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  1. Article ; Online: How ANGPTL3 Inhibition Will Help Our Clinical Practice?

    Bini, Simone / Tramontano, Daniele / Minicocci, Ilenia / Di Costanzo, Alessia / Tambaro, Federica / D'Erasmo, Laura / Arca, Marcello

    Current atherosclerosis reports

    2023  Volume 25, Issue 1, Page(s) 19–29

    Abstract: Purpose of review: This review aims to summarize the most recently published literature highlighting the potential of pharmacological inhibition of ANGPTL3 in treating patients suffering from dyslipidemias. The rational for this strategy will be ... ...

    Abstract Purpose of review: This review aims to summarize the most recently published literature highlighting the potential of pharmacological inhibition of ANGPTL3 in treating patients suffering from dyslipidemias. The rational for this strategy will be discussed considering evidence describing the role of ANGPTL3 in lipid metabolism and the consequences of its deficiency in humans.
    Recent findings: Recent trials have demonstrated the efficacy and safety of ANGPTL3 inhibition in treating homozygous familial hypercholesterolemia even in those patients carrying biallelic null/null variants, thus supporting the notion that the LDL-lowering effect of ANGPLT3 inhibition is LDLR-independent. The use of ANGPTL3 inhibition strategies has expanded its indications in hypertrygliceridemic patients with functional lipoprotein lipase activity. Contemporarily, the pharmacological research is exploring novel approaches to ANGPTL3 inhibition such as the use of a small interfering RNA targeting the ANGPTL3 transcript in the liver, a protein-based vaccine against ANGPTL3, and a CRISP-Cas-9 method for a liver-selective knock-out of ANGPTL3 gene. First, we will describe the molecular function of ANGPTL3 in lipoprotein metabolism. Then, we will revise the clinical characteristics of individuals carrying loss-of-function mutations of ANGPTL3, a rare condition known as familial hypobetalipoproteinemia type 2 (FHBL2) that represents a unique human model of ANGPTL3 deficiency. Finally, we will examine the lipid-lowering potential of pharmacological inhibition of ANGPTL3 based on the results of clinical trials employing Evinacumab, the first approved fully humanized monoclonal antibody against ANGPTL3. The future perspectives for ANGPTL3 inhibition will also be revised.
    MeSH term(s) Humans ; Angiopoietin-like Proteins ; Angiopoietin-Like Protein 3 ; Mutation ; Lipid Metabolism ; Liver/metabolism
    Chemical Substances Angiopoietin-like Proteins ; Angiopoietin-Like Protein 3 ; ANGPTL3 protein, human
    Language English
    Publishing date 2023-01-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057369-8
    ISSN 1534-6242 ; 1523-3804
    ISSN (online) 1534-6242
    ISSN 1523-3804
    DOI 10.1007/s11883-022-01076-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5534: Show issues Location:
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  2. Article: Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer.

    Tambaro, Federica / Imbimbo, Giovanni / Ferraro, Elisabetta / Andreini, Martina / Belli, Roberta / Amabile, Maria Ida / Ramaccini, Cesarina / Lauteri, Giulia / Nigri, Giuseppe / Muscaritoli, Maurizio / Molfino, Alessio

    Cancer & metabolism

    2024  Volume 12, Issue 1, Page(s) 1

    Abstract: Background: Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and ...

    Abstract Background: Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia.
    Methods: We considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases. We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5.
    Results: We found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027).
    Conclusion: In our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type.
    Language English
    Publishing date 2024-01-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2700141-6
    ISSN 2049-3002
    ISSN 2049-3002
    DOI 10.1186/s40170-023-00329-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Liquid Biopsy for Cancer Cachexia: Focus on Muscle-Derived microRNAs.

    Belli, Roberta / Ferraro, Elisabetta / Molfino, Alessio / Carletti, Raffaella / Tambaro, Federica / Costelli, Paola / Muscaritoli, Maurizio

    International journal of molecular sciences

    2021  Volume 22, Issue 16

    Abstract: Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia ... ...

