228 results on '"Biffoni, M"'
Search Results
2. TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells
- Author
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Bartucci, M, Dattilo, R, Moriconi, C, Pagliuca, A, Mottolese, M, Federici, G, Benedetto, A Di, Todaro, M, Stassi, G, Sperati, F, Amabile, M I, Pilozzi, E, Patrizii, M, Biffoni, M, Maugeri-Saccà, M, Piccolo, S, and De Maria, R
- Published
- 2015
- Full Text
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3. Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression
- Author
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Pagliuca, A, Valvo, C, Fabrizi, E, di Martino, S, Biffoni, M, Runci, D, Forte, S, De Maria, R, and Ricci-Vitiani, L
- Published
- 2013
- Full Text
- View/download PDF
4. BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by inducing luminal markers expression and epithelial–mesenchymal transition
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Coppola, V, Musumeci, M, Patrizii, M, Cannistraci, A, Addario, A, Maugeri-Saccà, M, Biffoni, M, Francescangeli, F, Cordenonsi, M, Piccolo, S, Memeo, L, Pagliuca, A, Muto, G, Zeuner, A, De Maria, R, and Bonci, D
- Published
- 2013
- Full Text
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5. Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer
- Author
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Musumeci, M, Coppola, V, Addario, A, Patrizii, M, Maugeri-Saccà, M, Memeo, L, Colarossi, C, Francescangeli, F, Biffoni, M, Collura, D, Giacobbe, A, D'Urso, L, Falchi, M, Venneri, M A, Muto, G, De Maria, R, and Bonci, D
- Published
- 2011
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6. Transfected human dendritic cells to induce antitumor immunity
- Author
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Rughetti, A, Biffoni, M, Sabbatucci, M, Rahimi, H, Pellicciotta, I, Fattorossi, A, Pierelli, L, Scambia, G, Lavitrano, M, Frati, L, and Nuti, M
- Published
- 2000
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7. 1665P Genomic mutational landscape of solid tumors: Preliminary results from ROME trial
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Botticelli, A., Scagnoli, S., Conte, P.F., Cremolini, C., Ascierto, P.A., Cappuzzo, F., Aglietta, M., Mazzuca, F., Capoluongo, E., Blandino, G., Malapelle, U., Nuti, M., D'Amati, G., Cerbelli, B., Pruneri, G., Biffoni, M., Giannini, G., Cognetti, F., Curigliano, G., and Marchetti, P.
- Published
- 2022
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8. Lymphocyte T subsets and natural killer cells in Italian and Philippino blood donors
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Pasqualetti, D., Ghirardini, A., Cafolla, A., Biffoni, M., Coluzzi, S., Vaglio, S., and Girelli, G.
- Published
- 2003
9. Familial papillary carcinoma of the thyroid: a report of nine first-degree relatives of four families
- Author
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Marchesi, M., Biffoni, M., Biancari, F., Faloci, C., Cresti, R., Mariotti, F., Nobili Benedetti, R., and Campana, F.P.
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- 2000
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10. Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XLinhibition in non-small cell lung cancer
- Author
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Zeuner, Francescangeli, Federica, Contavalli, P., Zapparelli, G., Apuzzo, Tiziana, Eramo, A., Baiocchi, M., De Angelis, M. L., Biffoni, M., Sette, G., Todaro, Stassi, G., and R. De Maria S.
- Published
- 2014
11. 307. Metabolic heterogeneity among Glioblastoma stem-like cells reflects differences in response to drug treatments
- Author
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Palma, A., Grande, S., Ricci-Vitiani, L., Luciani, A.M., Buccarelli, M., Biffoni, M., Molinari, A., Calcabrini, A., D’Amore, E., Guidoni, L., Pallini, R., Viti, V., and Rosi, A.
- Published
- 2018
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12. miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma
- Author
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Felli N, Felicetti F, Lustri AM, Errico MC, Bottero L, Cannistraci A, De Feo A, Petrini M, Pedini F, Biffoni M, Alvino E, Negrini M, Ferracin M, Mattia G, Carè A. PLoS One. 2013 and 8(2):e56824. doi: 10.1371/journal.pone.0056824. Epub 2013 Feb 21. PMID: 23437250 [PubMed - in process]
- Abstract
The abnormal expression of several microRNAs has a causal role in tumorigenesis with either antineoplastic or oncogenic functions. Here we demonstrated that miR-126 and miR-126* play a tumor suppressor role in human melanoma through the direct or indirect repression of several key oncogenic molecules. The expression levels of miR-126&126* were elevated in normal melanocytes and primary melanoma cell lines, whereas they markedly declined in metastatic cells. Indeed, the restored expression of miR-126&126* in two advanced melanoma cell lines was accompanied by a significant reduction of proliferation, invasion and chemotaxis in vitro as well as of growth and dissemination in vivo. In accordance, the reverse functional effects were obtained by knocking down miR-126&126* by transfecting antisense LNA oligonucleotides in melanoma cells. Looking for the effectors of these antineoplastic functions, we identified ADAM9 and MMP7, two metalloproteases playing a pivotal role in melanoma progression, as direct targets of miR-126&126*. In addition, as ADAM9 and MMP7 share a role in the proteolytic cleavage of the HB-EGF precursor, we looked for the effectiveness of this regulatory pathway in melanoma, confirming the decrease of HB-EGF activation as a consequence of miR-126&126*-dependent downmodulation of ADAM9 and MMP7. Finally, gene profile analyses showed that miR-126&126* reexpression was sufficient to inactivate other key signaling pathways involved in the oncogenic transformation, as PI3K/AKT and MAPK, and to restore melanogenesis, as indicated by KIT/MITF/TYR induction. In view of this miR-126&126* wide-ranging action, we believe that the replacement of these microRNAs might be considered a promising therapeutic approach. PMID: 23437250 [PubMed - in process]
- Published
- 2013
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13. NFI-A DIRECTS THE FATE OF HEMATOPOIETIC PROGENITORS TO THE ERYTHROID OR GRANULOCYTIC LINEAGE AND CONTROLS b-GLOBIN AND G-CSF RECEPTOR EXPRESSION
- Author
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STARNES LM, SORRENTINO A., Pelosi, E, Ballarino, Biffoni, M, Fatica, Alessandro, Bozzoni, Irene, Nervi, Clara, and Peschle, C.
- Published
- 2009
14. Human neural progenitor cells display limited cytotoxicity and increased oligodendrogenesis during inflammation [2]
- Author
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Ricci-Vitiani, L., Lombardi, D. G., Signore, M., Biffoni, M., Pallini, Roberto, Parati, E., Peschle, C., and De Maria Marchiano, Ruggero
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Inflammation ,Cultured ,Cells ,Cytotoxicity ,Stem Cells ,Animals ,Cells, Cultured ,Cytotoxicity, Immunologic ,Demyelinating Autoimmune Diseases, CNS ,Humans ,Mice ,Nerve Tissue Proteins ,Oligodendroglia ,Tumor Necrosis Factor Receptor-Associated Peptides and Proteins ,Cell Biology ,Demyelinating Autoimmune Diseases ,Immunologic ,Settore MED/04 - PATOLOGIA GENERALE ,CNS - Published
- 2007
15. Enhancement of Candida rugosa lipase activity by immunoglobulin light chain
- Author
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Barachini, 2. 7. S., Bartoli, L., Biffoni, M., Cernia, Enrico, Frati, Luigi, Morea, V., Nuti, Marianna, Palocci, Cleofe, RAHIMI KOSHKAKI, Hassan, Rughetti, Aurelia, Soro, Simonetta, Taurino, F., and Tramontano, A.
- Published
- 2003
16. Enhancement of Candida rugosa lipase activity by immunoglobulin light chain
- Author
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Barachini, S., Bartoli, L., Biffoni, M., Cernia, Enrico, Frati, Luigi, Morea, V., Nuti, Marianna, Palocci, Cleofe, RAHIMI KOSHKAKI, Hassan, Rughetti, Aurelia, Soro, Simonetta, and Taurino, F.
