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  1. Book ; Online: Liquid Biopsy as a Tool for Precision Oncology: New Challenges to Assess Clinical Response

    Ravegnini, Gloria / Del Re, Marzia / Grolla, Ambra A. / van Schaik, Ron H. N. / Angelini, Sabrina

    2020  

    Keywords Science: general issues ; Pharmacology ; liquid biopsy ; precision oncology ; ctDNA (circulating tumor DNA) ; Circulating molecular marker ; personalized medicine
    Size 1 electronic resource (78 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021230400
    ISBN 9782889662029 ; 2889662020
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article: Editorial: Liquid Biopsy as a Tool for Precision Oncology: New Challenges to Assess Clinical Response.

    Ravegnini, Gloria / Del Re, Marzia / Grolla, Ambra A / van Schaik, Ron H N / Angelini, Sabrina

    Frontiers in pharmacology

    2020  Volume 11, Page(s) 598261

    Language English
    Publishing date 2020-10-07
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2020.598261
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Recent Advances in NAMPT Inhibitors: A Novel Immunotherapic Strategy.

    Galli, Ubaldina / Colombo, Giorgia / Travelli, Cristina / Tron, Gian Cesare / Genazzani, Armando A / Grolla, Ambra A

    Frontiers in pharmacology

    2020  Volume 11, Page(s) 656

    Abstract: Nicotinamide adenine dinucleotide (NAD) is a cofactor of many enzymatic reactions as well as being a substrate for a number of NAD-consuming enzymes (e.g., PARPS, sirtuins, etc). NAD can be ... ...

    Abstract Nicotinamide adenine dinucleotide (NAD) is a cofactor of many enzymatic reactions as well as being a substrate for a number of NAD-consuming enzymes (e.g., PARPS, sirtuins, etc). NAD can be synthesized
    Language English
    Publishing date 2020-05-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2020.00656
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Identification of novel aza-analogs of TN-16 as disrupters of microtubule dynamics through a multicomponent reaction.

    Foroutan, Arash / Corazzari, Marco / Grolla, Ambra A / Colombo, Giorgia / Travelli, Cristina / Genazzani, Armando A / Theeramunkong, Sewan / Galli, Ubaldina / Tron, Gian Cesare

    European journal of medicinal chemistry

    2022  Volume 245, Issue Pt 1, Page(s) 114895

    Abstract: Despite novel biological targets emerging at an impressive rate for anticancer therapy, antitubulin drugs remain the backbone of numerous oncological protocols and their efficacy has been demonstrated in a wide variety of adult and pediatric cancers. In ... ...

    Abstract Despite novel biological targets emerging at an impressive rate for anticancer therapy, antitubulin drugs remain the backbone of numerous oncological protocols and their efficacy has been demonstrated in a wide variety of adult and pediatric cancers. In the present contribution, we set to develop analogs of a potent but neglected antitubulin agent, TN-16, originally discovered via modification of tenuazonic acid (3-acetyl-5-sec-butyltetramic acid). To this extent, we developed a novel multicomponent reaction to prepare TN-16, and then we applied the same reaction for the synthesis of aza-analogs. In brief, we prepared a library of 62 novel compounds, and three of these retained nanomolar potencies. TN-16 and the active analogs are cytotoxic on cancer cell lines and, as expected from antitubulin agents, induce G
    MeSH term(s) Child ; Humans ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Screening Assays, Antitumor ; Microtubules/drug effects ; Structure-Activity Relationship ; Tubulin/metabolism ; Tubulin Modulators/chemical synthesis ; Tubulin Modulators/chemistry ; Tubulin Modulators/pharmacology ; Pyrrolidinones/chemical synthesis ; Pyrrolidinones/chemistry ; Pyrrolidinones/pharmacology
    Chemical Substances Antineoplastic Agents ; TN 16 (33016-12-5) ; Tubulin ; Tubulin Modulators ; Pyrrolidinones
    Language English
    Publishing date 2022-11-03
    Publishing country France
    Document type Journal Article
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2022.114895
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 784: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Functionalization of β-cyclodextrin with a urea-based PSMA ligand and preliminary studies on targeting prostate cancer cells.

