Publications
75 results found
McDonald RW, Bunjobpon W, Liu T, et al., 2001, Synthesis and anticancer activity of nordihydroguaiaretic acid (NDGA) and analogues, ANTI-CANCER DRUG DESIGN, Vol: 16, Pages: 261-270, ISSN: 0266-9536
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- Citations: 36
Pardo OE, Arcaro A, Salerno G, et al., 2001, Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells, ONCOGENE, Vol: 20, Pages: 7658-7667, ISSN: 0950-9232
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- Citations: 64
Pardo OE, Arcaro A, Salerno G, et al., 2001, Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells, Oncogene, Vol: 20, Pages: 7658-7667, ISSN: 0950-9232
Here, we show that fibroblast growth factor-2 (FGF-2) induces proliferation of H-510 and H-69 small cell lung cancer (SCLC) cells. However, the optimal response to FGF-2 was obtained at 10-fold lower concentrations in H-510 cells. This correlated with the selective activation of the mitogen-activated protein kinase kinase (MEK) pathway in H-510, but not H-69 cells. Moreover, inhibition of MEK with PD098059 blocked FGF-2-induced proliferation in H-510 cells only. Similarly, ribosomal protein S6 kinase 2 (S6K2), a recently identified homologue of S6K1 was activated by FGF-2 in H-510, but not H-69 cells. This activation was independent of phosphatidylinositol-3 kinase, but was sensitive to inhibition of the MEK pathway. These data suggest that S6K2 is a novel downstream target of MEK. The potency of FGF-2 in H-510 cells might reflect this additional MEK/S6K2 signalling. In contrast to S6K2, S6K1 was activated in both SCLC cell lines. Inhibition of the mammalian target of rapamycin with 10 ng/ml rapamycin blocked S6K1 activation and proliferation of both lines. However, even at 100 ng/ml, rapamycin only partially inhibited S6K2. Strikingly, this correlated with inhibition of MEK signalling. Our data indicate that S6K1, and possibly S6K2, are involved in FGF-2-induced SCLC cell growth, a notion supported by the overexpression and higher baseline activity of both isoforms in SCLC lines, as compared to normal human type-II pneumocytes.
Pardo OE, Salerno G, Raguz S, et al., 2001, FGF-2 mediates survival of small cell lung cancer cells (SCLC) through a MEK-dependent pathway: Correlation with the translational regulation of Bcl-2 family members, BRITISH JOURNAL OF CANCER, Vol: 85, Pages: 22-22, ISSN: 0007-0920
Lukacs KV, Pardo OE, Colston MJ, et al., 2000, Heat shock proteins in cancer therapy, CANCER GENE THERAPY, Vol: 465, Pages: 363-368, ISSN: 0065-2598
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- Citations: 9
Pardo O, Tomas A, Mazurier A, et al., 2000, Crystal structure of bis(μ-chloro)bis [N,<i>O</i>-1-isoquinolinecarboxylatodimethylformamidecopper(II)], C<sub>26</sub>H<sub>26</sub>Cl<sub>2</sub>Cu<sub>2</sub>N<sub>4</sub>O<sub>6</sub>, ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES, Vol: 215, Pages: 111-112, ISSN: 1433-7266
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- Citations: 3
Lukacs KV, Porter CD, Pardo OE, et al., 1999, In vivo transfer of bacterial marker genes results in differing levels of gene expression and tumor progression in immunocompetent and immunodeficient mice., Hum Gene Ther, Vol: 10, Pages: 2373-2379, ISSN: 1043-0342
To optimize gene delivery for the treatment of malignant mesothelioma, expression of the beta-galactosidase marker gene was examined in a murine model of intraperitoneal malignant mesothelioma. The beta-galactosidase gene was delivered to the peritoneal cavity of tumor-bearing mice by various plasmid-liposome complexes or by replication-incompetent retrovirus, used alone or complexed to liposomes. In tumor samples from immunodeficient nude mice, moderate levels of gene expression were achieved by liposome-complexed plasmids. Retroviral gene delivery was more effective, and was increased nearly 10-fold by complexing the retrovirus to liposomes. In contrast, in tumor samples from immunocompetent CBA mice treated with the same vectors, no marker gene expression was detected. In immunodeficient mice, tumor growth was not affected by beta-galactosidase gene transfer. However, immunocompetent mice showed a significant decrease in tumor size and increase in survival time after beta-galactosidase delivery. Induction of cytotoxic T cells capable of lysing beta-Gal-transfected tumor cells suggests that tumor cells transduced with the bacterial beta-galactosidase gene may be eliminated in immunocompetent hosts. Our findings also indicate that plasmid-liposome complexes, which achieve a low level of gene expression, and retrovirus-liposome complexes, which result in nearly 100 times higher levels of gene expression in tumor cells in vivo, are similarly effective in inducing an antitumor immune response.
