The important roles of RET, VEGFR2 and the RAF/MEK/ERK pathway in cancer treatment with sorafenib.

AIM: To elucidate the roles of receptor tyrosine kinases RET and VEGFR2 and the RAF/MEK/ERK signaling cascade in cancer treatment with sorafenib. METHODS: The cell lines A549, HeLa, and HepG2 were tested. The enzyme activity was examined under cell-free conditions using 384-well microplate assays. Cell proliferation was evaluated using the Invitrogen Alarmar Blue assay. Gene expression was analyzed using the Invitrogen SYBR Green expression assays with a sequence detection system. Protein expression analysis was performed using Western blotting. RESULTS: Sorafenib potently suppressed the activities of cRAF, VEGFR2, and RET with IC(50) values of 20.9, 4 and 0.4 nmol/L, respectively. Sorafenib inhibited cRAF, VEGFR2, and RET via non-ATP-competitive, ATP-competitive and mixed-type modes, respectively. In contrast, sorafenib exerted only moderate cytotoxic effects on the proliferation of the 3 cell lines. The IC(50) values for inhibition of A549, HeLa, and HepG2 cells were 8572, 4163, and 8338 nmol/L, respectively. In the 3 cell lines, sorafenib suppressed the cell proliferation mainly by blocking the MEK/ERK downstream pathway at the posttranscriptional level, which in turn regulated related gene expression via a feed-back mechanism. CONCLUSION: This study provides novel evidence that protein kinases RET and VEGFR2 play crucial roles in cancer treatment with sorafenib.

[Assessment of therapeutic efficacy on treating advanced non-small cell lung cancer in the aged by Chinese medicine adopting the international questionnaire of quality of life].

OBJECTIVE: To assess the therapeutic efficacy of treating advanced non-small cell lung cancer (NSCLC) in the aged by Chinese medicine (CM) adopting the international questionnaire of quality of life (QOL). METHODS: 91 aged patients with advanced NSCLC were randomly assigned to three groups. There were 31 in the CM group (Group I), 30 in the chemotherapy group (Group II), and 30 in the CM and chemotherapy combination group (Group III). Oral administration of CM decoction and intravenous dripping of Chinese patent medicine was given to those in Group I. Patients in Group II received chemotherapeutic protocol alone. Patients in Group III received chemotherapeutic protocol while orally taking CM decoction. Twenty-eight days were taken as one therapeutic course, and two courses in total. Assessment was performed using European Organization for Research and Treatment of Lung Cancer Quality of Life Questionnaire LC-43 (EORTC QLQ-LC43) before treatment, the 10th day of the second therapeutic course, and the 28th day of the second therapeutic course, respectively. RESULTS: After two therapeutic courses of treatment, compared with Group II, better effects were obtained in Group I and Group III in the aspects of the physical function, roles function, emotional functions, social functions, general health state, and short breath, cough, fatigue, insomnia, poor appetite, and constipation (P<0.05, P<0.01). CONCLUSIONS: CM therapy could relieve the clinical symptoms of aged patients with advanced NSCLC and improve their QOL.

[Evaluation on effect of feiji recipe on quality of life of patients with non-small cell lung cancer by adopting international questionnaire of QOL].

OBJECTIVE: To evaluate the effect of Feiji Recipe (FJR) on quality of life (QOL) of patients with non-small cell lung cancer (NSCLC). METHODS: One hundred and two patients with NSCLC were randomly assigned into 2 groups. The 61 patients in the combined treated group were given FJR and chemotherapy and the 41 patients in the control group were treated with chemotherapy alone. They were observed for two treatment courses with QOL estimated by EORTC QLQ-C43 questionnaire and FACT-L questionnaire, the two international questionnaires as the tools for measurement, and referred to the traditional evaluating indexes of clinical efficiency. RESULTS: QOL in the combined treated group was improved after treatment with the improvement of scores in all domains, including functional and symptom sub-domain, while it in the control group deprived significantly, showing significant difference between the two groups (P < 0.05). Similar results were also shown in the evaluation of physical performance by Eastern Cooperative Oncology Group (ECOG) and Karnovfsky performance scoring. The gastrointestinal reaction and myelo-suppression were slighter in the combined treated group than those in the control group (P < 0.05), and no significant difference was shown between the response rate of the two groups (P > 0.05). CONCLUSION: FJR can improve QOL of patients with NSCLC, reduce the adverse reaction of chemotherapy, and improve patients' physical performance.