claudio pisano

Summary

Affiliation: Sigma Tau
Location: Pomezia, Italy
Summary:
Present title and affiliation:Head of Oncology Area – Research & Development
•Leading of 5 laboratories: Experimental Oncology, Experimental Angiogenesis, Receptorial Pharmacology, Molecular Onco-Dynamic, Molecular Pharmacology and Molecular Oncology and employed 30 staff members (50% with full position): 70% graduated (8 with a PhD degree) and 30% laboratory technicians. 27 fully employed staff members.

Previous position: Full position at “Centro di Genetica Evoluzionistica” – National Research Council (C.N.R.), Dept. of Genetics and Molecular Biology - University “La Sapienza”, Rome
09/1990-12/1996

Research activities:

At the Genetic and Molecular Biology, “Centro di Genetica Evoluzionistica” – National Research Council (C.N.R.), Dept. of Genetics and Molecular Biology - University of Rome “La Sapienza” Rome (1985-1996)

Main results:

oIdentification of specific genes/mechanisms/protein controlling the transiction between the transcribed “euchromatin” and the trancriptional “inactive” heterochromatin in Drosophila melanogaster.

oCharacterization of a multiple protein-binding elements of mouse CpG island. Identification of RanBP1as a gene enriched in CpG basis and demonstration that deregulated expression of the RanBP1 gene alters cell cycle progression in murine fibroblasts.



As the Head of Cellular Physiopathology Deptartment, Sigma-Tau
1997


oCharacterization of mechanism at bases of gastrosparing effect of a new ST (NSAID) anti-inflammatory drug, named Eufans, launched in Italy in 1999.

oCarnitine as a natural osmotic molecule. Two patents granted for tissue preservation and use in dialysis

oCarnitine is FDA approved for its use in dialysis



As the Head of Oncology Area
1998

oALC (acetylcarnitine) as an enhancer of gene expression in transfected cell: PATENT GENERATION .

oALC and their derivatives as protective agents against peripheral neuropathy and bone marrow injury induced by antitumor drugs and characterization of their mechanism of action. Use of ALC as enhancer of platinum compounds activity.


oALC is currently in Phase III of Clinical Trial in NSCLC in combination with cisplatin.

oCarnitine derivatives as a liposomal vehicle for antitumor agents and gene delivery : PATENT GENERATION.


oPhase II of Clinical Trial for topic delivery of PG’s.

oScreening and selection of new molecules for their anti-tumor and/or anti-angiogenic activity. Patents Generation

Classes of molecules investigated:

 DNA/Pro-apototic direct agents: Platins, Topoisomerase I inhibitors, Retinoid related molecules, Parp and Telomerase inhibitors;
 Antivascular/antiangiogenic/antimetastatic molecules: Combretastatins, heparin derivatives, RGD antagonist, heparanase inhibitors;
 Signalling/pathways modulator: PI3K, P53-mdm2, mTor, HDAC, HSP90;
 Metabolic inhibitors/activators: CPT-1, PDK-1, AMPK, and carnitine derivatives; Miscellaneous: PKCI’s, natural compounds, Topo I conjugates-RGD/oligonucleotides/liposomes.

Molecules elected for Clinical Development (main Results):

oGimatecan (Phase III, ovarian cancer)
oNamitecan (Phase II, cervix , H&N and neuroblastoma cancers )
oAdarotene (Phase I)- suggested indication in Phase II : Ovarian cancer in combination with Platins/taxanes
oSST0001 (Phase I-II, Multiple Myeloma)

Selected compounds (drug candidates, ongoing activities) for their high anti-tumor activity/T.I: belongig from different classes of:

o Combretastatin
o HDAC, HSP90 and PARP inhibitors



ADDITIONAL PROFESSIONAL ACTIVITIES:

Invited speaker to several international meetings; reviewer for different scientific journals (i.e. Cancer Research, Molecular Cancer Therapeutics, European Journal of Cancer, Journal of Medicinal Chemistry, etc); Invited as scientific expert at European Commission for Oncology Projects
Invited Professor for teaching “Pharmacogenomics” at the University of Sannio, Faculty of Biology (2003-2007) and “Pharmacology” at the University “ La Sapienza “ Rome, Faculty of Medicine (2008-2010), Italy.
Grants:
Coordinating Person of 2 Large Research Projects (> 12,000Keuro) granted from Italian Ministry of Research (projects including several Italian and International research groups) or as participant at EU project (heparanase project).
Publications:
1. Tarallo V, Lepore L, Marcellini M, Dal Piaz F, Tudisco L, Ponticelli S, Wendelboe Lund F, Roepstorff P, Orlandi A, Pisano C, De Tommasi N, De Falco S.The biflavonoid Amentoflavone inhibits neovascularization preventing the activity of pro-angiogenic vascular endothelial growth factors. J Biol Chem. 2011 Apr 6. [Epub ahead of print]

2. Meirovitz A, Hermano E, Lerner I, Zcharia E, Pisano C, Peretz T, Elkin M. Role of heparanase in radiation-enhanced invasiveness of pancreatic carcinoma. Cancer Res. 2011 Apr 1;71(7):2772-

3. Biroccio A, Porru M, Rizzo A, Salvati E, DAngelo C, Orlandi A, Passeri D, Franceschin M, Stevens MF, Gilson E, Beretta G, Zupi G, Pisano C, Zunino F, Leonetti C.DNA Damage Persistence as Determinant of Tumor Sensitivity to the Combination of Topo I Inhibitors and Telomere-Targeting Agents. Clin Cancer Res. 2011 Apr 15;17(8):2227-2236. Epub 2011 Feb 25.

4. Ritchie JP, Ramani VC, Ren Y, Naggi A, Torri G, Casu B, Penco S, Pisano C, Carminati P, Tortoreto M, Zunino F, Vlodavsky I, Sanderson RD, Yang Y. SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the heparanase/syndecan-1 axis. Clin Cancer Res. 2011 Mar 15;17(6):1382-93. Epub 2011 Jan 21.

5. Auzzas L, Larsson A, Matera R, Baraldi A, Deschênes-Simard B, Giannini G, Cabri W, Battistuzzi G, Gallo G, Ciacci A, Vesci L, Pisano C, Hanessian S. Non-Natural Macrocyclic Inhibitors of Histone Deacetylases: Design, Synthesis, and Activity. J Med Chem. 2010 Nov 12.

6. Shafat I, Ben-Arush MW, Issakov J, Meller I, Naroditsky I, Tortoteto M, Cassinelli G, Lanzi C, Pisano C, Ilan N, Vlodavsky I, Zunino F. Preclinical and clinical significance of heparanase in Ewings sarcoma. J Cell Mol Med. 2010 Oct 3. doi: 10.1111/j.1582-4934.2010.01190.x. [Epub ahead of print]

7. Dal Pozzo A, Esposito E, Ni M, Muzi L, Pisano C, Bucci F, Vesci L, Castorina M, Penco S. Conjugates of a Novel 7-Substituted Camptothecin with RGD-Peptides as α(v)β(3) Integrin Ligands: An Approach to Tumor-Targeted Therapy. Bioconjug Chem. 2010 Nov 17;21(11):1956-67. Epub 2010 Oct 15.

8. Congiu C, Onnis V, Vesci L, Castorina M, Pisano C. Synthesis and in vitro antitumor activity of new 4,5-dihydropyrazole derivatives. Bioorg Med Chem. 2010 Sep 1;18(17):6238-48. Epub 2010 Aug 9.




9. Musso L, Dallavalle S, Merlini L, Bava A, Nasini G, Penco S, Giannini G, Giommarelli C, De Cesare A, Zuco V, Vesci L, Pisano C, Dal Piaz F, De Tommasi N, Zunino F. Natural and semisynthetic azaphilones as a new scaffold for Hsp90 inhibitors. Bioorg Med Chem. 2010 Aug 15;18(16):6031-43. Epub 2010 Jul 1.

10. Pisano C, Vesci L, Milazzo FM, Guglielmi MB, Foderà R, Barbarino M, DIncalci M, Zucchetti M, Petrangolini G, Tortoreto M, Perego P, Zuco V, Orlandi A, Passeri D, Carminati P, Cavazza C, Zunino F. Metabolic approach to the enhancement of antitumor effect of chemotherapy: a key role of acetyl-L-carnitine. Clin Cancer Res. 2010 Aug 1;16(15):3944-53. Epub 2010 Jun 18.

11. Dal Piaz F, Tosco A, Eletto D, Piccinelli AL, Moltedo O, Franceschelli S, Sbardella G, Remondelli P, Rastrelli L, Vesci L, Pisano C, De Tommasi N. The identification of a novel natural activator of p300 histone acetyltranferase provides new insights into the modulation mechanism of this enzyme. Chembiochem. 2010 Apr 12;11(6):818-27.

