Loss of ß-arrestin-2 and Activation of CXCR2 Correlate with Lymph Node Metastasis in Non-small Cell Lung Cancer.

Background : Although ß-arrestin-2 (ß-arr2) and CXCR2 have been shown to affect various malignant tumors, their exact roles in lung cancer remain unclear. We investigated expression of ß-arr2 and CXCR2 in patients with non-small cell lung cancer (NSCLC) and their correlation with lymph node metastasis and prognosis. Methods : We reviewed medical records of 136 patients with NSCLC who underwent surgical resection, and assessed their specimens immunohistochemically for expression of ß-arr2 and CXCR2 in primary tumors and metastatic lymph nodes (MLNs), respectively. Results: High ß-arr2 expression was seen in 63 specimens (46.3%), and was significantly associated with male patients (P=0.011), squamous cell carcinoma (P=0.003), and lymph node metastasis (P<0.001). High CXCR2 expression was seen in 62 specimens (45.6%), and was significantly correlated only with lymph node metastasis (P<0.001). Expression of ß-arr2 was significantly lower at MLNs than at primary lesions (Z=-2.315; P=0.021; Wilcoxon signed-rank), whereas CXCR2 expression was significantly higher in MLNs than in primary lesions (Z=-3.712; P<0.001; Wilcoxon signed-rank). No relationship was seen between ß-arr2 and CXCR2 expression in primary lesions (r=-0.065, P=0.548; Spearman rank coefficient), but they were inversely related in MLNs (r=-0.263, P=0.012). Kaplan-Meier survival curve was shown that low ß-arr2 and high CXCR2 expressions was associated with poor survival (log-rank: χ2=5.926, P=0.015). Conclusions : ß-arr2 may promote lymph node metastasis in NSCLC by modulating CXCR2 activation.

MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer.

Breast cancer is the second leading cause of cancer induced death in women. Tamoxifen is an endocrine therapy which is administered to 70% of all breast cancer patients with estrogen receptor alpha (ERα) expression. Despite the initial response, most patients eventually acquire resistance to the drug. MicroRNAs (miRNAs) are a class of small non-coding RNAs which have the ability to post-transcriptionally regulate gene expression. Although the role of a few miRNAs has been described in tamoxifen resistance, little is known about how concerted actions of miRNAs targeting biological networks contribute to its resistance. In this study, we identified that miR-155 is frequently up-regulated in breast cancer with tamoxifen resistance. Ectopic expression of miR-155 induces cell survival and resistance to TAM, whereas inhibition of miR-155 causes cells to apoptosis and enhances TAM sensitivity. Further, we identified SOCS6 as a new direct target of miR-155. Sustained overexpression of miR-155 resulted in repression of SOCS6 protein and mRNA levels, and knockdown of miR-155 increased SOCS6 expression. Introduction of SOCS6 cDNA lacking the 3'-UTR abrogated miR-155-induced cell survival and chemoresistance. Finally, it was verified that SOCS6 or inhibition of STAT3 could inhibit miR-155 STAT3 activation and cell proliferation. In conclusion, our study reveals a molecular link between miR-155 and SOCS6-STAT3 and presents an evidence that miR-155 is a critical therapeutic target in breast cancer.

Percutaneous CT-guided microwave ablation as maintenance after first-line treatment for patients with advanced NSCLC.

