Preclinical Development of a Novel Class of CXCR4 Antagonist Impairing Solid Tumors Growth and Metastases
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Preclinical Development of a Novel Class of CXCR4 Antagonist Impairing Solid Tumors Growth and Metastases (770 views)

Portella L, Vitale R, De Luca S, D'Alterio C, Ieranò C, Napolitano M, Riccio A, Polimeno MN, Monfregola L, Barbieri A, Luciano A, Ciarmiello A, Arra C, Castello G, Amodeo P, Scala S

Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2013 Sep 13; 8(9): N/D-N/D.

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Paper type: Journal Article, Abstract, Conference

Impact factor: 3.534, 5-year impact factor: 4.015

Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84884132303&partnerID=40&md5=434f79a1b7515fbeacb8d1f6eba44719

Keywords: [cysteinyltryptophanylhistidylarginylcysteine], Arginylalanine [cysteinylarginyltyrosyltryptophanylcysteine], Arginylalanine[cysteinylarginylhistidyltryptophanylcysteine], Arginylalanine[cysteinylarginylphenylalanylphenylalanylcysteine], Chemokine Receptor Cxcr4, Cyclopeptide, Mitogen Activated Protein Kinase 1, Plerixafor, Unclassified Drug, Amino Acid Sequence, Animal Cell, Animal Experiment, Animal Model, Article, Calcium Transport, Cancer Cell, Cancer Inhibition, Cell Migration, Controlled Study, Drug Activity, Drug Design, Enzyme Induction, Female, Human, Human Cell, In Vitro Study, In Vivo Study, Kidney Cancer, Lung Metastasis, Melanoma B16, Melanoma Cell, Metastasis Inhibition, Mouse, Nonhuman, Osteosarcoma Cell, Receptor Binding, Tumor Xenograft, Wound Healing, Cell Line, Cell Movement, Cell Proliferation, Chemokine Cxcl12, Drug Screening Assays, Antitumor, Extracellular Signal-Regulated Map Kinases, Lung Neoplasms, Inbred Balb C, Inbred C57bl, Molecular Sequence Data, Phosphorylation, Protein Binding, Arginylalanine [cysteinylarginylhistidyltryptophanylcysteine], Arginylalanine [cysteinylarginylphenylalanylphenylalanylcysteine]

Affiliations:
*** IBB - CNR ***

Department of Oncological Immunology, ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI Fondazione Giovanni Pascale-IRCCS-ITALIA, Naples, Italy
Animal Facility, ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI Fondazione Giovanni Pascale-IRCCS-ITALIA, Naples, Italy
ICB-CNR, CNR, Pozzuoli, Italy
IBB-CNR, CNR, Naples, Italy
CROM, Mercogliano (AV), Italy
Azienda Sanitaria Locale n 5 Spezzino, La Spezia, Italy


References:
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Preclinical Development of a Novel Class of CXCR4 Antagonist Impairing Solid Tumors Growth and Metastases

The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X) in CXCL12, also found in the reverse orientation (X-Ar-Ar) in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells) and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.
Preclinical Development of a Novel Class of CXCR4 Antagonist Impairing Solid Tumors Growth and Metastases

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Preclinical Development of a Novel Class of CXCR4 Antagonist Impairing Solid Tumors Growth and Metastases

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Calce E, Vitale RM, Scaloni A, Amodeo P, De Luca S
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Vincenzi M, Costantini S, Scala S, Tesauro D, Accardo A, Leone M, Colonna G, Guillon J, Portella L, Trotta AM, Ronga L, Rossi F
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Neve Polimeno M, Ierano C, D'Alterio C, Simona Losito N, Napolitano M, Portella L, Scognamiglio G, Tatangelo F, Maria Trotta A, Curley S, Costantini S, Liuzzi R, Izzo F, Scala S
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Impact Factor: 4.112
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D'Alterio C, Avallone A, Tatangelo F, Delrio P, Pecori B, Cella L, Pelella A, D'Armiento FP, Carlomagno C, Bianco F, Silvestro L, Pacelli R, Napolitano M, Iaffaioli RV, Scala S
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Lusso P, Vangelista L, Cimbro R, Secchi M, Sironi F, Longhi R, Faiella M, Maglio O, Pavone V
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Napolitano M, Ottaiano A, Mauro F, Ieranò C, Satriano R, Pacelli R, Franco R, De Angelis V, Castello G, Scala S
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Impact Factor: 4.293
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Ierano C, Giuliano P, D'Alterio C, Cioffi M, Mettivier V, Portella L, Napolitano M, Barbieri A, Arra C, Liguori G, Franco R, Palmieri G, Rozzo C, Pacelli R, Castello G, Scala S
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Palladino P, Pedone C, Ragone R, Rossi F, Saviano M, Benedetti E
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13 Records (13 excluding Abstracts).
Total impact factor: 56.389 (56.389 excluding Abstracts).
Total 5 year impact factor: 50.003 (50.003 excluding Abstracts).

Last modified by Marco Comerci on Tuesday 09 April 2024, 12:56:55
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