    Abstract Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia reduces the tolerability of chemo/radio-therapy treatments and it is frequently the primary cause of death in advanced cancer patients. Early detection of this condition could make treatments more effective. However, early diagnostic biomarkers of cachexia are currently lacking. In recent years, although solid biopsy still remains the "gold standard" for diagnosis of cancer, liquid biopsy is gaining increasing interest as a source of easily accessible potential biomarkers. Moreover, the growing interest in circulating microRNAs (miRNAs), has made these molecules attractive for the diagnosis of several diseases, including cancer. Some muscle-derived circulating miRNA might play a pivotal role in the onset/progression of cancer cachexia. This topic is of great interest since circulating miRNAs might be easily detectable by means of liquid biopsies and might allow an early diagnosis of this syndrome. We here summarize the current knowledge on circulating muscular miRNAs involved in muscle atrophy, since they might represent easily accessible and promising biomarkers of cachexia.
    MeSH term(s) Adipose Tissue/metabolism ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Cachexia/diagnosis ; Cachexia/genetics ; Circulating MicroRNA/analysis ; Circulating MicroRNA/blood ; Circulating MicroRNA/genetics ; Energy Metabolism/physiology ; Humans ; Inflammation/pathology ; Liquid Biopsy/methods ; MicroRNAs/analysis ; MicroRNAs/blood ; MicroRNAs/genetics ; Muscle, Skeletal/metabolism ; Muscular Atrophy/pathology ; Neoplasms/complications ; Neoplasms/genetics ; Signal Transduction/genetics ; Weight Loss/genetics
    Chemical Substances Biomarkers, Tumor ; Circulating MicroRNA ; MicroRNAs
    Language English
    Publishing date 2021-08-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22169007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Evaluation of Browning Markers in Subcutaneous Adipose Tissue of Newly Diagnosed Gastrointestinal Cancer Patients with and without Cachexia.

    Molfino, Alessio / Belli, Roberta / Imbimbo, Giovanni / Carletti, Raffaella / Amabile, Maria Ida / Tambaro, Federica / di Gioia, Cira R T / Belloni, Elena / Ferraro, Elisabetta / Nigri, Giuseppe / Muscaritoli, Maurizio

    Cancers

    2022  Volume 14, Issue 8

    Abstract: We assessed the molecular phenotype of the browning of white adipose tissue in newly diagnosed cancer patients and controls undergoing surgery for gastrointestinal tumors and for non-malignant diseases, respectively. We collected subcutaneous adipose ... ...

    Abstract We assessed the molecular phenotype of the browning of white adipose tissue in newly diagnosed cancer patients and controls undergoing surgery for gastrointestinal tumors and for non-malignant diseases, respectively. We collected subcutaneous adipose tissue (SAT) samples and using RT-PCR, we analyzed the expression of markers of browning and using Western blot the protein levels of UCP1 and PGC1α. The
    Language English
    Publishing date 2022-04-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14081948
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  5. Article ; Online: The Fibrinogen-like Domain of ANGPTL3 Facilitates Lipolysis in 3T3-L1 Cells by Activating the Intracellular Erk Pathway.

    Bini, Simone / Pecce, Valeria / Di Costanzo, Alessia / Polito, Luca / Ghadiri, Ameneh / Minicocci, Ilenia / Tambaro, Federica / Covino, Stella / Arca, Marcello / D'Erasmo, Laura

    Biomolecules

    2022  Volume 12, Issue 4

    Abstract: Background: ANGPTL3 stimulates lipolysis in adipocytes, but the underlying molecular mechanism is yet unknown. The C-terminal fibrinogen-like domain of ANGPTL3 (ANGPTL3-Fld) activates the AKT pathway in endothelial cells. Hence, we evaluated whether ... ...

