OBJECTIVETo investigate the transcriptional activity of P53 in gastric cancer.

METHODSThe activity of p53 in gastric cancer was investigated by dual-luciferase reporter assay. The coding sequence of the p53 was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and sequenced. The expression of P21WAF1/Cip1, Gadd45alpha and Mdm2 was detected by immunohistochemistry in 76 samples of gastric carcinoma, and their adjacent tissues were analyzed as control.

RESULTSThe p53 activity was higher in human normal cell lines than that of gastric cancer. Furthermore, the transcriptional activity of P53 was lowest in MKN28 cells in which p53 was mutated. The expression level of P21WAF1/Cip1, Gadd45alpha and Mdm2 in the adjacent tissues was higher than that of cancer tissues (P<0.05), and there was a tendency of decline in the positive ratio with the poor differentiation of the carcinoma (P<0.05). In addition, a strong linear correlation was observed between P21WAF1/Cip1, Gadd45alpha and Mdm2 (P<0.05).

CONCLUSIONChanges of P53 transcriptional activity play an important role in the development of gastric cancer. p53 mutation could affect its transcriptional activity. P21WAF1/Cip1, Gadd45alpha and Mdm2 are a group of effecters that could reflect P53 transcriptional activity when detected together in cancer tissues.

Adult ; Aged ; Carcinoma ; genetics ; metabolism ; pathology ; Cell Cycle Proteins ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Nuclear Proteins ; Proto-Oncogene Proteins c-mdm2 ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Transcriptional Activation ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult

BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).

METHODSTwo hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.

RESULTSof the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.

CONCLUSIONSThe results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.