12. Oussedik K, François JC, Halby L, Senamaud-Beaufort C, Toutirais G, Dallavalle S, Pommier Y, Pisano C, Arimondo PB. Sequence-specific targeting of IGF-I and IGF-IR genes by camptothecins. FASEB J. 2010 Jul;24(7):2235-44. Epub 2010 Feb 23.

13. Tarallo V, Vesci L, Capasso O, Esposito MT, Riccioni T, Pastore L, Orlandi A, Pisano C, De Falco S. A Placental Growth Factor Variant Unable to Recognize Vascular Endothelial Growth Factor (VEGF) Receptor-1 Inhibits VEGF-Dependent Tumor Angiogenesis via Heterodimerization. Cancer Res. 2010 Mar 1;70(5):1804-13.

14. Zuco V, Supino R, Favini E, Tortoreto M, Cincinelli R, Croce AC, Bucci F, Pisano C, Zunino F. Efficacy of ST1968 (namitecan) on a topotecan-resistant squamous cell carcinoma. Biochem Pharmacol. 2010Feb 15; 79 (4): 535-541.

15. Stasi MA, Scioli MG, Arcuri G, Mattera GG, Lombardo K, Marcellini M, Riccioni T, De Falco S, Pisano C, Spagnoli LG, Borsini F, Orlandi A. Propionyl-L-Carnitine Improves Postischemic Blood Flow Recovery and Arteriogenetic Revascularization and Reduces Endothelial NADPH-Oxidase 4-Mediated Superoxide Production. Arterioscler Thromb Vasc Biol. 2010 Feb 5.

16. Frapolli R, Zucchetti M, Sessa C, Marsoni S, Viganò L, Locatelli A, Rulli E, Compagnoni A, Bello E, Pisano C, Carminati P, DIncalci M. Clinical pharmacokinetics of the new oral camptothecin gimatecan: The inter-patient variability is related to alpha(1)-acid glycoprotein plasma levels. Eur J Cancer. 2010 Feb;46(3):505-516.





17. Dal Pozzo A, Ni MH, Esposito E, Dallavalle S, Musso L, Bargiotti A, Pisano C, Vesci L, Bucci F, Castorina M, Foderà R, Giannini G, Aulicino C, Penco S. Novel tumor-targeted RGD peptide-camptothecin conjugates: synthesis and biological evaluation. Bioorg Med Chem. 2010 Jan 1;18(1):64-72.

18. Giommarelli C, Zuco V, Favini E, Pisano C, Dal Piaz F, De Tommasi N, Zunino F. The enhancement of antiproliferative and proapoptotic activity of HDAC inhibitors by curcumin is mediated by Hsp90 inhibition. Cell Mol Life Sci. 2010 Mar;67(6):995-1004.

19. Zucchetti M, Meco D, Di Francesco AM, Servidei T, Patriarca V, Cusano G, DIncalci M, Forestieri D, Pisano C, Riccardi R. Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts. Cancer Chemother Pharmacol. 2009 Dec 20. [Epub ahead of print]

20. G. Giannini, M. Marzi, M.D. Marzo, G. Battistuzzi, R. Pezzi, T. Brunetti, W. Cabri, L. Vesci, C. Pisano. Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors. Bioorg & Med Chem Lett. 2009 May 15;19(10):2840-3.

21. P. Vekhoff; L. Halby; K. Oussedik; S. Dallavalle; L. Merlini; C. Mahieu; A. Lansiaux; C. Bailly; A. Boutorine; G. Giannini; C. Pisano; P. B. Arimondo. Optimized synthesis and reinforced efficacy of novel triplex-forming camptothecin derivatives based on gimatecan. Bioconjug Chem. 2009 Apr;20(4):666-72.

22. Zinner RG, Barrett BL, Popova E, Damien P, Volgin AY, Gelovani JG, Lotan R, Tran HT, Pisano C, Mills GB, Mao L, Hong WK, Lippman SM, Miller JH. Algorithmic guided screening of drug combinations of arbitrary size for activity against cancer cells. Mol Cancer Ther. 2009 Mar;8(3):521-32. Epub 2009 Mar 10.

23. Giannini G, Marzi M, Pezzi R, Brunetti T, Battistuzzi G, Marzo MD, Cabri W, Vesci L, Pisano C. N-Hydroxy-(4-oxime)-cinnamide: A versatile scaffold for the synthesis of novel histone deacetilase (HDAC) inhibitors. Bioorg Med Chem Lett. 2009 Feb 12.

24. Dallavalle S, Cincinelli R, Nannei R, Merlini L, Morini G, Penco S, Pisano C, Vesci L, Barbarino M, Zuco V, De Cesare M, Zunino F. Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Eur J Med Chem. 2008 Nov 19.

25. Vekhoff P, Ceccaldi A, Polverari D, Pylouster J, Pisano C, Arimondo PB. Triplex Formation on DNA Targets: How To Choose the Oligonucleotide. Biochemestry 2008 Oct 28.


26. Valli C, Paroni G, Di Francesco AM, Riccardi R, Tavecchio M, Erba E, Boldetti A, Gianni M, Fratelli M, Pisano C, Merlini L, Antoccia A, Cenciarelli C, Terao M, Garattini E. Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity. Mol Cancer Ther. 2008 Sep;7(9):2941-54.

27. Simoni D, Romagnoli R, Baruchello R, Rondanin R, Grisolia G, Eleopra M, Rizzi M, Tolomeo M, Giannini G, Aloatti D, Castorina M, Marcellini M, Pisano C. Novel A-Ring and B-Ring Modified Combretastatin A-4 (CA-4) Analogues Endowed with Interesting Cytotoxic Activity. J Med Chem. 2008 Oct 9;51(19):6211-5.

28. Arosio D, Belvisi L, Colombo L, Colombo M, Invernizzi D, Manzoni L, Potenza D, Serra M, Castorina M, Pisano C, Scolastico C. A Potent Integrin Antagonist from a Small Library of Cyclic RGD Pentapeptide Mimics Including Benzyl-Substituted Azabicycloalkane Amino Acids. ChemMedChem. 2008 Oct;3(10):1589-603.

29. Pisano C, De Cesare M, Beretta GL, Zuco V, Pratesi G, Penco S, Vesci L, Foderà R, Ferrara FF, Guglielmi MB, Carminati P, Dallavalle S, Morini G, Merlini L, Orlandi A, Zunino F. Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968. Mol Cancer Ther. 2008 Jul;7(7):2051-9.

30. Pisano C, Zuco V, De Cesare M, Benedetti V, Vesci L, Foderà R, Bucci F, Aulicino C, Penco S, Carminati P, Zunino F. Intracellular accumulation and DNA damage persistence as determinants of human squamous cell carcinoma hypersensitivity to the novel camptothecin ST1968. Eur J Cancer. 2008 Apr 27.

31. Giannini G, Marzi M, Cabri W, Marastoni E, Battistuzzi G, Vesci L, Pisano C, Beretta GL, De Cesare M, Zunino F. E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation. Bioorg Med Chem Lett. 2008 May 1;18(9):2910-5.

32. Alloatti D, Giannini G, Cabri W, Lustrati I, Marzi M, Ciacci A, Gallo G, Tinti MO, Marcellini M, Riccioni T, Guglielmi MB, Carminati P, Pisano C. Synthesis and biological activity of fluorinated combretastatin analogues. Synthesis and biological activity of fluorinated combretastatin analogues. J Med Chem. 2008 May 8;51(9):2708-21.

33. Cenciarelli C, Tanzarella C, Vitale I, Pisano C, Crateri P, Meschini S, Arancia G, Antoccia A. The tubulin-depolymerising agent combretastatin-4 induces ectopic aster assembly and mitotic catastrophe in lung cancer cells H460. Apoptosis. 2008 May;13(5):659-69.



34. Hanessian S, Auzzas L, Giannini G, Marzi M, Cabri W, Barbarino M, Vesci L, Pisano C. omega-Alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: A study of chain-length and stereochemical dependence. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6261-5.

35. Pisano C, Vesci L, Foderà R, Ferrara F, Rossi C, De Cesare M, Zuco V, Pratesi G, Supino R, Zunino F. Antitumor activity of the combination of synthetic retinoid ST1926 and cisplatin in ovarian carcinoma models. Ann Oncol. 2007 Sep;18(9):1500-5.

36. Orlandi A, Francesconi A, Ferlosio A, Lascio AD, Marcellini M, Pisano C, Spagnoli LG. Propionyl-L-Carnitine Prevents Age-Related Myocardial Remodeling in the Rabbit. J Cardiovasc Pharmacol. 2007 Aug;50(2):168-175.