Lukacs KV, Porter CD, Pardo OE, et al., 1999, <i>In vivo</i> transfer of bacterial marker genes results in differing levels of gene expression and tumor progression in immunocompetent and immunodeficient mice, HUMAN GENE THERAPY, Vol: 10, Pages: 2373-2379, ISSN: 1043-0342
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- Citations: 9
Pardo OE, Seckl MJ, 1999, Fibroblast growth factor 2 (FGF-2) potently stimulates early signalling events and growth of small cell lung cancer cells, BRITISH JOURNAL OF CANCER, Vol: 80, Pages: 87-87, ISSN: 0007-0920
Pardo O, Tomas A, Viossat B, et al., 1999, Crystal structure of bis[<i>N,O</i>-1-isoquinolinecarboxylato]copper(II), C<sub>20</sub>H<sub>12</sub>CuN<sub>2</sub>O<sub>4</sub>, ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES, Vol: 214, Pages: 61-62, ISSN: 1433-7266
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- Citations: 6
Lukacs KV, Steel RM, Oakley RE, et al., 1998, Towards a clinical trial of HSP65 gene therapy for malignant mesothelioma, Thorax, Vol: 53, ISSN: 0040-6376
We have previously reported the effectiveness of single and repeat application of the heat shock protein-65 gene in murine models of malignant mesothelioma (Thorax, 52 Supplement 6, A27. In preparation for a clinical trial we have now optimised a number of key parameters needed for liposome mediated gene transfer. Both in vitro and in vivo studies have been undertaken to assess the optimal cationic lipid to achieve gene transfer. In vitro studies did not predict in vivo efficacy in a murine model in which asbestos-induced malignant mesothelioma cells were injected into the peritoneal cavity of syngenic mice. In the latter model, the lipids DC-Cholesterol and Genzyme lipid#89 were particularly effective. After 4 intraperitoneal injections of DNA-liposome complexes, 93% of mice were alive after one year. Histological analysis showed the presence of tumour infiltrating lymphocytes one month after the last of four injections, and the absence of tumours in the majority of animals after one year. Mice surviving for one year were re-challenged with a tumour dose lethal for naive mice and showed protection, indicating long term memory had been induced by the treatment. These data provide further evidence for the efficacy of Hsp65 gene therapy for malignant mesothelima.
Pardo OE, Colston JM, Lukacs KV, 1998, Cancer gene therapy with a heat shock protein gene, Gene Therapy of Cancer, Editors: Walden, Trefzer, Sterry, Farzaneh, Pages: 217-223
Lukacs KV, Pardo O, Porter C, et al., 1996, In vivo transfer of the β -galactosidase gene into malignant mesothelioma cells induces tumour rejection, Thorax, Vol: 51, ISSN: 0040-6376
Malignant mesothelioma is an aggressive, fatal serosal tumour with no effective treatment. However, the potential accessibility of the tumour, localized to the pleural or peritoneal cavities, and the relative absence of metastases makes it a suitable candidate for gene therapy. In order to optimize the gene delivery system we used the β-galactosidase (β-gal) reporter gene delivered into a model of malignant mesothelioma. Mice were injected with 106 AC29 tumour cells (an asbestos-induced mesothelioma cell line) into the peritoneal cavity. Three days later the β-gal gene was delivered either by retrovirus, non-capsulated retrovirus or cationic liposome-complexed plasmid DNA. Mice were sacrificed 12 days later, tumour size determined and both histological and quantitative β-gal assays carried out to detect transduced cells in tumour samples, spleen, liver and peritoneum. Untreated controls (tumor size: 1.68±0.15g) or animals treated with the vehicle (liposome) only (1.61±0.11g), rapidly developed disseminated tumours in the peritoneum. Mice injected with the non-capsulated virus showed no protection against tumour growth (1.88±0.17g). However, mice injected with retrovirus (0.65±0.1g) or plasmid-liposome complexes (0.14±0.12g) showed a highly significant decrease (p<0.001) in the tumour size. These data are in keeping with in vitro studies in which AC29 cells can be transfected with both retroviral and plasmid liposome vectors but not with the non-capsulated virus. However, neither histological analysis nor a quantitative assay detected β-gal positive cells in the tumour samples of treated mice. These results indicate the elimination of both transduced and untransduced tumour cells after in vivo gene transfer of a foreign protein. They also suggest that the efficiency of in vivo gene transfer is not accurately accessed by using bacterial marker genes, in keeping with data emerging in other areas of gene the
Lukacs KV, Pardo OE, Steel RM, et al., Cancer gene therapy with a heat shock protein gene, CANCER GENE THERAPY, Vol: 4, Pages: 310-310, ISSN: 0929-1903
Lukacs KV, Steel RM, Oakley RE, et al., Cancer gene therapy with a heat shock protein gene, CANCER GENE THERAPY, Vol: 4, Pages: O133-O133, ISSN: 0929-1903
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