Rosanna Cozzolino

University of Naples Federico II

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Paolo Laccetti

University of Naples Federico II

Patrizia Riccio

University of Naples Federico II

Maddalena Autiero

University of Naples Federico II

Claudia De Lorenzo

University of Naples Federico II

Luigi Celentano

University of Naples Federico II

Paolo Russo

University of Naples Federico II

Giuseppe D’Alessio

Université Libre de Bruxelles

Giovanni Mettivier

University of Naples Federico II

M.C. Montesi

Istituto Nazionale di Fisica Nucleare

Giuseppe Roberti

University of Naples Federico II

Cooperative Institutions

University of Naples Federico II

Federico II University Hospital

Istituto Nazionale di Fisica Nucleare, Sezione di Napoli

Institute for Experimental Endocrinology and Oncology

Institute of Biostructure and Bioimaging

National Research Council

Istituto Nazionale di Fisica Nucleare

Sapienza University of Rome

Istituto di Chimica Biomolecolare

Ceinge Biotecnologie Avanzate (Italy)

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Meccanismi d'azione di nuovi potenziali farmaci ad attività antitumorale, utilizzando sistemi in vitro ed in vivo

Rosanna Cozzolino

10.6092/unina/fedoa/1338

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A metabolically stable analogue of anandamide, Met-F-AEA, inhibits human thyroid carcinoma cell lines by activation of apoptosis

Investigational New Drugs (2009)

Rosanna Cozzolino Gaetano Calı̀Maurizio Bifulco Paolo Laccetti

Anandamide

Carcinoma Cell

10.1007/s10637-009-9221-0

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Citations (21)

Anti-ErbB2 Human Immunoagents

Claudia De Lorenzo Fulvia Troise Gennaro Riccio M. Borriello Valeria Cafaro

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Early detection of tumor masses by in vivo hematoporphyrin-mediated fluorescence imaging

Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment (2006)

Maddalena Autiero Luigi Celentano Rosanna Cozzolino Paolo Laccetti Marcello Marotta

Hematoporphyrin

Fluorescence-lifetime imaging microscopy

10.1016/j.nima.2006.10.117

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Hematoporphyrin mediated laser induced fluorescence in vivo imaging of tumor and organs structure in small animals

IEEE Symposium Conference Record Nuclear Science 2004. (2005)

Maddalena Autiero Luigi Celentano Rosanna Cozzolino Paolo Laccetti Maria Marotta

Recently we presented a prototype for fluorescence and radionuclide planar imaging system in small animals and its use in the analysis of solid surface tumors was assessed. The optical part is based on the detection of the red fluorescence radiation emitted by a hematoporphyrin (HP) compound injected systemically in the mice and accumulated in tumors, under green light illumination of the mouse body. Here we report on the improvement we made on the optical system, by using a high-sensitivity cooled CCD camera and optical magnification via a stereomicroscope. Our in vivo fluorescence measurements on tumor-bearing mice show that the use of the more sensitive, low noise, high resolution CCD camera not only allows for the detection of tumors and tissues where HP accumulates but also the investigation of their structure.

Hematoporphyrin

Fluorescence-lifetime imaging microscopy

Autofluorescence

10.1109/nssmic.2004.1466694

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Influence of conformational flexibility on biological activity in cyclic astin analogues

Biopolymers (2004)

Gabriella Saviano Ettore Benedetti Rosanna Cozzolino Antonia De Capua Paolo Laccetti

Abstract The astins, a family of natural antitumor cyclopeptides, from the roots of Aster tataricus, consist of a 16‐membered ring system containing uncoded amino acid residues. The backbone conformation, with a cis‐3,4‐dichlorinated proline residue, plays an important role in antineoplastic activity. The acyclic astins, on the other hand, do not show antitumor activity, suggesting that the cyclic nature of astins may be a key role in their biological properties. Although the antineoplastic activity of natural astins has been screened in vitro and in vivo, the mechanism of action has never been investigated. With the aim at elucidating the influence of conformational flexibility on biological activity, we have designed and synthesized several astin analogues containing either Aib and the nonproteinogenic Abu and (S)β 3 hPhe residues, able to modify the peptide backbone structure, or the peptide bond surrogate SO 2 NH. Tested for their antitumor effect, our astin‐related cyclopeptides are able to inhibit the growth of tumor cell lines, while the acyclic astins are inefficacious. The present work reports on the structure–activity study of a selected synthetic cyclotetrapeptide corresponding to the sequence c[ThrAib(S)β 3 hPheΨ(CH 2 SO 2 NH)Abu], synthesized by classical methods and characterized conformationally by two‐dimensional NMR and molecular dynamics analyses. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004