BACKGROUND: Systemic therapy is recommended for advanced non-small-cell lung cancer (NSCLC). However, conventional first-line treatment has generated a plateau in response rate of 25% to 35%. Few studies have shown patients benefit from microwave ablation (MWA) in combination with radiotherapy and chemotherapy. This study aims to evaluate safety and efficacy of percutaneous computed tomography-guided MWA as maintenance after first-line treatment for patients with advanced NSCLC. METHODS: Patients with histologically verified NSCLC stage IIIB or IV between January 2010 and March 2014 were involved. After completion of first-line treatment with partial response or stable disease, 35 patients with 39 tumors underwent 39 MWA procedures. Complications, progression-free survival (PFS), overall survival (OS), and correlated predictors were analyzed. RESULTS: During a median follow-up of 17.7 months and 10.8 months after initial MWA, local efficacy was 87.2%, median MWA-related local control time was 10.6 months, and tumor size was the only predictor (P=0.002). Median MWA-related PFS, MWA-related OS, PFS, and OS were 5.4, 10.6, 11.8 and 17.7 months, respectively. Local efficacy was significantly correlated with MWA-related PFS (P=0.003), MWA-related OS (P=0.000), and OS (P=0.001). There were no procedure-specific deaths. Total incidence of major complications was 12.8%, including pneumothorax resolved by closed pleural drainage and pneumonia controlled by antibiotics in a short time. CONCLUSION: This study concluded two points, including: 1) patients benefited from MWA as maintenance both in local control and survival; 2) as maintenance MWA was superior to conventional maintenance therapy with improved survival and well-tolerated complications. Therefore, MWA was a safe and effective maintenance after first-line treatment in patients with advanced NSCLC.

XRCC1 genetic polymorphisms and sensitivity to platinum-based drugs in non-small cell lung cancer: an update meta-analysis based on 4708 subjects.

OBJECTIVE: To evaluate the correlation between genetic polymorphisms in x-ray repair cross complementing group 1 (XRCC1) and sensitivity to platinum-based chemotherapy drugs in patients with non-small cell lung cancer. METHODS: Reports published before June 2014 were retrieved from the following databases: China Biology Medicine (CBM), China Academic Journal Full-Text Database (CNKI), China Science and Technology Journal Full-Text Database (VIP), Wanfang Data, PubMed and Excerpta Medica dataBASE (EMBASE). After extracting the data and evaluating the quality, meta-analysis was performed using RevMan5.2 software. RESULTS: A total of 29 studies with 4807 patients were included. Two polymorphisms (Arg399Gln and Arg194Trp) were analyzed. Meta-analysis showed that the efficacy of chemotherapy for patients with the TT genotype [TT vs. CC, OR=1.66, 95% OR=1.66, 95 CI (1.30-2.14)] and the CT genotype [CT vs. CC, OR=1.62, 95% CI (1.35-1.93)] at codon 194 of the XRCC1 gene was significantly higher than that for patients with the CC genotype. The efficacy of chemotherapy for patients with mutant (CT+TT) genotypes was significantly higher than for patients with the wild-type (CC) genotype [TT+CT vs. CC, OR=1.63; 95% CI (1.38-1.92)]. The sensitivity to chemotherapy in patients with the AG genotype at codon 399 of the XRCC1 gene was lower than in patients with the GG genotype [AG vs. GG, OR=0.72, 95% CI (0.55-0.92)] in Chinese population. However, we did not found this association in Caucasus population. CONCLUSION: Genetic polymorphisms in the XRCC1 gene are correlated with sensitivity to platinum-based chemotherapy in patients with non-small cell lung cancer.

EGFR mutations and clinical outcomes of chemotherapy for advanced non-small cell lung cancer: a meta-analysis.

BACKGROUND: This meta-analysis was performed to assess whether epidermal growth factor receptor (EGFR) mutation status was associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy. METHOD: We systematically identified eligible articles investigating the effects of chemotherapy in patients with NSCLC stratified by EGFR mutation status. The summary risk ratio (RR) for ORR and hazard ratios (HRs) for both PFS and OS were calculated using the inverse variance formula of meta-analysis. RESULTS: Identification for the current meta-analysis: 5 prospective studies (n=875) and 18 retrospective studies (n=1934) for ORR; 2 prospective studies (n=434) and 10 retrospective studies (n=947) for PFS; 2 prospective studies (n=438) and 7 retrospective studies (n=711) for OS. The ORR was significantly higher in patients with EGFR mutations in prospective studies (RR=1.42; 95% confidence interval [CI], 1.16-1.74; P=0.001), but not in retrospective studies (RR=1.12; 95% CI, 0.96-1.32; P=0.146). There was no obvious association between EGFR mutations and PFS both in prospective (HR=0.84; 95% CI: 0.65-1.09; P=0.197) and retrospective (HR=1.02; 95% CI: 0.87-1.18; P=0.838) studies. Association between EGFR mutations and OS was also not seen in prospective studies (HR=0.74; 95% CI: 0.27-2.05; P=0.566), but was seen in retrospective studies (HR=0.48; 95% CI: 0.33-0.72; P<0.001; I(2)=75.9%; P<0.001) with significant heterogeneity. CONCLUSION: EGFR mutations in advanced NSCLC may be associated with higher ORRs to chemotherapy, but may have nothing to do with PFS and OS. Further prospective studies are required to identify the influence of EGFR mutations on chemotherapy effects in advanced NSCLC.

