Administration of Valproic Acid Improves the Survival of Patients with Glioma Treated with Postoperative Radiotherapy.

OBJECTIVE: The aim of this study was to investigate the impact of valproic acid (VPA) on survival and prognosis of patients with glioma who underwent postoperative radiotherapy. METHODS: We obtained the case data with brain glioma who underwent postoperative radiotherapy from January 2012 to December 2019. This cohort was heterogeneous. We conducted single-factor analysis and multiple-factors analysis of the basic features, pathological classification, therapies of all 185 patients using Kaplan-Meier survival curve, log-rank survival significance test, and Cox regression analysis model. RESULTS: By the end of the last follow-up, 94 patients had died and 96 had recurred in all 185 cases. The median follow-up time of this study was 47 months. The median overall survival (OS) and progression-free survival (PFS) times were 34 and 27 months, respectively. The 1-, 3-, and 5-year OS rates were 86.49%, 48.11%, and 14.60%, respectively. The 1-, 3-, and 5-year PFS rates were 80.00%, 43.78%, and 12.97%, respectively. Univariate analysis revealed that age, pathological grade, and VPA administration were all associated with patients' prognosis (p < 0.05). A Cox multivariate analysis revealed that being 47 years or older, having a high pathological grade (WHO grades III and IV), and not taking VPA were all adverse prognostic factors for OS and PFS in patients with glioma. CONCLUSION: Age, pathological grade, and VPA administration are the influencing factors for the prognosis of glioma patients with postoperative radiotherapy. Patients with glioma who received VPA had a more favorable prognosis and a lower recurrence rate.

Syntaphilin downregulation facilitates radioresistance via mediating mitochondria distribution in esophageal squamous cell carcinoma.

Syntaphilin (SNPH) halts mitochondrial movements and regulates proliferation-motility phenotype switching of cancer cells. We sought to investigate the significance of SNPH-mediated mitochondria distribution in radioresistant (RR) phenotype switching in esophageal squamous cell carcinoma (ESCC). RR ESCC cells were established by long-term exposure to radiation. Effects of SNPH on proliferation, migration, mitochondrial distribution, radiation-induced oxidative damage and radiosensitivity were investigated by overexpressing or silencing SNPH. The mechanisms regulating SNPH expression and the potential molecules mediating the SNPH-re-expression-induced radiosensitization were explored. SNPH expression in specimens from 156 patients was analyzed to evaluate its clinical significance. We found that RR ESCC cells had a sparse mitochondrial network and lower SNPH level. SNPH reconstitution in RR ESCC cells inhibited migration, induced proliferation and mitochondrial aggregation, exacerbated the radiation-induced oxidative damage and ultimately promoted radiosensitization. Mechanistically, ubiquitin-proteasomal degradation and histone modification contributed to SNPH downregulation in RR ESCC cells. Subsequently, we found that CREB dephosphorylation facilitated the SNPH re-expression-induced radiosensitization. Furthermore, SNPH expression was correlated with the radiotherapeutic efficacy and served as an independent prognostic factor for survival of ESCC patients. Our study revealed that low SNPH expression was a novel indicator for radioresistance, and targeting SNPH could be a promising regimen to improve the radiotherapeutic efficiency in ESCC patients.

The Number of Negative Lymph Nodes is Positively Associated with Survival in Esophageal Squamous Cell Carcinoma Patients in China.

BACKGROUND: There is a controversial relationship between the negative lymph nodes (NLNs) and survival in patients with esophageal squamous cell carcinoma (ESCC). This study investigates the implications of total number of NLNs on thoracic ESCC patient prognosis. METHODS: 579 thoracic ESCC patients were categorized into four groups (0-9, 10-14, 15-19 and ≥20 NLNs). Univariate analysis was done by the log-rank tests while multivariate analysis was undertaken using Cox regression models. Survival analysis was determined employing the Kaplan-Meier method. RESULTS: When the numbers of NLNs were 9 or less, 10 to 14, 15 to 19 and 20 or more, patients of 3-year survival rates were 21.7%, 40.0%, 61.2% and 77.5%, respectively (P<0.001). In the node-negative and node-positive subgroups, 3-year survival rates were 34.9% and 14.3%, 50.9% and 19.3%, 65.6% and 51.8%, 81.4% and 68.9% respectively (P<0.001). Gender, tumor length, tumor differentiation, T and N stage as well as the total NLNs were found to be significantly linked to survival rates. Multivariate analysis showed tumor length, T stage, N stage and total NLNs were independent prognostic factors for ESCC patients. CONCLUSION: NLNs numbers is a significant independent prognostic indicator for thoracic ESCC patients' survival after curative esophagectomy.

