Overview

Extracellular vesicles (EVs) are size-heterogeneous membrane particles massively secreted from the cells. EVs carry RNA, proteins, and metabolites that can be exchanged by neighbouring or distant cells through body fluids. EVs can help understanding new layers of complexity of tumor biology and conditional microenvironment. In addition, circulating EVs can be exploited in liquid biopsies to detect cancer biomarkers or be eventually manipulated to understand relevance, stability, and function of the shared biological material.

Research directions

With this rationale in mind, EVs offer the following opportunities:

  • Develop new platforms for probing tumor biology:
    We sought to apply high-throughput procedures to isolate EVs from cell culture media or biological fluids (blood, urine, CSF, saliva) and develop quantitative approaches to probe markers mirroring the cell heterogeneity that characterizes complex disorders;
  • Understand the functional effect of the horizontal material transfer to recipient cells and the tumor microenvironment:
    Mostly focused at RNA and proteins dictating the sorting of specific molecules into secreted EVs;
  • Build novel vehicles
    EVs expose specific transmembrane proteins that can be exploited to potentially direct their biodistribution. Several tools can be explored for generating EV sub-populations characterized by a defined biodistribution and/or anti-cancer effects.

Group members

  • Vito Giuseppe D’Agostino, PI
  • Dalia Tarantino, Postdoc
  • Xhaferr Tanushi, Postdoc
  • Alessia Gabardi, Predoc
  • LM and LT Students

Selected publications

Pelisenco IA, Zizioli D, Guerra F, Grossi I, Bucci C, Mignani L, Girolimetti G, Di Corato R, D'Agostino VG, Marchina E, De Petro G, Salvi A. miR-23b-3p, miR-126-3p and GAS5 delivered by extracellular vesicles inhibit breast cancer xenografts in zebrafish. Cell Commun Signal. 2024 Nov 18;22(1):552. doi: 10.1186/s12964-024-01936-9. PMID: 39558342; PMCID: PMC11572517.

2: Gurrieri E, Carradori G, Roccuzzo M, Pancher M, Peroni D, Belli R, Trevisan C, Notarangelo M, Huang WQ, Carreira ASA, Quattrone A, Jenster G, Hagen TLMT, D'Agostino VG. CD81-guided heterologous EVs present heterogeneous interactions with breast cancer cells. J Biomed Sci. 2024 Oct 15;31(1):92. doi: 10.1186/s12929-024-01084-9. PMID: 39402557; PMCID: PMC11475557.

Mangiapane G, D'Agostino VG, Tell G. Emerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology. Cancer Gene Ther. 2024 Dec;31(12):1765-1772. doi: 10.1038/s41417-024-00836-x. Epub 2024 Sep 25. PMID: 39322751.

Cheng Z, Fobian SF, Gurrieri E, Amin M, D'Agostino VG, Falahati M, Zalba S, Debets R, Garrido MJ, Saeed M, Seynhaeve ALB, Balcioglu HE, Ten Hagen TLM. Lipid-based nanosystems: the next generation of cancer immune therapy. J Hematol Oncol. 2024 Jul 19;17(1):53. doi: 10.1186/s13045-024-01574-1. PMID: 39030582; PMCID: PMC11265205.

Cocchi S, Greco V, Sidarovich V, Vigna J, Broso F, Corallo D, Zasso J, Re A, Rosatti EF, Longhi S, Defant A, Ladu F, Sanna V, Adami V, D'Agostino VG, Sturlese M, Sechi M, Aveic S, Mancini I, Sighel D, Quattrone A. EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness. Int J Mol Sci. 2024 Apr 27;25(9):4795. doi: 10.3390/ijms25094795. PMID: 38732012; PMCID: PMC11084668.

Mangiapane G, Notarangelo M, Canarutto G, Fabbiano F, Dalla E, Degrassi M, Antoniali G, Gualandi N, De Sanctis V, Piazza S, D'Agostino VG, Tell G. The DNA- repair protein APE1 participates with hnRNPA2B1 to motif-enriched and prognostic miRNA secretion. Oncogene. 2024 Jun;43(24):1861-1876. doi: 10.1038/s41388-024-03039-8. Epub 2024 Apr 25. PMID: 38664500.