[Efficacy and safety of low-frequency rotary magnetic fields in the treatment of patients with advanced malignant tumors].

OBJECTIVE: To investigate the clinical efficacy and safety of low-frequency rotary magnetic fields in the treatment of patients with advanced malignant tumors. METHODS: 137 patients with advanced malignant tumors were exposed to 400 r/min, 0.4 T low-frequency rotary magnetic fields. An area including the primary tumor, local metastasis and metastatic lymph nodes was exposed daily, 2 hours per day for 30~50 days (average time of 42 days). RESULTS: All of the 137 patients completed the low-frequency rotary magnetic field treatment. There were 28 cases with complete response, 54 cases with partial response, and the clinical benefit rate was 59.9%. The tumor type, initial KPS and QOL showed statistical significance in the clinical benefit rate (P < 0.05). The median overall survival was 12 months, and the 1-year, 2-year and 3-year survival rates were 47.0%, 11.8%, 3.4%, respectively. The tumor type, initial KPS and QOL were identified by univariate log-rank test as significant prognostic factors for overall survival (P < 0.05). Multivariate analysis showed that the initial QOL was an independent prognostic factors (P = 0.037) . During the treatment, asthenia and local pain were observed in 11 patients, and 6 patients had mild tachycardia (increased 3 to 5/min) and/or temperature elevation (0.5 to 1.0°C). All above symptoms disappeared spontaneously. No treatment-related death was observed. CONCLUSIONS: Low-frequency rotary magnetic fields is an effective and safe method in the treatment of patients with advanced malignant tumors, and may prolong survival significantly.

[Relationship between P65 and radiotherapy-induced oral squamous cell carcinoma cell line apoptosis].

OBJECTIVE: To investigate the effects of different X-ray doses on the expression of nuclear factor-kappaB (NF-kappaB) P65 in human oral squamous cell carcinoma cell (OSCC) line and the relationship between NF-kappaB P65 and radiation-induced OSCC cell line apoptosis. METHODS: The squamous cell carcinoma of Tca8113 cell was cultivated in the 37 degrees C, 5% CO2 incubator after recovery. The experiment samples were divided into six groups (control group, 2, 4, 6, 8, 10 Gy). After growing to logarithm period, Tca8113 cells were irradiated using above-mentioned X-ray doses. The immunocyteochemistry and Western blot were used to detect the expression of NF-kappaB P65 after irradiation in various times (1, 3, 6, 10, 24, 48 h). The apoptosis rates under different radiotherapy dose were detected by flow cytometer and TDT-mediated dUTP-biotin nick end labeling (TUNEL). RESULTS: Compared with the control group, cytoplasm expression of P65 under different X-ray doses had statistically significant differences (P < 0.05). While the cytoplasm P65 protein expression at different time were compared each other, the 3 h group demonstrated significant difference (P < 0.05). Apoptosis rates in various groups, compared with control group, had statistically significant differences (P < 0.05). While the groups at different time points were compared each other, the apoptosis rates of 3 h group had significant differences (P < 0.05). CONCLUSION: X-ray can activate the NF-kappaB P65 in oral squmaous cell carcinoma cell lines. The correlation between expressional quantity of P65 and radiotherapy induced apoptosis of oral squamous cell carcinoma cell lines possesses positive correlation. The activated and intranuclear P65 may have radiotherapy resistant effect.

[Experimental study on the expression of NF-κB-P65 protein and apoptosis of adenoid cystic carcinoma cells after radiation treatment].