Intensity-modulated radiotherapy does not decrease the risk of malnutrition in esophageal cancer patients during radiotherapy compared to three-dimensional conformal radiation therapy.

BACKGROUND: Esophageal cancer is a lethal disease of global scope. Radiotherapy is the main method to treat esophageal cancer; however, it concurrently leads to malnutrition. Intensity-modulated radiotherapy (IMRT) is superior to three-dimensional conformal radiation therapy (3D-CRT) in dosimetry and clinical outcomes. In this cohort study, we aimed to compare the effect of 3D-CRT and IMRT on malnutrition status. METHODS: We retrospectively included 79 esophageal cancer patients (IMRT: n=27, 3D-CRT: n=52) who received radiotherapy. We collected nutrition indexes at the beginning, the second week, and the end of radiotherapy. Paired-T test was used to evaluate the nutrition status during radiotherapy in each group. Chi-square test and independent-sample T-test were applied to compare the dynamic changes of indexes between IMRT and 3D-CRT groups. RESULTS: The baselines of the two groups are comparable. Nutrition Risk Screening 2002 (NRS-2002) score, body weight, BMI, hemoglobin, lymphocyte, total protein, and albumin values were significantly reduced during radiotherapy in both groups. The dynamic changes of nutrition indexes during radiotherapy were not significantly different between the IMRT and 3D-CRT groups. Besides, no difference was found for radiation esophagitis or treatment completion between the two groups. CONCLUSIONS: Malnutrition occurs in esophageal cancer patients during radiotherapy. IMRT did not significantly decrease the risk of malnutrition compared to 3D-CRT.

The Clinical Prognostic Value of LRG1 in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Leucine-rich-alpha-2-glycoprotein1 (LRG1) is a new oncogene-related gene, which has been proven important for the development and poor prognosis of human cancers. However, whether it participates in esophageal squamous cell carcinoma (ESCC) progression remains unclear. OBJECTIVE: To investigate the expression level and functional influence of LRG1 in ESCC. METHODS: The expression of LRG1 was evaluated on the mRNA and protein level in ESCC patients. Then, correlation of LRG1 expression with clinicpathological variables was analyzed in ESCC. Besides, to clarify the biological function of LRG1, Eca109 and KYSE150 cells were transfected with LRG1 shRNA, the cell viability, clonal efficiency, apoptosis and invasion assays in vitro were performed. RESULTS: LRG1 was significantly over-expressed in ESCC and related to deeper invasion depth (T stage) and distal metastasis (M stage). Kaplan-Meier analysis indicated that LRG1 up-regulation in ESCC was closely correlated to worse clinical survival (overall survival and progression-free survival), all P<0.001. LRG1 was confirmed to be an independent poor premonitory indicator for clinical outcomes in ESCC through the univariate and multivariate analyses. Down-regulation of LRG1 in ESCC cells markedly suppressed cell proliferation and invasion, stimulated apoptosis (all p <0.01). CONCLUSION: LRG1 might play a significant role in the progression of ESCC, and could be served as a promising prognostic prediction for ESCC patients.

Monocarboxylate transporter 1 is an independent prognostic factor in esophageal squamous cell carcinoma.

The monocarboxylate transporter 1 (MCT1) has been reported to have significant prognostic value in several solid tumors. The present study aimed to explore its clinical significance in esophageal squamous cell carcinoma (ESCC). After acquiring and analyzing MCT1 (solute carrier family 16 member; SLC16A1) mRNA expression in The Cancer Genome Atlas (TCGA) database, the prognostic potential of MCT1 was assessed by immunohistochemistry (IHC). The impact of the knockdown of MCT1 by shRNA was evaluated using Cell Counting Kit­8 (CCK­8) and colony formation assays to determine whether MCT1 suppression affected the proliferation and survival of ESCC cells. MCT1 expression was found to correlate with T stage (P=0.005), N stage (P=0.036) and TNM stage (P=0.035). Kaplan­Meier survival analysis showed that patients in a high­MCT1 group had a lower overall survival (OS) (P<0.001) and lower progression­free survival (PFS) (P<0.001). The results of univariate and multivariate Cox regression analyses demonstrated that MCT1 is an independent prognostic factor for OS (P=0.001 and 0.01) and PFS (P=0.001 and 0.012). Downregulation of MCT1 suppressed proliferation and survival of ESCC cells in vitro. The proliferation rate and colony numbers were decreased in the sh­MCT1 groups (all P<0.05). Downregulation of MCT1 suppressed VEGF expression (all P<0.05). MCT1 may act as a biomarker for ESCC to identify patients with poor outcomes.