37. Cincinelli R, Dallavalle S, Nannei R, Merlini L, Penco S, Giannini G, Pisano C, Vesci L, Ferrara FF, Zuco V, Zanchi C, Zunino F. Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids. Bioorg Med Chem. 2007 May 3.

38. Gomez-Monterrey I, Campiglia P, Carotenuto A, Califano D, Pisano C, Vesci L, Lama T, Bertamino A, Sala M, di Bosco AM, Grieco P, Novellino E. Design, synthesis, and cytotoxic evaluation of a new series of 3-substituted spiro[(dihydropyrazine-2,5-dione)-6,3-(2,3-dihydrothieno[2,3-b]naphtho-4,9-dione)] derivatives. J Med Chem. 2007 Apr 19;50(8):1787-98.

39. De Cesare M, Beretta GL, Tinelli S, Benedetti V, Pratesi G, Penco S, Dallavalle S, Merlini L, Pisano C, Carminati P, Zunino F. Preclinical efficacy of ST1976, a novel camptothecin analog of the 7-oxyiminomethyl series. Biochem Pharmacol. 2007 Mar 1;73(5):656-64.

40. Di Francesco AM, Meco D, Torella AR, Barone G, DIncalci M, Pisano C, Carminati P, Riccardi R. The novel atypical retinoid ST1926 is active in ATRA resistant neuroblastoma cells acting by a different mechanism. Biochem Pharmacol. 2007 Mar 1;73(5):643-55.

41. Vitale I, Antoccia A, Cenciarelli C, Crateri P, Meschini S, Arancia G, Pisano C, Tanzarella C. Combretastatin CA-4 and combretastatin derivative induce mitotic catastrophe dependent on spindle checkpoint and caspase-3 activation in non-small cell lung cancer cells. Apoptosis. 2007 Jan;12(1):155-66.

42. Dallavalle S, Giannini G, Alloatti D, Casati A, Marastoni E, Musso L, Merlini L, Morini G, Penco S, Pisano C, Tinelli S, De Cesare M, Beretta GL, Zunino F. Synthesis and cytotoxic activity of polyamine analogues of camptothecin. J Med Chem. 2006 Aug 24;49(17):5177-86.




43. Parrella E, Gianni M, Fratelli M, Barzago MM, Raska I Jr, Diomede L, Kurosaki M, Pisano C, Carminati P, Merlini L, Dallavalle S, Tavecchio M, Rochette-Egly C, Terao M, Garattini E. Antitumor activity of the retinoid-related molecules (E)-3-(4-hydroxy-3-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamma and retinoid-independent pathways. Mol Pharmacol. 2006 Sep;70(3):909-24.

44. Simoni D, Romagnoli R, Baruchello R, Rondanin R, Rizzi M, Pavani MG, Alloatti D, Giannini G, Marcellini M, Riccioni T, Castorina M, Guglielmi MB, Bucci F, Carminati P, Pisano C. Novel combretastatin analogues endowed with antitumor activity. J Med Chem. 2006 Jun 1;49(11):3143-52.

45. Kadara H, Schroeder CP, Lotan D, Pisano C, Lotan R. Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis. Cancer Biol Ther. 2006 May;5(5):518-22.

46. Dal Pozzo A, Ni M, Muzi L, de Castiglione R, Mondelli R, Mazzini S, Penco S, Pisano C, Castorina M, Giannini G. Incorporation of the unusual C(alpha)-fluoroalkylamino acids into cyclopeptides: synthesis of arginine-glycine-aspartate (RGD) analogues and study of their conformational and biological behavior. J Med Chem. 2006 Mar 9;49(5):1808-17.

47. Margiotta N, Papadia P, Lazzaro F, Crucianelli M, De Angelis F, Pisano C, Vesci L, Natile G. Platinum-based antitumor drugs containing enantiomerically pure alpha-trifluoromethyl alanine as ligand. J Med Chem. 2005 Dec 1;48(24):7821-8.

48. Casiraghi G, Rassu G, Auzzas L, Burreddu P, Gaetani E, Battistini L, Zanardi F, Curti C, Nicastro G, Belvisi L, Motto I, Castorina M, Giannini G, Pisano C. Grafting aminocyclopentane carboxylic acids onto the RGD tripeptide sequence generates low nanomolar alphaVbeta3/alphaVbeta5 integrin dual binders. J Med Chem. 2005 Dec 1;48(24):7675-87.

49. Belvisi L, Riccioni T, Marcellini M, Vesci L, Chiarucci I, Efrati D, Potenza D, Scolastico C, Manzoni L, Lombardo K, Stasi MA, Orlandi A, Ciucci A, Nico B, Ribatti D, Giannini G, Presta M, Carminati P, Pisano C. Biological and molecular properties of a new alpha(v)beta3/alpha(v)beta5 integrin antagonist. Mol Cancer Ther. 2005 Nov;4(11):1670-80.

50. Belvisi L, Bernardi A, Colombo M, Manzoni L, Potenza D, Scolastico C, Giannini G, Marcellini M, Riccioni T, Castorina M, Logiudice P, Pisano C. Targeting integrins: Insights into structure and activity of cyclic RGD pentapeptide mimics containing azabicycloalkane amino acids. Bioorg Med Chem. 2006 Jan 1;14(1):169-80.

51. Di Francesco AM, Riccardi A, Barone G, Rutella S, Meco D, Frapolli R, Zucchetti M, DIncalci M, Pisano C, Carminati P, Riccardi R. The novel lipophilic camptothecin analogue gimatecan is very active in vitro in human neuroblastoma: a comparative study with SN38 and topotecan. Biochem Pharmacol. 2005 Oct 15;70(8):1125-36.

52. Ghirardi O, Lo Giudice P, Pisano C, Vertechy M, Bellucci A, Vesci L, Cundari S, Miloso M, Rigamonti LM, Nicolini G, Zanna C, Carminati P. Acetyl-L-Carnitine prevents and reverts experimental chronic neurotoxicity induced by oxaliplatin, without altering its antitumor properties. Anticancer Res. 2005 Jul-Aug;25(4):2681-7.

53. Cincinelli R, Dallavalle S, Nannei R, Carella S, De Zani D, Merlini L, Penco S, Garattini E, Giannini G, Pisano C, Vesci L, Carminati P, Zuco V, Zanchi C, Zunino F. Synthesis and structure-activity relationships of a new series of retinoid-related biphenyl-4-ylacrylic acids endowed with antiproliferative and proapoptotic activity. J Med Chem. 2005 Jul 28;48(15):4931-46.

54. Zuco V, Zanchi C, Lanzi C, Beretta GL, Supino R, Pisano C, Barbarino M, Zanier R, Bucci F, Aulicino C, Carminati P, Zunino F. Development of resistance to the atypical retinoid, ST1926, in the lung carcinoma cell line H460 is associated with reduced formation of DNA strand breaks and a defective DNA damage response. Neoplasia. 2005 Jul;7(7):667-77.

55. Mc Gee MM, Gemma S, Butini S, Ramunno A, Zisterer DM, Fattorusso C, Catalanotti B, Kukreja G, Fiorini I, Pisano C, Cucco C, Novellino E, Nacci V, Williams DC, Campiani G. Pyrrolo[1,5]benzoxa(thia)zepines as a new class of potent apoptotic agents. Biological studies and identification of an intracellular location of their drug target.
J Med Chem. 2005 Jun 30;48(13):4367-77.

56. Ghirardi O, Vertechy M, Vesci L, Canta A, Nicolini G, Galbiati S, Ciogli C, Quattrini G, Pisano C, Cundari S, Rigamonti LM. Chemotherapy-induced allodinia: neuroprotective effect of acetyl-L-carnitine. In Vivo. 2005 May-Jun;19(3):631-7.

57. Naggi, B. Casu, M. Perez, G. Torri, G. Cassinelli, S. Penco, C. Pisano, G. Giannini, R. I. Michaeli, and I. Vlodavsky. Modulation of the heparanase-inhibiting activity of heparin through selective desulfation, graded N-acetylation, and glycol-splitting. J. Biol Chemistry. 2005 April 1;280 (13):12103-12113.

58. S. Basciani, M. Brama, S. Mariani, G. De Luca, M. Arizzi, L. Vesci, C. Pisano, S. Dolci, G. Spera and L. Gnessi. Imatinib Mesylate Inhibits Leydig Cell Tumor Growth: Evidence for In Vitro and In Vivo Activity. Cancer Res. 2005 Mar 1;65(5):1897-903.



59. Gomez-Monterrey I, Santelli G, Campiglia P, Califano D, Falasconi F, Pisano C, Vesci L, Lama T, Greco P, Novellino E. Synthesis and Cytotoxic Evaluation of Novel Spirohydantoin Derivatives of the Dihydrothieno[2,3-b]naphtho-4,9-dione System. Journal of Medicinal Chemistry. 2005 Feb. 24;48(4):1152-1157.