Barros O, D'Agostino VG, Lara Santos L, Vitorino R, Ferreira R. Shaping the future of oral cancer diagnosis: advances in salivary proteomics. Expert Rev Proteomics. 2024 Apr;21(4):149-168. doi: 10.1080/14789450.2024.2343585. Epub 2024 Apr 24. PMID: 38626289.

Barros O, D'Agostino VG, Santos L, Ferreira R, Vitorino R. Revisiting Multi-Omics Data to Unravel Galectins as Prognostic Factors in Head and Neck Squamous Cell Carcinoma. Biomedicines. 2024 Feb 27;12(3):529. doi: 10.3390/biomedicines12030529. PMID: 38540141; PMCID: PMC10968280.

Basso M, Gori A, Nardella C, Palviainen M, Holcar M, Sotiropoulos I, Bobis-Wozowicz S, D'Agostino VG, Casarotto E, Ciani Y, Suetsugu S, Gualerzi A, Martin- Jaular L, Boselli D, Kashkanova A, Parisse P, Lippens L, et al. International Society for Extracellular Vesicles Workshop. QuantitatEVs: multiscale analyses, from bulk to single extracellular vesicle. J Extracell Biol. 2024 Jan;3(1):e137. doi: 10.1002/jex2.137. Epub 2024 Jan 24. PMID: 38405579; PMCID: PMC10883470.

Welsh JA, Goberdhan DCI, O'Driscoll L, Buzas EI, Blenkiron C, Bussolati B, Cai H, Di Vizio D, Driedonks TAP, Erdbrügger U, Falcon-Perez JM, Fu QL, Hill AF, Lenassi M, Lim SK, Mahoney MG, Mohanty S, Möller A, et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J Extracell Vesicles. 2024 Feb;13(2):e12404. doi: 10.1002/jev2.12404. Erratum in: J Extracell Vesicles. 2024 May;13(5):e12451. doi: 10.1002/jev2.12451. PMID: 38326288; PMCID: PMC10850029.

Mugoni V, Ciani Y, Quaini O, Tomasini S, Notarangelo M, Vannuccini F, Marinelli A, Leonardi E, Pontalti S, Martinelli A, Rossetto D, Pesce I, Mansy SS, Barbareschi M, Ferro A, Caffo O, Attard G, Di Vizio D, D'Agostino VG, Nardella C, Demichelis F. Integrating extracellular vesicle and circulating cell-free DNA analysis using a single plasma aliquot improves the detection of HER2 positivity in breast cancer patients. J Extracell Biol. 2023 Sep;2(9):e108. doi: 10.1002/jex2.108. Epub 2023 Sep 25. PMID: 38046436; PMCID: PMC10688391.

Cazzanelli G, Vedove AD, Parolin E, D'Agostino VG, Unzue A, Nevado C, Caflisch A, Lolli G. Reevaluation of bromodomain ligands targeting BAZ2A. Protein Sci. 2023 Sep;32(9):e4752. doi: 10.1002/pro.4752. PMID: 37574751; PMCID: PMC10464297.

Salvati E, Lewinska A, Dassi E, Wnuk M, D'Agostino VG. Editorial: RNA recognition landscapes and anticancer drug targeting. Front Oncol. 2023 Jun 19;13:1222883. doi: 10.3389/fonc.2023.1222883. PMID: 37404766; PMCID: PMC10315894.

Dalle Vedove A, Cazzanelli G, Corsi J, Sedykh M, D'Agostino VG, Caflisch A, Lolli G. Identification of a BAZ2A Bromodomain Hit Compound by Fragment Joining. ACS Bio Med Chem Au. 2021 Dec 15;1(1):5-10. doi:10.1021/acsbiomedchemau.1c00016. Epub 2021 Jul 7. PMID: 36147311; PMCID: PMC9484724.

Dalle Vedove A, Cazzanelli G, Batiste L, Marchand JR, Spiliotopoulos D, Corsi J, D'Agostino VG, Caflisch A, Lolli G. Identification of a BAZ2A-Bromodomain Hit Compound by Fragment Growing. ACS Med Chem Lett. 2022 Aug 3;13(9):1434-1443. doi: 10.1021/acsmedchemlett.2c00173. PMID: 36105334; PMCID: PMC9465710.

