Objective To observe the expression changes of matrix metalloproteinase 9(MMP-9),vascular endothelial growth factor(VEGF)in the esophageal squamous cell carcinomas,and to study the chinical significance. Methods The expression of MMP-9 and VEGF in 60 patients with esophageal carcinoma and 20 cases with adjacent normal mucosa were tested with immunohistochemical SP method. Results The positive rate of MMP-9,VEGF in the esophageal squamous cell carcinomas were 70%(42/60)and 80%(48/60),the positive rate of adjacent normal mucosa were 10%(2/20)and 20%(4/20).The positive rates of the two groups were compared,all the differences had statistical significance(P＜0.05); expressions of MMP-9,VEGF in the esophageal squamous cell carcinomas related to invasive depth of carcinoma and lymph node metastasis(P＜0.05).There were positive correlation(r=2.330,P＜0.05). Conclusion The higher expression of MMP-9 and VEGF in the esophageal squamous cell carcinomas played an important role in invasion and metastasis of esophagus squamous cancer.

BACKGROUNDOncogenesis, development, invasion and metastasis of lung cancer are modulated by relative genes of lung cancer, and the expression, deletion or mutation of these genes are regulated by cell membrane signal transduction system and cell membrane ionic channels. The aim of this study is to explore the electrophysiological properties of human lung adenocarcinoma cell line A549 and cell proliferation affected by tetraethylammonium chloride (TEA), one potassium channel blocker, so as to know whether the voltage-gated potassium channels are required for the proliferation of A549 cell line.

METHODSIonic currents were recorded by whole-cell patch-clamp recording technique. The proliferation activity of A549 cells was measured by MTT assay.

RESULTSMembrane current was observed when cells were held at -70mV and test potentials ranged from -30 to +110mV. The current exhibited properties of voltage-dependent, outward rectification and no or little inactivation over the 500ms voltage pulse. Exposure of tumor cells to 10mmol/L TEA reduced the peak outward potassium current (evoked by depolarization to +110mV) from (1057.52±59.17)pA to (212.26±11.96)pA, the ratio of suppression was 79.92% (P < 0.01). Obvious inhibitive effect of TEA with different concentrations ranged from 20 to 60mmol/L on proliferation activity of the cells was found.

CONCLUSIONSThe voltage-gated potassium channels exist in human lung adenocarcinoma cell line A549 and play a great role in proliferation of A549 cells. TEA can inhibit proliferation of A549 cell through blocking the potassium channels and the inhibition is dose-dependent.

BACKGROUNDWith the development of patch clamp and molecular biology technique, and the application of them in the investigation of tumor cellular membrane ion channnel, the ion channel is becoming the hot spot of the tumor base research gradually. The aim of this study is to investigate the electrophysiological properties of human lung adenocarcinoma cell line A-549 and the role of K+ channel in inhibition of cell proliferation by the recombinant mutant human tumor necrosis factor (rmhTNF).

METHODSIonic currents were recorded using the whole-cell patch clamp recording technique. The proliferation activity of A-549 cells was measured by MTT assay. The cell cycle and apoptosis rates of the carcinoma cells were measured by flow cytometric analysis (FCM).

RESULTSWhole-cell patch clamp recording revealed a voltage-gated K+ current in A-549 cells, which could be blocked by the K+ channel blocker, TEA and CsCl. The amplitude of K+ current was markedly diminished in all cells incubated with different concentration of rmhTNF (P < 0.01). Obvious inhibitive effect of rmhTNF on proliferation of the cells was found in vitro in a dose-dependent manner (P < 0.01), the maximal inhibitory rate was 38.68% when the concentration was 400U/mL. The rmhTNF inhibited the cell cycle shifting from G1 phase to S phase and promoted apoptosis as determined by FCM analysis. The proportion of G1 cells increased from 53.02% to 72.93%, and the apoptosis rate increased from 2.08% to 8.68%. The difference were significant between the control and the high concentration groups ( 200U/mL and 400U/mL) (P < 0.01).

CONCLUSIONSrmhTNF exerts its cytotoxic effects on A-549 cells through inhibiting cell cycle shifting and inducing apoptosis. The K+ channels on the A-549 cell membrane can be blocked by rmhTNF partly, and the effect of inhibiting proliferation and activating apoptosis on A-549 cells is a result of depression of the K+ channel.

Objective To explore the incidence and risk factors of perioperative major adverse cardiac events (MACE) in lung cancer patients with high-risk coronary heart disease undergoing pulmonary lobectomy. Methods The clinical dataof 1 647 high-risk coronary heart disease patients diagnosed with lung cancer undergoing lobectomy in our hospital was analyzed, and performed Framingham scoring. High-risk patients (score＞ 20％) were included in the study, and the periopertive major adverse cardiac events was defined as primary endpoint. The risk factors of MACE were analyzed. Results Perioperative MACE occurred in 26. 4％ of lung cancer patients with high-risk coronary heart disease undergoing lobectomy. Multivariate analysis demonstrated that hypertension, high density lipoprotein (HDL-C), diabetes, age, coronary angiography, stroke, smoking index in descending sequence were independent risk factors of perioperative cardiac events in lung cancer patients. While shorter operative time, coronary angiography and clinical intervention was protective factor. Conclusion Lung cancer patients with high-risk coronary heart disease undergoing lobectomy has higher risk of perioperative MACE. Preoperative sufficient cardiac risk scores, coronary angiography andclinical interventioncan reduce the incidence of perioperative MACE in lung cancer patients with high-risk coronary heart disease.

Objective To explore the incidence and risk factors of perioperative major adverse cardiac events (MACE) in lung cancer patients with high-risk coronary heart disease undergoing pulmonary lobectomy. Methods The clinical dataof 1 647 high-risk coronary heart disease patients diagnosed with lung cancer undergoing lobectomy in our hospital was analyzed, and performed Framingham scoring. High-risk patients (score＞ 20％) were included in the study, and the periopertive major adverse cardiac events was defined as primary endpoint. The risk factors of MACE were analyzed. Results Perioperative MACE occurred in 26. 4％ of lung cancer patients with high-risk coronary heart disease undergoing lobectomy. Multivariate analysis demonstrated that hypertension, high density lipoprotein (HDL-C), diabetes, age, coronary angiography, stroke, smoking index in descending sequence were independent risk factors of perioperative cardiac events in lung cancer patients. While shorter operative time, coronary angiography and clinical intervention was protective factor. Conclusion Lung cancer patients with high-risk coronary heart disease undergoing lobectomy has higher risk of perioperative MACE. Preoperative sufficient cardiac risk scores, coronary angiography andclinical interventioncan reduce the incidence of perioperative MACE in lung cancer patients with high-risk coronary heart disease.

To discuss the conformational change and the recognition mechanism of hydroxy isoindol ketone derivatives with HIV-1 integrase, fifty-eight hydroxy isoindol ketone derivatives were docked to the integrase using AutoDock program. Molecular dynamics simulation with 16 ns was carried out for the two complex modes, respectively, in which the corresponding small molecules exhibited strong inhibition ability. Main force acting on the association of small molecules with integrase was explored based on the docking complex model. After analyzing the hydrogen-bond and conformational changes, it was found that the hydrogen-bond between N155 and D64 was the key factor maintaining the DDE motif stability. Furthermore, the hydrophobic interactions between the loop region where Y143 located and the hydroxy isoindol ketone derivatives were found to play an important role for their recognition.