- Published
- 2003
17. Opportunities and Risks for Distributed Generation in the Context of Liberalized Energy Markets
- Author
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Biffoni, M., DE ROSSI, F., Massucco, Stefano, Silvestro, Federico, Burt, G., Galloway, S., and Mcdonald, J. R.
- Published
- 2002
18. Opportunities and Risks for Distributed Generation in the Context of Liberalized Energy Markets
- Author
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Biffoni, M, Burt, G, DE ROSSI, F, Massucco, Stefano, MC DONALD, J. R., and Silvestro, Federico
- Published
- 2002
19. GLIOBLASTOMA STEM CELLS: RADIOBIOLOGICAL RESPONSE TO IONISING RADIATIONS OF DIFFERENT QUALITIES.
- Author
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Pecchia, I., Dini, V., Ricci-Vitiani, L., Biffoni, M., Balduzzi, M., Fratini, E., Belli, M., Campa, A., Esposito, G., Cirrone, G., Romano, F., Stancampiano, C., Pelacchi, F., Pallini, R., and Tabocchini, M. A.
- Subjects
GLIOBLASTOMA multiforme treatment ,CANCER stem cells ,IONIZING radiation ,TUMORS ,PROTONS - Abstract
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour, with very poor prognosis. The high recurrence rate and failure of conventional treatments are expected to be related to the presence of radio-resistant cancer stem cells (CSCs) inside the tumour mass. CSCs can both self-renew and differentiate into the heterogeneous lineages of cancer cells. Recent evidence showed a higher effectiveness of C-ions and protons in inactivating CSCs, suggesting a potential advantage of Hadrontherapy compared with conventional radiotherapy for GBM treatment. To investigate the mechanisms involved in the molecular and cellular responses of CSCs to ionising radiations, two GBM stem cell (GSC) lines, named lines 1 and 83, which were derived from patients with different clinical outcomes and having different metabolic profiles (as shown by NMR spectroscopy), were irradiated with
137 Cs photons and with protons or C-ions of 62 MeV u-1 in the dose range of 5-40 Gy. The biological effects investigated were: cell death, cell cycle progression, and DNA damage induction and repair. Preliminary results show a different response to ionising radiation between the two GSC lines for the different end points investigated. Further experiments are in progress to consolidate the data and to get more insights on the influence of radiation quality. [ABSTRACT FROM AUTHOR]- Published
- 2015
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20. Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer.
- Author
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Zeuner, A, Francescangeli, F, Contavalli, P, Zapparelli, G, Apuzzo, T, Eramo, A, Baiocchi, M, De Angelis, M L, Biffoni, M, Sette, G, Todaro, M, Stassi, G, and De Maria, R
- Subjects
CANCER stem cells ,BCL genes ,LUNG cancer & genetics ,NEOPLASTIC cell transformation ,CANCER chemotherapy - Abstract
Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-X
L is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL . In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC. [ABSTRACT FROM AUTHOR]- Published
- 2014
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- View/download PDF
21. INHIBITION OF HUMAN NATURAL KILLER ACTIVITY B NAPHTALENE ANALGESICS
- Author
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Marino PAROLI, Biffoni, M., Paroli, Eugenio, and Maria Caterina Grassi
- Published
- 1990
22. Antitumor effect of miR-197 targeting in p53 wild-type lung cancer.
- Author
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Fiori, M E, Barbini, C, Haas, T L, Marroncelli, N, Patrizii, M, Biffoni, M, and De Maria, R
- Subjects
ANTINEOPLASTIC agents ,P53 protein ,LUNG cancer treatment ,MICRORNA ,NUCLEIC acids ,CANCER invasiveness - Abstract
Lung cancer is the leading cause of tumor-related death. The lack of effective treatments urges the development of new therapeutic approaches able to selectively kill cancer cells. The connection between aberrant microRNA (miRNA - miR) expression and tumor progression suggests a new strategy to fight cancer by interfering with miRNA function. In this regard, LNAs (locked nucleic acids) have proven to be very promising candidates for miRNA neutralization. Here, we employed an LNA-based anti-miR library in a functional screening to identify putative oncogenic miRNAs in non-small-cell lung cancer (NSCLC). By screening NIH-H460 and A549 cells, miR-197 was identified as a new functional oncomiR, whose downregulation induces p53-dependent lung cancer cell apoptosis and impairs the capacity to establish tumor xenografts in immunodeficient mice. We further identified the two BH3-only proteins NOXA and BMF as new miR-197 targets responsible for induction of apoptosis in p53 wild-type cells, delineating miR-197 as a key survival factor in NSCLC. Thus, we propose the inhibition of miR-197 as a novel therapeutic approach against lung cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
23. Duodenal tumors: four case reports.
- Author
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PASTA, V., BIFFONI, M., MARTINO, G., MALAVENDA, M. S., SOTTILE, D., MARINACCIO, L., MEROLA, R., VERGINE, M., BERNIERI, M. G., MONTI, M., and REDLER, A.
- Published
- 2013
24. Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy.
- Author
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Bartucci, M, Svensson, S, Romania, P, Dattilo, R, Patrizii, M, Signore, M, Navarra, S, Lotti, F, Biffoni, M, Pilozzi, E, Duranti, E, Martinelli, S, Rinaldo, C, Zeuner, A, Maugeri-Saccà, M, Eramo, A, and De Maria, R
- Subjects
CANCER stem cells ,CANCER chemotherapy ,SMALL cell lung cancer ,CANCER patients ,DNA damage ,CELL cycle - Abstract
Cancer stem cell (SC) chemoresistance may be responsible for the poor clinical outcome of non-small-cell lung cancer (NSCLC) patients. In order to identify the molecular events that contribute to NSCLC chemoresistance, we investigated the DNA damage response in SCs derived from NSCLC patients. We found that after exposure to chemotherapeutic drugs NSCLC-SCs undergo cell cycle arrest, thus allowing DNA damage repair and subsequent cell survival. Activation of the DNA damage checkpoint protein kinase (Chk) 1 was the earliest and most significant event detected in NSCLC-SCs treated with chemotherapy, independently of their p53 status. In contrast, a weak Chk1 activation was found in differentiated NSCLC cells, corresponding to an increased sensitivity to chemotherapeutic drugs as compared with their undifferentiated counterparts. The use of Chk1 inhibitors in combination with chemotherapy dramatically reduced NSCLC-SC survival in vitro by inducing premature cell cycle progression and mitotic catastrophe. Consistently, the co-administration of the Chk1 inhibitor AZD7762 and chemotherapy abrogated tumor growth in vivo, whereas chemotherapy alone was scarcely effective. Such increased efficacy in the combined use of Chk1 inhibitors and chemotherapy was associated with a significant reduction of NSCLC-SCs in mouse xenografts. Taken together, these observations support the clinical evaluation of Chk1 inhibitors in combination with chemotherapy for a more effective treatment of NSCLC. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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25. Identification and expansion of the tumorigenic lung cancer stem cell population.
- Author
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Eramo, A., Lotti, F., Sette, G., Pilozzi, E., Biffoni, M., Di Virgilio, A., Conticello, C., Ruco, L., Peschle, C., and De Maria, R.
- Subjects
LUNG cancer ,ONCOGENIC DNA viruses ,CELL populations ,CANCER patients ,GENETICS - Abstract
Lung carcinoma is often incurable and remains the leading cancer killer in both men and women. Recent evidence indicates that tumors contain a small population of cancer stem cells that are responsible for tumor maintenance and spreading. The identification of the tumorigenic population that sustains lung cancer may contribute significantly to the development of effective therapies. Here, we found that the tumorigenic cells in small cell and non-small cell lung cancer are a rare population of undifferentiated cells expressing CD133, an antigen present in the cell membrane of normal and cancer-primitive cells of the hematopoietic, neural, endothelial and epithelial lineages. Lung cancer CD133
+ cells were able to grow indefinitely as tumor spheres in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. The injection of 104 lung cancer CD133+ cells in immunocompromised mice readily generated tumor xenografts phenotypically identical to the original tumor. Upon differentiation, lung cancer CD133+ cells acquired the specific lineage markers, while loosing the tumorigenic potential together with CD133 expression. Thus, lung cancer contains a rare population of CD133+ cancer stem-like cells able to self-renew and generates an unlimited progeny of non-tumorigenic cells. Molecular and functional characterization of such a tumorigenic population may provide valuable information to be exploited in the clinical setting.Cell Death and Differentiation (2008) 15, 504–514; doi:10.1038/sj.cdd.4402283; published online 30 November 2007 [ABSTRACT FROM AUTHOR]- Published
- 2008
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26. Effects of urinary gonadotrophin preparations on human in-vitro immune function.