Survival Impact of Delaying Postoperative Radiotherapy in Patients with Esophageal Cancer.

The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards models were performed for both PFS and OS for all assumed predictor variables. Statistically significant predictor variables (P < .05) on univariate analysis were then included in multivariate Cox proportional-hazards models, which were performed to compare the effects of RT delay on PFS and OS. A total of 316 patients were finally enrolled in this prospectively multicentric study. Time to RT after surgery varied from 12 days to over 60 days (median, 26 days). Multivariate analysis showed that delay to RT longer than the median does not appear to be a survival cost. There was also no statistically difference in PFS (P = .513) or OS (P = .236) between patients stratified by quartiles (≤21 days vs ≧35 days). However, patients with particularly long delays (≧42 days) demonstrated a detrimental impact on OS (P = .021) but not PFS (P = .580). Delaying postoperative RT of esophageal cancer does not impact PFS, but results in a significant reduction on OS if delaying longer than 6 weeks.

miR-146a-5p mediates epithelial-mesenchymal transition of oesophageal squamous cell carcinoma via targeting Notch2.

This corrects the article DOI: 10.1038/bjc.2016.367.

The effects of air pollution on mortality and clinicopathological features of esophageal cancer.

This study aimed to estimate the associations between air pollution and esophageal cancer. In the ecologic cross-sectional study, correlation analyses were made between city-level mean concentrations of particulate matter less than 10µm in aerodynamic diameter (PM10), SO2, NO2 and city-level age-standardized mortality rates of esophageal cancer in Shandong Province, China. PM10 (p=0.046) and NO2 (p=0.03) both had significant linear correlations with esophageal cancer mortality rates. After introducing smoking as a risk factor in models of multiple linear regression analyses, PM10 was still an independent risk factor that increased esophageal cancer mortality rates. This study further compared clinicopathological features of 1,255 eligible esophageal squamous cell carcinoma patients by dividing them into different pollution level groups. There was statistically significant difference in gender distributions (p=0.02) between groups after subgroup analysis. Female patients accounted for a higher proportion in the high PM10 level group than in the low PM10 level group. It suggested that females were more sensitive to higher PM10 level pollution. The features that manifested the degree of malignancy of esophageal cancer, including primary tumor invasion, regional lymph nodes metastasis, histological grade, stage, lymph-vascular invasion and tumor size demonstrated no statistically significant difference between groups.

The clinical significance of isocitrate dehydrogenase 2 in esophageal squamous cell carcinoma.

Isocitrate dehydrogenase 2 (IDH2) is the rate-limiting enzyme in the tricarboxylic acid (TCA) cycle in cellular metabolism. Growing evidence indicates that IDH2 plays a crucial role in the development of cancer. We aimed to investigate the expression level of IDH2 and its prognostic value in esophageal squamous cell cancer (ESCC). We evaluate the IDH2 expression and prognostic value in ESCC by immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK8), clonogenic and invasion assays were performed to verify the IDH2 function in vitro. The protein expression level of IDH2 was significantly upregulated in ESCC tissues (IHC, Western blotting, all P<0.001) despite no significant difference at mRNA expression level (P>0.05). Kaplan-Meier analysis showed that IDH2 overexpression in ESCC patients was significantly related to worse overall survival (OS) and progression-free survival (PFS), P = 0.003 and 0.002, respectively. The univariate and multivariate analyses revealed that IDH2 overexpression served as an independent prognostic factor for OS and PFS (all P<0.005) in ESCC. The OD450 value, colony formation and invasive cell number were decreased in the shIDH2 groups (all P<0.0001). The upregulation of IDH2 in ESCC cells showed opposite effects (all P<0.05). Additionally, IDH2 knockdown phenotype can be rescued by shRNA-resistant IDH2 (all P<0.05). These results demonstrated that IDH2 was upregulated in ESCC and could be used as a valuable prognostic marker for ESCC patients.

