RESUMO
<p><b>OBJECTIVE</b>To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.</p><p><b>METHODS</b>A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed.</p><p><b>RESULTS</b>No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05).</p><p><b>CONCLUSION</b>Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.</p>
RESUMO
AIM: To investigate whether inactivation of extracellular signal-regulated kinase 1/2 ( Erk1/2 ) will affect the function of fibroblast growth factor 21 (FGF21) to regulate glucose and lipid metabolism .METHODS:Male db/db mice (8 weeks old) were treated with U0126 (an inhibitor of Erk1/2 kinase) for 1 week, and then treated with re-combinant human FGF21 protein and adenovirus-mediated FGF21 (Ad-FGF21).The profile changes of blood glucose and blood lipid were evaluated at 120 min or 4 weeks after FGF21 administration.Meanwhile, the molecular mechanism was ex-plored by in vitro study.RESULTS: Treatment of db/db mice with recombinant human FGF21 protein significantly re-duced blood glucose and triglyceride levels at 120 min after FGF21 administration , but these changes were comparable in U0126-treated mice .Furthermore , abnormal glucose and triglyceride levels , and glucose and insulin tolerance were strong-ly improved in db/db mice as accompanied with decreasing body fat content after 4 weeks of ad-FGF21 administration .In-terestingly, treatment with or without U0126 did not influence these effects of FGF21.Mechanically, treatment with Ad-FGF21 significantly upregulated the protein levels of p-Erk1/2 and peroxisome proliferator-activated receptor γ( PPARγ) as well as the expression of adiponectin at mRNA and protein levels in adipose tissues .However , treatment with or without U0126 did not change the profiles .On the other hand , in vitro experiments also indicated that treatment of adipocytes with recombinant human FGF 21 protein significantly activated Erk 1/2 phosphorylation , and upregulated the expression levels of PPARγand adiponectin (P<0.05).However, pre-administration of U0126 did not affect the profiles.CONCLUSION:Pharmaceutical inactivation of Erk 1/2 by U0216 does not affect the biological function of FGF 21 to regulate blood glucose balance and improve abnormal blood lipids in vivo.