- Author
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Biffoni, M, Marcucci, I, Ythier, A, and Eshkol, A
- Abstract
Among commercially available urinary human menopausal gonadotrophin (HMG) material, gonadotrophins comprise <5% of the total protein content. Thus, during a typical ovarian stimulation cycle with HMG, several milligrams of non-relevant proteins are administered that may lead to unwanted side effects, including allergic or other hypersensitivity reactions. The effects of two recombinant and four urinary gonadotrophin preparations of different purity upon the function of T cells from healthy blood donors were studied. Only one of the HMG preparations significantly enhanced the spontaneous proliferation of peripheral blood mononuclear cells. Phytohaemagglutinin-induced proliferation was not modified by any preparation, while two preparations significantly increased proliferation in the mixed lymphocyte reaction. Three of the HMG preparations induced the release of interleukin (IL)-1. Highly purified FSH, either urinary or recombinant, showed no effect. None of the preparations induced detectable IL-2 production, whereas only one HMG preparation tended to decrease IL-2 secretion. No major changes in CD25 expression were induced by any of the gonadotrophins. Cytokine measurement by immunoassays detected only IL-1β in two commercially available preparations. The various effects exhibited by the crude urinary preparations were not a result of the gonadotrophin content and differed from product to product, suggesting that the contaminants present in these preparations are not identical. This could contribute to unpredictable clinical manifestations of allergic or other immune reactions. [ABSTRACT FROM PUBLISHER]
- Published
- 1998
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27. Immunology: Allergenic potential of gonadotrophic preparations in experimental animals: relevance of purity.
- Author
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Biffoni, M., Battaglia, A., Borrelli, F., Cantelmo, A., Galli, G., and Eshkol, A.
- Abstract
Local reactions have been frequently reported following repeated injections of human menopausal gonadotrophins (HMG) for the treatment of infertility. Also immunoglobulin (Ig) E-mediated systemic reactions have sporadically been observed. Since most HMG preparations contain significant amounts of non-hormonal urine-derived proteins, it was suggested that these contaminating proteins are responsible for the various allergic reactions. In order to verify this hypothesis, different human follicle stimulating hormone (HFSH) and HMG preparations (Metrodin and Pergonal from Ares-Serono, and Humegon from Organon), were compared with a highly purified preparation (Metrodin HP from Ares-Serono) for the frequency and severity of allergic reactions induced in laboratory animals. The occurrence of anaphylactic shock or related symptoms was studied in sensitized guinea-pigs. The production of specific IgE was evaluated in serum from mice sensitized with the test drugs by the induction of passive cutaneous anaphylaxis in rats. In both models, two different schedules of sensitization were used. Severe allergic reactions were found in 20 and 7% of the guinea-pigs receiving highly purified FSH (Metrodin HP) in the two schedules, respectively, compared to 90 and 88% with the other preparations. Similarly significantly lower IgE titres were induced by highly purified FSH in respect to the other preparations. It can be concluded that the elimination of contaminating proteins significantly reduces the allergenicity of urine-derived HFSH preparations. [ABSTRACT FROM PUBLISHER]
- Published
- 1994
28. MicroRNA-221/-222 pathway controls melanoma progression
- Author
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Felicetti, F., Errico, M.C., Bottero, L., Segnalini, P., Biffoni, M., Felli, N., Mattia, G., Petrini, M., Colombo, M.P., and Carè, A.
- Published
- 2008
- Full Text
- View/download PDF
29. Human neural progenitor cells display limited cytotoxicity and increased oligodendrogenesis during inflammation.
- Author
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Ricci-Vitiani, L., Lombardi, D. G., Signore, M., Biffoni, M., Pallini, R., Parati, E., Peschle, C., and De Maria, R.
- Subjects
LETTERS to the editor ,CELL death - Abstract
A letter to the editor is presented concerning the limited cytotoxicity and increased oligodendrogenesis displayed by human neural progenitor cells during inflammation.
- Published
- 2007
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30. Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome.
- Author
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Marziali, G., Signore, M., Buccarelli, M., Grande, S., Palma, A., Biffoni, M., Rosi, A., D'Alessandris, Q.G., Martini, M., Larocca, L. M., De Maria, R., Pallini, R., and Ricci-Vitiani, L.
- Published
- 2016
- Full Text
- View/download PDF
31. Effects of β-casomorphins and Met-enkephalin on human natural killer activity
- Author
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Biffoni, M., Paroli, E., Carletti, M., and Antonilli, L.
- Published
- 1992
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- View/download PDF
32. Variability of treatment modalities and intensity in patients with severe haemophilia A on prophylaxis: results from the Italian national registry
- Author
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Lorenzo G. Mantovani, Adele Giampaolo, Francesca Abbonizio, Mauro Biffoni, Angelo Claudio Molinari, Giancarlo Castaman, Paolo Cortesi, Cortesi, P, Giampaolo, A, Abbonizio, F, Molinari, A, Castaman, G, Biffoni, M, and Mantovani, L
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Haemophilia A ,Haemophilia ,Hemophilia A ,Chemoprevention ,Severity of Illness Index ,Drug Administration Schedule ,Drug Costs ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Medicine ,Humans ,In patient ,Registries ,Precision Medicine ,Prophylaxi ,Child ,FVIII consumption ,Factor VIII ,business.industry ,Age Factors ,Infant, Newborn ,Infant ,Hematology ,General Medicine ,medicine.disease ,Personalized medicine ,Regimen ,Italy ,Treatment modality ,030220 oncology & carcinogenesis ,Child, Preschool ,Severe haemophilia A ,Female ,National registry ,business ,030215 immunology - Abstract
Background: A shift from a standard to a personalized prophylaxis has been increasingly adopted in patients with severe haemophilia A (SHA). This approach has raised the likelihood of a significant variability in the prophylactic approaches and the relative Factor VIII (FVIII) consumptions. The aim of our study was to assess the treatment variability of SHA patients without inhibitors and on prophylaxis regimen in Italy. Material and methods: Data reported in the National Registry of Congenital Coagulopathies (NRCC) were analysed to assess treatment distribution within SHA patients without inhibitors, focussing on FVIII consumption in 2017, associated with prophylaxis regimen. The analysis was stratified based on age groups and Italian regions to describe the variability of FVIII consumption in Italy. Results: In 2017, the Registry reported the therapeutic plans of 1068 SHA patients without inhibitors on prophylaxis. The mean (95% CI) individual consumption ranges from 123 127 IU (99 736-146 518) in the age group 0-6 years to 345 000 IU (336 000-354 000) in the age group >20 years. A significant FVIII consumption variability was identified within the adult population. Regions with less than 50 patients reported the higher variability in mean FVIII consumption per patient-year within the different age groups. Similar difference in FVIII consumption variability was reported also in the age groups comparing “low,” “middle” and “high” patient volume regions. Discussion: A reliable estimation of FVIII consumption for patients’ treatment is necessary to manage and plan the appropriate budget and keep treatment's costs affordable. However, without the implementation of a methodology aiming to assess the overall value produced by these FVIII consumptions, the scenario will keep driven by FVIII consumptions, its costs and the budget available. An effort by haemophilic community, haemophilia treatment centres and institutions is required to develop and share this cultural shift in improving haemophilia management and assessment.