60. C. Pisano, C. Aulicino, L. Vesci, B. Casu, A. Naggi, G. Torri, D. Ribatti, M. Rusnati, and M. Presta. Undersulfated, Low Molecular Weight Glycol-Split Heparin as an Antiangiogenic Vegf Antagonist. Glycobiology. 2005 Feb;15(2):1C-6C.

61. C. Pisano, L. Merlini, S. Penco, P. Carminati and F. Zunino. Cellular and pharmacological bases of antitumor activity of a novel adamantly retinoid ST1926. Journal of Chemotherapy. 2004 Nov;16(4).

62. R. Piergentili, S. Bonaccorsi, G. D. Raffa, C. Pisano, J. H. P. Hackstein, C. Mencarelli. Autosomal control of the Y-chromosome kl-3 loop of Drosophila melanogaster. Chromosoma. 2004 113: 188-196.

63. M. Errico, T. Riccioni, S. Iyer, C. Pisano, K. R. Acharya, M. G. Persico, S. De Falco. Identification of Placenta Growth Factor determinants for binding and activation of Flt-1 receptor. J. Biological Chemistry. 2004 Oct 15;279(42):43929-39.

64. P. Stano, S. Bufali, C. Pisano, F. Bucci, M. Barbarino, M. Santaniello, P. Carminati and P. L. Luisi. Novel Camptothecin Analogue (Gimatecan)-Containig Liposomes Prepared by the Ethanol Injection Method. Journal of Liposome Research. 2004 Vol. 14, Nos. 1 & 2, pp. 87-109.

65. Casu, M. Guerrini, S. Guglieri, A. Naggi, M. Perez, G. Torri, G. Cassinelli, D. Ribatti, P. Carminati, G. Giannini, S. Penco, C. Pisano, M. Belleri, M. Rusnati, and M. Presta. Undersulfated, Glycol-split Heparins Endowed with Antiangiogenic Activity. Journal of Medicinal Chemistry. 2004 Feb. 12;47(4):838-48.

66. E. Garattini, E. Parrella, L. Diomede, M. Gianni’, Y. Kalac, L. Merlini, S. Penco, D. Simoni, R. Zanier, G. Giannini, F. F. Ferrara, P. Carminati, M. Terao and C. Pisano. ST1926 a novel and orally active retinoid related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan.1;103(1):194-207.

67. V. Zuco, C. Zanchi, G. Cassinelli, C.Lanzi, R. Supino, C. Pisano, R. Zanier, V. Giordano, E. Garattini and F. Zunino. Induction of apoptosis and stress response in ovarian carcinoma cell lines treated with ST1926, an atypical retinoid. Cell Death and Differentiation. 2004 11, 280-289.




68. C. Pisano, G. Pratesi, D. Laccabue, F. Zunino, P. Lo Giudice, A. Bellucci, L. Pacifici, B. Camerini, L. Vesci, M. Castorina, S. Cicuzza, G. Tredici, P. Marmiroli, G. Nicolini, S. Galbiati, M. Calvani, P. Carminati and G. Cavaletti. Paclitaxel and cisplatin-induced neurotoxicity: a protective role of acetyl-l-carnitine. Clinical Cancer Res. 2003 Nov. 15; 9:5756-5767.

69. G. Petrangolini, G. Pratesi, M. De Cesare, R. Supino, M. Marcellini, V. Giordano, C. Pisano, D. Laccabue, C. Lanzi and F. Zunino. Antiangiogenic effect of the novel camptothecin ST1481 (Gimatecan) in human tumor xenografts. Molecular Cancer Research. 2003 Oct. vol. 1, 863-870.

70. Vlodavsky I, Zcharia E, Goldshmidt O, Eshel R, Katz BZ, Minucci S, Kovalchuk O, Penco S, Pisano C, Naggi A, Casu B. Involvement of heparanase in tumor progression and normal differentiation. Pathophysiol Haemost Thromb. 2003; 33 Suppl. 1:59-61.

71. Giannini G, Penco S, Pisano C, Riccioni T, Nasini G, Candiani G. Chrysanthones. A new source of fungal metabolites with potential antitumor and antiangiogenesis properties. Fitoterapia. 2003 Jun;74(4):323-7.2.

72. V. Zuco, R. Supino, M. de Cesare, N. Carenini, P. Perego, L. Gatti, G. Pratesi, C. Pisano, R. Martinelli, F. Bucci, R. Zanier, P. Carminati, F. Zunino. Cellular bases of the antitumor activity of a 7-substituted camptothecin in hormane-refractory human prostate carcinoma models. Biochemical Pharmacology. 2003 Apr 15;65(8):1281-94.

73. R. Cincinelli, S. Dallavalle, L. Merlini, S. Penco, C. Pisano, P. Carminati, G. Giannini, L. Vesci, C. Gaetano, B. Illy, V. Zuco, R. Supino and F. Zunino. A Novel Atypical Retinoid Endowed with Proapoptotic and Antitumor Activity. Journal of Medicinal Chemistry. 2003 Mar 13;46(6):909-12.

74. G. Pratesi, M. De Cesare, N. Carenini, P. Perego, S. C. Rigetti, C. Cucco, L. Merlini, C. Pisano, S. Penco, P. Carminati, L. Vesci, F. Zunino. Pattern of Antitumor Activity of a Novel camptothecin, ST1481, in a large panel of human tumor xenografs. Clinical Cancer Res. 2002 Dec. 8:3904-3909.

75. Casu B, Guerrini M, Naggi A, Perez M, Torri G, Ribatti D, Carminati P, Giannini G, Penco S, Pisano C, Belleri M, Rusnati M, Presta M. Short heparin sequences spaced by glycol-split uronate residues are antagonists of fibroblast growth factor 2 and angiogenesis inhibitors. Biochemistry. 2002 Aug. 20;41(33):10519-28.

76. L. Belvisi, A. Caporale, M. Colombo, L. Manzoni, D. Potenza, C. Scolastico, M. Castorina, M. Cati, G. Giannini, C. Pisano. Cyclic RGD Peptides Containing Azabicycloalkane Reverse-Turn Mimics. Helvetica Chimica Acta. Vol. 85, 2002.

77. Pisano C, Kollar P, Gianni’ M, Kalac Y, Giordano V, Ferrara F F, Tancredi R, Devoto A, Rinaldi A, Rambaldi A, Penco S, Marzi M, Moretti G, Vesci L, Tinti MO, Carminati P, Terao M, and Garattini E. Bis-indols a novel class of molecules enhancing the cyto-differentiating properties of retinoids in myeloid leukemia cells. Blood. 2002 Nov. 15;100(10):3719-30.

78. Coruzzi G, Coppelli G, Spaggiari S, Cavestro GM, Okolicsanyi L, Lo Giudice P, Pisano C, Tepperman BL. Gastroprotective effects of amtolmetin guacyl: a new non-steroidal anti-inflammatory drug that activates inducible gastric nitric oxide synthase. Digestive and Liver Disease. 2002 Jun;34(6):403-10.

79. Cavaletti G, Pezzoni G, Pisano C, Oggioni N, Sala F, Zoia C, Ferrarese C, Marmiroli P, Tredici G. Cisplatin-induced peripheral neurotoxicity in rats reduces the circulating levels of nerve growth factor. Neurosci Lett. 2002 Apr. 5;322(2):103-6.
80. De Cesare M, Pratesi G, Perego P, Carenini N, Tinelli S, Merlini L, Penco S, Pisano C, Bucci F, Vesci L, Pace S, Capocasa F, Carminati P, Zunino F. Potent antitumor activity and improved pharmacological profile of ST1481, a novel 7-substituted camptothecin. Cancer Res. 2001 Oct. 1;61(19):7189-95.
81. Dallavalle S, Ferrari A, Biasotti B, Merlini L, Penco S, Gallo G, Marzi M, Tinti MO, Martinelli R, Pisano C, Carminati P, Carenini N, Beretta G, Perego P, De Cesare M, Pratesi G, Zunino F. Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity. J Med Chem. 2001 Sep. 27;44(20):3264-74.
82. Cavaletti G, Tredici G, Zoia C, Carminati P, Pisano C. Acetyl-L-Carnitine reduces cisplatin neurotoxicity in the wistar rat. Journal of peripheral Nervous System. 2001 Sept. 6 (3): 136.
83. Perego P, De Cesare M, De Isabella P, Carenini N, Beggiolin G, Pezzoni G, Palumbo M, Tartaglia L, Pratesi G, Pisano C, Carminati P, Scheffer G L, Zunino F. A novel 7-modified camptothecin analog overcomes breast cancer resistance protein-associated resistance in a mitoxantrone-selected colon carcinoma cell line. Cancer Res 2001 Aug. 15;61(16):6034-7.
84. Belvisi L, Bernardi A, Checchia A, Manzoni L, Potenza D, Scolastico C, Castorina M, Cupelli A, Giannini G, Carminati P, Pisano C. Potent integrin antagonists from a small library of RGD-including cyclic pseudopeptides. Org Lett 2001 Apr. 5;3(7):1001-4.
85. M. Leng, D. Locker, M.-J. Giraud-Panis, A. Schwartz, F. P. Intini, G. Natile, C. Pisano, A. Boccarelli, D. Giordan, and M. Coluccia. Replacement of an NH3 by an Iminoether in Trasplatin Makes an Antitumor Drug from an Inactive Compound. Mol Pharmacol 2000; 58 (6):1525-1535.

