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Objective:To investigate the characteristics, process, and prognosis of esophageal stricture after circumferential endoscopic submucosal dissection (ESD), and to preliminarily analyze the prevention and treatment effects of simple dilation, stent placement, mucosal transplantation, and glucocorticoid (hereinafter referred to as hormone) application in esophageal stricture.Methods:From August 2017 to March 2022, at the First Affiliated Hospital of Zhengzhou University, the clinical and follow-up data of 55 patients who underwent circumferential ESD for early esophageal cancer and precancerous lesions were retrospectively analyzed. According to the prevention and treatment methods for esophageal stricture, the patients were divided into two groups: simple dilation group (23 cases) and combined dilation group (32 cases). The combined dilation group was divided into mucosal transplantation subgroup (9 cases), stent placement subgroup (14 cases), hormone application subgroup (7 cases), and bleomycin subgroup (2 cases, excluded from comparative analysis due to limited cases). Overall prognosis of patients was observed. Treatment efficacy, prognosis, and adverse events were compared among the simple dilation group, mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup. Independent samples t-test, chi-square test, and Fisher′s exact test were used for statistical analysis. Results:Among the 55 patients, the follow-up time was (894.1±417.7) days. Refractory esophageal stricture (total dilation times ≥ 5) occurred in 33 patients (60.0%). Fifty-two patients (94.5%) achieved clinical remission of the stricture. The total number of dilations was 5.8±4.0, and the average dysphagia-free period was (52.3±37.1) days. The dysphagia-free period of mucosal transplantation subgroup was longer than that of the simple dilation group, stent placement subgroup, and hormone application subgroup ((114.5±50.0) days vs. (40.9±20.0), (39.7±10.0), and (40.9±25.5) days, respectively), and the differences were statistically significant ( t=4.82, 3.77 and 3.14, P<0.001, =0.011, =0.009). There were no statistically significant differences between the simple dilation group and the mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup in the total number of dilations (6.8±4.8 vs. 3.0±2.5, 5.8±2.2, and 5.7±5.0), stricture remission rate (95.7%, 22/23 vs. 8/9, 13/14, and 7/7), and incidence of adverse events (17.4%, 4/23 vs. 5/9, 5/14, and 2/7; all P>0.05). Conclusions:Esophageal stricture formed after circumferential ESD shows the characteristics of recurrence and intractability. The over all number of dilations is high, and the average dysphagia-free period is short. Most patients can achieve clinical remission of the stricture after multiple times of endoscopic dilation treatment. However mucosal transplantation, stent placement, and hormone application cannot well intervene the natural process of esophageal stricture.
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Objective@#To construct the competitive endogenous RNA (ceRNA) network related to gastric cancer and explore the molecular mechanism.@*Methods@#The expression profiles of lncRNA, miRNA and mRNA in gastric cancer and paracancer tissues were analyzed by biochip technology, edgeR package in R software was used to filtrate differential expression genes (multiple change of >1.5 times, P<0.05) and volcano map was drawn. Based on the online miRNA-lncRNA prediction tool lncBase database and the miRNA Target gene prediction database (miRTarBase, target-scan, miRDB, starBase), the relationship between miRNA, lncRNA and mRNA was predicted. Cytoscape software was used to construct lncRNA-miRNA-mRNA ceRNA network and key genes (hub genes) were identified based on cytohubba calculation of degree score of each node. Then Hub genes related to the prognosis of gastric cancer were verified in the TCGA database. The GO and KEGG enrichment analysis of differentially expressed mRNA was performed using the online biological information annotation database DAVID, P<0.05 and false discovery rate (FDR)<0.05 were used as cut-off criteria. R software was used to download the RNA sequencing data and mirna-seq data of gastric cancer and adjacent tissues in TCGA database, edgeR package was used to screen out differentially expressed mRNA, miRNA and lncRNA, and some differentially expressed genes in our data were verified. In OncoLnc database, STAD project of TCGA data was selected and hub gene was input. Patients were divided into two groups based on the median value for hub genes and Kaplan-meier analysis was performed.@*Results@#The differentially expressed 766 mRNA, 110 lncRNA and 10 miRNA were screened out, among them 90 mRNA, 4 lncRNA and 6 miRNA were used to construct the ceRNA network, and 2 of the 20 hub genes were related to the prognosis of patients. MLK7-AS1, SPP1, SULF1, hsa-miR-1307-3p were upregulated in gastric cancer tissues from our biochip, while MT2A, MT1X were downregulated, which were consistent with the results of TCGA gastric cancer database. The differentially expressed mRNAs were significantly enriched in the biological process (BP) and the mineral absorption pathway. CHST1 was negatively correlated while miR-183-5p was positively corelated with the survival of patients.@*Conclusion@#The establishment of ceRNA network for gastric cancer is conducive to further understanding of the molecular biological mechanism. CHST1 and miR-183-5p can be used as prognostic factors of gastric cancer.
