UO EXPERIMENTAL MEDICINE AND SURGERY

This Operative Unit (OU) is responsible, in collaboration with national and international groups, to study targeted therapies in preclinical models of lung and breast, and new strategies to overcome the mechanisms of resistance to these treatments. The Coordinator and his staff have experience in group work in the area of ​​translational research of lung cancer and breast.
L’UO si occupa, in collaborazione con gruppi nazionali ed internazionali, di studiare terapie a bersaglio molecolare in modelli preclinici di polmone e mammella, e nuove strategie per superare i meccanismi di resistenza a tali trattamenti . Il Coordinatore ed i suoi collaboratori hanno esperienza nel lavoro di gruppo nell'area di ricerca traslazionale del carcinoma polmonare e mammario.

Responsable (RUO)
Prof.ssa Roberta Alfieri
Dipartimento di Medicina Sperimentale
Via Volturno 39, 43125 Parma
e-mail: roberta.alfieri@unipr.it
CV

Competences

  • proliferation assays and cell viability (colony assays, MTT, flow cytometry, thymidine incorporation)
  • studies of gene expression, signal transduction and protein analysis by Northern blotting assays, Western blotting and RT-PCR
  • use of radioisotopes for transport measurements and cell metabolism
  • studies of cell death mechanisms and autophagy
  • assessment of DNA damage at the level of single cells (Halo assay)
  • gene cloning, transfection and silencing
  • Studies in murine models
  • - saggi di proliferazione e vitalità cellulari (saggi di colonie, MTT, citometria a flusso, incorporazione di timidina)
    - studi di espressione genica, trasduzione del segnale e analisi proteica mediante saggi di Northern blotting, Western- blotting e RT- PCR
    -utilizzo di radioisotopi per misure di trasporto e di metabolismo cellulare
    - studi di meccanismi di morte cellulare e autofagia
    -valutazione del danno al DNA a livello di singole cellule (Halo assay)
    - clonaggio genico, trasfezioni e silenziamento
    - modelli murini sottocutanei (carcinoma del polmone in topi atimici)
    - modelli murini ortotopici (mesotelioma pleurico maligno nel ratto) e capacità di eseguire interventi chirurgici complessi
    - capacità di eseguire interventi chirurgici complessi su modelli suini e ovini
    - esperienza in studi di farmacocinetica/farmacodinamica in modelli ovini

Projects:
“Optimising EGFR inhibitor treatment in non small cell lung cancer” finanziato da AIRC (MI)
“Nanosistemi ibridi multifunzionali innovativi per applicazioni biomediche (BioNIMed)” finanziato da Cariparma
“Effetto dell’ipossia sulla risposta di cellule di carcinoma della mammella al trattamento con inibitori aromatasici” finanziato da Novartis Farma S.p.A (VA)

Collaborations
G. Sozzi, Istituto Nazionale Tumori di Milano
D. Generali, Breast Unit, Istituti Ospitalieri di Cremona
A. Ardizzoni, Oncologia Medica, Azienda Ospedaliero-Universitaria di Parma
S. Iannotta, CONSIGLIO NAZIONALE DELLE RICERCHE (CNR) - IMEM
L. Harris Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
G.J. Peters, Department of Medical Oncology, VU University Medical Center, Amsterdam

Patents
Composti inibitori irreversibili di EGFR con attività antiproliferativa PCT/IB2009/055980