86. Pisano C, Battistoni A, Antoccia A, Degrassi F, Tanzarella C. Changes in microtubule organization after exposure to a benzimidazole derivative in Chinese hamster cells. Mutagenesis 2000 Nov.;15(6):507-15.

87. De Cesare M, Zunino F, Pace S, Pisano C, Pratesi G. Efficacy and toxicity profile of oral topotecan in a panel of human tumour xenografts. Eur J Cancer 2000 Aug;36(12):1558-64.

88. Pisano C., Grandi D., Morini G., Coruzzi G, Coppelli G, Vesci L., Lo Giudice P, Pace S., Pacifici L., Longo A., Coruzzi G., Carminati P. Gastrosparing effects of new antiinflammatory drug amtolmetin guacyl in the rat: involvement of nitric oxide. Digestive and Liver Disease 1999 Apr;44(4):713-24.

89. Battistoni A., Guarguaglini G., Degrassi F., Pittoggi C., Palena A., Di Matteo G., Pisano C., Cundari E., Lavia P. Deregulated expression of the RanBP1 gene alters cell cycle progression in murine fibroblasts. J Cell Sci 1997 Oct;110(Pt 19):2345-57.

90. Cenci G., Bonaccorsi S., Pisano C., Verni F., Gatti M. Chromatin and microtubule organization during premeiotic, meiotic and early postmeiotic stages of Drosophila melanogaster spermatogenesis. J Cell Sci 1994 Dec;107(Pt 12):3521-34.

91. Pisano C., Bonaccorsi S., Gatti M. The Kl-3 loop of the Y chromosome of Drosophila melanogaster binds a tektin-like protein. Genetics 1993 Mar;133(3):569-79.

92. Di Franco C., Pisano C., Fourcade-Peronnet F., Echalier G., Junakovic N. Evidence for the novo rearrangements of Drosophila transposable elements induced by the passage to the cell culture. Genetica 1992;87(2):65-73.

93. Somma M.P., Pisano C., Lavia P. The housekeeping promoter from the mouse CpG island HTF9 contains multiple protein-binding elements that are functionally redundant. Nucleics Acids Res. 1991 Jun 11;19(11):2817-24.

94. Bonaccorsi S., Gatti M., Pisano C., Lohe A. Transcription of a satellite on two Y chromosome loops of drosophila melanogaster. Chromosoma1990 Aug;99(4):260-6.

95. Di Franco C., Pisano C., Dimitri P., Gigliotti S., Junakovic N. Genomic distribution of copia-like transposable elements in somatic tissues and during development of Drosophila melanogaster. Chromosoma1989 Dec;98(6):402-10.

96. Dimitri P., Pisano C. Positon effects variegation in Drosophila melanogaster: relationship between suppression effect and the amount of Y chromosome. Genetics1989 Aug;122(4):793-800.



97. Bonaccorsi S., Pisano C., Puoti F., Gatti M. Y chromosome loops in Drosophia melanogaster. Genetics 1988 Dec;120(4):1015-34.

Publications

  1. ncbi Combretastatin CA-4 and combretastatin derivative induce mitotic catastrophe dependent on spindle checkpoint and caspase-3 activation in non-small cell lung cancer cells
    Ilio Vitale
    Department of Biology, University Roma Tre, V le Marconi 446, 00146, Rome, Italy
    Apoptosis 12:155-66. 2007
  2. doi Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
    Claudia Valli
    Laboratory of Molecular Biology, Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20157 Milan, Italy
    Mol Cancer Ther 7:2941-54. 2008
  3. pmc Role of heparanase in radiation-enhanced invasiveness of pancreatic carcinoma
    Amichay Meirovitz
    Sharett Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Cancer Res 71:2772-80. 2011
  4. doi Intracellular accumulation and DNA damage persistence as determinants of human squamous cell carcinoma hypersensitivity to the novel camptothecin ST1968
    Claudio Pisano
    Sigma Tau S p A, Pomezia, Rome, Italy
    Eur J Cancer 44:1332-40. 2008
  5. doi E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation
    Giuseppe Giannini
    Sigma Tau Research and Development, Via Pontina Km 30 400, I 00040 Pomezia, Rome, Italy
    Bioorg Med Chem Lett 18:2910-5. 2008
  6. doi The tubulin-depolymerising agent combretastatin-4 induces ectopic aster assembly and mitotic catastrophe in lung cancer cells H460
    Chiara Cenciarelli
    Department of Biology, University Roma Tre, V le Marconi 446, 00146, Rome, Italy
    Apoptosis 13:659-69. 2008
  7. ncbi Omega-alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: a study of chain-length and stereochemical dependence
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, Montreal, Quebec, Canada
    Bioorg Med Chem Lett 17:6261-5. 2007
  8. ncbi Propionyl-L-carnitine prevents age-related myocardial remodeling in the rabbit
    Augusto Orlandi
    Department of Biopathology and Image Diagnostics, Anatomic Pathology Institute, Tor Vergata University, Italy
    J Cardiovasc Pharmacol 50:168-75. 2007
  9. ncbi Antitumor activity of the combination of synthetic retinoid ST1926 and cisplatin in ovarian carcinoma models
    C Pisano
    Research and Development, Sigma Tau, Pomezia Rome, Italy
    Ann Oncol 18:1500-5. 2007
  10. ncbi Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids
    Raffaella Cincinelli
    Dipartimento di Scienze Molecolari Agroalimentari, Universita di Milano, Via Celoria 2, 20133 Milano, Italy
    Bioorg Med Chem 15:4863-75. 2007

