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Objective To explore the serum expression of DKK1 protein, a Wnt signaling pathway inhibitor in patients with non-small cell lung cancer (NSCLC) and its relationship with osseous metastasis. Methods Serum DKK1 protein levels were assayed by enzyme-linked immunosorbent assay (ELISA) in NSCLC patients, including 33 NSCLC patients with osseous metastasis and 41 NSCLC patients without respectively, and 32 healthy volunteers were served as the control group. Furthermore, the differential expression of the serum DKK1 protein level between the patients and the volunteers was compared by using the variance analysis and the independent sample t test. The correlation between DKK1 expression and bone metastasis was detected by Pearson correlation analysis. Results Serum DKK1 protein level of NSCLC patients was (79.6±8.3) ng/ml, which was significantly higher than that in healthy volunteers [(21.5±6.4) ng/ml, t=13.17, P=0.001]. The serum DKK1 level in osseous metastasis group was (110.3±11.4) ng/ml, which was significantly higher than that in non-skeletal metastasis group [(60.7±10.5) ng/ml, t=14.128, P=0.003]. The positive association was observed between the DKK1 level in the peripheral blood and osseous metastasis in NSCLC patients (r=0.855, P<0.001). Conclusion The serum expression level of DKK1 protein in NSCLC patients is closely related to the osseous metastasis, which may be a predicting biomarker for the osseous metastasis.
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Objective To evaluate the level changes of serum WASP-family verprolin homologous protein-1 (WAVE1) and vascular endothelial growth factor-C (VEGF-C) and their clinical significance in patients with advanced non-small lung cancer (NSCLC) before and after chemotherapy.Methods Serum WAVE1 and VEGF-C were measured in 43 patients with advanced NSCLC by ELISA,and the results were compared with 43 healthy volunteers.Results The levels of serum WAVE1 and VEGF-C before chemotherapy in patients group were (0.573±0.082) ng/ml and (947.3±125.4) pg/ml respectively,while in healthy volunteers group,they were (0.256±0.064) ng/ml and (425.5±110.1) pg/ml respectively,which suggested that before chemotherapy the levels of serum WAVE1 and VEGF-C in NSCLC group were significantly higher than those of in the control (P ＜ 0.05).The serum levels of WAVE1 and VEGF-C in advanced NSCLC patients were closely related to lymph node metastasis status and distant metastasis status (P ＜ 0.05),but not to the gender,age,tumor length,histology type,differentiation grade and C-TNM stage (P ＞ 0.05).The serum WAVE1 and VEGF-C levels of the effective treatment group was (0.290±0.037) ng/ml and (596.1±127.5) pg/ml after chemotherapy respectively,which decreased obviously compared with the group before chemotherapy which levels were (0.517±0.051) ng/ml and (964.6±100.3) pg/ml (both P ＜ 0.05).But the serum WAVE1 and VEGF-C levels of the ineffective treatment group were (0.547±0.065) ng/ml and (957.0±111.2) pg/ml after treatment,which had no difference compared with the group before chemotherapy which levels were (0.517±0.051) ng/ml and (964.6±100.3) pg/ml (both P ＞ 0.05).Furthermore,statistically significant relationship was found between the serum WAVE1 and the VEGF-C levels (r =0.331,r =0.540,both P ＜ 0.05).Conclusion Serum WAVE1 and VEGF-C may be used as indicators for prediction of the efficacy of chemotherapy in patients with advanced NSCLC.
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Objective To observe the effect of rhTRAIL on survivin gene expression of human lung adeno-carcinoma A549 xenografted tumor in nude mice,and investigate the possible inhibitory mechanism of rhTRAIL on the implanted-tumor growth.Methods The solid tumor model was formed in nude mice with human lung adeno-carcinoma cell line.A549.24 mice were randomly divided into the four groups,rhTRAIL single treated group (1 μg/mL),rhTRAIL combined with cisplatin (DDP) treated group,cisplatin treated (1.5mg/kg) and 0.9％ sodium chloride injection(NS) control group.The rhTRAIL and DDP were injected once every other day by intraperitoneal injection to mice in the treated groups,lasting eight times,the same volume of saline solution was injected to the control group.After these,mice were killed and dissected completely.The expression level of survivin mRNA and protein in the tumor tissues was detected by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry,respectively.And the expression of survivin gene in serum of each group was tested by ELISA.Results The expression levels of survivin mRNA in implanted-tumor tissues in rhTRAIL,rhTRAIL combined with DDP,DDP and NS group were (48.7 ± 2.5) ％,(53.1 ± 4.6) ％,(99.1 ± 5.3) ％ and (95.6 ± 3.7) ％,respectively.While the protein expressions of survivin gene in those groups were (0.319 ± 0.025),(0.483 ± 0.058),(0.635 ± 0.041) and (0.619 ± 0.017),respectively.Moreover,the serum levels of survivin were (71.9 ± 7.05),(80.26 ± 10.80),(112.75 ± 15.41) and (105.03 ± 20.37),respectively.The data showed that the expression levels of rhTRAIL and rhTRAIL combined with DDP group were lower than that of DDP-treated group or the NS control group (P ＜ 0.0 5).Compared with the rhTRAIL combined with DDP group,the survivin gene expression level of rhTRAIL-single treated group decreased a little lower,but the difference was not significant (P ＞ 0.05).Conversely,the survivin gene level was increased to some degree compared with the NS control group,and uniformly there was no significant difference (P ＞ 0.05).Conclusion rhTRAIL can downregulate the expression level of survivin gene of human lung adeno-carcinoma A549 xenografted tumor in nude mice.It may be one of the possible inhibitory mechanisms of rhTRAIL on the implanted-tumor growth that rhTRAIL can downregulate survivin gene expression and promote tumor cell apoptosis.