Bibliografia

    1. La Monica S., Caffarra C., Saccani F., Galvani E., Galetti M., Fumarola C., Bonelli M., Cavazzoni A., Cretella D.,Sirangelo R., Gatti R., Tiseo M., Ardizzoni A., GIovannetti E., Petronini P.G., Alfieri R.R. (2013) Gefitinib inhibits invasive phenotype and epithelial-mesenchymal transition in drug-resistant NSCLC cells with MET amplification. PLOS ONE. 8: e78656.
    2. Vacondio F., Carmi C., Galvani E., Bassi M., Silva C., Lodola A., Rivara S., Cavazzoni A., Alfieri R.R., Petronini P.G., Mor M. (2013) Long-lasting inhibition of EGFR autophosphorylation in A549 tumor cells by intracellular accumulation of non-covalent inhibitors. Bioorganic & Medicinal Chemistry Letters 23:5290-5294.
    3. Fumarola C., Caffarra C., La Monica S., Galetti M, Alfieri R.R., Cavazzoni A., Galvani E., Generali D., Petronini P.G., Bonelli M. (2013) Effects of sorafenib on energy metabolism in breast cancer cells: role of AMPK-mTORC1 signaling. Breast Cancer Res Treat:141:67-78.
    4. Mozzoni P, Banda I, Goldoni M, Corradi M, Tiseo M, Acampa O, Balestra V, Ampollini L, Casalini A, Carbognani P, Mutti A.Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer. Biomarkers. 2013 Oct 8.
    5. Ampollini L, Barbagallo M, Ziegler S, Ortu A. The authors respond to: Noninvasive mechanical ventilation and helmet after lung resection: oxygenation improvement: a small step or a large step? Respir Care. 2013 May;58(5):e66.
    6. Ampollini L, Barbagallo M, Ziegler S, Ortu A.The authors respond to: Complications following pulmonary lobectomy: the role of helmet noninvasive ventilation. Respir Care. 2013 May;58(5):e64-5.
    7. De Filippo M, Saba L, Concari G, Nizzoli R, Ferrari L, Tiseo M, Ardizzoni A, Sverzellati N, Paladini I, Ganazzoli C, Sconfienza LM, Carrafiello G, Brunese L, Genovese EA, Ampollini L, Carbognani P, Rusca M, Zompatori M, Rossi C. Predictive factors of diagnostic accuracy of CT-guided transthoracic fine-needle aspiration for solid noncalcified, subsolid and mixed pulmonary nodules. Radiol Med. 2013 Oct;118(7):1071-1081.
    8. Genestreti G, Ampollini L, Burgio MA, Rolli L, Sanna S, Scarpi E, Monti M, Salvatore LB, Giannone L, Santo A, Mezzetti M, Casanova C, BuosiR, Rusca M, Amadori D, Gavelli G. Multicenter institutional experience of surgically resected thymic epithelial tumors (TETs): an observational report on behalf of F.O.N.I.C.A.P. (ForzaOperativaNazionaleInterdisciplinareControilCancro del Polmone). Ann SurgOncol. 2013 Sep;20(9):2958-63.
    9. Ventura L, Ampollini L, Gnetti L, Rusca M. Recurrent supraclavicular hydatid cyst. Eur J Cardiothorac Surg. 2013 Apr 26.
    10. Brigotti M., Arfilli V., Carnicelli D., Rocchi L., Calcabrini C., Ricci F., Pagliaro P, Tazzari P.L., Alfieri R.R., Petronini P.G., Sestili P.(2013) Shiga Toxin 1, as DNA Repair Inhibitor, Synergistically Potentiates the Activity of the Anticancer Drug Mafosfamide on Raji Cells. Toxins 5:431-44.
    11. Rocchi L., Alfieri R.R., Petronini P.G., Montanaro L, Brigotti M. (2013) 5’-untranslated region of the heat shock protein 70 mRNA drives translation under hypertonic conditions. Biochem. Biophys. Res Commun.431:321-5
    12. Galvani E., Giovannetti E., Saccani F., Cavazzoni A., Leon L.G., Dekker H., Alfieri R., Carmi C., Mor M., Ardizzoni A., Petronini P.G., Peters G.J. (2013) Molecular mechanisms underlying the antitumor activity of 3-aminopropanamide irreversible inhibitors of the epidermal growth factor receptor in non-small cell lung cancer. Neoplasia. 15: 61-72.