Detail Information

Publications73

  1. ncbi Combretastatin CA-4 and combretastatin derivative induce mitotic catastrophe dependent on spindle checkpoint and caspase-3 activation in non-small cell lung cancer cells
    Ilio Vitale
    Department of Biology, University Roma Tre, V le Marconi 446, 00146, Rome, Italy
    Apoptosis 12:155-66. 2007
    ....
  2. doi Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
    Claudia Valli
    Laboratory of Molecular Biology, Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20157 Milan, Italy
    Mol Cancer Ther 7:2941-54. 2008
    ..Cells defective for homologous recombination are particularly sensitive to ST1926, indicating that this process is important for the protection of cells from the RRM-dependent DNA damage and cytotoxicity...
  3. pmc Role of heparanase in radiation-enhanced invasiveness of pancreatic carcinoma
    Amichay Meirovitz
    Sharett Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Cancer Res 71:2772-80. 2011
    ....
  4. doi Intracellular accumulation and DNA damage persistence as determinants of human squamous cell carcinoma hypersensitivity to the novel camptothecin ST1968
    Claudio Pisano
    Sigma Tau S p A, Pomezia, Rome, Italy
    Eur J Cancer 44:1332-40. 2008
    ..A high intracellular accumulation, resulting in fast apoptosis or DNA damage persistence, appeared to be a critical determinant of SCC sensitivity to ST1968...
  5. doi E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation
    Giuseppe Giannini
    Sigma Tau Research and Development, Via Pontina Km 30 400, I 00040 Pomezia, Rome, Italy
    Bioorg Med Chem Lett 18:2910-5. 2008
    ..A selected compound of this series exhibited an excellent antitumor activity against human gastrointestinal tumor xenografts...
  6. doi The tubulin-depolymerising agent combretastatin-4 induces ectopic aster assembly and mitotic catastrophe in lung cancer cells H460
    Chiara Cenciarelli
    Department of Biology, University Roma Tre, V le Marconi 446, 00146, Rome, Italy
    Apoptosis 13:659-69. 2008
    ....
  7. ncbi Omega-alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: a study of chain-length and stereochemical dependence
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, Montreal, Quebec, Canada
    Bioorg Med Chem Lett 17:6261-5. 2007
    ..However, no significant difference in antiproliferative activity was observed between two enantiomers bearing the benzyl ether moiety...
  8. ncbi Propionyl-L-carnitine prevents age-related myocardial remodeling in the rabbit
    Augusto Orlandi
    Department of Biopathology and Image Diagnostics, Anatomic Pathology Institute, Tor Vergata University, Italy
    J Cardiovasc Pharmacol 50:168-75. 2007
    ..Our results demonstrated that long-term PLC treatment partially prevents age-related interstitial remodeling and suggests that a more complex interstitial cell-to-cell signaling regulates senescent myocardium properties...
  9. ncbi Antitumor activity of the combination of synthetic retinoid ST1926 and cisplatin in ovarian carcinoma models
    C Pisano
    Research and Development, Sigma Tau, Pomezia Rome, Italy
    Ann Oncol 18:1500-5. 2007
    ..Since the pro-apoptotic effect is associated with activation of p53, in this study we have investigated the efficacy of combination of ST1926 with cisplatin, a DNA-damaging agent that is known to induce p53-dependent apoptosis...
  10. ncbi Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids
    Raffaella Cincinelli
    Dipartimento di Scienze Molecolari Agroalimentari, Universita di Milano, Via Celoria 2, 20133 Milano, Italy
    Bioorg Med Chem 15:4863-75. 2007
    ....
  11. ncbi Design, synthesis, and cytotoxic evaluation of a new series of 3-substituted spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives
    Isabel Gomez-Monterrey
    Dipartimento di Chimica Farmaceutica e Tossicologica, University of Naples Federico II, Napoli, Italy
    J Med Chem 50:1787-98. 2007
    ..In addition, the topoisomerase II inhibition activity and DNA-binding properties were investigated...
  12. ncbi Preclinical efficacy of ST1976, a novel camptothecin analog of the 7-oxyiminomethyl series
    Michelandrea De Cesare
    Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy
    Biochem Pharmacol 73:656-64. 2007
    ..On the basis of its excellent activity in preclinical models, ST1976 is a promising candidate for clinical development...
  13. ncbi The novel atypical retinoid ST1926 is active in ATRA resistant neuroblastoma cells acting by a different mechanism
    Angela Maria Di Francesco
    Division of Pediatric Oncology, Catholic University of Rome, Largo A Gemelli 8, 00168 Rome, Italy
    Biochem Pharmacol 73:643-55. 2007
    ..In vivo, orally administered ST1926, appeared to inhibit tumor growth of NB xenografts with tolerable toxicity. Overall, our results support the view that ST1926 might represent a good drug candidate in this pediatric tumor...
  14. ncbi Synthesis and cytotoxic activity of polyamine analogues of camptothecin
    Sabrina Dallavalle
    Dipartimento di Scienze Molecolari Agroalimentari, Universita di Milano, Via Celoria 2, 20133 Milano, Italy
    J Med Chem 49:5177-86. 2006
    ....
  15. ncbi Novel combretastatin analogues endowed with antitumor activity
    Daniele Simoni
    Dipartimento di Scienze Farmaceutiche, Universita di Ferrara, Via Fossato di Mortara 17 19, 44100 Ferrara, Italy
    J Med Chem 49:3143-52. 2006
    ..Interestingly, both the pharmacokinetic profile of 29 and its in vivo antitumor effect and those of 30, active even after oral administration, suggest additional pharmacological differences between these compounds and CA-4P...
  16. ncbi Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis
    Humam Kadara
    Department of Thoracic Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Biol Ther 5:518-22. 2006
    ..However, silencing of GDF-15 induction by RNA interference failed to decrease the ability of CD437 and ST1926 to induce apoptosis. These results demonstrate that GDF-15 is dispensable for the pro-apoptotic activity of CD437 and ST1926...
  17. ncbi Incorporation of the unusual C(alpha)-fluoroalkylamino acids into cyclopeptides: synthesis of arginine-glycine-aspartate (RGD) analogues and study of their conformational and biological behavior
    Alma Dal Pozzo
    Istituto di Ricerche Chimiche e Biochimiche G Ronzoni, Via G Colombo 81, 20133 Milano, Italy
    J Med Chem 49:1808-17. 2006
    ..Significant interproton distances, derived from nuclear Overhauser effect (NOE) experiments, were used to determine the absolute configuration of the side chains...
  18. doi Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968
    Claudio Pisano
    Sigma Tau, Pomezia, Italy
    Mol Cancer Ther 7:2051-9. 2008
    ..Based on its outstanding efficacy superior to that of irinotecan and of its good therapeutic index, ST1968 has been selected for clinical development...
  19. doi Novel A-ring and B-ring modified combretastatin A-4 (CA-4) analogues endowed with interesting cytotoxic activity
    Daniele Simoni
    Dipartimento di Scienze Farmaceutiche, Universita di Ferrara, Ferrara, Italy
    J Med Chem 51:6211-5. 2008
    ..Heterocombretastatins 9a,b inhibit tubulin polymerization similarly to CA-4 by having a binding to colchicine site five times stronger...
  20. doi Conjugates of a novel 7-substituted camptothecin with RGD-peptides as α(v)β₃ integrin ligands: An approach to tumor-targeted therapy
    Alma Dal Pozzo
    Istituto di Ricerche Chimiche e Biochimiche G Ronzoni, Milano, Italy
    Bioconjug Chem 21:1956-67. 2010
    ..The rationale, synthetic strategy, and preliminary biological results will be presented...
  21. doi Synthesis and in vitro antitumor activity of new 4,5-dihydropyrazole derivatives
    Cenzo Congiu
    Dipartimento di Tossicologia, Sezione di Chimica Farmaceutica, Universita degli Studi di Cagliari, Via Ospedale 72, Cagliari I 09124, Italy
    Bioorg Med Chem 18:6238-48. 2010
    ..Compound 31 (IC(50)=5.16 microM) showed inhibition of tubulin polymerization comparable to that of CA-4 (IC(50)=4.92 microM)...
  22. doi Natural and semisynthetic azaphilones as a new scaffold for Hsp90 inhibitors
    Loana Musso
    Dipartimento di Scienze Molecolari Agroalimentari, Universita di Milano, Via Celoria 2, 20133 Milano, Italy
    Bioorg Med Chem 18:6031-43. 2010
    ..Preliminary results indicated in vivo activity of bulgarialactone B against an ascitic ovarian carcinoma xenograft, thus supporting the therapeutic potential of this novel series of Hsp90 inhibitors...
  23. doi Metabolic approach to the enhancement of antitumor effect of chemotherapy: a key role of acetyl-L-carnitine
    Claudio Pisano
    Oncology Area Research and Development, Sigma Tau, Pomezia, Italy
    Clin Cancer Res 16:3944-53. 2010
    ..Because acetylation may influence p53 activity/stability and, therefore, the response to platinum compounds, this study was designed to investigate the effect of ALC in combination with platinum compounds...
  24. doi The identification of a novel natural activator of p300 histone acetyltranferase provides new insights into the modulation mechanism of this enzyme
    Fabrizio Dal Piaz
    Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Salerno, Via Ponte Don Melillo 1, 84084 Fisciano, SA, Italy
    Chembiochem 11:818-27. 2010
    ..Besides, the studies performed at a cellular and molecular level on both the inhibitors and the activator provided new insights into the modulation mechanism of p300/CBP by small molecules...