- Published
- 2021
33. Multicentre harmonisation of a six-colour flow cytometry panel for naïve/memory T cell immunomonitoring
- Author
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Chiara Agrati, Belinda Palermo, Massimo Sanchez, Floriana Iacobone, Mauro Biffoni, Rita Casetti, Giorgio Fedele, Francesca Urbani, Valentina La Sorsa, Pasqualina Leone, Cristina Capuano, Marianna Nuti, Helena Stabile, Iole Macchia, Andrea Rozo Gonzalez, Filippo Belardelli, Carla Buccione, Giovanna Schiavoni, Ilaria Grazia Zizzari, Paola Rizza, Maria Carollo, Cinzia Fionda, Matilde Sinibaldi, Irene Ruspantini, Valentina Tirelli, Concetta Quintarelli, Aurelia Rughetti, Paola Nisticò, Roberta Maggio, Angela Gismondi, Stefania Morrone, Macchia, I., La Sorsa, V., Ruspantini, I., Sanchez, M., Tirelli, V., Carollo, M., Fedele, G., Leone, P., Schiavoni, G., Buccione, C., Rizza, P., Nistico, P., Palermo, B., Morrone, S., Stabile, H., Rughetti, A., Nuti, M., Zizzari, I. G., Fionda, C., Maggio, R., Capuano, C., Quintarelli, C., Sinibaldi, M., Agrati, C., Casetti, R., Rozo Gonzalez, A., Iacobone, F., Gismondi, A., Belardelli, F., Biffoni, M., and Urbani, F.
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,Oncology ,Receptors, CCR7 ,medicine.medical_specialty ,CD3 Complex ,Article Subject ,Operating procedures ,Immunology ,T cells ,Color ,CD8-Positive T-Lymphocytes ,flow cytometry ,harmonization ,Immunophenotyping ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,T-Lymphocyte Subsets ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Observer Variation ,medicine.diagnostic_test ,business.industry ,General Medicine ,RC581-607 ,Clinical trial ,030104 developmental biology ,Lazio region ,medicine.anatomical_structure ,Italy ,030220 oncology & carcinogenesis ,Leukocytes, Mononuclear ,Leukocyte Common Antigens ,Immunologic diseases. Allergy ,business ,Observer variation ,Immunologic Memory ,Immunologic memory ,Memory T cell ,Biomarkers ,Research Article - Abstract
Background. Personalised medicine in oncology needs standardised immunological assays. Flow cytometry (FCM) methods represent an essential tool for immunomonitoring, and their harmonisation is crucial to obtain comparable data in multicentre clinical trials. The objective of this study was to design a harmonisation workflow able to address the most effective issues contributing to intra- and interoperator variabilities in a multicentre project. Methods. The Italian National Institute of Health (Istituto Superiore di Sanità, ISS) managed a multiparametric flow cytometric panel harmonisation among thirteen operators belonging to five clinical and research centres of Lazio region (Italy). The panel was based on a backbone mixture of dried antibodies (anti-CD3, anti-CD4, anti-CD8, anti-CD45RA, and anti-CCR7) to detect naïve/memory T cells, recognised as potential prognostic/predictive immunological biomarkers in cancer immunotherapies. The coordinating centre distributed frozen peripheral blood mononuclear cells (PBMCs) and fresh whole blood (WB) samples from healthy donors, reagents, and Standard Operating Procedures (SOPs) to participants who performed experiments by their own equipment, in order to mimic a real-life scenario. Operators returned raw and locally analysed data to ISS for central analysis and statistical elaboration. Results. Harmonised and reproducible results were obtained by sharing experimental set-up and procedures along with centralising data analysis, leading to a reduction of cross-centre variability for naïve/memory subset frequencies particularly in the whole blood setting. Conclusion. Our experimental and analytical working process proved to be suitable for the harmonisation of FCM assays in a multicentre setting, where high-quality data are required to evaluate potential immunological markers, which may contribute to select better therapeutic options.
- Published
- 2020
34. Laryngeal neuroendocrine tumor with elevated serum calcitonin: a diagnostic and therapeutic challenge. Case report and review of literature
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Tiziana Feola, Giulia Puliani, Franz Sesti, Roberta Modica, Marco Biffoni, Cira Di Gioia, Raffaella Carletti, Emanuela Anastasi, Valentina Di Vito, Roberta Centello, Andrea Lenzi, Andrea M. Isidori, Antongiulio Faggiano, Elisa Giannetta, Feola, T., Puliani, G., Sesti, F., Modica, R., Biffoni, M., Di Gioia, C., Carletti, R., Anastasi, E., Di Vito, V., Centello, R., Lenzi, A., Isidori, A. M., Faggiano, A., and Giannetta, E.
- Subjects
0301 basic medicine ,Larynx ,Calcitonin ,Male ,medicine.medical_specialty ,calcium gluconate infusion test ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Case Report ,everolimus ,larynx ,medullary thyroid carcinoma ,neck ,neuroendocrine tumor ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Gastroenterology ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Humans ,Lymph node ,Laryngeal Neoplasms ,lcsh:RC648-665 ,medicine.diagnostic_test ,business.industry ,Thyroid ,everolimu ,Middle Aged ,medicine.disease ,Primary tumor ,Neuroendocrine Tumors ,030104 developmental biology ,medicine.anatomical_structure ,Fine-needle aspiration ,Differential diagnosis ,business - Abstract
Introduction: Laryngeal neuroendocrine neoplasms (NENs) are a rare group of NENs of the neck, which commonly show immunostaining for calcitonin. Laryngeal NENs with calcitonin hypersecretion and lymph node metastases represent a diagnostic and therapeutic challenge, which should be included in the differential diagnosis of medullary thyroid carcinoma (MTC). We report a complex case of laryngeal NEN with calcitonin hypersecretion and a review of the literature. Case Presentation: A 59-year-old man presented with dysphagia, dyspnea, and lateral cervical mass; he was a smoker. At first imaging, a laryngeal lesion with lateral cervical lymphadenopathies was found, and it resulted as a moderately differentiated neuroendocrine tumor (G2), Ki67 = 5%, positive for calcitonin. Increased levels of serum calcitonin (50 pg/ml) were found. The patient started somatostatin analogs for lesions positivity to somatostatin receptor-based imaging. After 5 months, the disease progressed at 18F-fluorodeoxyglucose (18F-FDG) PET-CT, and also new painful cutaneous lesions occurred. Considering high serum levels of calcitonin, differential diagnosis with MTC was required. Patient performed a thyroid color Doppler ultrasound, nodule fine needle aspiration, calcitonin dosage in fine needle washout fluid, and a calcium gluconate stimulation test. After multidisciplinary evaluation, we decided to perform a total thyroidectomy associated with lateral cervical lymphadenectomy and resection of skin metastases. No MTC was found. Two of the five resected lymph nodes, left upper parathyroid, and skin lesions were metastases of NEN G2, positive for calcitonin. After 2 months, new painful skin lesions occurred, and a target therapy with everolimus 10 mg/day was started. After 6 months of therapy, partial metabolic response with a reduction of 53.7% of radiotracer uptake at primary tumor was detected together with an improvement of patient's quality of life. Conclusions: The present case is the seventh described in the literature of laryngeal NEN associated with elevated serum calcitonin levels and the first case with parathyroid metastasis, suggesting the importance of a correct differential diagnosis between MTC and calcitonin-secreting laryngeal NEN, using an integrated approach of biochemistry and advanced imaging. This is also the first time that somatostatin analogs and then everolimus were used in this setting, resulting in clinical and partial metabolic response.
- Published
- 2020
35. Inhibition of human natural killer activity by naphtalene analgesics
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Paroli, M., Biffoni, M., Paroli, E., and Grassi, M.C.
