RESUMEN
The purpose of this study was to investigate the effect of endotoxin presence in plasmid DNA preparations on the efficiency of transfection achieved in vivo with B16(F10) and Renca tumors and to determine transgene localization. Our data show that endotoxin markedly decreases the efficiency of transfection. Furthermore, the transgene transferred in vivo can be found in both neoplastic and normal (most likely myofibroblast) cells lying in proximity of the administration site.
Asunto(s)
Endotoxinas/farmacología , Neoplasias/genética , Plásmidos/administración & dosificación , Plásmidos/genética , Transfección/métodos , Transgenes/genética , Animales , Expresión Génica , Genes Reporteros/genética , Ratones , Neoplasias/patologíaRESUMEN
We investigated the feasibility of transferring naked plasmid DNA containing a therapeutic gene (IL-12) into mice harboring growing Renca tumors. We found that naked DNA transferred into growing Renca and B16(F10) tumors gives higher expression level of reporter gene than complexes of DNA with DDAB/DOPE or DC-Chol/DOPE. Transfer of naked DNA carrying the IL-12 gene into growing Renca tumors causes a distinct therapeutic effect that depends on the time span between inoculation of mice with cancer cells and the beginning of the therapy. Therapy started on day 3 resulted in total cure (100%) of mice.
Asunto(s)
Carcinoma de Células Renales/terapia , Terapia Genética/métodos , Interleucina-12/genética , Interleucina-12/uso terapéutico , Neoplasias Renales/terapia , Animales , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Genes Reporteros , Neoplasias Renales/genética , Neoplasias Renales/patología , Liposomas , Luciferasas/análisis , Luciferasas/genética , Melanoma Experimental , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Plásmidos , Transfección/métodos , Células Tumorales CultivadasRESUMEN
PURPOSE: There have been no studies to date which look at the relative effectiveness of different regimens of chemotherapy in women who have breast cancer and who carry a BRCA1 germ-line mutation. We wished to compare rates of response to neo-adjuvant chemotherapy in BRCA1 mutation carriers and non-carrier controls. EXPERIMENTAL DESIGN: From a registry of 3,479 patients, we identified 44 Polish women who carried a BRCA1 founder mutation and who had been treated with neo-adjuvant chemotherapy for breast cancer, and 41 age- and hospital-matched controls. RESULTS: 35 of the 44 BRCA1 mutation carriers (80%) experienced a partial or complete response to neo-adjuvant chemotherapy, compared to 39 of the 41 (95%) non-carriers (P=0.05). In the hereditary subgroup, response rates differed depending on whether or not a taxane (docetaxel) was given. Six of the 15 BRCA1 carrier women given docetaxel with doxorubicin responded (complete or partial), compared to 29 of 29 given other (DNA-damaging) therapies (P=0.001). Among the non-carriers, the rates of response to the two categories of chemotherapy were similar. CONCLUSIONS: Breast cancers among BRCA1 carriers frequently do not exhibit sensitivity to docetaxel in the neo-adjuvant setting. It is likely that normal BRCA1 is required for clinical response to mitotic spindle poisons.