapeutic targets.
    Keywords cholesterol ; cancer ; lipid rafts ; cell death ; invasion ; metastases ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
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  4. Article ; Online: Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path

    Elisabetta Iessi / Rosa Vona / Camilla Cittadini / Paola Matarrese

    Biomedicines, Vol 9, Iss 1942, p

    2021  Volume 1942

    Abstract: In cancer cells, metabolic adaptations are often observed in terms of nutrient absorption, biosynthesis of macromolecules, and production of energy necessary to meet the needs of the tumor cell such as uncontrolled proliferation, dissemination, and ... ...

    Abstract In cancer cells, metabolic adaptations are often observed in terms of nutrient absorption, biosynthesis of macromolecules, and production of energy necessary to meet the needs of the tumor cell such as uncontrolled proliferation, dissemination, and acquisition of resistance to death processes induced by both unfavorable environmental conditions and therapeutic drugs. Many oncogenes and tumor suppressor genes have a significant effect on cellular metabolism, as there is a close relationship between the pathways activated by these genes and the various metabolic options. The metabolic adaptations observed in cancer cells not only promote their proliferation and invasion, but also their survival by inducing intrinsic and acquired resistance to various anticancer agents and to various forms of cell death, such as apoptosis, necroptosis, autophagy, and ferroptosis. In this review we analyze the main metabolic differences between cancer and non-cancer cells and how these can affect the various cell death pathways, effectively determining the susceptibility of cancer cells to therapy-induced death. Targeting the metabolic peculiarities of cancer could represent in the near future an innovative therapeutic strategy for the treatment of those tumors whose metabolic characteristics are known.
    Keywords cancer cell metabolism ; cell death ; anticancer therapy ; chemoresistance ; glucose ; glycolysis ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Sex differences in antiviral immunity in SARS-CoV-2 infection: Mitochondria and mitomiR come into view.

    Iessi, Elisabetta / Cittadini, Camilla / Anticoli, Simona / Fecchi, Katia / Matarrese, Paola / Ruggieri, Anna

    Acta physiologica (Oxford, England)

    2020  Volume 231, Issue 2, Page(s) e13571

    MeSH term(s) Animals ; Antibodies, Viral/genetics ; Antibodies, Viral/immunology ; COVID-19/genetics ; COVID-19/immunology ; Female ; Immunity, Innate ; Male ; MicroRNAs/genetics ; Mitochondria/genetics ; Mitochondria/immunology ; Oxidative Stress ; SARS-CoV-2/immunology ; Sex Characteristics
    Chemical Substances Antibodies, Viral ; MicroRNAs
    Keywords covid19
    Language English
    Publishing date 2020-11-05
    Publishing country England
    Document type Editorial
    ZDB-ID 2218636-0
    ISSN 1748-1716 ; 1748-1708
    ISSN (online) 1748-1716
    ISSN 1748-1708
    DOI 10.1111/apha.13571
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  6. Article: On the role of sphingolipids in cell survival and death.

    Iessi, Elisabetta / Marconi, Matteo / Manganelli, Valeria / Sorice, Maurizio / Malorni, Walter / Garofalo, Tina / Matarrese, Paola

    International review of cell and molecular biology

    2020  Volume 351, Page(s) 149–195

    Abstract: Sphingolipids, universal components of biological membranes of all eukaryotic organisms, from yeasts to mammals, in addition of playing a structural role, also play an important part of signal transduction pathways. They participate or, also, ignite ... ...

    Abstract Sphingolipids, universal components of biological membranes of all eukaryotic organisms, from yeasts to mammals, in addition of playing a structural role, also play an important part of signal transduction pathways. They participate or, also, ignite several fundamental subcellular signaling processes but, more in general, they directly contribute to key biological activities such as cell motility, growth, senescence, differentiation as well as cell fate, i.e., survival or death. The sphingolipid metabolic pathway displays an intricate network of reactions that result in the formation of multiple sphingolipids, including ceramide, and sphingosine-1-phosphate. Different sphingolipids, that have key roles in determining cell fate, can induce opposite effects: as a general rule, sphingosine-1-phosphate promotes cell survival and differentiation, whereas ceramide is known to induce apoptosis. Furthermore, together with cholesterol, sphingolipids also represent the basic lipid component of lipid rafts, cholesterol- and sphingolipid-enriched membrane microdomains directly involved in cell death and survival processes. In this review, we briefly describe the characteristics of sphingolipids and lipid membrane microdomains. In particular, we will consider the involvement of various sphingolipids per se and of lipid rafts in apoptotic pathway, both intrinsic and extrinsic, in nonapoptotic cell death, in autophagy, and in cell differentiation. In addition, their roles in the most common physiological and pathological contexts either as pathogenetic elements or as biomarkers of diseases will be considered. We would also hint how the manipulation of sphingolipid metabolism could represent a potential therapeutic target to be investigated and functionally validated especially for those diseases for which therapeutic options are limited or ineffective.
    MeSH term(s) Animals ; Cell Death ; Cell Survival ; Humans ; Membrane Microdomains/metabolism ; Mitochondria/metabolism ; Sphingolipids/metabolism
    Chemical Substances Sphingolipids
    Language English
    Publishing date 2020-03-12
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2427220-6
    ISSN 1937-6448 ; 0074-7696
    ISSN 1937-6448 ; 0074-7696
    DOI 10.1016/bs.ircmb.2020.02.004
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  7. Article ; Online: Chlorpromazine affects glioblastoma bioenergetics by interfering with pyruvate kinase M2.