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Objective To study the therapeutic effect and safety of pleurodesis with medical thoracoscopy by powdery talc on treatment of malignant pleural effusion.Methods Retrospective analysis were done in 74 cases of malignant pleural effusion accepted simple powdery talc pleurodesis under medical thoracoscopy.Results The doses of powdery talc were from 1g to 5g,average 2.18g in the course of the treatment.After operation,45 (60.8％) cases which were complete remission(CR) were full pleural adhesion and complete lung recruitment,14cases (18.9％),which were partial remission(PR),were less pleural adhesion and most lung recruitment,and 10cases(13.6％) were stable diseases(SD),while 5cases(6.7％),which were progressive diseases(PD),were without pleural reaction.The total effective rate,including CR,PR and SD,was 93.3 ％ (69/74).The complications of simple powdery talcage under medical thoracoscopy were included in:95.9％ (71/74) with chest pain,64.8％ (48/74) with fever,28.4％ (21/74) with shortness of breath,12.2 ％ (9/74) with mediastinal and subcutaneous emphysema,5.4％ (4/74) with nausea and vomiting,4.1％ (3/74) with abdominal distension,while the complications of acute pulmonary edema,massive hemorrhage,pulmonary embolism and wound infection were not observed.Conclusion Treatment of malignant pleural effusion by simple powdery talcage under medical thoracoscopy has definite clinic therapeutic effect,which is safe,cost-effective,less trauma and worthy of clinical application.
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<p><b>BACKGROUND</b>The excision repair cross-complementing gene 1 (ERCC1), which is important in the repair of cisplatin-DNA adducts, is reported to be related to cisplatin resistance in tumor cells. The aim of this study is to investigate the influence of low-dose cisplatin on expression of ERCC1 gene and to confirm the correlation between ERCC1 and cisplatin resistance in human lung adenocarcinoma cell lines.</p><p><b>METHODS</b>A549 and A549/DDP cell lines were treated with 10 μmol/L cisplatin for 12, 24, 48 and 72 h, or treated with 5, 10, 20, 40 μmol/L cisplatin for 24 h respectively. Then the expression of ERCC1 mRNA and protein was measured by RT-PCR and immunocytohistology SABC assay respectively. The resistance of A549/DDP cells was measured by MTT assay.</p><p><b>RESULTS</b>After treating with 10 μmol/L cisplatin for 12 h, up-regulation of ERCC1 mRNA and protein was observed in A549 cells, then reached the peak levels in 72 h group. After treating with 5 μmol/L cisplatin for 24 h, up-regulation of ERCC1 mRNA and protein was observed in A549 cells, and when treated with 20 μmol/L cisplatin for 24 h, the ERCC1 mRNA and protein reached the peak levels. Comparing with the parental cells, ERCC1 expression increased obviously in A549/DDP cells, which were established by continuous low-dose cisplatin treatment.</p><p><b>CONCLUSIONS</b>Up-regulation of ERCC1 expression can be induced by low-dose cisplatin in human lung adenocarcinoma cell line A549, and ECRR1 may play roles in cisplatin resistance.</p>
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<p><b>BACKGROUND</b>Tumor-necrosis factor related to apoptosis inducing ligand protein(TRAIL), like tumor-necrosis factor (TNF) and Fas, is a member of TNF cytokine supper family. Many researches have showed that TNF-α can reverse the resistance to some chemotherapeutic agents in cancer cell lines, and some anticancer drugs can result in up-regulations of death receptor (DR) and further lead to the enhancement of apoptosis induced by TRAIL. In order to clarify if TRAIL can reverse the resistance to cisplatin in cancer cells, the effects of recombinant human tumor-necrosis factor related to apoptosis inducing ligand protein (rhTRAIL) on apoptosis in human lung adenocarcinoma cell lines resistant to cisplatin (DDP) in vitro was explored.