In vitro evaluation of dual agonists for PPARγ/ß from the flower of Edgeworthia gardneri (wall.) Meisn.

ETHNOPHARMACOLOGICAL RELEVANCE: In Tibet, the flower of Edgeworthia gardneri (Wall.) Meisn., locally named "Lvluohua, [symbols: see text]", has been traditionally used to treat diabetes mellitus for many years. AIM OF THIS STUDY: To evaluate the activity of dual agonists for PPARγ/ß from the flower of E.gardneri in vitro. MATERIALS AND METHODS: HeLa cells were transiently co-transfected with the re-constructed plasmids of pBIND-PPARγ-LBD or pBIND-PPARß-LBD and rL4.35. The activities of crude extracts, secondary fractions and compounds from the flower of E.gardneri were evaluated with the transfected cells. Rosiglitazone (at 0.5 µg/mL) and L-165041 (at 0.5 µg/mL) were used as the positive controls for PPARγ and PPARß respectively. RESULTS: The results demonstrated that n-hexane, ethyl acetate and n-butanol extracts from the flower of E.gardneri were able to significantly activate PPARγ and PPARß respectively, and the activity of ethyl acetate extract was much better. We further observed that, among the 11 secondary fractions of ethyl acetate extract, the fr. 9 could activate PPARγ and PPARß significantly. Moreover, umbelliferone (from fr.9) and pentadecanoic acid could activate PPARγ and PPARß at the same time. CONCLUSIONS: The extracts from the flower of E.gardneri could significantly activate PPARγ and PPARß. Besides, umbelliferone and pentadecanoic acid isolated from the flower of E.gardneri were the new agonists for PPARγ and PPARß.

Clinical experience with radio-, chemo- and hyperthermotherapy combined trimodality on locally advanced esophageal cancer.

Esophageal cancer is a highly malignant and lethal disease with a low 5-year survival rate. Therefore, an effective treatment modality is required. To investigate the treatment efficacy and toxicity of radio-, chemo- and hyper-thermotherapy combined trimodality on locally advanced esophageal cancer, the medical records of 78 patients with pathologically confirmed esophageal cancer treated with chemoradiotherapy plus hyperthemia at our institution were retrospectively investigated and the 3-year outcome was carefully assessed. All 78 patients received intensity-modulated radiation therapy at a total dose of 60-66 Gy, in a conventional schedule of 1.8-2.1 Gy/fraction, 5 fractions/week. They also received 4-6 courses of chemotherapy, consisting of 450 mg/m2 5-fluorouracil for 1-5 days and 25 mg/m2 cisplatin for 1-5 days, in addition to 6-12 sessions of hyperthermia, performed twice a week. Out of the 78 cases, complete remission of the primary tumor was observed in 31 (39.7%), partial remission in 44 (56.4%) and no change in 3 (3.9%) cases. The treatment response rate was 96.1%. The overall survival (OS) rate at 1, 2 and 3 years was 67.9, 41.0 and 33.3%, respectively. No significant difference in adverse effects was observed between this treatment regimen and other similar studies. Our preliminary results demonstrated that the chemo-, radio- and hyperthermotherapy combined trimodality exhibited excellent short-term clinical outcomes as regards tumor response rate and a sound long-term OS, with endurable adverse events. This trimodal treatment requires further investigation to establish its beneficial role in the treatment of patients with locally advanced esophageal cancer.