    13. Galvani E., Alfieri R., Giovannetti E., Cavazzoni A., La Monica S., Galetti M., Fumarola C., Bonelli M., Mor M., Tiseo M., Peters G.J., Petronini P.G., Ardizzoni A. (2013) Epidermal growth factor receptor tyrosine kinase inhibitors: current status and future perspectives in the development of novel irreversible inhibitors for the treatment of mutant non-small cell lung cancer. Current Pharmaceutical Design. 19: 818-832.
    14. Cavazzoni A, Alfieri R.R., Cretella D., Saccani F., Ampollini L., Galetti M., Quaini F., Graiani G., Madeddu D., Mozzoni P., Galvani E., La Monica S., Bonelli M., Fumarola C., Mutti A., Carbognani C., Tiseo M., Barocelli E., Petronini P.G., Ardizzoni A. (2012) Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines. Molecular Cancer. 11:91
    15. Motta A, Segnana P, Verin L, Monica SL, Fumarola C, Bucci G, Gussago F, Cantoni AM, Ampollini L, Migliaresi C. Physico-chemical characterization and biological evaluation of two fibroin materials. J Tissue Eng Regen Med. 2012 Sep 13.
    16. Ambrosini-Spaltro A, Campanini N, Bortesi B, Azzoni C, Naldi N, Ampollini L, Tiseo M, Ardizzoni A, Rusca M, Carbognani P, Silini EM. EGFR mutation-specific antibodies in pulmonary adenocarcinoma: a comparison with DNA direct sequencing.Appl.Immunohistochem.Mol.Morphol. 2012 Jul;20(4):356-62.
    17. Rolli L, Ampollini L, Carbognani P, Rusca M. Intrathoracic costal exostosis. Eur J Cardiothorac Surg. 2012 Dec;42(6):1051.
    18. Barbagallo M, Ortu A, Spadini E, Salvadori A, Ampollini L, Internullo E, Ziegler S, Fanelli G. Prophylactic use of helmet CPAP after pulmonary lobectomy: a prospective randomized controlled study. Respir Care. 2012 Sep;57(9):1418-24.
    19. Carmi C., Mor M., Petronini P.G., Alfieri R. (2012) Clinical perspectives for irreversible tyrosine kinase inhibitors in cancer. Biochemical Pharmacology. 84:1388-1399.
    20. .Cavazzoni A., Bonelli M.A., Fumarola C., La Monica S., Airoud K., Bertoni R., Alfieri R.R., Galetti M., Tramonti S., Galvani E., Harris A.L., Martin L., Andreis D.,, Bottini A., Generali D., Petronini P.G. (2012) Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. Cancer Letters 323:77-87. 11.
    21. Carmi C., Galvani E., Vacondio F., Silvia R., Lodola A., Russo S., Aiello S., Bordi F., Costantino G, Cavazzoni A., Alfieri R., Ardizzoni A., Petronini P.G., Mor M. (2012) Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides. J. Med Chem. 55:2251-64.
    22. Caminiti C, Diodati F, Bacchieri D, Carbognani P, Del Rio P, Iezzi E, Palli D, Raboini I, Vecchione E, Cisbani L. Evaluation of a pilot surgical adverse event detection system for Italian hospitals. Int J Qual Health Care. 2012 Apr;24(2):114-20.
    23. Alfieri R.R., Galetti M., Tramonti S., Andreoli R., Mozzoni P., Cavazzoni A., Bonelli M., Fumarola C., La Monica S., Galvani E., De Palma G., Mutti A.,Mor M., Tiseo M., Mari E., Ardizzoni A., Petronini P.G. (2011) Metabolism of the EGFR tyrosin kinase inhibitor gefitinib by cytochrome P450 1A1 enzyme in EGFR-wild type non small cell lung cancer cell lines. Molecular Cancer 10:143.
    24. Carmi C., Lodola A., Rivara S., Vacondio F., Cavazzoni A., Alfieri R.R., Ardizzoni A., Petronini P:G., Mor M (2011) Epidermal growth factor receptor irreversibile inhibitors: chemical exploration of the cysteine-trap portion. Mini-Reviews in Medicinal Chemistry 11: 1019-1030.