  25. doi A placental growth factor variant unable to recognize vascular endothelial growth factor (VEGF) receptor-1 inhibits VEGF-dependent tumor angiogenesis via heterodimerization
    Valeria Tarallo
    Angiogenesis Lab and Stem Cell Fate Lab, Institute of Genetics and Biophysics Adriano Buzzati Traverso, Consiglio Nazionale delle Ricerche, Naples, Italy
    Cancer Res 70:1804-13. 2010
    ..The PlGF1-DE variant, and not PlGF1wt as previously reported, acts as a "dominant negative" of VEGF and is a new candidate for antiangiogenic gene therapy in cancer treatment...
  26. doi Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts
    Massimo Zucchetti
    Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, Italy
    Cancer Chemother Pharmacol 66:635-41. 2010
    ..This study compared the antitumor activity and the pharmacological profile of gimatecan given orally and irinotecan (CPT-11) on pediatric tumor xenografts...
  27. doi Propionyl-L-carnitine improves postischemic blood flow recovery and arteriogenetic revascularization and reduces endothelial NADPH-oxidase 4-mediated superoxide production
    Maria Antonietta Stasi
    Dept of Biopathology and Image Diagnostics, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy
    Arterioscler Thromb Vasc Biol 30:426-35. 2010
    ....
  28. doi Clinical pharmacokinetics of the new oral camptothecin gimatecan: the inter-patient variability is related to alpha1-acid glycoprotein plasma levels
    Roberta Frapolli
    Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy
    Eur J Cancer 46:505-16. 2010
    ..To determine the pharmacokinetics of gimatecan, a camptothecin with a lipophilic substitution in position 7, given orally to patients participating in the phase I study...
  29. doi Novel tumor-targeted RGD peptide-camptothecin conjugates: synthesis and biological evaluation
    Alma Dal Pozzo
    Istituto di Ricerche Chimiche e Biochimiche G Ronzoni, Via G Colombo 81, 20133 Milano, Italy
    Bioorg Med Chem 18:64-72. 2010
    ..On the basis of these results, information was acquired for additional development of derivatives with different linkers and better solubility for in vivo evaluation...
  30. doi Efficacy of ST1968 (namitecan) on a topotecan-resistant squamous cell carcinoma
    Valentina Zuco
    Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy
    Biochem Pharmacol 79:535-41. 2010
    ..e., slow proliferation and target downregulation) owing to its peculiar pharmacokinetic behaviour...
  31. doi Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors
    Giuseppe Giannini
    Sigma Tau Research and Development, Pomezia, Roma, Italy
    Bioorg Med Chem Lett 19:2840-3. 2009
    ..HDAC inhibition profile and antiproliferative activity were evaluated...
  32. doi Algorithmic guided screening of drug combinations of arbitrary size for activity against cancer cells
    Ralph G Zinner
    Department of Thoracic Head and Neck Medical Oncology, Unit 432, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 8:521-32. 2009
    ..These results suggest that when guided by MACS, screening larger drug combinations may be feasible as a first step in combination drug discovery in a relatively small number of experiments...
  33. doi Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors
    Sabrina Dallavalle
    Dipartimento di Scienze Molecolari Agroalimentari, Universita di Milano, Via Celoria 2, 20133 Milano, Italy
    Eur J Med Chem 44:1900-12. 2009
    ..Compounds selected for in vivo evaluation exhibited a significant antitumor activity on three tumor models at well tolerated doses, thus suggesting a good therapeutic index...
  34. doi Triplex formation on DNA targets: how to choose the oligonucleotide
    Pierre Vekhoff
    UMR 5153 CNRS, Museum National d Histoire Naturelle USM0503, 43 rue Cuvier, 75231 Paris Cedex 05, France
    Biochemistry 47:12277-89. 2008
    ..An equation to choose between a GU and TM motif is given...
  35. ncbi Platinum-based antitumor drugs containing enantiomerically pure alpha-trifluoromethyl alanine as ligand
    Nicola Margiotta
    Dipartimento Farmaco Chimico, Universita di Bari, Via E Orabona 4, I 70125 Bari, Italy
    J Med Chem 48:7821-8. 2005
    ..Flow cytometric analysis on NCI-H460 tumor cells (absence of G2/M arrest, which instead is observed in the case of cisplatin) suggests a mechanism of action different from that of cisplatin...
  36. ncbi Grafting aminocyclopentane carboxylic acids onto the RGD tripeptide sequence generates low nanomolar alphaVbeta3/alphaVbeta5 integrin dual binders
    Giovanni Casiraghi
    Dipartimento Farmaceutico, Universita di Parma, Parco Area delle Scienze 27A, I 43100 Parma, Italy
    J Med Chem 48:7675-87. 2005
    ..The results prove that the principle of isosteric dipeptide replacement for peptidomimetics design and synthesis can be violated, without detriment to the development of highly effective integrin binders...
  37. ncbi Identification of placenta growth factor determinants for binding and activation of Flt-1 receptor
    Michela Errico
    Institute of Genetics and Biophysics Adriano Buzzati Traverso, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy
    J Biol Chem 279:43929-39. 2004
    ..This variant failed to induce in vitro capillary-like tube formation of primary endothelial cells or neo-angiogenesis in an in vivo chorioallantoic membrane assay...
  38. ncbi Induction of apoptosis and stress response in ovarian carcinoma cell lines treated with ST1926, an atypical retinoid
    V Zuco
    Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy
    Cell Death Differ 11:280-9. 2004
    ..The results are consistent with apoptosis induction through p53-dependent and -independent pathways, regulated by MAP kinases, which likely play a protective role...
  39. ncbi Paclitaxel and Cisplatin-induced neurotoxicity: a protective role of acetyl-L-carnitine
    Claudio Pisano
    Research and Development, Sigma Tau S p A Industrie Farmaceutiche Riunite, Rome, Italy
    Clin Cancer Res 9:5756-67. 2003
    ..In this study we have tested the hypothesis that ALC may have a protective role on cisplatin and paclitaxel-induced neuropathy...
  40. ncbi Involvement of heparanase in tumor progression and normal differentiation
    I Vlodavsky
    Technion, Haifa, Israel
    Pathophysiol Haemost Thromb 33:59-61. 2003
  41. ncbi Chrysanthones, a new source of fungal metabolites with potential antitumor and antiangiogenesis properties
    G Giannini
    Sigma Tau S p A, Research and Development, Via Pontina 30 400, 00040 Pomezia, Italy
    Fitoterapia 74:323-7. 2003
    ..In general, compared to the activity of known antiproliferative and antiangiogenic compounds, chrysanthones showed weaker activities. However, they present a basis for the synthesis of new derivatives...
  42. ncbi A novel atypical retinoid endowed with proapoptotic and antitumor activity
    Raffaella Cincinelli
    Dipartimento di Scienze Molecolari Agroalimentari, Universita di Milano, Milano, Italy
    J Med Chem 46:909-12. 2003
    ....
  43. doi The enhancement of antiproliferative and proapoptotic activity of HDAC inhibitors by curcumin is mediated by Hsp90 inhibition
    Chiara Giommarelli
    Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
    Cell Mol Life Sci 67:995-1004. 2010
    ....
  44. ncbi Short heparin sequences spaced by glycol-split uronate residues are antagonists of fibroblast growth factor 2 and angiogenesis inhibitors
    Benito Casu
    G Ronzoni Institute for Chemical and Biochemical Research, 20133 Milan, Italy
    Biochemistry 41:10519-28. 2002
    ..Finally, it inhibited angiogenesis in a chick embrio chorioallantoic membrane (CAM) assay in which heparin is inactive...
  45. ncbi Cisplatin-induced peripheral neurotoxicity in rats reduces the circulating levels of nerve growth factor
    G Cavaletti
    Department of Neuroscience, Neurology Unit, S Gerardo Hospital, Via Donizetti 106, 20052 Monza, Italy
    Neurosci Lett 322:103-6. 2002
    ..Our findings are in agreement with previous in vitro and in vivo results and further suggest that NGF plays a specific role in the course of CDDP-induced primary sensory neuron damage...
  46. ncbi Potent antitumor activity and improved pharmacological profile of ST1481, a novel 7-substituted camptothecin
    M De Cesare
    Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy
    Cancer Res 61:7189-95. 2001
    ..Overall, the results support the preclinical interest of ST1481 in terms of efficacy, potency, toxicity profile, and ability to overcome multidrug resistance...
  47. ncbi Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity
    S Dallavalle
    Dipartimento di Scienze Molecolari Agroalimentari, Sezione di Chimica, , Via Celoria 2, 20133 Milan, Italy
    J Med Chem 44:3264-74. 2001
    ..In the range of optimal doses (2-3 mg/kg), the improved efficacy of 15 was documented in terms of inhibition of tumor growth and rate of complete response...
  48. ncbi A novel 7-modified camptothecin analog overcomes breast cancer resistance protein-associated resistance in a mitoxantrone-selected colon carcinoma cell line
    P Perego
    Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy
    Cancer Res 61:6034-7. 2001
    ..These results may have therapeutic implications because the antitumor efficacy of ST1481 is in part related to a good bioavailability after oral administration, and the drug is currently under Phase I clinical evaluation...
  49. ncbi Potent integrin antagonists from a small library of RGD-including cyclic pseudopeptides
    L Belvisi
    Dipartimento di Chimica Organica e Industriale, , via Venezian 21, I-20133 Milano, Italy