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Objective@#To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues. @*Methods@#From August 2011 to May 2013, 73 patients with ESCC, who received radical resection in The First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospital, were enrolled. The expressions of ESCCAL-1 in esophageal tumor tissues and corresponding adjacent non-tumor tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). T test, chi square test and multivariate analysis were performed for statistical analysis. @*Results@#The expression of ESCCAL-1 was 28.03±9.37 in esophageal tumor tissues of patients with ESCC, which was higher than that in corresponding adjacent normal tissues (11.39±4.15), and the difference was statistically significant (t=2.964, P<0.01). However there were no statistically significant differences in the expressions of ESCCAL-1 among the patients with different age, gender, histological grade, classification of Union for International Cancer Control (UICC), T stage or lymph nodes metastasis (all P>0.05). The median disease-free survival (DFS) time and overall survival (OS) time of patients with low ESCCAL-1 expression were 39 months and 42 months, respectively, which were longer than those of patients with high ESCCAL-1 expression (30 months and 37 months), and the differences were statistically significant (χ2=9.049, P=0.003; χ2=10.165, P=0.001). The results of multivariate analysis showed that ESCCAL-1 expression was the independent risk factor of DFS and OS (high risk (HR)=2.45, 95% confidence interval (CI) 1.22 to 4.93, P=0.012; HR=2.29, 95%CI 1.14 to 4.59, P=0.019). @*Conclusions@#ESCCAL-1 may be involved the genesis and development of ESCC. The expression of ESCCAL-1 in esophageal tumor tissues may be a prognostic parameter for patients with ESCC receiving radical resection.
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Objective@#To explore the expression of long noncoding RNA (lncRNA) HOXA11-AS in esophageal squamous cell carcinoma tissues and the relationship of HOXA11-AS level with clinical outcomes.@*Methods@#Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression level of HOXA11-AS in cell lines HET-1A, EC9706, EC109, and in tumor tissue and paired adjacent tissue samples from 73 ESCC patients who received surgical resection.The correlations of the expression level of HOXA11-AS with clinicopathological features and prognosis were also analyzed.@*Results@#The relative expression levels of HOXA11-AS in tumor tissue and paired adjacent tissue were 0.832±0.387 and 2.486±1.087, respectively, with significant difference (P<0.001). The expression of HOXA11-AS was upregulated in 63.0%(46/73)ESCC tissues. The relative expression levels of HOXA11-AS in HET-1A, EC-9706 and EC-109 cells were 1.000, 23.553±3.221 and 17.217±1.968, respectively. The expression level of HOXA11-AS was upregulated in ESCC cell lines (P<0.001). High expression level of HOXA11-AS was correlated with histological grade and lymph node metastasis of ESCC patients (P<0.05). However, it was not associated with the age, gender, depth of infiltration and TNM staging (P>0.05). The median overall survival (OS) and median disease-free survival (DFS) of patients with low HOXA11-AS expression were 43 months and 42 months, respectively, significantly longer than 37 months and 28 months of patients with HOXA11-AS high expression (P<0.05). Cox model multivariate analysis showed that the expression of HOXA11-AS and lymph node metastasis were independent factors of poor prognosis of ESCC patients.@*Conclusions@#The expression of HOXA11-AS is upregulated in esophageal cancer cell lines and tissues. High expression of HOXA11-AS is associated with poor prognosis of ESCC patients.Therefore, LncRNA HOXA11-AS may serve as a predictive marker of postoperative ESCC patients.
