المؤلفون: Sacco, M G, Soldati, S^{Aff1, Aff2}, Indraccolo, S, Cató, E Mira, Cattaneo, L^{Aff1, Aff4}, Scanziani, E, Vezzoni, P

المصدر: Gene Therapy. 10(22):1903-1909

المؤلفون: Sacco, M G, Soldati, S^{Aff1, Aff2}, Mira Cató, E, Cattaneo, L^{Aff1, Aff3}, Pratesi, G, Scanziani, E, Vezzoni, P

المصدر: Gene Therapy. 9(19):1338-1341

المؤلفون: Sacco, M G, Benedetti, S, Catò, E Mira, Caniatti, M, Ceruti, R, Scanziani, E, Pirola, B, Villa, A, Finocchiaro, G, Vezzoni, P

المصدر: Gene Therapy. 6(11):1893-1897

المؤلفون: Sacco, M G, Catò, E Mira, Ceruti, R, Soldati, S, Indraccolo, S, Caniatti, M, Scanziani, E, Vezzoni, P

المصدر: Gene Therapy; Jan2001, Vol. 8 Issue 1, p67, 4p

مصطلحات موضوعية: GENE therapy, BREAST cancer, METASTASIS

مستخلص: Tumor growth and metastasis are angiogenesis-dependent. The possibility of inhibiting tumor growth by interfering with the formation of new vessels has recently raised considerable interest. We previously reported that it is possible to inhibit primary tumor growth and metastasis in a transgenic model of spontaneous breast tumor, which shows many similarities to its human counterpart (including ability to metastasize) by intratumoral administration of a DNA construct carrying the murine angiostatin cDNA driven by liposomes. Here we report that it is also possible to achieve this goal by a systemic (intraperitoneal) delivery of therapeutic DNA constructs carrying genes coding for mouse and human anti-angiogenic factors which include angiostatin, endostatin and TIMP-2. These findings may be relevant to the design of therapeutic interventions in humans. [ABSTRACT FROM AUTHOR]

: Copyright of Gene Therapy is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Sacco, M G, Barbieri, O, Piccini, D, Noviello, E, Zoppé, M, Zucchi, I, Frattini, A, Villa, A, Vezzoni, P

المصدر: Gene Therapy; Mar1998, Vol. 5 Issue 3, p388, 6p

مصطلحات موضوعية: ADENOCARCINOMA, PLASMIDS, GENE transfection, TRANSGENIC mice, CELL lines

مستخلص: Oncogene-bearing transgenic mice develop various kinds of tumors depending on both the regulatory sequences and the specific oncogene used. These mice not only help to clarify the pathogenetic pathways leading to tumor formation, but can also be useful as models to test novel therapeutic strategies, including gene therapy. We have previously reported the establishment of an MMTV-neu (ErbB-2) transgenic mouse lineage, in which 100% of females develop breast tumors with many features similar to their human counterparts; these tumors are due to the overexpression of the activated rat neu oncogene in the mammary gland. From one such mouse we established a cell line of mammary adenocarcinoma named MG1361. We report here that the growth of this cell line can be inhibited in vitro and in vivo by transfection of a plasmid vector carrying an antisense anti-neu construct. This inhibitory effect is specific, as it is related to the expression of the antisense transgene (determined by RT-PCR), and to a reduction in neu mRNA and protein, as determined by Northern and Western blot analyses. Moreover, inoculation of cells carrying the antisense or the control vector in nude mice demonstrated that the morphological and biochemical effects elicited by the antisense construct resulted in a significantly slower rate of in vivo growth of tumor xenografts. Finally, significant mammary tumor growth inhibition was obtained after liposome-mediated direct inoculation of the same antisense vector in tumors spontaneously arising in MMTV-neu mice. Taken together, these findings suggest that targeting neu expression by an integrated large anti-neu antisense segment affects the in vivo growth of these tumors. [ABSTRACT FROM AUTHOR]

: Copyright of Gene Therapy is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Sacco MG; Istituto di Tecnologie Biomediche Avanzate, CNR, Milan, Italy., Benedetti S, Duflot-Dancer A, Mesnil M, Bagnasco L, Strina D, Fasolo V, Villa A, Macchi P, Faranda S, Vezzoni P, Finocchiaro G