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- 1990
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36. TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells
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Alfredo Pagliuca, Matilde Todaro, Marcello Maugeri-Saccà, Emanuela Pilozzi, A Di Benedetto, Marcella Mottolese, Francesca Sperati, Giulia Federici, M Patrizii, Stefano Piccolo, Chiara Moriconi, Giorgio Stassi, Rosanna Dattilo, Monica Bartucci, Marco Biffoni, R De Maria, Maria Ida Amabile, Bartucci, M, Dattilo, R, Moriconi, C, Pagliuca, A, Mottolese, M, Federici, G, Benedetto, AD, Todaro, M, Stassi, G, Sperati, F, Amabile, MI, Pilozzi, E, Patrizii, M, Biffoni, M, Maugeri-Saccà, M, Piccolo, S, and De Maria, R
- Subjects
cancer stem cells ,TAZ ,Animals ,Biomarkers, Tumor ,Breast Neoplasms ,Cell Line, Tumor ,Disease-Free Survival ,Female ,Gene Expression Regulation, Neoplastic ,Humans ,Mice ,Neoplasm Metastasis ,Neoplasm Recurrence, Local ,Neoplastic Stem Cells ,Transcription Factors ,Xenograft Model Antitumor Assays ,Cancer Research ,Bioinformatics ,chemotherapy ,Metastasis ,taz ,breast cancer ,education.field_of_study ,Tumor ,Intracellular Signaling Peptides and Proteins ,Cell cycle ,Local ,metastasis ,Molecular Biology ,Genetics ,Stem cell ,Population ,Biology ,Cell Line ,breast cancer , cancer stem cells, TAZ ,Breast cancer ,Cancer stem cell ,Settore MED/04 - PATOLOGIA GENERALE ,medicine ,education ,Hippo signaling pathway ,Neoplastic ,Cancer ,medicine.disease ,Neoplasm Recurrence ,Gene Expression Regulation ,Transcriptional Coactivator with PDZ-Binding Motif Proteins ,Cancer research ,Trans-Activators ,Biomarkers - Abstract
Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs is the only cell population endowed with metastatic potential. Gene-expression profile studies comparing metastagenic and non-metastagenic cells identified TAZ, a transducer of the Hippo pathway and biomechanical cues, as a central mediator of BCSCs metastatic ability involved in their chemoresistance and tumorigenic potential. Overexpression of TAZ in low-expressing dBCCs induced cell transformation and conferred tumorigenicity and migratory activity. Conversely, loss of TAZ in BCSCs severely impaired metastatic colonization and chemoresistance. In clinical data from 99 BC patients, high expression levels of TAZ were associated with shorter disease-free survival in multivariate analysis, thus indicating that TAZ may represent a novel independent negative prognostic factor. Overall, this study designates TAZ as a novel biomarker and a possible therapeutic target for BC.
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- 2015
37. Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer
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Matilde Todaro, Federica Francescangeli, M L De Angelis, Giovanni Sette, R De Maria, Giorgio Stassi, Tiziana Apuzzo, G Zapparelli, Paola Contavalli, Adriana Eramo, Ann Zeuner, Mauro Biffoni, Marta Baiocchi, Zeuner, A., Francescangeli, F., Contavalli, P., Zapparelli, G., Apuzzo, T., Eramo, A., Baiocchi, M., De Angelis, M., Biffoni, M., Sette, G., Todaro, M., Stassi, G., and De Maria, R.
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Lung Neoplasms ,Mice, SCID ,Pharmacology ,Piperazines ,Antineoplastic Agent ,Nitrophenols ,Mice ,Mice, Inbred NOD ,Carcinoma, Non-Small-Cell Lung ,Cytotoxic T cell ,Non-Small-Cell Lung ,education.field_of_study ,Sulfonamides ,Tumor ,Animals ,Antineoplastic Agents ,Biphenyl Compounds ,Cell Line, Tumor ,Cell Proliferation ,Cell Survival ,Female ,Humans ,Neoplastic Stem Cells ,Tumor Burden ,Xenograft Model Antitumor Assays ,bcl-X Protein ,Molecular Biology ,Cell Biology ,Stem cell ,Human ,medicine.drug ,Xenograft Model Antitumor Assay ,Population ,Biology ,SCID ,Sulfonamide ,Cell Line ,Cancer stem cell ,medicine ,education ,Lung cancer ,Piperazine ,Settore MED/04 - Patologia Generale ,Original Paper ,Nitrophenol ,Animal ,Cell growth ,Carcinoma ,medicine.disease ,Gemcitabine ,Lung Neoplasm ,Cell culture ,Biphenyl Compound ,Cancer research ,Inbred NOD ,Neoplastic Stem Cell - Abstract
Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL. In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC.
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- 2014
38. Erythropoietin activates cell survival pathways in breast cancer stem-like cells to protect them from chemotherapy
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Flora Iovino, Rosanna Dattilo, Giorgio Stassi, Monica Bartucci, Giulia Federici, Alice Turdo, Ruggero De Maria, Matilde Todaro, Marco Biffoni, Ann Zeuner, Todaro, M, Turdo, A, Bartucci, M, Iovino, F, Dattilo, R, Biffoni, M, Stassi, G, Federici, G, De Maria, R, and Zeuner, A
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MAPK/ERK pathway ,Oncology ,Cancer Research ,medicine.medical_treatment ,Fluorescent Antibody Technique ,Apoptosis ,Mice, SCID ,Immunoenzyme Techniques ,Mice ,Cell Movement ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Tumor Cells, Cultured ,Cultured ,Blotting ,Anemia ,Flow Cytometry ,Tumor Cells ,TRIALS ,Disease Progression ,Neoplastic Stem Cells ,Female ,Western ,Signal Transduction ,medicine.drug ,STIMULATING AGENTS ,EXPRESSION ,medicine.medical_specialty ,Blotting, Western ,Antineoplastic Agents ,Breast Neoplasms ,SCID ,RECOMBINANT-HUMAN-ERYTHROPOIETIN, STIMULATING AGENTS, EXPRESSION, MORTALITY, TRIALS, ANEMIA, ALPHA, ALDH1 ,Breast cancer ,In vivo ,Internal medicine ,medicine ,Animals ,Humans ,Breast cancer, Cancer stem cells ,ALDH1 ,Erythropoietin ,Protein kinase B ,Cell Proliferation ,Settore MED/04 - Patologia Generale ,Chemotherapy ,business.industry ,MORTALITY ,Cancer ,RECOMBINANT-HUMAN-ERYTHROPOIETIN ,medicine.disease ,ALPHA ,Tumor progression ,Inbred NOD ,business - Abstract
Recombinant erythropoietin (EPO) analogs [erythropoiesis-stimulating agents (ESA)] are clinically used to treat anemia in patients with cancer receiving chemotherapy. After clinical trials reporting increased adverse events and/or reduced survival in ESA-treated patients, concerns have been raised about the potential role of ESAs in promoting tumor progression, possibly through tumor cell stimulation. However, evidence is lacking on the ability of EPO to directly affect cancer stem–like cells, which are thought to be responsible for tumor progression and relapse. We found that breast cancer stem–like cells (BCSC) isolated from patient tumors express the EPO receptor and respond to EPO treatment with increased proliferation and self-renewal. Importantly, EPO stimulation increased BCSC resistance to chemotherapeutic agents and activated cellular pathways responsible for survival and drug resistance. Specifically, the Akt and ERK pathways were activated in BCSC at early time points following EPO treatment, whereas Bcl-xL levels increased at later times. In vivo, EPO administration counteracted the effects of chemotherapeutic agents on BCSC-derived orthotopic tumor xenografts and promoted metastatic progression both in the presence and in the absence of chemotherapy treatment. Altogether, these results indicate that EPO acts directly on BCSC by activating specific survival pathways, resulting in BCSC protection from chemotherapy and enhanced tumor progression. Cancer Res; 73(21); 6393–400. ©2013 AACR.
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- 2013
39. EGFR inhibition abrogates Leiomyosarcoma cell chemoresistance through inactivation of survival pathways and impairment of CSC potential
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Cristina Colarossi, Lorenzo Memeo, Adriana Eramo, Valentina Salvati, Giovanni Sette, Enrico De Antoni, Paola Di Matteo, Katia Fecchi, Mauro Biffoni, Ruggero De Maria, Vincenzo Canzonieri, Vito D'Andrea, Michele Signore, Sette, G, Salvati, V, Memeo, L, Fecchi, K, Colarossi, C, Di Matteo, P, Signore, M, Biffoni, M, D'Andrea, V, De Antoni, E, Canzonieri, V, De Maria, R, and Eramo, A.