Ciani C, Pérez-Ràfols A, Bonomo I, Micaelli M, Esposito A, Zucal C, Belli R, D'Agostino VG, Bianconi I, Calderone V, Cerofolini L, Massidda O, Whalen MB, Fragai M, Provenzani A. Identification and Characterization of an RRM-Containing, RNA Binding Protein in Acinetobacter baumannii. Biomolecules. 2022 Jun 30;12(7):922. doi: 10.3390/biom12070922. PMID: 35883478; PMCID: PMC9313427.

Manganelli M, Grossi I, Corsi J, D'Agostino VG, Jurikova K, Cusanelli E, Molfino S, Portolani N, Salvi A, De Petro G. Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma. Int J Mol Sci. 2022 May 31;23(11):6183. doi: 10.3390/ijms23116183. PMID: 35682861; PMCID: PMC9181112.

Biagini V, Busi F, Anelli V, Kerschbamer E, Baghini M, Gurrieri E, Notarangelo M, Pesce I, van Niel G, D'Agostino VG, Mione M. Zebrafish Melanoma- Derived Interstitial EVs Are Carriers of ncRNAs That Induce Inflammation. Int J Mol Sci. 2022 May 14;23(10):5510. doi: 10.3390/ijms23105510. PMID: 35628321; PMCID: PMC9143139.

Gurrieri E, D'Agostino VG. Strategies to functionalize extracellular vesicles against HER2 for anticancer activity. Extracell Vesicles Circ Nucl Acids. 2022 Apr 18;3(2):93-101. doi: 10.20517/evcna.2022.07. PMID: 39698443; PMCID: PMC11648518.

Licata NV, Cristofani R, Salomonsson S, Wilson KM, Kempthorne L, Vaizoglu D, D'Agostino VG, Pollini D, Loffredo R, Pancher M, Adami V, Bellosta P, Ratti A, Viero G, Quattrone A, Isaacs AM, Poletti A, Provenzani A. C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation. EMBO J. 2022 Jan 4;41(1):e105026. doi: 10.15252/embj.2020105026. Epub 2021 Nov 18. PMID: 34791698; PMCID: PMC8724771.

Pasetto L, Callegaro S, Corbelli A, Fiordaliso F, Ferrara D, Brunelli L, Sestito G, Pastorelli R, Bianchi E, Cretich M, Chiari M, Potrich C, Moglia C, Corbo M, Sorarù G, Lunetta C, Calvo A, Chiò A, Mora G, Pennuto M, Quattrone A, Rinaldi F, D'Agostino VG, Basso M, Bonetto V. Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis. MolNeurodegener. 2021 Aug 10;16(1):52. doi: 10.1186/s13024-021-00470-3. PMID: 34376243; PMCID: PMC8353748.

Pasini L, Notarangelo M, Vagheggini A, Burgio MA, Crinò L, Chiadini E, Prochowski AI, Delmonte A, Ulivi P, D'Agostino VG. Unveiling mutational dynamics in non-small cell lung cancer patients by quantitative EGFR profiling in vesicular RNA. Mol Oncol. 2021 Sep;15(9):2423-2438. doi: 10.1002/1878-0261.12976. Epub 2021 May 20. PMID: 33942501; PMCID: PMC8410558.

Mangiapane G, Parolini I, Conte K, Malfatti MC, Corsi J, Sanchez M, Pietrantoni A, D'Agostino VG, Tell G. Enzymatically active apurinic/apyrimidinic endodeoxyribonuclease 1 is released by mammalian cells through exosomes. J Biol Chem. 2021 Jan-Jun;296:100569. doi: 10.1016/j.jbc.2021.100569. Epub 2021 Mar 19. PMID: 33753167; PMCID: PMC8080531.

Notarangelo M, Ferrara D, Potrich C, Lunelli L, Vanzetti L, Provenzani A, Basso M, Quattrone A, D'Agostino VG. Rapid Nickel-based Isolation of Extracellular Vesicles from Different Biological Fluids. Bio Protoc. 2020 Feb 5;10(3):e3512. doi: 10.21769/BioProtoc.3512. PMID: 33654737; PMCID: PMC7842538.