</p><p><b>METHODS</b>Human lung adenocarcinoma cell lines resistant to cisplatin, A549/DDP cells, were cultured in regular condition. At 24 hours after TRAIL and DDP, alone or combined, microculture tetrazolium (MTT) dye was used to evaluate the cytotoxic effects. And besides, to detect the apoptotic effects of rhTRAIL on A549/DDP cells, flow cytometry assay was used to test the apoptosis proportion, diphenylamine assay (DPA) was applied to detect the percent of DNA fragmentation and Caspase-3 chluorometric assay was performed to test the activity of Caspase-3 among these cells.</p><p><b>RESULTS</b>A549/DDP cells were not sensitive to low-dose rhTRAIL alone. The rate of growth inhibition and the apoptotic indexes such as the apoptosis proportion, the percent of DNA fragmentation and the activity of Caspase-3, had all no significant changes with rhTRAIL concentration less than 25μg/L (P > 0.05). But treated with higher-dose rhTRAIL more than 50μg/L, the four values changed obviously: 68.6%, (27.13± 0.66)%, (37.4±2.0)% and 0.117±0.011, respectively (P < 0.05). With combination of different concentration of rhTRAIL and 3mg/L DDP, the cyto-toxic and apoptotic effect was comparatively more apparent. The combination of rhTRAIL and 3mg/L DDP presented synergistic effect on A549/DDP, 12.5μg/L concentration of rhTRAIL together with 3mg/L DDP could kill 30.4% of A549/DDP cells. Furthermore, the rate of cell apoptosis, percent of DNA fragmentation and activity of caspase-3 increased to (19.39±0.54)%,(17.3±4.1)% and 0.138±0.009, which were significantly different from those of rhTRAIL alone (P < 0.01).</p><p><b>CONCLUSIONS</b>High-dose rhTRAIL can also induce the cells resistant to cisplatin to apoptosis, but the cytotoxic and apoptotic effects of rhTRAIL alone are weaker than those of combination of rhTRAIL and low-dose cisplatin which can augment the apoptotic effect induced by rhTRAIL. rhTRAIL is expected to be an efficient biologic drug for treatment of lung cancer resistant to chemotherapy.</p>
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OBJECTIVE: To study the effect of Xingding Injection on the expression of heat shock protein 72 (HSP 72) in vascular endothelial cells after ultraviolet radiation. METHODS: Porcine aortic endothelial cells were cultured for 72 hours in culture mediums with different concentrations (0.1, 0.5, 1.0, 5.0, 10 mg/ml) of Xingding Injection. Ultraviolet radiation was administered to the cultured cells for 30 minutes. Western-blot assay was used to measure the expression of HSP 72 in the vascular endothelial cells. RESULTS: There was no expression of HSP 72 in the cultured vascular endothelial cells without ultraviolet radiation, but there was some expression of HSP 72 after ultraviolet radiation. Xingding Injection of different concentrations could significantly improve the expression of HSP 72. The expression of HSP 72 in the vascular endothelial cells cultured in culture medium with 1.0 mg/ml Xingding Injection was the highest, and there was no more increase of expression when the concentration was higher, instead the expression decreased. CONCLUSION: Xingding Injection can protect the vascular endothelial cells from injury during stress. It may be one of its mechanisms in preventing and treating cardio-cerebrovascular disorders.
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ATM: To explore the effect and mechanism on blood pressure and heart protection of renal hypertension in rats treated with ?_1 receptor antisense oligodeoxynucleotides (?_1-AS-ODN) by delivery with cationic liposomes DOTAP/DOPE. METHODS: 24 SD rats were divided randomly into 4 groups of 6 each group: two groups of 2K1C rats were treated via tail vein injection with ?_1-AS-ODN or inverted oligonucleotides against rat ?_1-AR mRNA (?_1-IN-ODN) of 0.5 mg?kg~(-1) once. 6 untreated 2K1C rats and shamed rats served as positive and normal controls. Blood pressure (BP), cardiac haemodynamics, and left ventricular index (LVW/BW) were measured. The histological changes of myocardium were observed by optical microscope and the expressions of Bcl-2 and Bax in myocardium were examined by immunohistochemical method. RESULTS: The single dose management of ?_1-AS-ODN decreased blood pressure to 120 mmHg for 27 days and improved the LV function obviously (P