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3 results on '"Valtorta, Silvia"'

1. Evaluation of the role of tumor-associated macrophages in an experimental model of peritoneal carcinomatosis using (18)F-FDG PET.

Author

Cottone L, Valtorta S, Capobianco A, Belloli S, Rovere-Querini P, Fazio F, Manfredi AA, and Moresco RM

Subjects
Animals, Biological Transport, Diffusion, Disease Models, Animal, Disease Progression, Female, Macrophages metabolism, Mice, Mice, Inbred BALB C, Peritoneal Neoplasms metabolism, Peritoneal Neoplasms pathology, Fluorodeoxyglucose F18 metabolism, Macrophages diagnostic imaging, Peritoneal Neoplasms diagnostic imaging, Peritoneal Neoplasms immunology, Positron-Emission Tomography
Abstract

Unlabelled: PET is widely used at the clinical and preclinical levels for tumor assessment and evaluation of treatment efficacy. Here, we established and took advantage of a preclinical model of peritoneal carcinomatosis to evaluate the contribution of inflammatory infiltrating macrophages in tumor progression that was followed using (18)F-FDG PET., Methods: Groups of mice with peritoneal carcinomatosis were longitudinally evaluated with (18)F-FDG PET. Intraperitoneal depletion of macrophages was achieved by an approach (i.e., administration of clodronate encapsulated into liposomes) that proved to be safe and effective. Sham liposomes were used in control animal cohorts., Results: (18)F-FDG PET allowed us to detect and monitor peritoneal lesion growth and diffusion. Macrophage-depleted animals showed a substantial reduction in tumor burden paralleled by a decrement in the extent of radioactivity distribution. A significant correlation between lesion dimension and metabolic volume was observed not only in macrophage-depleted but also in sham-treated mice., Conclusion: (18)F-FDG PET allowed a noninvasive detection of peritoneal carcinomatosis lesions. Although macrophages play a key role in the early growth and spreading of lesions in the peritoneal cavity, neoplastic cells apparently represent the major player in this system in the uptake of (18)F-FDG.

Published
2011
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3. Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis

Author

Cottone, Lucia, Capobianco, Annalisa, Gualteroni, Chiara, Monno, Antonella, Raccagni, Isabella, Valtorta, Silvia, Canu, Tamara, Di Tomaso, Tiziano, Lombardo, Angelo, Esposito, Antonio, Moresco, Rosa Maria, Del Maschio, Alessandro, Naldini, Luigi, Rovere-Querini, Patrizia, Bianchi, Marco E., Manfredi, Angelo A., Cottone, L, Capobianco, A, Gualteroni, C, Monno, A, Raccagni, I, Valtorta, S, Canu, T, Tomaso, T, Lombardo, A, Esposito, A, Moresco, R, Maschio, A, Naldini, L, Rovere Querini, P, Bianchi, M, Manfredi, A, De Tomaso, T, Lombardo, ANGELO LEONE, Esposito, Antonio, Moresco, Rm, DEL MASCHIO, Alessandro, Naldini, Luigi, ROVERE QUERINI, Patrizia, Bianchi, MARCO EMILIO, and Manfredi, ANGELO ANDREA M. A.

Subjects
0301 basic medicine, green fluorescent protein, Pathology, medicine.medical_specialty, Murine colon adenocarcinoma cell line, Phagocyte, Macrophage, Immunology, Damage-associated molecular pattern, chemical and pharmacologic phenomena, High Mobility Box 1, macrophage, HMGB1, GFP, BoxA, damage-associated molecular pattern, Small hairpin RNA, 03 medical and health sciences, 0302 clinical medicine, vascularization, In vivo, Leukocytes, medicine, Extracellular, DAMP, short hairpin RNA, Immunology and Allergy, MC-38, murine colon adenocarcinoma cell line, Original Research, Gene knockdown, peritoneal carcinomatosi, biology, business.industry, Macrophages, Tumor-Derived, Leukocyte, 030104 developmental biology, medicine.anatomical_structure, Alarmin, Oncology, 030220 oncology & carcinogenesis, biology.protein, ShRNA, business, leukocyte, Peritoneal carcinomatosis
Abstract

The factors that determine whether disseminated transformed cells in vivo yield neoplastic lesions have only been partially identified. We established an ad hoc model of peritoneal carcinomatosis by injecting colon carcinoma cells in mice. Tumor cells recruit inflammatory leukocytes, mostly macrophages, and generate neoplastic peritoneal lesions. Phagocyte depletion via clodronate treatment reduces neoplastic growth. Colon carcinoma cells release a prototypic damage-associated molecular pattern (DAMP)/alarmin, High Mobility Group Box1 (HMGB1), which attracts leukocytes. Exogenous HMGB1 accelerates leukocyte recruitment, macrophage infiltration, tumor growth and vascularization. Lentiviral-based HMGB1 knockdown or pharmacological interference with its extracellular impair macrophage recruitment and tumor growth. Our findings provide a preclinical proof of principle that strategies based on preventing HMGB1-driven recruitment of leukocytes could be used for treating peritoneal carcinomatosis.

Published
2016

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