    Org Lett 3:1001-4. 2001
    ..The solid-phase synthesis and activity of these RGD derivatives is described. The approach led to two of the most active known inhibitors of alpha(V)beta3 receptor...
  50. pmc The kl-3 loop of the Y chromosome of Drosophila melanogaster binds a tektin-like protein
    C Pisano
    Istituto Pasteur, Fondazione Cenci Bolognetti, Roma, Italy
    Genetics 133:569-79. 1993
    ..This finding supports the hypothesis that the Y loops fulfill a protein-binding function required for the proper assembly of the axoneme components...
  51. ncbi Autosomal control of the Y-chromosome kl-3 loop of Drosophila melanogaster
    Roberto Piergentili
    Dipartimento di Genetica e Biologia Molecolare, Universita di Roma La Sapienza, P le Aldo Moro 5, 00185 Rome, Italy
    Chromosoma 113:188-96. 2004
    ....
  52. ncbi Chromatin and microtubule organization during premeiotic, meiotic and early postmeiotic stages of Drosophila melanogaster spermatogenesis
    G Cenci
    Istituto Pasteur, Fondazione Cenci Bolognetti, Roma, Italy
    J Cell Sci 107:3521-34. 1994
    ..In addition, by means of bromo-deoxyuridine incorporation experiments, we were able to demonstrate that premeiotic DNA synthesis occurs very early during spermatocyte growth...
  53. ncbi Targeting integrins: insights into structure and activity of cyclic RGD pentapeptide mimics containing azabicycloalkane amino acids
    Laura Belvisi
    Dipartimento di Chimica Organica e Industriale and Centro Interdisciplinare Studi Bio molecolari e Applicazioni Industriali, CISI, Universita degli Studi di Milano, via G Venezian 21, I 20133 Milan, Italy
    Bioorg Med Chem 14:169-80. 2006
    ....
  54. ncbi The novel lipophilic camptothecin analogue gimatecan is very active in vitro in human neuroblastoma: a comparative study with SN38 and topotecan
    Angela Maria Di Francesco
    Division of Paediatric Oncology, Catholic University, Rome, Italy
    Biochem Pharmacol 70:1125-36. 2005
    ..We propose that DNA strand breaks efficiency as measured by the Comet assay might provide important information about the stability of the ternary complexes induced by camptothecin compounds...
  55. ncbi Acetyl-L-Carnitine prevents and reverts experimental chronic neurotoxicity induced by oxaliplatin, without altering its antitumor properties
    Orlando Ghirardi
    Research and Development, Sigma Tau S p A Industrie Farmaceutiche Riunite, Rome, Italy
    Anticancer Res 25:2681-7. 2005
    ..Acetyl-L-carnitine (ALC), a natural compound with neuroprotective action, was tested to determine whether it plays a protective role in OHP-induced neuropathy...
  56. ncbi Synthesis and structure-activity relationships of a new series of retinoid-related biphenyl-4-ylacrylic acids endowed with antiproliferative and proapoptotic activity
    Raffaella Cincinelli
    Dipartimento di Scienze Molecolari Agroalimentari, Universita di Milano, Via Celoria 2, 20133 Milano, Italy
    J Med Chem 48:4931-46. 2005
    ..Among the compounds investigated, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation...
  57. ncbi Pyrrolo[1,5]benzoxa(thia)zepines as a new class of potent apoptotic agents. Biological studies and identification of an intracellular location of their drug target
    Margaret M Mc Gee
    Department of Biochemistry, Trinity College, Dublin 2, Ireland
    J Med Chem 48:4367-77. 2005
    ..Interestingly, compound 6 displayed cytotoxic activity against a panel of human tumor cell lines but demonstrated negligible toxicity in vivo with no effect on the animals' hematology parameters...
  58. ncbi Chemotherapy-induced allodinia: neuroprotective effect of acetyl-L-carnitine
    Orlando Ghirardi
    Research and Development, Sigma Tau S p A Industrie Farmaceutiche Riunite, Rome, Italy
    In Vivo 19:631-7. 2005
    ..In addition, the possible interaction between ALC and vincristine antineoplastic action was assessed...
  59. ncbi Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity
    Sabrina Basciani
    Department of Medical Physiopathology, Policlinico Umberto I, University of Rome La Sapienza, Rome, Italy
    Cancer Res 65:1897-903. 2005
    ..No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy...
  60. ncbi Synthesis and cytotoxic evaluation of novel spirohydantoin derivatives of the dihydrothieno[2,3-b]naphtho-4,9-dione system
    Isabel Gomez-Monterrey
    Dipartimento di Chimica Farmaceutica e Tossicologica, University of Naples Federico II, Napoli, Italy
    J Med Chem 48:1152-7. 2005
    ....
  61. ncbi Undersulfated, low-molecular-weight glycol-split heparin as an antiangiogenic VEGF antagonist
    Claudio Pisano
    Sigma Tau Research Department, 0040 Pomezia, Rome, Italy
    Glycobiology 15:1C-6C. 2005
    ..Undersulfated, LMW glycol-split heparins may therefore provide the basis for the design of novel nonanticoagulant angiostatic compounds...
  62. ncbi Modulation of the heparanase-inhibiting activity of heparin through selective desulfation, graded N-acetylation, and glycol splitting
    Annamaria Naggi
    G Ronzoni Institute for Chemical and Biochemical Research, Via G Colombo, 81, 20133 Milan, Italy
    J Biol Chem 280:12103-13. 2005
    ....
  63. ncbi Antiangiogenic effects of the novel camptothecin ST1481 (gimatecan) in human tumor xenografts
    Giovanna Petrangolini
    Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
    Mol Cancer Res 1:863-70. 2003
    ..In conclusion, the available results support the possibility that the antiangiogenic properties of ST1481 contribute to its antitumor potential and that this effect might be enhanced by the continuous low-dose treatment...
  64. ncbi Biological and molecular properties of a new alpha(v)beta3/alpha(v)beta5 integrin antagonist
    Laura Belvisi
    Organic and Industrial Chemistry Department, Centre for Biomolecular Interdisciplinary Studies and Industrial Applications, University of Milan, Italy
    Mol Cancer Ther 4:1670-80. 2005
    ..Taken together, these observations indicate that ST1646 represents a dual alpha(v)beta3/alpha(v)beta5 integrin antagonist with interesting biochemical and biological features to be tested in cancer therapy...
  65. ncbi Novel camptothecin analogue (gimatecan)-containing liposomes prepared by the ethanol injection method
    Pasquale Stano
    Institute of Polymers, ETH Zentrum, Universitatstrasse 6, Zurich, Switzerland
    J Liposome Res 14:87-109. 2004
    ..05). Finally, our study showed that the liposomal formulation was able to realize a delivery system of a water-insoluble drug, providing a Gimatecan formulation for intravenous administration with a preserved antitumoral activity...
  66. ncbi Cellular bases of the antitumor activity of a 7-substituted camptothecin in hormone-refractory human prostate carcinoma models
    Valentina Zuco
    Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy
    Biochem Pharmacol 65:1281-94. 2003
    ..A role of cell cycle checkpoints activated by DNA damage in cell response is supported by the modulation of transcriptional profile...
  67. pmc Development of resistance to the atypical retinoid, ST1926, in the lung carcinoma cell line H460 is associated with reduced formation of DNA strand breaks and a defective DNA damage response
    Valentina Zuco
    Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan 20133, Italy
    Neoplasia 7:667-77. 2005
    ..The defective DNA damage response, accompanied by a reduced susceptibility to apoptosis in resistant cells, provides further support to the involvement of genotoxic stress as a critical event in mediating apoptosis induction by ST1926...
  68. ncbi Bis-indols: a novel class of molecules enhancing the cytodifferentiating properties of retinoids in myeloid leukemia cells
    Claudio Pisano
    Istituto di Ricerche Farmacologiche Mario Negri, Laboratory of Molecular Biology, Centro Catullo e Daniela Borgomainerio, Milano, Italy
    Blood 100:3719-30. 2002
    ..This demonstrates an important role for the mitogen-activated protein kinase in the molecular mechanisms underlying the pharmacologic activity of the bis-indol...
  69. ncbi Pattern of antitumor activity of a novel camptothecin, ST1481, in a large panel of human tumor xenografts
    Graziella Pratesi
    Istituto Nazionale Tumori, 20133 Milan, Italy
    Clin Cancer Res 8:3904-9. 2002
    ..Based on its therapeutic efficacy in a human non-small cell lung carcinoma model and its favorable pharmacological profile, the novel analogue was selected for further preclinical development...
  70. doi Synthesis and biological activity of fluorinated combretastatin analogues
    Domenico Alloatti
    R and D, Sigma Tau Industrie Farmaceutiche Riunite S p A, Via Pontina Km 30 400, 00040 Pomezia, Italy
    J Med Chem 51:2708-21. 2008
    ..The position of a fluorine atom on the double bond may affect the inhibition of tubulin polymerization and cytotoxic activity of these compounds...
  71. ncbi ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis
    Enrico Garattini
    Laboratory of Molecular Biology, Centro Catullo e Daniela Borgomainerio, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
    Blood 103:194-207. 2004
    ....
  72. ncbi Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamm
    Edoardo Parrella
    Institut de Genetique et Biologie Moleculaire, Illkirch, France
    Mol Pharmacol 70:909-24. 2006
    ....
  73. ncbi Undersulfated and glycol-split heparins endowed with antiangiogenic activity
    Benito Casu
    G Ronzoni Institute for Chemical and Biochemical Research, 20133 Milan, Italy
    J Med Chem 47:838-48. 2004
    ....