PURPOSE: To detect the expression of p65, a subunit of NF-κB proteins, and apoptosis after adenoid cystic carcinoma cells(ACC-2) irradiated by high energy X-ray, and to investigate the interaction between them. METHODS: ACC-2 cells were cultured and then irradiated by high energy X-ray of different dose(2, 4, 6, 8,10Gy). At the next six time points(1, 3, 6, 10, 24, 48h), the expression of p65 protein in cytoplasm and nucleus was detected by immunocytochemistry and Western blotting. The apoptotic cells were counted by flow cytometry and then observed by TUNEL technique. The data of radiant intensity and apoptotic rate were statistically analyzed by Spearman method with SPSS11.5 software package. RESULTS: In ordinary condition, p65 protein seldom appeared in the nucleus, and mostly stained in the cytoplasm by immunocytochemistry. After irradiation, the protein was observed around the nuclear. Then it went through the nuclear membrane more and more as time going on, finally to the center of the nucleus. The quantity of p65 among the total protein changed gradually after radiation, rising at first, which got to a peak after about 6 to 10 hours, according to the results of Western blotting. At the same time point, p65 protein was found to have a higher expression with a higher dose of irradiation correspondingly. The proportion of apoptotic cells also varied from time to time, and an obvious valley of the apoptotic curve was at the 10th hour after radiation. Compared with the outcome of Western blotting, the results indicated a negative correlation between the apoptotic rate and the radiant intensity or p65 protein expression(P<0.05). CONCLUSIONS: The expression of p65 protein is affected by the irradiation of p65 of high energy X-ray, which is dose-time dependent. The proportion of apoptotic cells decreases as the expression increases.

[Efficacy of late accelerated hyperfractionated conformal radiotherapy combined with capecitabine for esophageal carcinoma].

OBJECTIVE: To evaluate the efficacy of late accelerated hyperfractionated conformal radiotherapy (LACF) combined with capecitabine on esophageal carcinoma. METHODS: One hundred and sixty eight patients of esophageal cancer were randomly divided into 3 groups, including the radiotherapy alone group (CF) which received conventional conformal radiotherapy to a total of 60 - 66 Gy, LCAF group which received conventional fractionated conformal radiotherapy during the first two-thirds of the treatment to a dose about 40 Gy/20F/4W, then followed by late accelerated hyperfractionated conformal radiotherapy, twice daily radiotherapy at 1.3 Gy per fraction to a total dose about 64 - 69 Gy, and LCAF + C group (late accelerated hyperfractionated radiotherapy combined with capecitabine), in which patients were treated as the same as the LCAF group, except that they were treated with capecitabine (1.5 g po bid) from beginning of the radiotherapy to the end. RESULTS: The short-term results of the 3 groups were 74.0%, 85.5% and 95.2%, respectively (P = 0.006). The local control rates at 1, 3 and 5 years were 64.0%, 30.0%, 24.0% in the CF group, 81.8%, 65.5%, 58.2% in the LCAF group and 90.1%, 77.8%, 74.6% in the LCAF+C group, respectively. The 1-, 3- and 5-year survival rates of the 3 groups were 58.0%, 20.0%, 8.0%; 78.2%, 36.4%, 17.0% and 85.7%, 55.6%, 30.2%, respectively. The effect of LCAF+C group was better than that of LCAF group and CF group. The incidence of acute tracheitis and acute esophagitis in the LCAF+C group and LCAF group was higher than that in the CF group, but there was no stastistically significant difference between the 2 groups. There was no statistically significant difference in distant metastasis in the 3 groups. CONCLUSIONS: Capecitabine, as an effective chemosensitizater combined with late accelerate hyperfractionated radiotherapy can improve the short-term results of treatment of esophageal cancer. The value of this combined treatment in distant metastasis reqires further study in the clinic.

[Clinical value of preoperative serum VEGF, CRP and IL-6 levels in colorectal carcinoma].