المصدر: Gene therapy [Gene Ther] 1996 Dec; Vol. 3 (12), pp. 1151-6.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9421525 Publication Model: Print Cited Medium: Print ISSN: 0969-7128 (Print) Linking ISSN: 09697128 NLM ISO Abbreviation: Gene Ther Subsets: MEDLINE

مواضيع طبية MeSH: Gene Transfer Techniques* , Genetic Therapy*, Adenocarcinoma/*therapy , Antineoplastic Agents/*therapeutic use , Ganciclovir/*therapeutic use , Mammary Neoplasms, Experimental/*therapy , Mammary Tumor Virus, Mouse/*genetics , Thymidine Kinase/*genetics, Adenocarcinoma/drug therapy ; Animals ; Antineoplastic Agents/pharmacokinetics ; Cell Line/transplantation ; Female ; Ganciclovir/pharmacokinetics ; Genes, erbB-2 ; Genetic Vectors ; Humans ; Mammary Neoplasms, Experimental/drug therapy ; Mice ; Mice, Transgenic ; Rats ; Thymidine Kinase/metabolism ; Tumor Cells, Cultured

مستخلص: Mice transgenic for the activated rat neu oncogene under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) (neu+ mice), develop breast tumors in 100% of cases. We have previously reported that double transgenic mice obtained from crossing neu+ mice with mice transgenic for the herpes simplex virus thymidine kinase (HSVtk) gene can be used as a suitable model to test the 'suicide gene' strategy for mammary tumor gene therapy in vivo. In the present study, we evaluated the efficacy of the HSVtk/ganciclovir (GCV) system in the neu+ mice by inoculating cells producing a retroviral vector bearing the HSVtk gene in the mammary tumors on one side of the animals, and comparing their weight with that of the contralateral tumors, after systemic GCV administration. A statistically significant effect of this therapy was clearly seen (P < 0.001) but complete eradication of the tumors could not be achieved. This was not due to the inefficient delivery of GCV, as no HSVtk expression was detected in the residual tumors, but could be related to the low transduction efficiency (< 10%) and to inability of the 'bystander effect' (probably due to the absence of functional gap-junctions among mammary tumor cells) to kill nontransduced neoplastic cells. These data suggest that results obtained by in vivo models using transplanted tumor cell lines as targets for gene therapy might not be immediately transferable to spontaneously arising tumors in animals or humans.

المؤلفون: Sacco MG; Istituto di Tecnologie Biomediche Avanzate, CNR, Milano, Italy., Mangiarini L, Villa A, Macchi P, Barbieri O, Sacchi MC, Monteggia E, Fasolo V, Vezzoni P, Clerici L

المصدر: Gene therapy [Gene Ther] 1995 Sep; Vol. 2 (7), pp. 493-7.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9421525 Publication Model: Print Cited Medium: Print ISSN: 0969-7128 (Print) Linking ISSN: 09697128 NLM ISO Abbreviation: Gene Ther Subsets: MEDLINE

مواضيع طبية MeSH: Antiviral Agents/*therapeutic use , Ganciclovir/*therapeutic use , Genes, erbB-2/*genetics , Mammary Neoplasms, Experimental/*drug therapy , Simplexvirus/*genetics , Thymidine Kinase/*genetics, Animals ; Base Sequence ; Female ; Gene Expression ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/pathology ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Simplexvirus/enzymology

مستخلص: Females from a mouse lineage transgenic for the activated rat neu oncogene under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) all develop breast tumors with high reproducibility within the first 2-3 months of life. These animals were crossed with mice from a lineage transgenic for the herpes simplex virus thymidine kinase gene (HSVtk) under the control of its own promoter and polyoma enhancer. Double transgenic mice (for both neu and tk) developed breast neoplasias with the same kinetics as the neu-only mice. Tumor-bearing double transgenic mice, treated intratumorally with the antiviral agent ganciclovir (GCV), showed an inhibiting effect on tumor growth. However, this effect was not seen either on GCV-treated neu-only transgenic mice or on saline-injected controls. This suggests that tk-engineered breast tumors are susceptible to GCV administered locally, and implies that neu-mice could be a useful model for testing the effectiveness of HSVtk-bearing vectors followed by systemic GCV on breast cancer cells.