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dc.contributor.authorMastini, Cristina
dc.contributor.authorBecker, Pablo D
dc.contributor.authorIezzi, Manuela
dc.contributor.authorCurcio, Claudia
dc.contributor.authorMusiani, Piero
dc.contributor.authorForni, Guido
dc.contributor.authorCavallo, Federica
dc.contributor.authorGuzmán, Carlos A
dc.date.accessioned2008-06-24T11:32:05Z
dc.date.available2008-06-24T11:32:05Z
dc.date.issued2008-05
dc.identifier.citationIntramammary application of non-methylated-CpG oligodeoxynucleotides (CpG) inhibits both local and systemic mammary carcinogenesis in female BALB/c Her-2/neu transgenic mice. 2008, 8 (3):230-42notCurr Cancer Drug Targetsen
dc.identifier.issn1873-5576
dc.identifier.pmid18473736
dc.identifier.urihttp://hdl.handle.net/10033/30393
dc.description.abstractCpG are powerful drugs activating the innate immune system. In this study, the ability of their intramammary administration in impeding the devastating progression of carcinogenesis in all the mammary glands of female BALB/c mice transgenic for the rat neu transforming oncogene was assessed. Starting when in situ carcinomas were scattered over all their mammary glands (week 10), mice received CpG injections in the stroma of the fourth left gland. Local neoplastic progression was inhibited by six monthly administrations. CpG not only delayed the onset of carcinomas in the injected gland, but also hampered their progression. Extended latency was observed for tumors in glands both close to and far from the injection site. When the experiment ended (week 45), no tumors were palpable in 67% of the injected glands and a markedly impaired tumor growth was evident in the others. An impressive local infiltrate of CD11b(+) cells with the morphologic features of macrophages, plasma cells, B220(+) B cells, and CD4(+) and CD8(+) T cells was quickly recruited to the CpG-treated glands. High quantities of IFN-gamma producing cells were only present in the ipsilateral axillary draining lymph nodes of the treated glands. Enhanced natural killer (NK) lytic activity was also detected in the spleens. Inhibition of progression was weaker when only four injections were given, and abolished by in vivo depletion of NK cells. CpG monotherapy is thus effective in an aggressive model of autochthonous cancer. The results strongly support the administration of CpG as a local monotherapy of multiple invasive microscopic lesions.
dc.language.isoenen
dc.subject.meshAdjuvants, Immunologicen
dc.subject.meshAnimalsen
dc.subject.meshAntineoplastic Agentsen
dc.subject.meshCell Line, Tumoren
dc.subject.meshCell Transformation, Neoplasticen
dc.subject.meshDNAen
dc.subject.meshDisease Progressionen
dc.subject.meshFemaleen
dc.subject.meshGlycoproteinsen
dc.subject.meshImmunity, Naturalen
dc.subject.meshInjectionsen
dc.subject.meshInterferon Type IIen
dc.subject.meshKiller Cells, Naturalen
dc.subject.meshLymph Nodesen
dc.subject.meshLymphocyte Depletionen
dc.subject.meshMammary Glands, Animalen
dc.subject.meshMammary Neoplasms, Experimentalen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMice, Transgenicen
dc.subject.meshNeoplasm Invasivenessen
dc.subject.meshRatsen
dc.subject.meshTime Factorsen
dc.titleIntramammary application of non-methylated-CpG oligodeoxynucleotides (CpG) inhibits both local and systemic mammary carcinogenesis in female BALB/c Her-2/neu transgenic mice.en
dc.typeArticleen
dc.contributor.departmentMolecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Torino, 10126 Torino, Italy.en
dc.identifier.journalCurrent cancer drug targetsen
refterms.dateFOA2009-05-05T00:00:00Z
html.description.abstractCpG are powerful drugs activating the innate immune system. In this study, the ability of their intramammary administration in impeding the devastating progression of carcinogenesis in all the mammary glands of female BALB/c mice transgenic for the rat neu transforming oncogene was assessed. Starting when in situ carcinomas were scattered over all their mammary glands (week 10), mice received CpG injections in the stroma of the fourth left gland. Local neoplastic progression was inhibited by six monthly administrations. CpG not only delayed the onset of carcinomas in the injected gland, but also hampered their progression. Extended latency was observed for tumors in glands both close to and far from the injection site. When the experiment ended (week 45), no tumors were palpable in 67% of the injected glands and a markedly impaired tumor growth was evident in the others. An impressive local infiltrate of CD11b(+) cells with the morphologic features of macrophages, plasma cells, B220(+) B cells, and CD4(+) and CD8(+) T cells was quickly recruited to the CpG-treated glands. High quantities of IFN-gamma producing cells were only present in the ipsilateral axillary draining lymph nodes of the treated glands. Enhanced natural killer (NK) lytic activity was also detected in the spleens. Inhibition of progression was weaker when only four injections were given, and abolished by in vivo depletion of NK cells. CpG monotherapy is thus effective in an aggressive model of autochthonous cancer. The results strongly support the administration of CpG as a local monotherapy of multiple invasive microscopic lesions.


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