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539. Clinical Study of Gendicine Therapy with Radio-Frequency-Hyperthermia; a Case Report
CANCER-TARGETED GENE & CELL THERAPY II 539. Clinical Study of Gendicine Therapy with Radio-Frequency-Hyperthermia; a Case Report
Hiromasa Kurosaki,1 Maiko Tobari,2 Mariko Kurosaki,1 Shinji Mori.1 1 Cancro Clinic, Tokyo, Japan; 2Shanghai Hospital of Civil Aviation, Shanghai, China.
(Introduction) Gendicine is a cancer therapeutic drug composed of recombinant adenovirus-p53 tumor-suppressor gene, and has already been shown to have a hyperthermia-sensitizing effect. (Case report) The patient was a 60-year-old woman who had received 6 courses of chemotherapy with paclitaxel and carboplatin following surgery for double cancer of the ovary and endometrium. Her CA19-9 level had been reduced from 2000 to 20 U/mL; however, it was gradually increased to 62 U/mL at 16 months after the surgery. PET-CT showed a swollen abdominal lymph node (13 mm × 10 mm), with a standardized uptake value (SUV) of 2.9.
Her CA19-9 level was also reduced from 62 to 33 U/mL. There were no adverse effects other than fever during the treatment period. As of one year after the end of Gendicine therapy, PET-CT showed no evidence of recurrence, and her CA19-9 level was stable (24 U/ml). As of two year after the end of Gendicine therapy, her CA19-9 level was high (50 U/ml) but PET-CT showed no evidence of recurrence. (Conclusion) Gendicine therapy combined with hyperthermia has the potential to treat advanced or refractory cancer.
540. Effects of siRNAs Targeting Endoglin in Human Microvascular Endothelial Cells In Vitro
The patient refused to receive second-line chemotherapy, and thus, after providing her informed consent, she was treated with Gendicine (6 vials for 6 weeks), followed by hyperthermia using radiofrequency 3 days after the start of Gendicine therapy. PET-CT, performed at 8 weeks after the end of Gendicine and thermmal therapy, showed the lymph node to be reduced to 10 mm × 7 mm, with a SUV of 2.1.
Molecular Therapy Volume 19, Supplement 1, May 2011 Copyright © The American Society of Gene & Cell Therapy
Tanja Dolinsek,1 Bostjan Markelc,1 Gregor Sersa,1 Simona Kranjc,1 Maja Cemazar.1 1 Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia. Endoglin is an accessory protein of the TGF-β receptor complex. It participates in activation of a signaling pathway, which results in cell proliferation and migration. The expression of endoglin is highly elevated in endothelial cells of blood vessels within and surrounding tumors. The aim of our study was to evaluate the effect of different siRNA molecules targeting endoglin on the expression level and on the survival and proliferation of human microvascular endothelial cell line HMEC-1 in vitro. First, we determined that HMEC-1 cells have high expression level of endoglin using qRT.PCR. Using lipofection, different siRNAs against endoglin were trasnfected into HMEC-1 cells. To determine the silencing effect of selected siRNAs, levels of mRNA were measured with qRT-PCR and cell survival and proliferation were measured with Alamar blue assay. Effect of siRNAs on endothelial cell tube formation was also determined. After transfection of cells with three designed siRNAs, mRNA of endoglin after transfection of selected siRNA was reduced up to 96%. This silencing effect was reflected in reduced cell proliferation that was measured for 6 days as well as cell survival. In addition, silencing of endoglin reduced ability of HMEC-1 cells to form the tubes in vitro. The obtained results demonstrate that choosing the right siRNA is a crucial step for effective silencing of endoglin that result in changed behavior of HMEC-1 cells.
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Hiromasa Kurosaki,1 Maiko Tobari,2 Mariko Kurosaki,1 Shinji Mori.1 1 Cancro Clinic, Tokyo, Japan; 2Shanghai Hospital of Civil Aviation, Shanghai, China.
(Introduction) Gendicine is a cancer therapeutic drug composed of recombinant adenovirus-p53 tumor-suppressor gene, and has already been shown to have a hyperthermia-sensitizing effect. (Case report) The patient was a 60-year-old woman who had received 6 courses of chemotherapy with paclitaxel and carboplatin following surgery for double cancer of the ovary and endometrium. Her CA19-9 level had been reduced from 2000 to 20 U/mL; however, it was gradually increased to 62 U/mL at 16 months after the surgery. PET-CT showed a swollen abdominal lymph node (13 mm × 10 mm), with a standardized uptake value (SUV) of 2.9.
Her CA19-9 level was also reduced from 62 to 33 U/mL. There were no adverse effects other than fever during the treatment period. As of one year after the end of Gendicine therapy, PET-CT showed no evidence of recurrence, and her CA19-9 level was stable (24 U/ml). As of two year after the end of Gendicine therapy, her CA19-9 level was high (50 U/ml) but PET-CT showed no evidence of recurrence. (Conclusion) Gendicine therapy combined with hyperthermia has the potential to treat advanced or refractory cancer.
540. Effects of siRNAs Targeting Endoglin in Human Microvascular Endothelial Cells In Vitro
The patient refused to receive second-line chemotherapy, and thus, after providing her informed consent, she was treated with Gendicine (6 vials for 6 weeks), followed by hyperthermia using radiofrequency 3 days after the start of Gendicine therapy. PET-CT, performed at 8 weeks after the end of Gendicine and thermmal therapy, showed the lymph node to be reduced to 10 mm × 7 mm, with a SUV of 2.1.
Molecular Therapy Volume 19, Supplement 1, May 2011 Copyright © The American Society of Gene & Cell Therapy
Tanja Dolinsek,1 Bostjan Markelc,1 Gregor Sersa,1 Simona Kranjc,1 Maja Cemazar.1 1 Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia. Endoglin is an accessory protein of the TGF-β receptor complex. It participates in activation of a signaling pathway, which results in cell proliferation and migration. The expression of endoglin is highly elevated in endothelial cells of blood vessels within and surrounding tumors. The aim of our study was to evaluate the effect of different siRNA molecules targeting endoglin on the expression level and on the survival and proliferation of human microvascular endothelial cell line HMEC-1 in vitro. First, we determined that HMEC-1 cells have high expression level of endoglin using qRT.PCR. Using lipofection, different siRNAs against endoglin were trasnfected into HMEC-1 cells. To determine the silencing effect of selected siRNAs, levels of mRNA were measured with qRT-PCR and cell survival and proliferation were measured with Alamar blue assay. Effect of siRNAs on endothelial cell tube formation was also determined. After transfection of cells with three designed siRNAs, mRNA of endoglin after transfection of selected siRNA was reduced up to 96%. This silencing effect was reflected in reduced cell proliferation that was measured for 6 days as well as cell survival. In addition, silencing of endoglin reduced ability of HMEC-1 cells to form the tubes in vitro. The obtained results demonstrate that choosing the right siRNA is a crucial step for effective silencing of endoglin that result in changed behavior of HMEC-1 cells.
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