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Leiomyosarcoma ,Pathology ,Cellular differentiation ,Cancer Treatment ,lcsh:Medicine ,Tumor initiation ,Metastasis ,Mice ,Molecular Cell Biology ,Basic Cancer Research ,lcsh:Science ,Extracellular Signal-Regulated MAP Kinases ,Animals ,Cell Differentiation ,Cell Proliferation ,Cell Survival ,Drug Resistance, Neoplasm ,Female ,Humans ,Neoplasm Grading ,Neoplastic Stem Cells ,Phenotype ,Phosphoproteins ,Protein Kinase Inhibitors ,Proto-Oncogene Proteins c-akt ,Quinazolines ,Receptor, Epidermal Growth Factor ,Signal Transduction ,Vincristine ,Xenograft Model Antitumor Assays ,Biochemistry, Genetics and Molecular Biology (all) ,Agricultural and Biological Sciences (all) ,Multidisciplinary ,Cell Death ,Gefitinib ,ErbB Receptors ,Oncology ,Medicine ,Oncology Agents ,Sarcoma ,Research Article ,medicine.medical_specialty ,EGFR ,Biology ,Cell Growth ,Side population ,Settore MED/04 - PATOLOGIA GENERALE ,Cancer stem cell ,medicine ,lcsh:R ,Mesenchymal stem cell ,Chemotherapy and Drug Treatment ,medicine.disease ,Embryonic stem cell ,Cancer research ,lcsh:Q - Abstract
BACKGROUND: Tumor cells with stem-like phenotype and properties, known as cancer stem cells (CSC), have been identified in most solid tumors and are presumed to be responsible for driving tumor initiation, chemoresistance, relapse, or metastasis. A subpopulation of cells with increased stem-like potential has also been identified within sarcomas. These cells are endowed with increased tumorigenic potential, chemoresistance, expression of embryonic markers, and side population(SP) phenotype. Leiomyosarcomas (LMS) are soft tissue sarcomas presumably arising from undifferentiated cells of mesenchymal origin, the Mesenchymal Stem Cells (MSC). Frequent recurrence of LMS and chemoresistance of relapsed patients may likely result from the failure to target CSC. Therefore, therapeutic cues coming from the cancer stem cell (CSC) field may drastically improve patient outcome. METHODOLOGY/PRINCIPAL FINDINGS: We expanded LMS stem-like cells from patient samples in vitro and examined the possibility to counteract LMS malignancy through a stem-like cell effective approach. LMS stem-like cells were in vitro expanded both as "tumor spheres" and as "monolayers" in Mesenchymal Stem Cell (MSC) conditions. LMS stem-like cells displayed MSC phenotype, higher SP fraction, and increased drug-extrusion, extended proliferation potential, self-renewal, and multiple differentiation ability. They were chemoresistant, highly tumorigenic, and faithfully reproduced the patient tumor in mice. Such cells displayed activation of EGFR/AKT/MAPK pathways, suggesting a possibility in overcoming their chemoresistance through EGFR blockade. IRESSA plus Vincristine treatment determined pathway inactivation, impairment of SP phenotype, high cytotoxicity in vitro and strong antitumor activity in stem-like cell-generated patient-like xenografts, targeting both stem-like and differentiated cells. CONCLUSIONS/SIGNIFICANCE: EGFR blockade combined with vincristine determines stem-like cell effective antitumor activity in vitro and in vivo against LMS, thus providing a potential therapy for LMS patients.
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- 2012
40. Isolation and characterization of CD146+ multipotent mesenchymal stromal cells
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Marta Baiocchi, Mauro Valtieri, Giada Tomaselli, Cesare Peschle, Massimo Negrini, Alessandro Fatica, Germana Castelli, Mauro Biffoni, Antonio Sorrentino, Manuela Ferracin, Sorrentino A., Ferracin M., Castelli G., Biffoni M., Tomaselli G., Baiocchi M., Fatica A., Negrini M., Peschle C., and Valtieri M.
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Cancer Research ,Time Factors ,Cellular differentiation ,Cell Culture Techniques ,Cell Separation ,Regenerative medicine ,education.field_of_study ,UMBILICAL-CORD ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Differentiation ,Hematology ,COLONY-STIMULATING FACTOR ,Cell biology ,RECEPTORS ,Phenotype ,medicine.anatomical_structure ,Intercellular Signaling Peptides and Proteins ,Stem cell ,GROWTH-FACTOR ,Stromal cell ,Blotting, Western ,Molecular Sequence Data ,Population ,CD146 Antigen ,Biology ,Cell Line ,Immunophenotyping ,Chondrocytes ,Genetics ,medicine ,Humans ,HEMATOPOIETIC STEM-CELLS ,HUMAN PERIPHERAL-BLOOD ,education ,Molecular Biology ,Cell Proliferation ,Gene Expression Profiling ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Biology ,IN-VITRO ,Microarray Analysis ,Chondrogenesis ,ENDOTHELIAL-CELLS ,MicroRNAs ,PROGENITOR CELLS ,Immunology ,Bone marrow ,Stromal Cells ,HUMAN BONE-MARROW - Abstract
Mesenchymal stromal cells (MSCs) represent a bone marrow (BM) population, classically defined by five functional properties: extensive proliferation, ability to differentiate into osteoblasts, chondrocytes, adipocytes, and stromal cells-supporting hematopoiesis. However, research progress in this area has been hampered by lack of suitable markers and standardized procedures for MSC isolation. We have isolated a CD146(+) multipotent MSC population from 20 human BM donors displaying the phenotype of self-renewing osteoprogenitors; an extensive 12-week proliferation; and the ability to differentiate in osteoblasts, chondrocytes, adipocytes, and stromal cells supporting hematopoiesis. Furthermore, the CD146(+) MSCs secrete a complex combination of growth factors (GFs) controlling hematopoietic stem cells (HSCs) function, while providing a >2-log increase in the long-term culture (LTC) colony output in 8-week LTC over conventional assays. The hematopoietic stromal function exhibited by the MSCs was further characterized by manipulating LTCs with the chemical inhibitors Imatinib or SU-5416, targeting two GF receptors (GFRs), KIT or VEGFR2/1, respectively. Both treatments similarly impaired LTC colony output, indicating key roles for these two GF/GFR interactions to support LTC-initiating cell activity. CD146(+) MSCs may thus represent a tool to explore the MSC-HSC cross-talk in an in vitro surrogate model for HSC "niches," and for regenerative therapy studies. In addition, the MSC microRNA (miRNA) expression profile was analyzed by microarrays in both basic conditions and chondrogenic differentiation. Our analysis revealed that several miRNAs are modulated during chondrogenesis, and many of their putative targets are genes involved in chondrogenic differentiation.
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- 2008
41. Identification and expansion of human colon-cancer-initiating cells
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Lucia Ricci-Vitiani, Dario Giuseppe Lombardi, Cesare Peschle, Emanuela Pilozzi, Mauro Biffoni, Matilde Todaro, Ruggero De Maria, RICCI-VITIANI L, LOMBARDI DG, PILOZZI E, BIFFONI M, TODARO M, PESCHLE C, and DE MARIA R
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AC133 Antigen ,Animals ,Antigens, CD ,Cell Differentiation ,Cell Line, Tumor ,Cell Proliferation ,Colonic Neoplasms ,Glycoproteins ,Humans ,Mice ,Mice, SCID ,Neoplasm Transplantation ,Neoplastic Stem Cells ,Peptides ,Phenotype ,Transplantation, Heterologous ,Multidisciplinary ,Colorectal cancer ,Cellular differentiation ,Population ,Tumor initiation ,Biology ,Colon carcinomas ,medicine.disease_cause ,SCID ,Cell Line ,Side population ,Cancer stem cell ,Settore MED/04 - PATOLOGIA GENERALE ,medicine ,Antigens ,education ,education.field_of_study ,Transplantation ,Heterologous ,Tumor ,Cancer ,medicine.disease ,CD ,Immunology ,Cancer research ,Carcinogenesis - Abstract
Colon carcinoma is the second most common cause of death from cancer. The isolation and characterization of tumorigenic colon cancer cells may help to devise novel diagnostic and therapeutic procedures. Although there is increasing evidence that a rare population of undifferentiated cells is responsible for tumour formation and maintenance, this has not been explored for colorectal cancer. Here, we show that tumorigenic cells in colon cancer are included in the high-density CD133+ population, which accounts for about 2.5% of the tumour cells. Subcutaneous injection of colon cancer CD133+ cells readily reproduced the original tumour in immunodeficient mice, whereas CD133- cells did not form tumours. Such tumours were serially transplanted for several generations, in each of which we observed progressively faster tumour growth without significant phenotypic alterations. Unlike CD133- cells, CD133+ colon cancer cells grew exponentially for more than one year in vitro as undifferentiated tumour spheres in serum-free medium, maintaining the ability to engraft and reproduce the same morphological and antigenic pattern of the original tumour. We conclude that colorectal cancer is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells, which should therefore be the target of future therapies.