Fabbiano F, Corsi J, Gurrieri E, Trevisan C, Notarangelo M, D'Agostino VG. RNA packaging into extracellular vesicles: An orchestra of RNA-binding proteins? J Extracell Vesicles. 2020 Dec;10(2):e12043. doi: 10.1002/jev2.12043. Epub 2020 Dec 28. PMID: 33391635; PMCID: PMC7769857.

Pisapia L, Hamilton RS, Farina F, D'Agostino V, Barba P, Strazzullo M, Provenzani A, Gianfrani C, Del Pozzo G. Tristetraprolin/ZFP36 Regulates the Turnover of Autoimmune-Associated HLA-DQ mRNAs. Cells. 2019 Dec 4;8(12):1570.doi: 10.3390/cells8121570. PMID: 31817224; PMCID: PMC6953012.

Mandrioli J, Crippa V, Cereda C, Bonetto V, Zucchi E, Gessani A, Ceroni M, Chio A, D'Amico R, Monsurrò MR, Riva N, Sabatelli M, Silani V, Simone IL, Sorarù G, Provenzani A, D'Agostino VG, Carra S, Poletti A. Proteostasis and ALS: protocol for a phase II, randomised, double-blind, placebo-controlled, multicentre clinical trial for colchicine in ALS (Co-ALS). BMJ Open. 2019 May 30;9(5):e028486. doi: 10.1136/bmjopen-2018-028486. PMID: 31152038; PMCID: PMC6549675.

Notarangelo M, Zucal C, Modelska A, Pesce I, Scarduelli G, Potrich C, Lunelli L, Pederzolli C, Pavan P, la Marca G, Pasini L, Ulivi P, Beltran H, Demichelis F, Provenzani A, Quattrone A, D'Agostino VG. Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood. EBioMedicine. 2019 May;43:114-126. doi: 10.1016/j.ebiom.2019.04.039. Epub 2019 Apr 29. PMID: 31047861; PMCID: PMC6558028.

D'Agostino VG, Sighel D, Zucal C, Bonomo I, Micaelli M, Lolli G, Provenzani A, Quattrone A, Adami V. Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery. SLAS Discov. 2019 Mar;24(3):314-331. doi: 10.1177/2472555218818065. Epub 2019 Jan 7. PMID: 30616427.

Tebaldi T, Zuccotti P, Peroni D, Köhn M, Gasperini L, Potrich V, Bonazza V, Dudnakova T, Rossi A, Sanguinetti G, Conti L, Macchi P, D'Agostino V, Viero G, Tollervey D, Hüttelmaier S, Quattrone A. HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA. Mol Cell. 2018 Jul 19;71(2):256-270.e10. doi: 10.1016/j.molcel.2018.06.032. PMID: 30029004; PMCID: PMC6060611.

Dalle Vedove A, Spiliotopoulos D, D'Agostino VG, Marchand JR, Unzue A, Nevado C, Lolli G, Caflisch A. Structural Analysis of Small-Molecule Binding to the BAZ2A and BAZ2B Bromodomains. ChemMedChem. 2018 Jul 18;13(14):1479-1487. doi: 10.1002/cmdc.201800234. Epub 2018 Jun 21. PMID: 29770599.

Thongon N, Zucal C, D'Agostino VG, Tebaldi T, Ravera S, Zamporlini F, Piacente F, Moschoi R, Raffaelli N, Quattrone A, Nencioni A, Peyron JF, Provenzani A. Cancer cell metabolic plasticity allows resistance to NAMPT inhibition but invariably induces dependence on LDHA. Cancer Metab. 2018 Mar 8;6:1. doi: 10.1186/s40170-018-0174-7. PMID: 29541451; PMCID: PMC5844108.

Manzoni L, Zucal C, Maio DD, D'Agostino VG, Thongon N, Bonomo I, Lal P, Miceli M, Baj V, Brambilla M, Cerofolini L, Elezgarai S, Biasini E, Luchinat C, Novellino E, Fragai M, Marinelli L, Provenzani A, Seneci P. Interfering with HuR-RNA Interaction: Design, Synthesis and Biological Characterization of Tanshinone Mimics as Novel, Effective HuR Inhibitors. J Med Chem. 2018 Feb 22;61(4):1483-1498. doi: 10.1021/acs.jmedchem.7b01176. Epub 2018 Jan 31. PMID: 29313684.