Preoperative serum lipids as prognostic predictors in esophageal squamous cell carcinoma patients with esophagectomy.

This study was to evaluate the prognostic significance of serum lipids in esophageal squamous cell carcinoma patients who underwent esophagectomy. Preoperative serum lipids were collected from 214 patients who were diagnosed with esophageal squamous cell carcinoma. All of the patients received esophagectomy in Qilu Hospital of Shandong University from January 2007 to December 2008. The records and data were analyzed retrospectively. We found that low total cholesterol (for T stage, p = 0.006; for TNM stage, p = 0.039) and low-density lipoprotein cholesterol (for T stage, p = 0.031; for TNM stage, p = 0.035) were associated with advanced T stage and TNM stage. Kaplan-Meier survival analysis indicated that low total cholesterol and low-density lipoprotein cholesterol were associated with shorter disease-free survival(for total cholesterol, p = 0.045; for low-density lipoprotein cholesterol, p < 0.001) and overall survival (for total cholesterol, p = 0.043; for low-density lipoprotein cholesterol, p < 0.001). Lower low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LHR) indicated poorer disease-free survival and overall survival (both p < 0.001). In the multivariate analysis, low-density lipoprotein cholesterol and LHR were independent prognostic factors for disease-free survival and overall survival. In conclusion, our study indicated that preoperative serum total cholesterol and low-density lipoprotein cholesterol are prognostic factors for esophageal squamous cell carcinoma patients who underwent esophagectomy. LHR can serve as a promising serum lipids-based prognostic indicator.

Prognostic significance of microRNA-100 in solid tumors: an updated meta-analysis.

OBJECTIVE: The aim of this study was to identify prognostic significance of microRNA-100 (miR-100) in solid tumor. METHODS: Literature search was conducted in databases such as PubMed, Embase, and Web of Science, using the following words "(microRNA-100 OR miR-100 OR mir100) AND (tumor OR neoplasm OR cancer OR carcinoma OR malignancy)." The search was updated up until July 10, 2016. Newcastle-Ottawa scale was used to evaluate the quality of studies. Pooled hazard ratio (HR) with 95% confidence interval (CI) for patients' survival was calculated by using a fixed-effects or a random-effects model on the basis of heterogeneity. Subgroup analysis, sensitive analysis, and meta-regression were used to investigate the sources of heterogeneity. Publication bias was evaluated by using Begg's and Egger's tests. RESULTS: A total of 16 articles with 1,501 patients were included in the present meta-analysis. It was demonstrated that a lower expression of miR-100 plays a negative role in the overall survival (OS) of patients with solid tumor (HR =1.92; 95% CI =1.25-2.94). In addition, the association between miR-100 and prognosis was also revealed in the following subgroups: non-small-cell lung cancer (NSCLC; HR =2.46; 95% CI =1.98-3.06), epithelial ovarian cancer (EOC; HR =2.29, 95% CI =1.72-3.04), and bladder cancer (BC; HR =4.14, 95% CI =1.85-9.27). CONCLUSION: This meta-analysis indicates that lower expression of miR-100 is related to poorer OS in patients with solid tumor, especially in those with NSCLC, EOC, and BC. MiR-100 is a promising prognosis predictor and may be a potential target for therapy in the future.

miR-146a-5p mediates epithelial-mesenchymal transition of oesophageal squamous cell carcinoma via targeting Notch2.

BACKGROUND: Our previous study found that dysregulated microRNA-146a-5p (miR-146a-5p) is involved in oesophageal squamous cell cancer (ESCC) proliferation. This article aimed to evaluate its detailed mechanisms in ESCC epithelial-mesenchymal transition (EMT) progression. METHODS: Invasion assay, qRT-PCR and western blotting were used to validate the roles of miR-146a-5p and Notch2 in EMT progression. miRNA target gene prediction databases and dual-luciferase reporter assay were used to validate the target gene. RESULTS: miR-146a-5p inhibitor led to increase of invaded ESCC cells, while miR-146a-5p mimics inhibited invasion ability of ESCC cells. Protein level of E-cadherin decreased, whereas those of Snail and Vimentin increased in the anti-miR-146a-5p group, which demonstrated that miR-146a-5p inhibits EMT progression of ESCC cells. miRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-146a-5p and dual-luciferase reporter assay validated it. Importantly, shRNA-Notch2 restrained EMT and partially abrogated the inhibiting effects of miR-146a-5p on EMT progression of ESCC cells. CONCLUSIONS: miR-146a-5p functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the EMT progression of ESCC.

