T. Lillehammer, B. Engesaeter, L. Prasmickaite, G. Maelandsmo, O. Fodstad, O. Engebraaten
{"title":"Combined treatment with Ad-hTRAIL and DTIC or SAHA is associated with increased mitochondrial-mediated apoptosis in human melanoma cell lines.","authors":"T. Lillehammer, B. Engesaeter, L. Prasmickaite, G. Maelandsmo, O. Fodstad, O. Engebraaten","doi":"10.1097/00008390-200609001-00010","DOIUrl":"https://doi.org/10.1097/00008390-200609001-00010","url":null,"abstract":"BACKGROUND\u0000Currently, dacarbazine (DTIC) is the only approved systemic treatment for metastatic malignant melanoma. However, the modest treatment effect encourages studies on novel therapeutic molecules, delivery systems and combination therapies. Full-length TRAIL, delivered from an adenoviral vector (Ad-hTRAIL), was studied in combination with DTIC or the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in human melanoma cell lines.\u0000\u0000\u0000METHODS\u0000The cytotoxic potential of the combination treatments was assessed by cell viability measurements and CalcuSyn analysis. Involvement of apoptosis was analyzed by TUNEL staining, mitochondrial membrane potential measurements, and activation and expression levels of caspases and other mediators of apoptosis.\u0000\u0000\u0000RESULTS\u0000Ad-hTRAIL in combination with DTIC or SAHA resulted in additive or synergistic growth inhibition compared to each treatment used as single agent. Both combinations augmented apoptosis, which was mediated through the death receptor (DR) pathway by enhanced activation of caspase-8, and through increased loss of mitochondrial integrity. Provoked cleavage of Bid, which bridges the extrinsic and intrinsic apoptosis pathways, and downregulation of the anti-apoptotic mediators Bcl-X(L), Mcl-1 and XIAP (but not Bcl-2) were critical contributing factors. Increased levels of DR4 and DR5 were not a common underlying mechanism as DTIC did not affect the levels of either of the receptors. However, SAHA-induced expression of DR4 may have reduced the TRAIL resistance in the SKMEL-28 cell line.\u0000\u0000\u0000CONCLUSION\u0000Administration of Ad-hTRAIL in combination with DTIC or SAHA enhances apoptosis in human melanoma cell lines, and suggests that the therapeutic potential of such treatment strategies should be further evaluated for possible clinical use.","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"67 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2006-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130019674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Jakob, C. Mühle, Jung Park, Susi Weiss, S. Waddington, H. Schneider
{"title":"No evidence for germ-line transmission following prenatal and early postnatal AAV-mediated gene delivery.","authors":"M. Jakob, C. Mühle, Jung Park, Susi Weiss, S. Waddington, H. Schneider","doi":"10.1055/S-2006-946205","DOIUrl":"https://doi.org/10.1055/S-2006-946205","url":null,"abstract":"BACKGROUND\u0000Recombinant adeno-associated viruses have been used successfully in a number of pre-clinical and clinical gene therapy studies. Since there is a broad consensus that gene therapy must not lead to germ-line transmission, the potential of such vectors for inadvertent gene transfer into germ cells deserves special attention. This applies in particular to pre- or perinatal vector application which has been considered for diseases presenting with morbidity already at birth.\u0000\u0000\u0000METHODS\u0000AAV serotype 2 derived vectors carrying a beta-galactosidase reporter gene or human clotting factor IX cDNA were injected intraperitoneally or via a yolk sac vein into mouse fetuses or administered intravascularly to newborn mice. Tissue samples of the treated animals including the gonads as well as sperm DNA, obtained by differential lysis of one testis of each male animal, and the offspring of all treated mice were investigated for the presence of vector DNA by nested PCR. In positive samples, the copy number of the vector was determined by quantitative real-time PCR.\u0000\u0000\u0000RESULTS\u0000AAV vectors administered intraperitoneally or intravascularly to fetal or newborn mice reached the gonads of these animals and persisted there for time periods greater than one year. Intravascular injection of the vector resulted more frequently in gene transfer to the gonads than intraperitoneal injection. Vector copy numbers in the gonads ranged from 0.3 to 74 per 10(4) cell equivalents. However, neither in isolated sperm DNA from the treated animals nor in their offspring were vector sequences detectable.\u0000\u0000\u0000CONCLUSIONS\u0000These data suggest the risk of inadvertent germ-line transmission following prenatal or early postnatal AAV type 2 mediated gene delivery to be very low.","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2006-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114517549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Oi, W. Davies, H. Tazelaar, K. Bailey, M. Federspiel, S. Russell, C. McGregor
{"title":"Ex vivo hypothermic recirculatory adenoviral gene transfer to the transplanted pig heart.","authors":"K. Oi, W. Davies, H. Tazelaar, K. Bailey, M. Federspiel, S. Russell, C. McGregor","doi":"10.1016/j.ymthe.2005.06.075","DOIUrl":"https://doi.org/10.1016/j.ymthe.2005.06.075","url":null,"abstract":"","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"78 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134059176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fanjam Andrianaivo, M. Lecocq, S. Wattiaux‐De Coninck, R. Wattiaux, M. Jadot