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- 2007
42. Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma.
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Verrienti A, Pecce V, Grani G, Del Gatto V, Barp S, Maranghi M, Giacomelli L, Di Gioia C, Biffoni M, Filetti S, Durante C, and Sponziello M
- Abstract
Purpose: Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm, accounting for approximately 85% of all follicular cell-derived thyroid nodules. This study aimed to assess the diagnostic potential of circulating microRNA-146a-5p and microRNA-221-3p as biomarkers for PTC and their usefulness in monitoring disease progression during patient follow-up., Methods: An observational study was conducted on two cohorts of PTC patients and healthy controls (HCs) using digital PCR. We collected patients' clinical, biochemical, and imaging data during the post-surgery surveillance. We analyzed the levels of circulating miRNAs in serum samples of patients before surgery and during the follow-up, including those with indeterminate/biochemical incomplete response (IndR/BIR) and residual thyroid tissues (Thy Residue)., Results: Both miR-146a-5p and miR-221-3p were confirmed as effective biomarkers for PTC diagnosis. They enabled differentiation between pre-surgery PTC patients and HCs with an area under the curve (AUC) of 92% and 87.3%, respectively, using a threshold level of 768,545 copies/uL for miR-146a-5p and 389,331 copies/uL for miR-221-3p. It was found that miRNA fold change levels, rather than absolute levels, can be useful during patient follow-up. In particular, we found that a fold change of 2 for miR-146a-5p and 2.2 for miR-221-3p can identify a progressive disease, regardless of the presence of TgAbs or remnant thyroid., Conclusion: MiRNA-146a-5p and miRNA-221-3p, particularly the former, could be valuable diagnostic biomarkers for PTCs. They also seem to be effective in monitoring disease progression during patient follow-up by evaluating their fold change, even when thyroglobulin is uninformative., (© 2024. The Author(s).)
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- 2024
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43. Author Correction: Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B.
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Musella M, Guarracino A, Manduca N, Galassi C, Ruggiero E, Potenza A, Maccafeo E, Manic G, Mattiello L, Soliman Abdel Rehim S, Signore M, Pietrosanto M, Helmer-Citterich M, Pallocca M, Fanciulli M, Bruno T, De Nicola F, Corleone G, Di Benedetto A, Ercolani C, Pescarmona E, Pizzuti L, Guidi F, Sperati F, Vitale S, Macchia D, Spada M, Schiavoni G, Mattei F, De Ninno A, Businaro L, Lucarini V, Bracci L, Aricò E, Ziccheddu G, Facchiano F, Rossi S, Sanchez M, Boe A, Biffoni M, De Maria R, Vitale I, and Sistigu A
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- 2024
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44. Advancements in 3D In Vitro Models for Colorectal Cancer.
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Vitale S, Calapà F, Colonna F, Luongo F, Biffoni M, De Maria R, and Fiori ME
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- Humans, Animals, In Vitro Techniques methods, Cell Line, Tumor, Colorectal Neoplasms genetics
- Abstract
The process of drug discovery and pre-clinical testing is currently inefficient, expensive, and time-consuming. Most importantly, the success rate is unsatisfactory, as only a small percentage of tested drugs are made available to oncological patients. This is largely due to the lack of reliable models that accurately predict drug efficacy and safety. Even animal models often fail to replicate human-specific pathologies and human body's complexity. These factors, along with ethical concerns regarding animal use, urge the development of suitable human-relevant, translational in vitro models., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
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- 2024
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45. Drawing as a Way of Knowing : How a Mapping Model Assists Preoperative Evaluation of Patients with Thyroid Carcinoma.
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Biffoni M, Grani G, Melcarne R, Geronzi V, Consorti F, Ruggieri G, Galvano A, Razlighi MH, Iannuzzi E, Engel TD, Pace D, Di Gioia CRT, Boniardi M, Durante C, and Giacomelli L
- Abstract
Background : Effective pre-surgical planning is crucial for achieving successful outcomes in endocrine surgery: it is essential to provide patients with a personalized plan to minimize operative and postoperative risks. Methods: Preoperative lymph node (LN) mapping is a structured high-resolution ultrasonography examination performed in the presence of two endocrinologists and the operating surgeon before intervention to produce a reliable "anatomical guide". Our aim was to propose a preoperative complete model that is non-invasive, avoids overdiagnosis of thyroid microcarcinomas, and reduces medical expenses. Results: The use of 'preoperative echography mapping' has been shown to be successful, particularly in patients with suspected or confirmed neoplastic malignancy. Regarding prognosis, positive outcomes have been observed both post-surgery and in terms of recurrence rates. We collected data on parameters such as biological sex, age, BMI, and results from cytologic tests performed with needle aspiration, and examined whether these parameters predict tumor malignancy or aggressiveness, calculated using a multivariate analysis (MVA). Conclusions: A standard multidisciplinary approach for evaluating neck lymph nodes pre-operation has proven to be an improved diagnostic and preoperative tool.
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- 2024
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46. Extracellular vesicles produced by irradiated endothelial or Glioblastoma stem cells promote tumor growth and vascularization modulating tumor microenvironment.
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Castellani G, Buccarelli M, D'Alessandris QG, Ilari R, Cappannini A, Pedini F, Boe A, Lulli V, Parolini I, Giannetti S, Biffoni M, Zappavigna V, Marziali G, Pallini R, and Ricci-Vitiani L
- Abstract
Background: Glioblastoma (GBM) is the most lethal primary brain tumor in adult, characterized by highly aggressive and infiltrative growth. The current therapeutic management of GBM includes surgical resection followed by ionizing radiations and chemotherapy. Complex and dynamic interplay between tumor cells and tumor microenvironment drives the progression and contributes to therapeutic resistance. Extracellular vesicles (EVs) play a crucial role in the intercellular communication by delivering bioactive molecules in the surrounding milieu modulating tumor microenvironment., Methods: In this study, we isolated by ultracentrifugation EVs from GBM stem-like cell (GSC) lines and human microvascular endothelial cells (HMVECs) exposed or not to ionizing irradiation. After counting and characterization, we evaluated the effects of exposure of GSCs to EVs isolated from endothelial cells and vice versa. The RNA content of EVs isolated from GSC lines and HMVECs exposed or not to ionizing irradiation, was analyzed by RNA-Seq. Periostin (POSTN) and Filamin-B (FLNB) emerged in gene set enrichment analysis as the most interesting transcripts enriched after irradiation in endothelial cell-derived EVs and GSC-derived EVs, respectively. POSTN and FLNB expression was modulated and the effects were analyzed by in vitro assays., Results: We confirmed that ionizing radiations increased EV secretion by GSCs and normal endothelial cells, affected the contents of and response to cellular secreted EVs. Particularly, GSC-derived EVs decreased radiation-induced senescence and promoted migration in HMVECs whereas, endothelial cell-derived EVs promoted tumorigenic properties and endothelial differentiation of GSCs. RNA-Seq analysis of EV content, identified FLNB and POSTN as transcripts enriched in EVs isolated after irradiation from GSCs and HMVECs, respectively. Assays performed on POSTN overexpressing GSCs confirmed the ability of POSTN to mimic the effects of endothelial cell-derived EVs on GSC migration and clonogenic abilities and transdifferentiation potential. Functional assays performed on HMVECs after silencing of FLNB supported its role as mediator of the effects of GSC-derived EVs on senescence and migration., Conclusion: In this study, we identified POSTN and FLNB as potential mediators of the effects of EVs on GSC and HMVEC behavior confirming that EVs play a crucial role in the intercellular communication by delivering bioactive molecules in the surrounding milieu modulating tumor microenvironment., (© 2024. The Author(s).)