    25. Al-Trawneh S.A., Zahra J.A., Kamal M. R., El-Abadelah M.M., Zani F., Incerti M., Cavazzoni A., Alfieri R.R., Petronini P.G., Vicini P. (2010) Synthesis and biological evaluation of tetracyclic fluoroquinolones as antibacterial and anticancer agents. Bioorganic & Medicinal Chemistry 18: 5873-5884.
    26. Stavroulias D, Ampollini L, Carbognani P, Rusca M. Late presentation of congenital H-type tracheoesophageal fistula in an immunocompromised patient. Eur J Cardiothorac Surg. 2011 Aug;40(2):e98-100.
    27. Ampollini L, Carbognani P. Images in clinical medicine.Madelung's disease. N Engl J Med. 2011 Feb 3;364(5):465.
    28. Ampollini L, Del Rio P, Sianesi M, Rusca M, Carbognani P.Transcervical video-assisted thymectomy: preliminary results of a modified surgical approach. Langenbecks Arch Surg. 2011 Feb;396(2):267-71.
    29. Bilancia R, Ampollini L, Cattelani L, Carbognani P, Rusca M Schwannoma of the cervical vagus nerve. Ann Thorac Surg. 2011 Jan;91(1):e13.
    30. Corradi M, Poli D, Tillo R, Goldoni M, Acampa O, Mozzoni P, Sabbadini F, Pinelli S, Carbognani P, Internullo E, Casalini A, Gervasi G, Filetti A, Mutti A.Early molecular diagnosis of lung cancer: a method to rule out the disease. G Ital Med LavErgon.2011 Jul-Sep;33(3 Suppl):92-5.
    31. Ruffini E, Van Raemdonck D, Detterbeck F, Rocco G, Thomas P, Venuta F Management of thymic tumors: a survey of current practice among members of the European Society of Thoracic Surgeons. European Society of Thoracic Surgeons Thymic Questionnaire Working Group. J ThoracOncol. 2011 Mar;6(3):614-23
    32. Brigotti M., Tazzari P.L., Ravanelli E., Carnicelli D., Barbieri S., Rocchi L., Arfilli V., Scavia G., Ricci F., Bontadini A., Alfieri, R.R., Petronini P.G., Pecoraro C., Tozzi A.E., Caprioli A. (2010) Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration. Journal of Leukocyte Biology 88: 201-210 I.F.4.626
    33. Galetti M., Alfieri R.R., Cavazzoni A., La Monica S., Bonelli M.,Fumarola C., Mozzoni P., De Palma G., Andreoli R., Mutti A.,Mor M., Tiseo M., Ardizzoni A., Petronini P.G. (2010) Functional characterization of gefitinib uptake in non small cell lung cancer cell lines. Biochem. Pharmacol. 80:179-187.
    34. Ampollini L, Sonvico F, Barocelli E, Cavazzoni A, Bilancia R, Mucchino C,Cantoni AM, Carbognani P. Intrapleural polymeric films containing cisplatin for malignant pleural mesothelioma in a rat tumour model: a preliminary study. Eur J Cardiothorac Surg. 2010;37(3):557-65.
    35. Carmi C., Cavazzoni A., Vezzosi S., Bordi F., Vacondio F., Silva C., Rivara S., Lodola A. , Alfieri R.R , La Monica S., Galetti M., Ardizzoni A., Petronini P.G., Mor M. (2010) Novel Irreversible Epidermal Growth Factor Receptor Inhibitors by Chemical Modulation of the Cysteine-trap Portion. J Med Chem. 53: 2038-2050.
    36. Bonelli M. A., Fumarola C., Alfieri R.R., La Monica S., Cavazzoni A., Galetti M., Gatti R., Belletti S., Harris A.L., Fox S.B. Evans D.B., Dowsett M., Martin L.A., Bottini A., Generali D., Petronini P.G. (2010) Synergistic activity of letrozole and sorafenib on breast cancer cells. Breast Cancer Res Treat 124: 79-88.