Lal P, Cerofolini L, D'Agostino VG, Zucal C, Fuccio C, Bonomo I, Dassi E, Giuntini S, Di Maio D, Vishwakarma V, Preet R, Williams SN, Fairlamb MS, Munk R, Lehrmann E, Abdelmohsen K, Elezgarai SR, Luchinat C, Novellino E, Quattrone A, Biasini E, Manzoni L, Gorospe M, Dixon DA, Seneci P, Marinelli L, Fragai M, Provenzani A. Regulation of HuR structure and function by dihydrotanshinone-I. Nucleic Acids Res. 2017 Sep 19;45(16):9514-9527. doi: 10.1093/nar/gkx623. PMID: 28934484; PMCID: PMC5766160.

Bono S, Lulli M, D'Agostino VG, Di Gesualdo F, Loffredo R, Cipolleschi MG, Provenzani A, Rovida E, Dello Sbarba P. Different BCR/Abl protein suppression patterns as a converging trait of chronic myeloid leukemia cell adaptation to energy restriction. Oncotarget. 2016 Dec 20;7(51):84810-84825. doi: 10.18632/oncotarget.13319. PMID: 27852045; PMCID: PMC5356700.

Becattini B, Zani F, Breasson L, Sardi C, D'Agostino VG, Choo MK, Provenzani A, Park JM, Solinas G. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage. FASEB J. 2016 Sep;30(9):3124-32. doi: 10.1096/fj.201600393R. Epub 2016 May 26. PMID: 27230858; PMCID: PMC6191003.

Latorre E, Carelli S, Raimondi I, D'Agostino V, Castiglioni I, Zucal C, Moro G, Luciani A, Ghilardi G, Monti E, Inga A, Di Giulio AM, Gorio A, Provenzani A. The Ribonucleic Complex HuR-MALAT1 Represses CD133 Expression and Suppresses Epithelial-Mesenchymal Transition in Breast Cancer. Cancer Res. 2016 May 1;76(9):2626-36. doi: 10.1158/0008-5472.CAN-15-2018. Epub 2016 Apr 20. PMID: 27197265.

Thongon N, Castiglioni I, Zucal C, Latorre E, D'Agostino V, Bauer I, Pancher M, Ballestrero A, Feldmann G, Nencioni A, Provenzani A. The GSK3β inhibitor BIS I reverts YAP-dependent EMT signature in PDAC cell lines by decreasing SMADs expression level. Oncotarget. 2016 May 3;7(18):26551-66. doi: 10.18632/oncotarget.8437. PMID: 27034169; PMCID: PMC5041998.

Crippa V, D'Agostino VG, Cristofani R, Rusmini P, Cicardi ME, Messi E, Loffredo R, Pancher M, Piccolella M, Galbiati M, Meroni M, Cereda C, Carra S, Provenzani A, Poletti A. Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases. Sci Rep. 2016 Mar 10;6:22827. doi: 10.1038/srep22827. PMID: 26961006; PMCID: PMC4785366.

D'Agostino VG, Lal P, Mantelli B, Tiedje C, Zucal C, Thongon N, Gaestel M, Latorre E, Marinelli L, Seneci P, Amadio M, Provenzani A. Dihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post- transcriptional function. Sci Rep. 2015 Nov 10;5:16478. doi: 10.1038/srep16478. PMID: 26553968; PMCID: PMC4639722.

Zucal C, D'Agostino VG, Casini A, Mantelli B, Thongon N, Soncini D, Caffa I, Cea M, Ballestrero A, Quattrone A, Indraccolo S, Nencioni A, Provenzani A. EIF2A-dependent translational arrest protects leukemia cells from the energetic stress induced by NAMPT inhibition. BMC Cancer. 2015 Nov 5;15:855. doi: 10.1186/s12885-015-1845-1. PMID: 26542945; PMCID: PMC4636066.