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- 2024
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47. CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis.
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Romagnoli G, D'Alessandris QG, Capone I, Tavilla A, Canini I, Lapenta C, Buccarelli M, Giordano M, Tirelli V, Sanchez M, Fragale A, Giannetti S, Di Bonaventura R, Lauretti L, Biffoni M, Ricci-Vitiani L, Pallini R, and Gabriele L
- Subjects
- Humans, Programmed Cell Death 1 Receptor metabolism, Prognosis, CD8-Positive T-Lymphocytes, Tumor Microenvironment, Hepatitis A Virus Cellular Receptor 2, Glioblastoma
- Abstract
Glioblastoma, isocitrate dehydrogenase-wildtype (GB), is the most common and aggressive primary brain malignancy with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GB and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumour microenvironment (TME) immunity. This study aimed to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single-cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression-free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) were found to be linked to clinical outcome. Low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios-HR [95%CI]: 0.14 [0.04-0.52] p < 0.001, 0.39 [0.16-0.96] p = 0.04, respectively). The CD8+CD103+ Trm subgroups were also age-related predictors for survival in GB., (© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
48. MiR126-targeted-nanoparticles combined with PI3K/AKT inhibitor as a new strategy to overcome melanoma resistance.
- Author
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Arasi MB, De Luca G, Chronopoulou L, Pedini F, Petrucci E, Flego M, Stringaro A, Colone M, Pasquini L, Spada M, Lulli V, Perrotta MC, Calin GA, Palocci C, Biffoni M, Felicetti F, and Felli N
- Subjects
- Humans, Animals, Mice, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Signal Transduction, Cell Line, Tumor, Phosphoinositide-3 Kinase Inhibitors pharmacology, Phosphoinositide-3 Kinase Inhibitors therapeutic use, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, MicroRNAs pharmacology
- Abstract
Metastatic melanoma poses significant challenges as a highly lethal disease. Despite the success of molecular targeting using BRAF
V600E inhibitors (BRAFis) and immunotherapy, the emergence of early recurrence remains an issue and there is the need for novel therapeutic approaches. This study aimed at creating a targeted delivery system for the oncosuppressor microRNA 126 (miR126) and testing its effectiveness in combination with a phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor for treating metastatic melanoma resistant to BRAFis. To achieve this, we synthesized chitosan nanoparticles containing a chemically modified miR126 sequence. These nanoparticles were further functionalized with an antibody specific to the chondroitin sulfate proteoglycan 4 (CSPG4) melanoma marker. After evaluation in vitro, the efficacy of this treatment was evaluated through an in vivo experiment using mice bearing resistant human melanoma. The co-administration of miR126 and the PI3K/AKT inhibitor in these experiments significantly reduced tumor growth and inhibited the formation of liver and lung metastases. These results provide evidence for a strategy to target an oncosuppressive nucleic acid sequence to tumor cells while simultaneously protecting it from plasma degradation. The system described in this study exhibits encouraging potential for the effective treatment of therapy-resistant metastatic melanoma while also presenting a prospective approach for other forms of cancer., Competing Interests: Declaration of interests The authors declare that the data presented in this study are the subject of an industrial invention patent field on behalf of the Istituto Superiore di Sanità., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
49. C-Cell Hyperplasia and Cystic Papillary Thyroid Carcinoma in a Patient with Type 1B Pseudohypoparathyroidism and Hypercalcitoninaemia: Case Report and Review of the Literature.
- Author
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Ferrari D, Pandozzi C, Filice A, Nardi C, Cozzolino A, Melcarne R, Giacomelli L, Biffoni M, Di Gioia C, Merenda E, Del Sindaco G, Pagnano A, Pofi R, and Giannetta E
- Abstract
Hypercalcitoninaemia has been described in patients with pseudohypoparathyroidism (PHP) type 1A and 1B. Elevated calcitonin levels are thought to result from impaired Gsα receptor signaling, leading to multiple hormone resistance. Evidence on the risk of medullary thyroid carcinoma (MTC) or C-cell hyperplasia in PHP patients with hypercalcitoninaemia is lacking. A 43-year-old Caucasian man was referred to our endocrinology clinic for chronic hypocalcemia associated with elevated serum parathormone levels and a single cystic thyroid nodule. The patient did not show skeletal deformities, and screening for concomitant hormone resistances was negative, except for the presence of elevated serum calcitonin levels. The workup led to a molecular diagnosis of sporadic PHP1B. Fine needle aspiration of the thyroid nodule was not diagnostic. The calcium stimulation test yielded an abnormal calcitonin response. Given the scarcity of data on the risk of thyroid malignancy in PHP and calcium stimulation test results, total thyroidectomy was performed. Histological examination revealed cystic papillary thyroid cancer in a background of diffuse C-cell hyperplasia. To our knowledge, we are the first to describe a rare form of thyroid cancer combined with C-cell hyperplasia in a patient with PHP and hypercalcitoninaemia. In the present case, a mere receptor resistance might not fully explain the elevated calcitonin levels, suggesting that hypercalcitoninaemia should be carefully evaluated in PHP patients, especially in the case of concomitant thyroid nodules. Further studies on larger cohorts are needed to elucidate this topic.
- Published
- 2023
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50. The autophagic protein FYCO1 controls TNFRSF10/TRAIL receptor induced apoptosis and is inactivated by CASP8 (caspase 8).
- Author
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Coppola V, Marino I, Warnken U, Falchi M, Pasquini L, Biffoni M, De Maria R, and Haas TL
- Subjects
- Caspase 8 metabolism, Apoptosis, Caspases metabolism, TNF-Related Apoptosis-Inducing Ligand pharmacology, TNF-Related Apoptosis-Inducing Ligand metabolism, CASP8 and FADD-Like Apoptosis Regulating Protein metabolism, Tumor Necrosis Factor-alpha metabolism, Caspase 9 metabolism, Receptors, TNF-Related Apoptosis-Inducing Ligand metabolism, Autophagy
- Abstract
Apoptosis is a tightly controlled cell death program executed by proteases, the so-called caspases. It plays an important role in tissue homeostasis and is often dysregulated in cancer. Here, we identified FYCO1, a protein that promotes microtubule plus end-directed transport of autophagic and endosomal vesicles as a molecular interaction partner of activated CASP8 (caspase 8). The absence of FYCO1 sensitized cells to basal and TNFSF10/TRAIL-induced apoptosis by receptor accumulation and stabilization of the Death Inducing Signaling Complex (DISC). Loss of FYCO1 resulted in impaired transport of TNFRSF10B/TRAIL-R2/DR5 (TNF receptor superfamily member 10b) to the lysosomes in TNFSF10/TRAIL-stimulated cells. More in detail, we show that FYCO1 interacted via its C-terminal GOLD domain with the CCZ1-MON1A complex, which is necessary for RAB7A activation and for the fusion of autophagosomal/endosomal vesicles with lysosomes. We demonstrated that FYCO1 is a novel and specific CASP8 substrate. The cleavage at aspartate 1306 resulted in the release of the C-terminal GOLD domain, inactivating FYCO1 function, and allowing for the progression of apoptosis. Furthermore, the lack of FYCO1 resulted in a stronger and prolonged formation of the TNFRSF1A/TNF-R1 signaling complex. Thus, FYCO1 limits the ligand-induced and steady-state signaling of TNFR-superfamily members, providing a control mechanism that fine-tunes both apoptotic and inflammatory answers. Abbreviations : AP: affinity purification; CHX: cycloheximide; co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; DISC: death-inducing signaling complex; DR: death receptors; doxy: doxycycline; GEF: guanine nucleotide exchange factor; ind: inducible; KD: knockdown; KO: knockout; MS: mass spectrometry; shRNA: short hairpin RNA; siRNA: small interfering RNA; TIP: two-step co-immunoprecipitation; WB: western blot.
- Published
- 2023
- Full Text
- View/download PDF
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