    Imperio, Daniela / Grolla, Ambra A / Moro, Marianna / Bortolotto, Valeria / Del Grosso, Erika / Genazzani, Armando A / Panza, Luigi

    Bioorganic & medicinal chemistry letters

    2022  Volume 73, Page(s) 128890

    Abstract: Targeted delivery of drugs into specific cancer cells is an effective way to enhance the efficacy and minimize the side effects of therapy. Prostate malignant cells overexpress the prostate-specific membrane antigen (PSMA), a membrane protein that may be ...

    Abstract Targeted delivery of drugs into specific cancer cells is an effective way to enhance the efficacy and minimize the side effects of therapy. Prostate malignant cells overexpress the prostate-specific membrane antigen (PSMA), a membrane protein that may be a valid target for selective drug administration. To target prostate cancer cells, a β-cyclodextrin perfunctionalised with dipeptide-like urea arms, a well-established mimic of a selective ligand against PSMA, is herein reported, to develop a multivalent drug delivery and targeting system. Firstly, fluorescein was used to validate the system on cells that express high levels of PSMA (prostate tumoral cells, LNCap) or very low levels of PSMA (non-tumoral cells, Hek293T). Then, the antineoplastic agent doxorubicin complexed with β-cyclodextrin functionalized with PSMA-like ligand takes less time to induce cytotoxicity on LNCap cells compared to doxorubicin alone. This might represent a promising drug-delivery approach to selectively target prostate cancer cells.
    MeSH term(s) Antigens, Surface/metabolism ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Glutamate Carboxypeptidase II/metabolism ; HEK293 Cells ; Humans ; Ligands ; Male ; Prostatic Neoplasms/pathology ; Urea/pharmacology ; Urea/therapeutic use ; beta-Cyclodextrins
    Chemical Substances Antigens, Surface ; Ligands ; beta-Cyclodextrins ; Doxorubicin (80168379AG) ; Urea (8W8T17847W) ; Glutamate Carboxypeptidase II (EC 3.4.17.21)
    Language English
    Publishing date 2022-07-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2022.128890
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3203: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids.

    Mola, Silvia / Pinton, Giulia / Erreni, Marco / Corazzari, Marco / De Andrea, Marco / Grolla, Ambra A / Martini, Veronica / Moro, Laura / Porta, Chiara

    International journal of molecular sciences

    2021  Volume 22, Issue 9

    Abstract: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a long latency period and dismal prognosis. Recently, tazemetostat (EPZ-6438), an inhibitor of the histone methyltransferase EZH2, has entered clinical trials due to the ... ...

    Abstract Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a long latency period and dismal prognosis. Recently, tazemetostat (EPZ-6438), an inhibitor of the histone methyltransferase EZH2, has entered clinical trials due to the antiproliferative effects reported on MPM cells. However, the direct and indirect effects of epigenetic reprogramming on the tumor microenvironment are hitherto unexplored. To investigate the impact of tumor-associated macrophages (TAMs) on MPM cell responsiveness to tazemetostat, we developed a three-dimensional MPM spheroid model that recapitulates in vitro, both monocytes' recruitment in tumors and their functional differentiation toward a TAM-like phenotype (Mo-TAMs). Along with an increased expression of genes for monocyte chemoattractants, inhibitory immune checkpoints, immunosuppressive and M2-like molecules, Mo-TAMs promote tumor cell proliferation and spreading. Prolonged treatment of MPM spheroids with tazemetostat enhances both the recruitment of Mo-TAMs and the expression of their protumor phenotype. Therefore, Mo-TAMs profoundly suppress the antiproliferative effects due to EZH2 inhibition in MPM cells. Overall, our findings indicate that TAMs are a driving force for MPM growth, progression, and resistance to tazemetostat; therefore, strategies of TAM depletion might be evaluated to improve the therapeutic efficacy of pharmacological inhibition of EZH2.
    MeSH term(s) Benzamides/pharmacology ; Biphenyl Compounds/pharmacology ; Cell Proliferation ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors ; Humans ; Mesothelioma/drug therapy ; Mesothelioma/metabolism ; Mesothelioma/pathology ; Monocytes/drug effects ; Monocytes/pathology ; Morpholines/pharmacology ; Pyridones/pharmacology ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/pathology ; Tumor Cells, Cultured ; Tumor Microenvironment ; Tumor-Associated Macrophages/drug effects ; Tumor-Associated Macrophages/pathology
    Chemical Substances Benzamides ; Biphenyl Compounds ; Morpholines ; Pyridones ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; tazemetostat (Q40W93WPE1)
    Language English
    Publishing date 2021-04-22
    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/ijms22094391
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) neutralization counteracts T cell immune evasion in breast cancer.