    Abstract Background: ANGPTL3 stimulates lipolysis in adipocytes, but the underlying molecular mechanism is yet unknown. The C-terminal fibrinogen-like domain of ANGPTL3 (ANGPTL3-Fld) activates the AKT pathway in endothelial cells. Hence, we evaluated whether ANGPTL3-Fld stimulates lipolysis in adipocytes through the MAPK kinase pathway.
    Materials and methods: 3T3-L1 adipocytes were treated with isoproterenol (ISO), ANGPTL3-Fld, or both. Lipolysis was evaluated through the release of free fatty acids (FFAs) in the culture medium. The activation status of intracellular kinases was evaluated with and without the inhibition of the BRAF-ERK arm of the MAPK pathway.
    Results: ANGPTL3-Fld alone was not able to activate lipolysis, while the combination of ANGPTL3-Fld and ISO determined a 10-fold enrichment of the FFA concentration in the culture medium with an incremental effect (twofold) when compared with ISO alone. ANGPTL3-Fld alone inhibited hormone-sensitive lipase (HSL), whereas the treatment with ISO induced the activation of HSL. The net balance of ANGPTL3-Fld and ISO cotreatment resulted in HSL activation. The results indicate that ANGPTL3-Fld generated an intracellular activation signal involving the MAPK-ERK pathway, possibly through the PDGFRβ-PLCγ-AMPK axis.
    Conclusion: ANGPTL3-Fld appears to act as a facilitator of lipolysis in adipocytes, and this effect was driven by a signal mediated by a pathway that is different from the canonical β-adrenergic stimulus.
    MeSH term(s) 3T3-L1 Cells ; Angiopoietin-Like Protein 3/metabolism ; Animals ; Endothelial Cells/metabolism ; Fatty Acids, Nonesterified ; Fibrinogen/metabolism ; Isoproterenol/pharmacology ; Lipolysis ; MAP Kinase Signaling System ; Mice ; Sterol Esterase/metabolism
    Chemical Substances Angiopoietin-Like Protein 3 ; Angptl3 protein, mouse ; Fatty Acids, Nonesterified ; Fibrinogen (9001-32-5) ; Sterol Esterase (EC 3.1.1.13) ; Isoproterenol (L628TT009W)
    Language English
    Publishing date 2022-04-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12040585
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Changes of gene expression in peripheral blood mononuclear cells of lung cancer patients with or without anorexia.

    Molfino, Alessio / Ambrosani, Francesca / Tambaro, Federica / Belli, Roberta / Imbimbo, Giovanni / Udali, Silvia / Moruzzi, Sara / Pattini, Patrizia / Ramaccini, Cesarina / Castagna, Annalisa / Muscaritoli, Maurizio / Friso, Simonetta

    Clinical nutrition (Edinburgh, Scotland)

    2022  Volume 42, Issue 1, Page(s) 9–17

    Abstract: Background & aims: Anorexia is a disabling symptom in cancer and we aimed at investigating the role of changes in gene expression in lung cancer patients presenting with anorexia.: Methods: Genome-wide transcriptomic profiling was assessed in PBMCs ... ...

    Abstract Background & aims: Anorexia is a disabling symptom in cancer and we aimed at investigating the role of changes in gene expression in lung cancer patients presenting with anorexia.
    Methods: Genome-wide transcriptomic profiling was assessed in PBMCs RNA from newly diagnosed lung cancer patients and in a control group. RT-qPCR was used for selected genes.
    Results: RNA-Seq analysis revealed among groups a large number of differentially expressed genes mainly implicated in immune system regulation, oxidative stress and cytokine-mediated inflammation signaling pathways. In particular, we identified a total of 983 DEGs (843 up-regulated; 140 down-regulated) in anorexic cancer compared to controls. A selected number of DEGs including ADAM8, SMAD4, CCR4 and CLU were differentially expressed within cancer group according to the presence/absence of anorexia. In terms of RT-qPCR, ADAM8 was less expressed in cancer patients than controls (p < 0.001), and in anorexic patients vs controls (p = 0.001). The expression of SMAD4 was lower in cancer vs controls (p = 0.005), and in anorexic patients vs controls (p = 0.009). We observed lower CCR4 expression in both anorexic and non-anorexic vs control (p = 0.004, p = 0.011, respectively) and a similar trend was present for CLU.
    Conclusions: Our data shed new light on the role of specific genes and their associated molecular pathways as potential key mechanisms for the development of anorexia and may represent a novel landmark for understanding the complex pathophysiology of impaired appetite in cancer.
    MeSH term(s) Humans ; Anorexia/genetics ; Leukocytes, Mononuclear ; Lung Neoplasms/genetics ; Gene Expression Profiling ; Gene Expression ; Membrane Proteins ; ADAM Proteins
    Chemical Substances ADAM8 protein, human (EC 3.4.24.-) ; Membrane Proteins ; ADAM Proteins (EC 3.4.24.-)
    Language English
    Publishing date 2022-11-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604812-2
    ISSN 1532-1983 ; 0261-5614
    ISSN (online) 1532-1983
    ISSN 0261-5614
    DOI 10.1016/j.clnu.2022.11.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1774: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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