Prognostic and diagnostic potential of isocitrate dehydrogenase 1 in esophageal squamous cell carcinoma.

We aimed to investigate the pattern of expression and clinical significance of isocitrate dehydrogenase 1(IDH1) in esophageal squamous cell carcinoma (ESCC). The IDH1 expression was determined by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis using 38 pairs of frozen tissues. Enzyme-linked immunosorbent assay was employed to measure 67 pairs of serum samples from patients and their controls to evaluate its diagnostic value. Immunohistochemistry analysis of 111 formalin-fixed paraffin embedded tissue samples was conducted for explaining its prognostic value. After shRNA transfection, CCK8 and clonal efficiency assays were carried on for verifying the function of IDH1 in vitro. Increased expression at mRNA (P < 0.001) and protein levels (immunohistochemistry: P < 0.001, Western blot analysis: P < 0.001) were observed. Similarly, the IDH1 expression in serum from patients with ESCC was significantly upregulated relative to that from healthy controls (P < 0.001). Kaplan-Meier curve indicated that IDH1 upregulation predicted worse overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses identified IDH1 expression as an independent prognostic factor for OS and PFS. Furthermore, OD450 values and colony numbers were decreased in sh-IDH1 groups (all P < 0.05). In conclusion, IDH1 is upregulated in patients with ESCC and can be used as a good potential biomarker for diagnosis and prognosis.

Impacts of physically active and under-active on clinical outcomes of esophageal cancer patients undergoing esophagectomy.

Physical activity has been reported to positively influence quality of life and survival in certain cancers. However, the associations between them in esophageal cancer are previously undefined. The aims of this study are to investigate whether physically active esophageal cancer patients have improved quality of life and lower risk of recurrence as well as death compared with physically inactive patients. We evaluated the relationships between postoperative leisure time physical activity and quality of life and recurrence and death among patients diagnosed with esophageal cancer. We respectively used generalized estimating equations and Cox proportional regression to analysis quality of life and survival, adjusting for known potential confounding factors. Comparing esophageal cancer patients reporting more than 9 MET hours per week of postoperative leisure time physical activity with those reporting less, we found improved quality of life. Additionally, we also found that postoperative leisure time physical activity ≥9 MET hours per week, compared with less, was associated with a 23% lower risk of all-cause mortality (HR, 0.666; 95% CI, 0.481-0.921; P=0.014) and a 53% lower risk of recurrence (HR, 0.306; 95% CI 0.218-0.429; P<0.001). Leisure time physical activity was significantly associated with quality of life and risk of recurrence and death of esophageal cancer patients. Clinicians should consider increasing physical activity, regardless of previous behaviors, as a part of primary cancer treatment. The ultimate goal is to improve quality of life and prolong survival of cancer survivors.

Serum miR-1297: a promising diagnostic biomarker in esophageal squamous cell carcinoma.

We aimed to value the diagnostic potential of serum miR-1297 in esophageal squamous cell cancer (ESCC). Its expression level was detected in 156 pairs of patients with ESCC and healthy volunteers using quantitative real-time polymerase chain reaction (qRT-PCR) method. It was statistically decreased in ESCC patients compared with healthy controls. AUC based on serum miR-1297 was 0.840 ± 0.035 in discovery group and 0.837 ± 0.034 in validation group. Further analysis on early-stage patients revealed that the AUC was 0.819 ± 0.053 in discovery group and 0.814 ± 0.044 in validation group. Its sensitivity and specificity were promising. In conclusion, serum miR-1297 can serve as an ideal indicator for the diagnosis of ESCC.

Notch2 as a promising prognostic biomarker for oesophageal squamous cell carcinoma.