    Travelli, Cristina / Colombo, Giorgia / Aliotta, Martina / Fagiani, Francesca / Fava, Natalia / De Sanctis, Rita / Grolla, Ambra A / Garcia, Joe G N / Clemente, Nausicaa / Portararo, Paola / Costanza, Massimo / Condorelli, Fabrizio / Colombo, Mario Paolo / Sangaletti, Sabina / Genazzani, Armando A

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 10

    Abstract: Background: Nicotinamide phosphoribosyltransferase (NAMPT) is a key intracellular enzyme that participates in nicotinamide adenine dinucleotide (NAD) homeostasis as well as a released cytokine (eNAMPT) that is elevated in inflammatory conditions and in ... ...

    Abstract Background: Nicotinamide phosphoribosyltransferase (NAMPT) is a key intracellular enzyme that participates in nicotinamide adenine dinucleotide (NAD) homeostasis as well as a released cytokine (eNAMPT) that is elevated in inflammatory conditions and in cancer. In patients with breast cancer, circulating eNAMPT is elevated and its plasma levels correlate with prognosis and staging. In light of this, we investigated the contribution of eNAMPT in triple negative mammary carcinoma progression by investigating the effect of its neutralization via a specific neutralizing monoclonal antibody (C269).
    Methods: We used female BALB/c mice injected with 4T1 clone 5 cells and female C57BL6 injected with EO771 cells, evaluating tumoral size, spleen weight and number of metastases. We injected two times a week the anti-eNAMPT neutralizing antibody and we sacrificed the mice after 28 days. Harvested tumors were analyzed by histopathology, flow cytometry, western blot, immunohistochemistry, immunofluorescence and RNA sequencing to define tumor characteristics (isolating tumor infiltrating lymphocytes and tumoral cells) and to investigate the molecular mechanisms behind the observed phenotype. Moreover, we dissected the functional relationship between T cells and tumoral cells using three-dimensional (3D) co-cultures.
    Results: The neutralization of eNAMPT with C269 led to decreased tumor size and reduced number of lung metastases. RNA sequencing and functional assays showed that eNAMPT controlled T-cell response via the programmed death-ligand 1/programmed cell death protein 1 (PD-L1/PD-1) axis and its neutralization led to a restoration of antitumoral immune responses. In particular, eNAMPT neutralization was able to activate CD8
    Conclusions: These studies indicate for the first time eNAMPT as a novel immunotherapeutic target for triple negative breast cancer.
    MeSH term(s) Humans ; Female ; Mice ; Animals ; Breast Neoplasms ; Nicotinamide Phosphoribosyltransferase/metabolism ; Immune Evasion ; Cytokines/metabolism ; Prognosis
    Chemical Substances Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; Cytokines
    Language English
    Publishing date 2023-10-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-007010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Editorial

    Gloria Ravegnini / Marzia Del Re / Ambra A. Grolla / Ron H. N. van Schaik / Sabrina Angelini

    Frontiers in Pharmacology, Vol

    Liquid Biopsy as a Tool for Precision Oncology: New Challenges to Assess Clinical Response

    2020  Volume 11

    Keywords liquid biopsy ; precision oncology ; ctDNA (circulating tumor DNA) ; Circulating molecular marker ; personalized medicine ; Therapeutics. Pharmacology ; RM1-950
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids

    Silvia Mola / Giulia Pinton / Marco Erreni / Marco Corazzari / Marco De Andrea / Ambra A. Grolla / Veronica Martini / Laura Moro / Chiara Porta

    International Journal of Molecular Sciences, Vol 22, Iss 4391, p

    2021  Volume 4391

    Abstract: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a long latency period and dismal prognosis. Recently, tazemetostat (EPZ-6438), an inhibitor of the histone methyltransferase EZH2, has entered clinical trials due to the ... ...