Cyclic peptide

Residue (chemistry)

10.1002/bip.20145

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Two novel human anti-ErbB2 immunoagents are active on trastuzumab-resistant tumours

British Journal of Cancer (2010)

Teresa Gelardi V. Damiano Roberta Rosa Roberto Bianco Rosanna Cozzolino

Overexpression of ErbB2 receptor in breast cancer is associated with disease progression and poor prognosis. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer, has proven to be effective; however, a relevant problem for clinical practice is that a high fraction of breast cancer patients shows primary or acquired resistance to trastuzumab treatment. We tested on trastuzumab-resistant cells two novel human anti-tumour immunoconjugates engineered in our laboratory by fusion of a human anti-ErbB2 scFv, termed Erbicin, with either a human RNase or the Fc region of a human IgG1. Both Erbicin-derived immunoagents (EDIAs) are selectively cytotoxic for ErbB2-positive cancer cells in vitro and vivo, target an ErbB2 epitope different from that recognised by trastuzumab and do not show cardiotoxic effects. We report that EDIAs are active also on trastuzumab-resistant tumour cells both in vitro and in vivo, most likely because of the different epitope recognised, as EDIAs, unlike trastuzumab, were found to be able to inhibit the signalling pathway downstream of ErbB2. These results suggest that EDIAs are immunoagents that could not only fulfil the therapeutic need of patients ineligible to trastuzumab treatment due to cardiac dysfunction but also prove to be useful for breast cancer patients unresponsive to trastuzumab treatment.

10.1038/sj.bjc.6605499

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Citations (35)

Synthetic astin analogues kill cell by an apoptotic mechanism

Rosanna Cozzolino Pasquale Palladino A Capua Gabriella Saviano Francesco Rossi

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In VivoTumor Detection in Small Animals by Hematoporphyrin-Mediated Fluorescence Imaging

Photomedicine and Laser Surgery (2010)

Maddalena Autiero Rosanna Cozzolino Paolo Laccetti Marcello Marotta Maria Quarto

Noninvasive in vivo imaging of human tumors implanted in mice provides a reliable and economic tool for the investigation of tumor progression and metastasis and of the effectiveness of the antiblastic drugs on them. The purpose of this study is to report on the performance achievable by the well-known and extensively investigated HP-FRI (HematoPorphyrin (HP)-mediated Fluorescence Reflectance Imaging) when a high-quality image-acquisition device is used.Previous articles of ours showed that HP-FRI still represents a useful, simple and reliable optical imaging technique to detect surface tumors. Therefore, it is particularly suitable to be used in combination with other imaging modalities in a multimodal imaging system endowed with diagnostic capabilities much better than each separate modality.Six-week-old Crl:CD-1 nude mice were subcutaneously inoculated with tumor cells. Tumor-bearing mice were irradiated in vivo by a frequency-doubled pulsed Nd:YAG laser (lambda = 532 nm). A cooled CCD digital camera recorded fluorescence light emitted by HP injected in mice through a cut-on long-wavelength pass filter.The system we developed allows in vivo imaging of surface tumors on small animals with a large field of view, high photometric sensitivity, adequate space resolution, and short measurement time. The estimated spatial resolution is 730 microm for a fluorescence source placed about 0.5 mm under the mouse skin. The first exploration of the capabilities of this HP-FRI setup on few mice shows that it allows the detection of (a) both types of investigated tumors, (b) early stage and late stage but visually unrecognizable tumors, (c) the gross structure of tumors, and (d) the discrimination of necrotic and nonnecrotic tumor regions.

Hematoporphyrin

Fluorescence-lifetime imaging microscopy

Molecular Imaging

10.1089/pho.2009.2567

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Citations (4)

A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent

British Journal of Cancer (2004)

Claudia De Lorenzo Annarita Tedesco Giuseppe Terrazzano Rosanna Cozzolino Paolo Laccetti

A new human, compact antibody was engineered by fusion of a human, antitumour ErbB2-directed scFv with a human IgG1 Fc domain. Overexpression of the ErbB2 receptor is related to tumour aggressiveness and poor prognosis. This new immunoagent meets all criteria for a potential anticancer drug: it is human, hence poorly or not immunogenic; it binds selectively and with high affinity to target cells, on which it exerts an effective and selective antiproliferative action, including both antibody-dependent and complement-dependent cytotoxicity; it effectively inhibits tumour growth in vivo. Its compact molecular size should provide for an efficient tissue penetration, yet suitable to a prolonged serum half-life.

10.1038/sj.bjc.6602110

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Citations (46)