We aimed to examine Notch2 expression in oesophageal squamous cell carcinoma (ESCC) patients and to evaluate its prognostic potential. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were utilized to investigate the Notch2 expression status and prognostic value. Furtherly, CCK8 and clonogenic assays were conducted to determine if Notch2 inhibition by shRNA could lead to a decrease in the proliferation and survival of ESCC cells. A notably higher Notch2 expression level was found in ESCC tissues at the mRNA (P < 0.0001) and protein levels (IHC: P = 0.004; western blot: P = 0.021). Log-rank analysis demonstrated that Notch2 overexpression was significantly associated with worse overall survival (OS) (29.1% vs. 49.1%; P = 0.013) and progression-free survival (PFS) (15.3% vs. 34.4%; P = 0.006) rates in ESCC patients. The multivariate analysis revealed Notch2 as an independent prognostic factor for OS and PFS (P = 0.002 and 0.006, resp.). Besides, in vitro assays showed that OD450 values and colony formations were significantly reduced in Notch2-shRNA group (all P < 0.0001). In conclusion, these results show that Notch2 is up-regulated in ESCC tissues and could serve as a promising biomarker for identifying individuals with poor prognostic potential.

Association of SOX2 and Nestin DNA amplification and protein expression with clinical features and overall survival in non-small cell lung cancer: A systematic review and meta-analysis.

Up to now, the prognosis of non-small cell lung cancer (NSCLC) is poor. With progress of cancer biology, a number of genes have been investigated for predicting prognosis of NSCLC, such as cancer stem cell markers SRY (sex determining region Y)-box 2 (SOX2) and Nestin. Recently, a series of studies have been performed to examine the associations of SOX2 and Nestin with clinical parameters and prognosis in NSCLC, however, the results were not consistent. In the present study, we conducted a systematic review and meta-analysis to summarize the associations. Four English databases (PubMed, ISI web of science, Embase, and Ovid) were used to search the relevant studies with the last date of November 10, 2015. The pooling analyses were stratified by DNA amplification and protein expression. The pooling ORs or HRs were used to assess the strength of the associations. Finally, we included 19 articles for SOX2 and six articles for Nestin according to the inclusion and exclusion criteria. The pooling analyses revealed that there were significant associations between SOX2 DNA amplification and clinical features of NSCLC, gender, smoking status, squamous cell cancer (SCC) histology, and differentiations. And significant associations were also identified between SOX2 protein expression and clinical parameters, smoking status and SCC histology. For Nestin, its protein expression was correlated with lymph node metastasis and stage. Simultaneously, we found that high/positive SOX2 alterations, either DNA amplification or protein expression, were favorable for overall survival (OS) in NSCLC. On the contrary, high/positive Nestin protein expression was poor for OS.

Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.

Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.

Prognostic and diagnostic potential of miR-146a in oesophageal squamous cell carcinoma.

BACKGROUND: Accumulating evidence indicates that dysregulated microRNA-146a (miR-146a) is involved in tumour genesis and cancer progression. We aimed to evaluate its expression level and the potential for the diagnosis and prognosis in oesophageal squamous cell cancer (ESCC). METHODS: We examined miR-146a expression in 62 pairs of ESCC cancerous and matched paracancerous tissue, 115 formalin-fixed paraffin-embedded (FFPE) tissue samples and serum samples from 154 ESCC patients and 154 healthy volunteers using quantitative reverse transcription-PCR (qRT-PCR). Kaplan-Meier method, Cox regression and receiver-operating characteristic (ROC) curve analysis were applied to analyse its prognostic and diagnostic value. RESULTS: MicroRNA-146a expression level was significantly decreased in ESCC tissue compared with paracancerous tissue (P<0.001). Its regulation level was negatively associated with T factor and TNM stage. Kaplan-Meier curve revealed that its downregulation level predicted worse overall survival (OS) and progression-free survival (PFS). Both univariate and multivariate analyses identified miR-146a expression as independent prognostic factor for OS and PFS. Serum miR-146a was significantly reduced in ESCC patients than in healthy controls (P<0.001). Area under the curve ROC value, sensitivity and specificity for this marker were 0.863 ± 0.033, 85.7% and 68.6% in the Discovery Group, and 0.891 ± 0.027, 82.1% and 83.3% in the Validation Group. CONCLUSIONS: MicroRNA-146a is significantly reduced in cancerous tissue and serum samples of ESCC patients. It is an ideal biomarker for the prognosis and diagnosis of ESCC.