RESUMEN
The effect of barley ß-glucan on soybean oil digestion characteristics before and after fermentation was studied in an in vitro-simulated gastrointestinal digestion model. The addition of barley ß-glucan made the system more unstable, the particle size increased significantly, and confocal laser imaging showed that it was easier to form agglomerates. The addition of barley ß-glucan increased the proportion of unsaturated fatty acids in digestion products, and reduced digestibility of soybean oil. In a co-culture model of Caco-2/HT29 and HepG2 cells, the effects of digestive products of soybean oil and barley ß-glucan before and after fermentation on lipid metabolism in HepG2 cells were investigated. The results showed that adding only soybean oil digestion products significantly increased triglycerides (TG) content and lipid accumulation in basolateral HepG2 cells. When fermented barley ß-glucan was added, lipid deposition was significantly decreased, and the lipid-lowering activity was better than that of unfermented barley ß-glucan.
Asunto(s)
Hordeum , Hipercolesterolemia , beta-Glucanos , Humanos , Aceite de Soja/metabolismo , Técnicas de Cocultivo , Células CACO-2 , beta-Glucanos/farmacología , DigestiónRESUMEN
OBJECTIVE: Gene therapy is a frontier in modern medicine. In the present study, we explored a new technique for the effective treatment of multidrug-resistant (MDR) breast cancer by combining fully the advantages of multidisciplinary fields, including image-guided minimally invasive interventional oncology, radiofrequency technology, and direct intratumoral gene therapy. RESULTS: Combination treatment with PHSP-TK plus RFH resulted in significantly higher TK gene transfection/expression, as well as a lower cell proliferation rate and a higher cell apoptosis index, than those of control groups. In vivo validation experiments with MRI confirmed that combination therapy resulted in a significant reduction of relative tumor volume compared with those of control animals, which was supported by the results of histologic and apoptosis analyses. MATERIALS AND METHODS: The heat shock protein promoter (PHSP) was used to precisely control the overexpression of thymidine kinase (TK) (PHSP-TK). Serial in vitro experiments were performed to confirm whether radiofrequency hyperthermia (RFH) could enhance PHSP-TK transfection and expression in a MDR breast cancer cell line (MCF7/Adr). Serial in vivo experiments were then carried out to validate the feasibility of the new technique, termed interventional RFH-enhanced direct intratumoral PHSP-TK gene therapy. The therapeutic effect of combination therapy was evaluated by MRI and confirmed by subsequent laboratory correlation. CONCLUSIONS: This study has established "proof-of-principle" of a new technique, interventional RFH-enhanced local gene therapy for MDR breast cancer, which may open new avenues for the effective management of MDR breast cancers via the simultaneous integration of interventional oncology, RF technology, and direct intratumoral gene therapy.
Asunto(s)
Neoplasias de la Mama , Terapia Genética/métodos , Hipertermia Inducida/métodos , Timidina Quinasa/genética , Transfección/métodos , Animales , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Genes Transgénicos Suicidas , Proteínas de Choque Térmico/genética , Humanos , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Regiones Promotoras Genéticas , Timidina Quinasa/administración & dosificación , Timidina Quinasa/biosíntesis , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Breast cancer is the most frequent malignancy in women worldwide. Although it is commonly treated via chemotherapy, responses vary among its subtypes, some of which are relatively insensitive to chemotherapeutic drugs. Recent studies have shown that hyperthermia can enhance the effects of chemotherapy in patients with refractory breast cancer or without surgical indications. Recent advances in molecular imaging may not only improve early diagnosis but may also facilitate the development and response assessment of targeted therapies. Combining advanced techniques such as molecular imaging and hyperthermia-integrated chemotherapy should open new avenues for effective management of breast cancer.