BACKGROUNDTo explore the possibility of targeting blockage of Wnt signal transduction pathway of nm23-H1 gene transfection in human high-metastatic large cell lung cancer cell line L9981, and to provide evidence to elucidate the signal conductive mechanism of nm23-H1 mediated tumor metastasis suppression.

METHODSThe expression of GSK-3β and β-catenin of Wnt signal pathway was detected in cytoplasm and nucleus in L9981 cell line with nm23-H1 deletion, L9981-pLXSN cell line transfected with vector and L9981-nm23-H1 cell line transfected with nm23-H1 gene by Western blot.

RESULTS(1)GSK-3β expression in L9981-nm23-H1 cytoplasm (6 341±541) was significantly higher than those in L9981 (3 736±298) and L9981-pLXSN (3 613±383) cell lines ( P < 0.001); (2)GSK-3β expression in L9981-nm23-H1 nucleus (4 356±490) was significantly higher than those in L9981 (657±57) and L9981-pLXSN (705±75) cell lines ( P < 0.001); (3)β-catenin expression in L9981-nm23-H1 cytoplasm (3 649±118) was significantly higher than those in L9981 (1 401±31) and L9981-pLXSN (1 350±55) cell lines ( P < 0.001); (4)No statistical difference of the β-catenin expression in nucleus was observed among L9981-nm23-H1 (2 945±68), L9981 (2 604±23) and L9981-pLXSN (2 652±53)( P > 0.05); (5)No significant difference of GSK-3β or β-catenin expression in cytoplasm and nucleus was observed between L9981 and L9981-pLXSN ( P > 0.05).

CONCLUSIONS(1)nm23-H1 gene can remarkably upregulate the expression of GSK-3β in cytoplasm and nucleus, and β-catenin expression in cytoplasm in L9981-nm23-H1 cell, but can not induce the nucleus accumulation of β-catenin. (2)Regulation of GSK-3β and β-catenin expression, and targeting blockage of Wnt signaling pathway may be one of molecular mechanisms that nm23-H1 contributes to play a vital role in the "Lung Cancer Metastasis Suppressive Cascade".

BACKGROUNDTo study the effect and safety of tissue specific gene therapy of suicide gene for lung adenocarcinoma.

METHODSRetroviral vector of G1CEACDNa contained a carcinoembryonic antigen (CEA) promoter regulated cytosine deaminase expression cassete (CEA/CD). By means of infection of virus, tissue specific expressing vectors and non-specific expressing vectors were transfected into A549 cell, which was CEA-producing lung adenocarcinoma cell line and then xenografted in nude mice, and the anti-tumor effect was evaluated. Then the retrovirus was injected directly into the tumor mass on nude mice, and the sensitivity of the xenograft to G1CEACDNa/5-fluorocytosine (5-FC) and the side effects were observed.

RESULTS(1) After transfected and untransfected A549 cells were implanted into nude mice, there was no difference in tumor formation among all the groups. (2) After 5-FC administration, the tumor transfected with tissue-specific gene displayed a higher sensitivity to the drug than those treated with non-specific in vitro gene-therapy. (3) The tumor-bearing nude mice were randomized in a blind manner based on comparable size to receive the supernatant of recombinant retrovirus G1CEACDNa followed by 5-FC, and significant growth suppression could be observed. (4) Comparing to the group with injection of 5-fluorouracil (5-FU) alone, tissue-specific suicide gene therapy showed lower suppression to bone marrow.

CONCLUSIONSThe results suggest that tissue-specific suicide gene therapy may play an important role in individual treatment of lung cancer.

BACKGROUNDTo compare the therapeutic effect, adverse reaction and effect on immunity of chemotherapy combined Aidi injection (AI) with those of chemotherapy alone in the treatment of advanced non small cell lung cancer (NSCLC).

METHODSNinety eight cases of advanced NSCLC were randomly divided into two groups, trial group and control group. In the trial group, NP plus AI (60 80 ml) were given intravenously by dissolving in 400 ml of normal saline per day for 8-10 days, while in the control group, only NP chemotherapy was given. Navelbine (25 mg/m², d1, 8) and cisplastin (40 mg/m², d1-3) were chosen in the chemotherapy. Each patient received at least two cycles of treatment.