    Abstract Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a long latency period and dismal prognosis. Recently, tazemetostat (EPZ-6438), an inhibitor of the histone methyltransferase EZH2, has entered clinical trials due to the antiproliferative effects reported on MPM cells. However, the direct and indirect effects of epigenetic reprogramming on the tumor microenvironment are hitherto unexplored. To investigate the impact of tumor-associated macrophages (TAMs) on MPM cell responsiveness to tazemetostat, we developed a three-dimensional MPM spheroid model that recapitulates in vitro, both monocytes’ recruitment in tumors and their functional differentiation toward a TAM-like phenotype (Mo-TAMs). Along with an increased expression of genes for monocyte chemoattractants, inhibitory immune checkpoints, immunosuppressive and M2-like molecules, Mo-TAMs promote tumor cell proliferation and spreading. Prolonged treatment of MPM spheroids with tazemetostat enhances both the recruitment of Mo-TAMs and the expression of their protumor phenotype. Therefore, Mo-TAMs profoundly suppress the antiproliferative effects due to EZH2 inhibition in MPM cells. Overall, our findings indicate that TAMs are a driving force for MPM growth, progression, and resistance to tazemetostat; therefore, strategies of TAM depletion might be evaluated to improve the therapeutic efficacy of pharmacological inhibition of EZH2.
    Keywords malignant pleural mesothelioma ; tumor-associated macrophages ; monocytes ; EZH2 ; spheroids ; epigenetic reprogramming ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    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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  10. Article ; Online: The Cytokine Nicotinamide Phosphoribosyltransferase (eNAMPT; PBEF; Visfatin) Acts as a Natural Antagonist of C-C Chemokine Receptor Type 5 (CCR5).

    Torretta, Simone / Colombo, Giorgia / Travelli, Cristina / Boumya, Sara / Lim, Dmitry / Genazzani, Armando A / Grolla, Ambra A

    Cells

    2020  Volume 9, Issue 2

    Abstract: 1) Background: Extracellular nicotinamide phosphoribosyltrasferase (eNAMPT) is released by various cell types with pro-tumoral and pro-inflammatory properties. In cancer, eNAMPT regulates tumor growth through the activation of intracellular pathways, ... ...

    Abstract (1) Background: Extracellular nicotinamide phosphoribosyltrasferase (eNAMPT) is released by various cell types with pro-tumoral and pro-inflammatory properties. In cancer, eNAMPT regulates tumor growth through the activation of intracellular pathways, suggesting that it acts through a putative receptor, although its nature is still elusive. It has been shown, using surface plasma resonance, that eNAMPT binds to the C-C chemokine receptor type 5 (CCR5), although the physiological meaning of this finding is unknown. The aim of the present work was to characterize the pharmacodynamics of eNAMPT on CCR5. (2) Methods: HeLa CCR5-overexpressing stable cell line and B16 melanoma cells were used. We focused on some phenotypic effects of CCR5 activation, such as calcium release and migration, to evaluate eNAMPT actions on this receptor. (3) Results: eNAMPT did not induce ERK activation or cytosolic Ca
    MeSH term(s) Animals ; Calcium/metabolism ; Calcium Signaling/genetics ; Cell Movement/genetics ; Chemokine CCL5/metabolism ; Cytokines/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Melanoma/metabolism ; Melanoma/pathology ; Mice ; Nicotinamide Phosphoribosyltransferase/metabolism ; Protein Binding/genetics ; Protein Kinase C/metabolism ; Receptors, CCR5/genetics ; Receptors, CCR5/metabolism ; Recombinant Proteins/metabolism ; Signal Transduction/genetics ; Transfection
    Chemical Substances CCL5 protein, human ; CCR5 protein, human ; CCR5 protein, mouse ; Chemokine CCL5 ; Cytokines ; Receptors, CCR5 ; Recombinant Proteins ; Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; nicotinamide phosphoribosyltransferase, human (EC 2.4.2.12) ; nicotinamide phosphoribosyltransferase, mouse (EC 2.4.2.12) ; Protein Kinase C (EC 2.7.11.13) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-02-21
    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/cells9020496
    Database MEDical Literature Analysis and Retrieval System OnLINE

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