OBJECTIVE: To determine the preoperative serum VEGF, IL-6, and CRP levels in colorectal carcinoma, and to explore their correlation with disease status and prognosis. METHODS: Serum VEGF and IL-6 levels were assessed using ELISA, and CRP was measured by immunoturbidimetry. They were compared between the colorectal carcinoma group and the control group. The five-year survival rate and poor prognostic factors were analyzed by Kaplan-Meier and Log-rank method, respectively. RESULTS: The serum VEGF, IL-6, and CRP levels in colorectal carcinoma were (591 ± 312) pg/ml, (13.2 ± 3.7) pg/ml, and (1.14 ± 0.87) mg/dl, respectively, higher than that in the control group. The two groups showed significant difference in VEGF and CRP (P < 0.001, P = 0.002). VEGF expression was higher in male than that in female [(638 ± 387) pg/ml vs. (552 ± 271) pg/ml, P = 0.042]. The cases with tumor size smaller than 5 cm had lower VEGF expression compared with that in cases with tumor size ≥ 5 cm [(538 ± 275) pg/ml vs. (647 ± 331) pg/ml, P = 0.009]. IL-6 expression showed significant difference in males (11.7 ± 3.2) and females (15.2 ± 4.0) pg/ml, (P = 0.011). The five-year survival rate in the group with VEGF < 591 pg/ml was 86.8% (33/38), higher than that in the ≥ 591 pg/m group. High VEGF level tended to reduce survival (χ(2) = 0.933, P = 0.344). VEGF ≥ 591 pg/ml was a factor of poor prognosis in colorectal carcinoma, assessed by Log-rank methods (P < 0.05). Tumor size and VEGF concentration were risk factors of prognosis (P = 0.032, OR = 0.985; P = 0.011, OR = 0.976). CONCLUSIONS: Serum VEGF and IL-6 expressions have gender differences. Serum VEGF can be used as a biomaker of clinical diagnosis of colorectal cancer, and has an important significance on the prognosis of patients.

[Effect of actovegin on intestinal mucosa and expression of bcl-2/bax genes in rats with acute radiation enteritis].

OBJECTIVE: To evaluate the effect of actovegin (Nycomed, deproteinized hemoderivative of calf blood injection) on intestinal mucosa in rats with acute radiation enteritis, and observe the changes of expression of apoptosis-related bcl-2/bax genes. METHODS: An abdominal irradiation in a dose of 9.0 Gy X-ray of linear accelerator was performed once on a group of Wistar rats to establish a model of acute intestinal radiation enteritis. The experimental rats were randomly divided into five groups. Group 1 was normal control group; group 2 was model control group; groups 3, 4 and 5 were treated with low, middle and high dose of actovegin, respectively. After the model was established, actovegin injection was given intraperitoneally for successive 4 days. Corresponding intestinal tissues were taken for morphological examination with an image analysis system. The expression of apoptosis related bax and bcl-2 protein in the intestinal mucosal epithelial cells was determined by immunohistochemistry. RESULTS: The groups 4 and 5 had significantly higher height of intestinal villi, the depth of crypt, the thickness of the mucosa and entire wall (254.66/261.71 microm, 166.47/165.41 microm, 510.44/511.71 microm, 610.38/608.98 microm), compared with those of the model control group (239.12 microm, 151.45 microm, 420.27 microm and 579.32 microm), respectively (P < 0.05). Treatment with middle and high doses of actovegin also significantly down-regulated the expression of activating apoptosis protein bax (24.54/23.24) compared with that of model control group (59.32) (P < 0.05) and up-regulated the expression of inhibiting apoptosis protein bcl-2 (55.54/52.21) compared with that of model control group (20.32) (P < 0.05). The ratio of bcl-2/bax was significantly higher in the groups 4 and 5 (2.2632, 2.1275) compared with that in the model control group (0.3425) (P < 0.01). CONCLUSION: Actovegin accelerates the recovery of the acute radiation-injured intestinal mucosal epithelium by decreasing apoptosis via down-regulation of the expression of activating apoptosis protein bax and up-regulation of inhibiting apoptosis protein bcl-2.

[Radiosensitization by double suicide gene system in ACC-2 cell].