RESULTSThe effective rate in the trial group and the control group was 53.1% and 44.9% respectively, without significant difference between the two groups ( P > 0.05). But the rate of progression, adverse reactions in bone marrow and digestive tract, and change of immunity in the trial group were all lower than those in the control group ( P < 0.05), and the improvement in Karnofsky score in the trial group was higher than that in the control group ( P < 0.05).

CONCLUSIONSChemotherapy of NP combined with AI shows benefit in the treatment of advanced NSCLC. AI could decrease the influence on immunity and adverse reaction of chemotherapy, and improve the quality of life in patients with NSCLC.

BACKGROUNDTo compare the efficacy and side effects between cisplatin solution and cisplatin powder combination regimens for lung cancer.

METHODSA total of 223 patients were enrolled into this study. EP protocol was given to patients with small cell lung cancer (SCLC), and NP protocol to non small cell lung cancer (NSCLC). The 223 patients were randomly divided into cisplatin solution group and cisplatin powder group, and the same drugs and dosage were used in the two groups for the same type of lung cancer.

RESULTSResponse rates of the cisplatin solution group and the cisplatin powder group were 84.8% and 82.4% for SCLC ( P > 0.05), and 31.6% and 29.9% for NSCLC ( P > 0.05), respectively. The major side effects were gastrointestinal reactions and myelosuppression. Significantly higher incidence of nausea/vomiting was found in cisplatin solution group than that in cisplatin powder group for either SCLC or NSCLC ( P < 0.05). There was a remarkable difference in cost of hospitalization between the two groups ( P < 0.05).

CONCLUSIONSCisplatin solution is as effective as cisplatin powder in the treatment of lung cancer. However, the more severe nausea/vomiting reactions and higher cost of cisplatin solution should be considered in its clinical application.

BACKGROUNDTo observe and compare the efficacy and safety of IEP and EP regimens for small cell lung cancer (SCLC).

METHODSSixty-four patients with SCLC pathologically proved were randomly divided into IEP group ( n =32) and EP group ( n =32).

RESULTSAll the 64 patients were evaluable for response and toxicity. In IEP group, the total responsive rate, responsive rates of limited-stage patients and extensive-stage patients were 84.4%(27/32), 100.0%(15/15) and 70.6%(12/17) respectively; while in EP group, those were 75.0%(24/32), 85.7%(12/14) and 66.7% (12/18) respectively. The median duration of remission was 6 months and 1-year survival rate was 62.5% in IEP group, and 5 months and 56.2% in EP group. There was no significant difference in response rate, median duration of remission and 1-year survival between the two groups ( P > 0.05). The main toxicity was myelosuppression. Incidences of leukopenia at grade III-IV, nausea, vomiting and alopecia were significantly higher in the IEP arm than those in the EP arm ( P < 0.01 ).

CONCLUSIONSHigh response rates and tolerable toxicities are attainable for small cell lung cancer treated with IEP and EP. IEP regimen shows a similar response rate compared with EP regimen. They might be considered as relevant regimens in initial patients with small cell lung cancer.

BACKGROUNDTo evaluate the efficacy and toxicity of combined chemotherapy of domestic paclitaxel and vinorelbine plus cisplatin and carboplatin in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSA total of 181 initially treated patients with advanced NSCLC were enrolled in this study and treated by NP (vinorelbine plus cisplatin), TC (domestic paclitaxel plus carboplatin) and TP (domestic paclitaxel plus cisplatin). The efficacy and side effects were analysed after at least two cycles of chemotherapy.

RESULTSThe overall response rates (CR+PR) were 42.4% in the NP arm, 40.3% in the TC arm and 43.3% in the TP arm respectively. No significant statistical difference was found among the three groups ( Chi-square= 0.108 6 , P > 0.05). The median survival times were 8.4 months, 9.4 months and 8.9 months respectively in the NP, TC and TP groups ( P > 0.05). The 1-, 2-, 3-year survival rates were 39.0%, 16.9%, 5.1% in the NP group and 41.9%, 21.0%, 6.5% in the TC group and 40.0%, 18.3%, 5.0% in the TP group respectively. No significant statistical difference was found among the three groups ( Chi-square=0.140 4, P > 0.05). The major side effects were myelosuppression, alopecia and nausea/vomiting in the three groups. There were no chemotherapy-related death among the three groups.

CONCLUSIONSThe combined regimens of NP, TC and TP are effective and well-tolerated regimens for advanced NSCLC.