{"title":"Hydrodynamics-based transfection of the liver: entrance into hepatocytes of DNA that causes expression takes place very early after injection.","authors":"Fanjam Andrianaivo, M. Lecocq, S. Wattiaux‐De Coninck, R. Wattiaux, M. Jadot","doi":"10.1016/j.ymthe.2004.06.054","DOIUrl":"https://doi.org/10.1016/j.ymthe.2004.06.054","url":null,"abstract":"","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133079204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The DNA minor groove binding agents Hoechst 33258 and 33342 enhance recombinant adeno-associated virus (rAAV) transgene expression.","authors":"Lina Li, Linda Yang, R. Kotin","doi":"10.1016/j.ymthe.2004.06.755","DOIUrl":"https://doi.org/10.1016/j.ymthe.2004.06.755","url":null,"abstract":"","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"1642 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115836919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Ohana, P. Schachter, B. Ayesh, A. Mizrahi, T. Birman, T. Schneider, I. Matouk, S. Ayesh, P. Kuppen, N. de Groot, A. Czerniak, A. Hochberg
{"title":"Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat liver metastases.","authors":"P. Ohana, P. Schachter, B. Ayesh, A. Mizrahi, T. Birman, T. Schneider, I. Matouk, S. Ayesh, P. Kuppen, N. de Groot, A. Czerniak, A. Hochberg","doi":"10.1016/J.YMTHE.2004.06.218","DOIUrl":"https://doi.org/10.1016/J.YMTHE.2004.06.218","url":null,"abstract":"","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"81 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133067356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Protopopov, Jinfeng Li, G. Winberg, R. Gizatullin, V. Kashuba, G. Klein, E. Zabarovsky
{"title":"Human cell lines engineered for tetracycline‐regulated expression of tumor suppressor candidate genes from a frequently affected chromosomal region, 3p21","authors":"A. Protopopov, Jinfeng Li, G. Winberg, R. Gizatullin, V. Kashuba, G. Klein, E. Zabarovsky","doi":"10.1002/jgm.283","DOIUrl":"https://doi.org/10.1002/jgm.283","url":null,"abstract":"We modified a tetracycline‐regulated system that can control the activity of individual genes quantitatively and reversibly in transgenic mammals. Despite these advances, there remained one problem in the intensive use of the tet‐system: the limited range of acceptor cell lines, expressing a tetracycline‐controlled transcriptional activator (tTA). This study describes in detail new vectors and a unifying strategy to generate tTA‐expressing cell lines.","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"19 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117363297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Cunningham, Qing‐Hai Meng, N. Klein, R. McAnulty, S. Hart
{"title":"Evaluation of a porcine model for pulmonary gene transfer using a novel synthetic vector","authors":"S. Cunningham, Qing‐Hai Meng, N. Klein, R. McAnulty, S. Hart","doi":"10.1002/jgm.270","DOIUrl":"https://doi.org/10.1002/jgm.270","url":null,"abstract":"The pig lung, given its gross anatomical, histological and physiological similarities to the human lung, may be useful as a large animal model, in addition to rodents, in which to assess the potential of vectors for pulmonary airway gene transfer. The aim of this study was to assess the utility of the pig lung as a model of gene transfer to the human lung with a synthetic vector system.","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"119480552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Wetzel, P. Menten, Ghislain Opdenakker, J. V. Damme, H. Gröne, Nathalia A. Giese, Annunciata Vecchi, Silvano Sozzani, Jan J. Cornelis, Jean Rommelaere, C. Dinsart
{"title":"Transduction of human MCP‐3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts","authors":"K. Wetzel, P. Menten, Ghislain Opdenakker, J. V. Damme, H. Gröne, Nathalia A. Giese, Annunciata Vecchi, Silvano Sozzani, Jan J. Cornelis, Jean Rommelaere, C. Dinsart","doi":"10.1002/jgm.191","DOIUrl":"https://doi.org/10.1002/jgm.191","url":null,"abstract":"The oncosuppressive properties of some autonomous parvoviruses such as H‐1 virus, together with their low pathogenicity, make them attractive vectors for tumor‐directed gene therapy. Indeed, it was recently shown that these viruses became endowed with an enhanced oncosuppressive activity after they had been engineered to deliver a recognized therapeutic transgene. This prompted us to use a parvoviral vector to analyse the antineoplastic capacity of MCP‐3 (monocyte chemotactic protein‐3), a CC chemokine which has a broad spectrum of target cells, and can thus be considered to be a promising candidate for cancer treatment.","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120737820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Pakkanen, M. Laitinen, M. Hippeläinen, M. Hiltunen, E. Alhava, S. Ylä-Herttuala
{"title":"Periadventitial lacZ gene transfer to pig carotid arteries using a biodegradable collagen collar or a wrap of collagen sheet with adenoviruses and plasmid-liposome complexes.","authors":"T. Pakkanen, M. Laitinen, M. Hippeläinen, M. Hiltunen, E. Alhava, S. Ylä-Herttuala","doi":"10.1016/S0021-9150(00)80460-8","DOIUrl":"https://doi.org/10.1016/S0021-9150(00)80460-8","url":null,"abstract":"","PeriodicalId":328333,"journal":{"name":"The Journal of Gene Medicine","volume":"325 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133524193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}