PURPOSE: To investigate the radiosensitization by prodrug and CD-TK double suicide gene therapy system in adenoid cystic carcinoma cells (ACC-2). METHODS: The eukaryotic expression plasmids pIRES-CD and pIRES-TK were introduced into ACC-2 cells by electroporation. Then ACC-2 cells stably expressing CD and TK gene were obtained by 10-day positive selection with 400 micro g/mL G418 . The total RNA was extracted and the expression of the CD and TK gene in transfected ACC-2 cells was identified by RT-PCR. The positive transfected ACC-2 cells were treated with radiotherapy of different dose (0,2,4,6,8,10 Gy) and prodrug system in aerobic and anoxic condition. Then cell clone formation assay was used to study the radiosensitization by CD-TK double suicide gene therapy and prodrug system in ACC-2.The data was analyzed by multiple factor ANOVA using SPSS11.5 software package. RESULTS: RT-PCR analysis demonstrated that CD and TK genes were effectively expressed in ACC-2 cells. With the increased of X-ray dose, the colony forming rate dropped significantly after radiotherapy. In aerobic condition, the survival fraction of group ACC-2/CD-TK+prodrug were significantly lower than that of group ACC-2 and group ACC-2/CD-TK with the same dose (P<0.05). In anoxic condition, the survival fraction of group ACC-2/CD-TK+pro-drug was significantly lower than that of experimental group ACC-2 and group ACC-2/CD-TK with the same dose (P<0.05). The colony forming rate in aerobic condition was significantly lower than that in anoxic condition of the same cell group and dose. CONCLUSION: The radiosensitivity and the killing effect of X ray to ACC-2 cells can be increased by CD-TK double suicide gene therapy and the prodrug system.

Effects of experimental colitis on the expressions of calcitonin gene-related peptide and vanilloid receptor 1 in rat spinal cord sensory neurons.

To study the acute and long-term effects of local gut inflammation on the sensitivity of the spinal sensory neurons, the expressions of vanilloid receptor 1 (VR1) and calcitonin gene-related peptide (CGRP) in the colon-innervated primary sensory neurons in dorsal root ganglia (DRG) were examined in rats with trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. The neurons projecting to the distal colon were identified by DiI(3) retrograde labelling. Macroscopic examination, mean damage score and myeloperoxidase (MPO) activity were determined to assess the inflammatory status of the colon tissue. The number of CGRP and VR1 immunoreactive neurons at different stages of inflammation (on days 7, 21 and 42 after TNBS treatment) were compared. On day 7 after TNBS treatment, macroscopic damage of the mucosa could be easily detected and the percentage of colon-innervated DRG neurons expressing CGRP and VR1 increased nearly two folds respectively [(95.38±9.45)% vs (42.86±.02)% for CGRP, (89.23±8.21)% vs (32.54±4.58)% for VR1]. When the colon inflammatory reaction was resolved on days 21 and 42 after TNBS treatment, the percentage of colon-innervated DRG neurons expressing CGRP and VR1 were still higher than that in the control group [(86.25±8.21)%, (68.28±7.12)% vs (42.86±5.02)% for CGRP; (67.22±6.52)%, (56.25±4.86)% vs (32.54±4.58)% for VR1]. These results suggest that the local gut inflammation increases the expressions of CGRP and VR1 in gut-innervated DRG sensory neurons. More importantly, this abnormal status persists even after the gut inflammatory reaction has been resolved for certain time.

[Clinical analysis of 108 cases with adenocarcinoma Barretts's esophagus].

