Haishengsu as an adjunct therapy to conventional chemotherapy in patients with non-small cell lung cancer: a pilot randomized and placebo-controlled clinical trial.

OBJECTIVE: To investigate the effect of Haishengsu, an extract from Tegillarca granosa, on non-small cell lung cancer as an adjunct to conventional chemotherapy. DESIGNS/SETTINGS: Randomized, double-blind, placebo-controlled trial was conducted in 83 patients. The Haishengsu (n=42, 2.4mg Haishengsu in 250ml normal saline, iv, for 15 days) and the placebo group (n=41, 250ml normal saline, iv) were also treated with two cycles (28 days for each cycle) of conventional chemotherapy consisting mitomycin, vindesine and cisplatin. RESULTS: The curative effect of conventional chemotherapy was observed in 62% of Haishengsu group patients and in 39% in of the placebo group patients (P=0.04, RR 1.59, 95% CI: 1.01-2.49). Improvement in Karnofsky performance status scores was seen in 66.7% of Haishengsu group patients and in 17.1% of the placebo group patients (P<0.01, RR 3.63, 95%CI: 1.77-7.41). The ratio of patients with no or only mild gastrointestinal reaction in the Haishengsu and the placebo group was 83.3% and 39.0%, respectively (P<0.01, RR 2.13, 95% CI: 1.42-3.20). CONCLUSIONS: This study suggests that Haishengsu may be an effective adjunct therapy to the conventional chemotherapy for non-small cell lung cancer. The short-term therapeutic effect of chemotherapy may be improved and the chemotherapy-induced nausea or vomiting may be reduced by concurrent Haishengsu administration.

[Molecular design and biological activity of BCR-ABL tyrosine kinase inhibitors].

OBJECTIVE: To discover BCR-ABL tyrosine kinase inhibitors through structure based virtual screening. METHODS: Docking screening against the distinctive inactive conformation of the catalytic domain of BCR-ABL tyrosine kinase was performed on 3D database. The MTT assay was performed to assess the viability of the tumor cells treated with selected compounds. The amount and kinase activity of BCR-ABL protein were detected in the presence of compounds by Western blot analysis and immunoprecipitation. RESULTS: From the top 1,000 compounds with the best DOCK energy score, 15 compounds were selected for biological assay. Eight out of 15 compounds showed notable inhibitory activity against Ph+ human K562 cells with IC50 values ranging from 10 to 200 micromol/L. In cell-based assays of ABL tyrosine phosphorylation, the ability of two kinds of novel, structurally diverse, lead compounds to inhibit ABL kinase activity was observed. However, no significant differences in the amount of BCR-ABL protein were noted on the ABL immunoblot in the presence of these lead compounds. CONCLUSIONS: Two promising lead compounds were discovered to inhibit BCR-ABL tyrosine kinase activity. Virtual screening technique has been proven to narrow down the size of screening compound libraries to the most prospective drug candidates with high success rates.

[Preliminary studies on the mechanisms of a new anti-tumor agent PH II-7 with special preference to multidrug resistant tumor cells].

OBJECTIVE: To determine the anti-tumor activity of PH II-7 in vitro and explore preliminarily its mechanisms. METHODS: The anti-tumor activity was measured using colorimetric MTT assay. Apoptosis was determined with fluorescence-activated cell sorter (FACS), electron microscopy and agarose gel electrophoresis. The expressions of mdr1 and sorcin genes were determined by Northern blot assay. RESULTS: PH II-7 inhibited the proliferation of various human tumor cells derived from different tumor cell lines. The IC50 values varied from 0.34-18.61 mumol/L. Especially, PH II-7 had strong inhibitory effect on multidrug resistant tumor cells, whereas adriamycin (ADR) was resistant. Apoptosis was induced in HL60 and HL60/ADR cells treated with 1 microgram/ml PH II-7, while PH II-7 inhibited the expressions of mdr1 and sorcin genes. CONCLUSIONS: PH II-7 is a new potential agent which has strong inhibitory effect on both multidrug resistant cells and their parental cells. PH II-7 may increase the intracellular drug concentration in MDR cells by inhibiting the expressions of the MDR-related genes mdr1 and sorcin and induce the apoptosis of MDR cells and their parental tumor cells.