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Objective@#To investigate the relationship of heterogeneity of esophageal squamous cell carcinoma (ESCC) and chemotherapy sensitivity.@*Methods@#Five different region specimens isolated from primary tumor(R1~R5)and 1 specimen(R6)isolated from adjacent non-neoplastic tissue from 10 ESCC patients who underwent surgical treatment were cultured in vitro. The inhibitory effect of cisplatin on proliferation of ESCC cells from different regions was determined by methyl thiazolyl tetrazolium (MTT). The cell cycle and apoptosis induced by cisplatin was determined by flow cytometry (FCM) analysis. The mRNA levels of ATP7A and ATP7B were determined by quantitive RT-PCR (qRT-PCR).@*Results@#The result showed that different regions of each specimen exhibited different chemotherapy sensitivity to cisplatin, and the cell survival rates of region R6 of each specimen were higher than other regions from the same specimen. The cell survival rate of region R3 from the tenth specimen was (81.42±8.84)%, which is significantly higher than (11.90±2.75)% of region R5 (P<0.01). FCM analysis showed that significant differences of early apoptosis and later apoptosis were observed in six specimens induced by cisplatin (P<0.05), and significant differences of cell cycle and G1 period were observed in seven specimens (P<0.05). The qRT-PCR results showed that the mRNA level of ATP7A in region R1, R2, R3, R4 and R5 was (100.00±3.42)%, (118.10±2.21)%, (75.40±4.15)%, (95.40±3.32)% and (41.70±2.57)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7A in region R6 was (175.20±5.32)%, significantly higher than those of regions from R1 to R5 (P<0.05). The mRNA level of ATP7B in region R1, R2, R3, R4 and R5 was (100.00±4.89)%, (73.60±2.65)%, (175.60±6.12)%, (46.10±4.62)% and (363.70±8.67)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7B in region R6 was (1 165.40±7.25)%, significantly higher than those of regions from R1 to R5 (P<0.05).@*Conclusion@#The intratumor heterogeneity of ESCC results in the heterogeneity of resistance to cisplatin, which affects the chemotherapeutic effect.
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Background and purpose: In recent years indirubin-3'-monoxime has been found to be capable of inhibiting some cell proliferation in vitro and in vivo studies, but human colon cancer HT-29 cells, therefore the purpose in this paper was to study the effect of indirubin-3'-monoxime on proliferation and apoptosis of HT-29 cells and its associated mechanism. Methods: HT-29 cells were treated with indirubin-3'-monoxime. The proliferative status of cells was measured by methabenzthiazuron (MTT) assay, flow cytometry (FCM) was used to measure the apoptosis rate. RT-PCR was used to measure the transcription of apoptosis suppressor gene bcl-2, survivin and apoptosis promoting gene Bar. Results: Indimbin-3'-monoxime inhibited growth of HT-29 cells in a dose-dependent and time-dependent manner (F=11.25, P<0.01). The apoptosis rate increased after the treatment by indirubin-3'-monoxime at 10 μmol/L. There were significant differences between different time groups (F=195.25, P<0.01). The transcription of survivin (F=78.75, P<0.01) and Bax (F=87.61, P<0.01) mRNA in HT-29 cells were increased; the transcription of bcl-2 was significantly decreased (F=95.82, P<0.01). Conclusion: Indirubin-3'-monoxime has obviously inhibited proliferation and induce apoptosis of colon cancer HT-29 cells, its mechanism may be related to decrease the bcl-2/Bax ratio.
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Background and purpose:Postoperative recurrence of esophageal cancer is one of the main factors that affect the patients’ prognosis and quality of life. This study mainly investigated the clinical features of thoracic stomach cancer (TSC) after surgical treatment for esophageal carcinoma. Methods:We retrospectively reviewed 51 cases of postoperative TSC in our hospital. Results:10.97% of the cases with TSC were diagnosed by endoscopy. There were 13 cases who also had anastomotic recurrence. The locations of 46 cases (90.2%) in 51 patients were same as the primary cancer. 48 cases of them were squamous cell carcinoma and 3 cases were adenocarcinoma at the time of esophagectomy for esophageal carcinoma. Endoscopic manifestations were puffiness-infiltrating type 39.2%(20/51), massive type 15.7%(8/51), ulcerative type 7.8%(4/51) and ulcer-infiltrating type 33.3%(17/51) and diffuse infiltrating type 3.9(2/51). Conclusion:The incidence of TSC after surgical treatment for esophageal carcinoma was high. The main cause was that the local residual cancer invaded the gastric wall. The gastroscopic features of TSC were different from gastric cancer. The follow up with endoscopy for the postoperative patients with esophageal carcinoma is a primary way to diagnose TSC.