Caffa I, D'Agostino V, Damonte P, Soncini D, Cea M, Monacelli F, Odetti P, Ballestrero A, Provenzani A, Longo VD, Nencioni A. Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition. Oncotarget. 2015 May 20;6(14):11820-32. doi: 10.18632/oncotarget.3689. PMID: 25909220; PMCID: PMC4494907.

Zucal C, D'Agostino V, Loffredo R, Mantelli B, NatthakanThongon, Lal P, Latorre E, Provenzani A. Targeting the multifaceted HuR protein, benefits and caveats. Curr Drug Targets. 2015;16(5):499-515. doi: 10.2174/1389450116666150223163632. PMID: 25706256.

Soncini D, Caffa I, Zoppoli G, Cea M, Cagnetta A, Passalacqua M, Mastracci L, Boero S, Montecucco F, Sociali G, Lasigliè D, Damonte P, Grozio A, Mannino E, Poggi A, D'Agostino VG, Monacelli F, Provenzani A, Odetti P, Ballestrero A, Bruzzone S, Nencioni A. Nicotinamide phosphoribosyltransferase promotes epithelial-to-mesenchymal transition as a soluble factor independent of its enzymatic activity. J Biol Chem. 2014 Dec 5;289(49):34189-204. doi: 10.1074/jbc.M114.594721. Epub 2014 Oct 20. PMID: 25331943; PMCID: PMC4256351.

D'Agostino VG, Adami V, Provenzani A. A novel high throughput biochemical assay to evaluate the HuR protein-RNA complex formation. PLoS One. 2013 Aug 12;8(8):e72426. doi: 10.1371/journal.pone.0072426. PMID: 23951323; PMCID: PMC3741180.

Viiri J, Amadio M, Marchesi N, Hyttinen JM, Kivinen N, Sironen R, Rilla K, Akhtar S, Provenzani A, D'Agostino VG, Govoni S, Pascale A, Agostini H, Petrovski G, Salminen A, Kaarniranta K. Autophagy activation clears ELAVL1/HuR-mediated accumulation of SQSTM1/p62 during proteasomal inhibition in human retinal pigment epithelial cells. PLoS One. 2013 Jul 29;8(7):e69563. doi: 10.1371/journal.pone.0069563. PMID: 23922739; PMCID: PMC3726683.

Venesio T, Balsamo A, D'Agostino VG, Ranzani GN. MUTYH-associated polyposis (MAP), the syndrome implicating base excision repair in inherited predisposition to colorectal tumors. Front Oncol. 2012 Aug 2;2:83. doi:10.3389/fonc.2012.00083. PMID: 22876359; PMCID: PMC3410368.

D'Agostino VG, Minoprio A, Torreri P, Marinoni I, Bossa C, Petrucci TC, Albertini AM, Ranzani GN, Bignami M, Mazzei F. Functional analysis of MUTYH mutated proteins associated with familial adenomatous polyposis. DNA Repair (Amst). 2010 Jun 4;9(6):700-7. doi: 10.1016/j.dnarep.2010.03.008. Epub 2010 Apr 24. PMID: 20418187.

Molatore S, Russo MT, D'Agostino VG, Barone F, Matsumoto Y, Albertini AM, Minoprio A, Degan P, Mazzei F, Bignami M, Ranzani GN. MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay. Hum Mutat. 2010 Feb;31(2):159-66. doi: 10.1002/humu.21158. PMID: 19953527.

Di Pietro C, Ragusa M, Barbagallo D, Duro LR, Guglielmino MR, Majorana A, Angelica R, Scalia M, Statello L, Salito L, Tomasello L, Pernagallo S, Valenti S, D'Agostino V, Triberio P, Tandurella I, Palumbo GA, La Cava P, Cafiso V, Bertuccio T, Santagati M, Li Destri G, Lanzafame S, Di Raimondo F, Stefani S, Mishra B, Purrello M. The apoptotic machinery as a biological complex system: analysis of its omics and evolution, identification of candidate genes for fourteen major types of cancer, and experimental validation in CML and neuroblastoma. BMC Med Genomics. 2009 Apr 30;2:20. doi: 10.1186/1755-8794-2-20. PMID: 19402918; PMCID: PMC2683874.