    37. De Palma G, Mozzoni P, Acampa O, Internullo E, Carbognani P, Rusca M, Goldoni M, Corradi M, Tiseo M, Apostoli P, Mutti A. Expression levels of some antioxidant and epidermal growth factor receptor genes in patients with early-stage non-small cell lung cancer. J Nucleic Acids. 2010;2010.
    38. Ampollini L, Carbognani P, Rusca M, Bobbio A. Resection of giant typical carcinoid tumor with cardiopulmonary bypass support. ThoracCardiovasc Surg. 2010 Dec;58(8):500-2.
    39. Ampollini L, Carbognani P, Cattelani L, Bilancia R, Rusca M. Cavernous hemangioma of the posterior mediastinum. Ann Thorac Surg. 2010 Dec;90(6):e96.
    40. Ampollini L, Stavroulias D, Bilancia R, Cattelani L, Carbognani P, Rusca M.Complete tracheal disruption by motor-saw. Asian CardiovascThorac Ann. 2010 Aug;18(4):399-400.
    41. Ampollini L, Cattelani L, Carbognani P, Rusca M. Spontaneous abdominal--intercostal hernia. Eur J Cardiothorac Surg. 2011 Feb;39(2):275.
    42. Stavroulias D, Ampollini L, Carbognani P, Rusca M. Post-pneumonectomy cavity: is there still a cavity? Ann Thorac Surg. 2010 Jan;89(1):312.
    43. Ampollini L, Sonvico F, Barocelli E, Cavazzoni A, Bilancia R, Mucchino C, Cantoni AM, Carbognani P.Intrapleural polymeric films containing cisplatin for malignant pleural mesothelioma in a rat tumour model: a preliminary study. Eur J Cardiothorac Surg. 2010 Mar;37(3):557-65.
    44. De Palma G, Mozzoni P, Acampa O, Internullo E, Carbognani P, Rusca M, Goldoni M, Corradi M, Tiseo M, Apostoli P, Mutti A. Expression levels of some antioxidant and epidermal growth factor receptor genes in patients with early-stage non-small cell lung cancer. J Nucleic Acids. 2010;2010.
    45. Poli D, Goldoni M, Corradi M, Acampa O, Carbognani P, Internullo E, Casalini A, Mutti A. Determination of aldehydes in exhaled breath of patients with lung cancer by means of on-fiber-derivatisation SPME-GC/MS. J Chromatogr B AnalytTechnol Biomed Life Sci. 2010 Oct 1;878(27):2643-51.
    46. Ampollini L, Soltermann A, Felley-Bosco E, Lardinois D, Arni S, Speck RF, Weder W, Opitz I. Immuno-chemotherapy reduces recurrence of malignant pleural mesothelioma: an experimental setting. Eur J Cardiothorac Surg. 2009 Mar;35(3):457-62.
    47. Bobbio A, Chetta A, Internullo E, Ampollini L, Carbognani P, Bettati S, Rusca M, Olivieri D. Exercise capacity assessment in patients undergoing lung resection. Eur J Cardiothorac Surg. 2009 Mar;35(3):419-22.
    48. La Monica S., Galetti M., Alfieri R.R., Cavazzoni A., Ardizzoni A., Tiseo M., Capelletti M., Goldoni M., Tagliaferri S., Mutti A., Fumarola C., Bonelli M., Generali D., Petronini P.G. (2009) Everolimus restores gefitinib sensitivity in resistant non-small cell lung cancer cell lines. Biochem. Pharmacol. 78:460-468
    49. Mirandola P., Gobbi G., Sponzilli I., Malinverno C., Cavazzoni A., Alfieri R., Petronini P.G., Vitale M. (2009) TRAIL-induced apoptosis of FHIT-negative lung cancer cells is inhibited by FHIT re-expression. J Cell Physiol. 220:492-498
    50. Zuliani V, Carmi C. Rivara M, Fantini M Lodola A, Vacondio F, Bordi F, Plazzi PV, Cavazzoni A, Galetti M, Alfieri RR, Petronini PG, Mor. (2009) 5-Benzylidene-hydantoins: synthesis and antiproliferative activity on A549 lung cancer cell line. Eur J Med Chem 44: 3471-79.
    51. Tanzi S, Tiseo M, Internullo E, Cacciani G, Capra R, Carbognani P, Rusca M, Rindi G, Ardizzoni A. Localized malignant pleural mesothelioma: report of two cases. J Thorac Oncol. 2009;4(8):1038-40.