OBJECTIVE: To investigate the prognostic factors and to analyze the efficacy of chemotherapy and/or radiotherapy for Barrett's esophageal adenocarcinoma after radical surgical resection. METHODS: The clinical data of 108 patients with adenocarcinoma Barrett's esophagus picking out from 783 esophageal adenocarcinoma patients surgically treated between June 1978 to June 2001 in the Shandong Provincial Hospital and Shandong Qianfoshan Hospital were analyzed retrospectively. 60Co gamma-irradiation or 6MVX-ray with conventional fraction were used for radiotherapy with a total volume dosage of 55-70 Gy. The chemotherapy was either FAM (iv infusion of 5-Fu 500 mg, d1-d5; ADM 50 mg d1; MMC 12 mg, d1) or CMF regimen (iv infusion of CTX 800 mg d1, d8; MTX 30 mg d1; 5-Fu 500 mg, d1-d5) for 4-6 cycles. The Kaplan-Meier amalysis was used to estimate the survival rate. Log rank test was used for comparison of the survival difference among different groups. RESULTS: In this series, 76 of 92 patients who underwent radical surgical resection received postoperative radiotherapy alone, and 16 received radiotherapy plus chemotherapy. Twelve of the other 16 patients who underwent palliative surgical resection received chemotherapy plus radiotherapy, the remaining 4 patients died of operative complications during surgery. The overall 1-, 3- and 5-year survival rate of this series was 81.5%, 51.9% and 22.2%, respectively. In the radical resection group, it was 15.8% for the patients received radiotherapy alone versus 75.0% for those treated by chemotherapy plus radiotherapy. The 5-year survival rate was 33.3% for the patients without extra-esophageal infiltration and 33.3% for the patients without lymph node metastasis, respectively. However, it was only 9.1% for the patients with extra-esophageal infiltration and 14.3% for those with lymph node metastasis, respectively. For the patients who had palliative surgical resection, though they received chemotherapy plus radiotherapy postoperatively, none of them survived longer than 5-year. Statistically significant difference among these groups was demonstrated by Log rank test (P < 0.05). CONCLUSION: Chemotherapy plus radiotherapy after radical surgical resection may improve the survival of patients with adenocarcinoma in Barrett's esophagus adenocarcinoma patient. The pathological stage, extra-esophageal infiltration, lymph node metastasis and postoperative chemotherapy plus radiotherapy are important prognostic factors.

[Anti-nasopharyngeal carcinoma effect in vivo and in vitro of Avastin and adenovirus-thymidine kinase suicide gene].

OBJECTIVE: To evaluate the effect of Avastin and adenovirus-thymidine kinase/ Ganciclovir (Ad-TK/GCV) suicide gene system on nasopharyngeal carcinoma in vivo and in vitro. METHODS: The expression of vascular endothelial growth factor (VEGF) by CNE1 cell line was detected by VEGF ELISA. The effect of Avastin and Ad-TK/GCV on CNE1 cell was detected by methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry analysis and Hoechst 33342 staining were adopted to explore the killing mechanism of Ad-TK/GCV. The nude mice models of CNE1 cell xenografts were established. After intra-tumoral injection of PBS, Avastin, Ad-TK/GCV, Ad-Lac-Z/GCV and Ad-TK/GCV + Avastin, tumor volume was measured and tumor inhibitory rate was calculated. Then the tumors were removed and subjected to histological examination. RESULTS: CNE1 cells could produce VEGF. Avastin had no direct effect on CNE1 cells. The killing effect of Ad-TK/GCV increased with the increase of Ad-TK multiple of infection and the prodrug concentration, which was enhanced by the existence of bystander effect. Compared with control group, the death cell rate (P = 0.000) and apoptosis cell rate (P = 0.000) had significant difference. The study in vivo showed the tumors treated with Avastin, Ad-TK/GCV and Ad-TK/GCV + Avastin grew slowly compared with control. Tumor volume of treated groups was significantly smaller than that of control (all P < 0.05 or P = 0.000). Tumor weight of treated groups was significantly lower than that of control (all P = 0.000). The histological examination showed local necrosis in Ad-TK/GCV group and Ad-TK/GCV + Avastin group, poor angiogenesis in Avastin group and Ad-TK/GCV + Avastin group. CONCLUSIONS: Avastin had no direct effect on CNE1 cells in vitro. Ad-TK/GCV suicide gene system killed NPC cells by inducing cell necrosis and apoptosis, which could be enhanced by the existence of bystander effect. Avastin and Ad-TK/GCV suicide gene system could inhibit the growth of NPC CNE1 cell xenografts. Combination therapy had a synergic effect.