    Abbruzzese, Claudia / Matteoni, Silvia / Matarrese, Paola / Signore, Michele / Ascione, Barbara / Iessi, Elisabetta / Gurtner, Aymone / Sacconi, Andrea / Ricci-Vitiani, Lucia / Pallini, Roberto / Pace, Andrea / Villani, Veronica / Polo, Andrea / Costantini, Susan / Budillon, Alfredo / Ciliberto, Gennaro / Paggi, Marco G

    Cell death & disease

    2023  Volume 14, Issue 12, Page(s) 821

    Abstract: Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and effective therapeutic approaches are urgently required. In ... ...

    Abstract Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and effective therapeutic approaches are urgently required. In our attempts to identify repositionable drugs in glioblastoma therapy, we identified the neuroleptic drug chlorpromazine (CPZ) as a very promising compound. Here we aimed to further unveil the mode of action of this drug. We performed a supervised recognition of the signal transduction pathways potentially influenced by CPZ via Reverse-Phase Protein microArrays (RPPA) and carried out an Activity-Based Protein Profiling (ABPP) followed by Mass Spectrometry (MS) analysis to possibly identify cellular factors targeted by the drug. Indeed, the glycolytic enzyme PKM2 was identified as one of the major targets of CPZ. Furthermore, using the Seahorse platform, we analyzed the bioenergetics changes induced by the drug. Consistent with the ability of CPZ to target PKM2, we detected relevant changes in GBM energy metabolism, possibly attributable to the drug's ability to inhibit the oncogenic properties of PKM2. RPE-1 non-cancer neuroepithelial cells appeared less responsive to the drug. PKM2 silencing reduced the effects of CPZ. 3D modeling showed that CPZ interacts with PKM2 tetramer in the same region involved in binding other known activators. The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.
    MeSH term(s) Humans ; Glioblastoma/pathology ; Chlorpromazine/pharmacology ; Chlorpromazine/therapeutic use ; Pyruvate Kinase/metabolism ; Cell Line, Tumor ; Energy Metabolism
    Chemical Substances Chlorpromazine (U42B7VYA4P) ; Pyruvate Kinase (EC 2.7.1.40)
    Language English
    Publishing date 2023-12-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-023-06353-3
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  8. Article ; Online: Association between sex hormones and anti-S/RBD antibody responses to COVID-19 vaccines in healthcare workers.

    Anticoli, Simona / Dorrucci, Maria / Iessi, Elisabetta / Chiarotti, Flavia / Di Prinzio, Reparata Rosa / Vinci, Maria Rosaria / Zaffina, Salvatore / Puro, Vincenzo / Colavita, Francesca / Mizzoni, Klizia / Meschi, Silvia / Vonesch, Nicoletta / Albano, Christian / Ortona, Elena / Ruggieri, Anna / Tomao, Paola

    Human vaccines & immunotherapeutics

    2023  Volume 19, Issue 3, Page(s) 2273697

    Abstract: Healthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at a high risk of exposure and transmission of pathogens to patients. Neutralizing antibodies developed after COVID-19 vaccination ... ...

    Abstract Healthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at a high risk of exposure and transmission of pathogens to patients. Neutralizing antibodies developed after COVID-19 vaccination decline within few months of vaccination. Several factors, including age and sex, can affect the intensity, efficacy, and duration of immune response to vaccines. However, sex-specific analyses of humoral responses to COVID-19 vaccines are lacking. This study aimed to evaluate sex-based differences in anti-S/RBD (Receptor Binding Domain) responses at three different time points after the second dose of mRNA COVID-19 vaccine in HCWs in relation to age, and to investigate the role of sex hormones as potential markers of response. Anti-S/RBD levels after two doses of the mRNA vaccine were collected from 521 HCWs naïve to COVID-19, working at two Italian Clinical Centers. Multiple regression analysis was applied to evaluate the association between anti-S levels and sex, age, and plasma levels of sex hormones. Significantly higher anti-S/RBD response to the COVID-19 vaccination was found in female HCWs, and a significant and more abrupt decline in response with time was observed in women than that in men. A novel, positive association of testosterone plasma levels and higher anti-S levels in male HCWs was found, suggesting its potential role as sex specific marker in males. In conclusion, understanding the sex-based differences in humoral immune responses to vaccines may potentially improve vaccination strategies and optimize surveillance programs for HCWs.
    MeSH term(s) Humans ; Female ; Male ; Antibody Formation ; COVID-19 Vaccines ; COVID-19/prevention & control ; Vaccination ; Gonadal Steroid Hormones ; Antibodies, Neutralizing ; Health Personnel ; Antibodies, Viral
    Chemical Substances COVID-19 Vaccines ; Gonadal Steroid Hormones ; Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2664176-8
    ISSN 2164-554X ; 2164-5515
    ISSN (online) 2164-554X
    ISSN 2164-5515
    DOI 10.1080/21645515.2023.2273697
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    Zs.A 6967: Show issues Location:
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  9. Article: Sex differences in antiviral immunity in SARS-CoV-2 infection: Mitochondria and mitomiR come into view

    Iessi, Elisabetta / Cittadini, Camilla / Anticoli, Simona / Fecchi, Katia / Matarrese, Paola / Ruggieri, Anna

    Acta Physiol (Oxf)

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #884550
    Database COVID19

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  10. Article ; Online: Sex differences in antiviral immunity in SARS‐CoV‐2 infection

    Iessi, Elisabetta / Cittadini, Camilla / Anticoli, Simona / Fecchi, Katia / Matarrese, Paola / Ruggieri, Anna

    Acta Physiologica ; ISSN 1748-1708 1748-1716

    mitochondria and mitomiR come into view

    2020  

    Keywords Physiology ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    DOI 10.1111/apha.13571
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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