Identification of RNF150 as the hub gene associated with microsatellite instability in gastric cancer.

Gastric cancer (GC) is a common digestive tract malignancy with the sixth global incidence and third cancer-related deaths, respectively. Microsatellite instability (MSI), accounting for one of the molecular subtypes of GC, plays an important role in GC and is affected by a sophisticated network of gene interactions. In this study, we aimed to explore the expression pattern and clinical performance of MSI related gene in GC patients. Weighted gene co-expression network analysis (WGCNA) was exploited to single out the vital module and core genes in TCGA database. We applied the protein-protein interaction (PPI) and survival analysis to propose and confirm RNF150 as the hub gene in GC. Finally, we utilized immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) to explore the expression pattern of RNF150 in GC patients. With the highest weight correlation and standard correlation, RNF150 was selected as the hub gene for following validation. In validation, data obtained from the test sets showed a lower expression of RNF150 in MSI GC compared to microsatellite stability (MSS) GC. Moreover, survival analysis shows that MSI GC patients with a lower RNF150 expression level displayed the longer OS time. Compared to the expression in normal gastric tissues, the protein level of RNF150 was virtually up-regulated in ten cases of GC tissues. Furthermore, RNF150 protein level was decreased in MSI GC samples compared to MSS GC samples. When validated the mRNA expression with RT-PCR in fresh GC tissues, we also found the similar trend. RNF150 was identified as a novel MSI-related gene in GC. It is expected to be an auspicious prognostic biomarker for GC patients.

Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

10,11-Dehydrocurvularin attenuates inflammation by suppressing NLRP3 inflammasome activation.

10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1ß secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Self-made wire loop snare successfully treats gastric persimmon stone under endoscopy.

BACKGROUND: Large gastric persimmon stones are generally resistant to standard endoscopic treatments. We applied an alternative endoscopic method using a hand-made snare for the treatment of large gastric phytobezoars. AIM: To explore the clinical efficacy of a self-made wire loop snare to treat giant gastric persimmon stones. METHODS: A retrospective study evaluated the clinical data of 38 patients with gastroliths admitted to Taihe Hospital in Shiyan City, Hubei Province, China, between March 2015 and October 2020. The patients were divided into observation (n = 23) and control (n = 15) groups. Patients in the observation group were treated with self-made wire loop snares for lithotripsy, and patients in the control group were treated with traditional foreign body forceps, snares, injection needles, and other tools. Successful stone removal, treatment time, and hospital stay were compared. RESULTS: The average operating time was significantly shorter (P < 0.001) in the observation group (53.4 min) than that in the control group (172.8 min). The average hospital stay of the observation group (5.4 d) was significantly shorter (P < 0.001) than that in the control group (10.3 d). Successful one-time treatment was significantly more frequent (P < 0.001) in the observation group (87%) than in the control group (7%). CONCLUSION: Self-made guidewire loop snares were successfully used to treat gastrolithiasis, and were significantly more effective than foreign body forceps, snares, and other traditional methods.

The efficacy and safety of keverprazan, a novel potassium-competitive acid blocker, in treating erosive oesophagitis: a phase III, randomised, double-blind multicentre study.

BACKGROUND: Keverprazan is a novel potassium-competitive acid blocker (P-CAB) with a strong acid-suppressive capacity that may provide clinical benefit in acid-related diseases. AIMS: This study aimed to explore the non-inferior efficacy and safety of keverprazan to lansoprazole in treating erosive oesophagitis (EO). METHODS: This was a phase III, randomised, double-blind multicentre study. Patients were randomised to receive keverprazan 20 mg once daily or lansoprazole 30 mg once daily for 4-8 weeks. EO healing rates and adverse events (AEs) were compared between the keverprazan group and the lansoprazole group. RESULTS: A total of 238 patients comprised the full analysis set (FAS) while 221 patients comprised the per-protocol set (PPS). For FAS analysis, the EO healing rates at week 8 were 95.8% (114/119) and 89.9% (107/119) for keverprazan and lansoprazole respectively. For PPS analysis, the EO healing rates at week 8 were 99.1% (110/111) and 92.7% (102/110) for keverprazan and lansoprazole respectively. Non-inferiority of keverprazan compared with lansoprazole according to EO healing rates at 8 weeks was demonstrated in both FAS (difference: 5.8% [95% CI: -0.6% to 12.3%]; p = 0.081) and PPS (difference: 6.1% [95% CI: 1.1%-11.2%]; p = 0.018) analysis. Drug-related AEs were reported in 34.5% (41/119) patients of the keverprazan group and 25.2% (30/119) patients of the lansoprazole group with no significant difference (p = 0.156). No severe AE happened in the keverprazan group. CONCLUSIONS: This study demonstrated the non-inferior efficacy of keverprazan to lansoprazole in treating EO. The incidences of drug-related AEs were comparable between keverprazan and lansoprazole.

Clinicopathological features of esophageal schwannomas in mainland China: systematic review of the literature.

OBJECTIVE: Esophageal schwannoma (ES) are rare and mostly benign neurogenic tumors. The clinical misdiagnosis rate of it is high. In this study, the clinicopathologic features of ES in mainland China were studied to better understand the disease and improve the diagnosis and treatment rate. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. The keywords "esophageal schwannoma", "esophageal neurinoma" and "esophageal neurilemoma" were searched for databases such as Pubmed, EMbase, Wanfang Database and Chinese National Knowledge Infrastructure. The search time frame for database was until July 2019. Combined with our patient, the clinicopathological data and the diagnosis and treatment of ES were summarized. RESULTS: ES occurs in the upper part of the mediastinum and in the thoracic esophagus in most patients in the neck, upper and middle segments. CT and PET/CT examinations can be used for diagnosis, but the differentiation value of both benign and malignant ES is similar. The histopathological findings of forceps biopsy specimens are often difficult to diagnose, and deep tissue biopsies may increase pathological accuracy. EUS-FNA is also recommended for ES diagnosis, but it may also be misdiagnosed. Pathological features include a fusiform arrangement in a palisade-like structure or a tumor cell arranged in a network to form a loose structure. ES characteristic immunohistochemistry results showed that S-100 protein has strong immunological activity. CONCLUSION: The definitive diagnosis requires immunohistochemistry, especially immunological reaction with S-100 protein. The appropriate treatment plan should be selected according to the diameter of the lesion. The overall prognosis of ES is good, but attention should be paid to follow-up.

MicroRNA-23 regulates the growth, metastasis and chemosensitivity of human gastric cancer cells by targeting MAP3K9.

PURPOSE: The efficient therapeutic targets which could be utilized for gastric cancer are limited. In this context, this study was undertaken to evaluate possible anticancer activity of miR-23 against gastric cancer. METHODS: The normal GES-1 and human AGS, SNU-1 and SNU-5 gastric cancer cells were used in this study. qRT-PCR was used for the determination of miR-23 expression. MTT assay was used for cell viability and acridine orange (AO)/ethidium bromide (EB) assay was used for detection of apoptosis. The experiments were performed in triplicate. RESULTS: The microRNA (miR)-23 was downregulated in gastric cancer cells and showed inhibitory effect on cell growth which was manifested as decline in cell survival. Additionally, the chemosensitivity of gastric cancer cells to cisplatin was enhanced with miR-23 overexpression. Furthermore, miR-23 also inhibited the migration and invasion of cancer cells. MAP3K9 was shown to be the target gene of miR-23 and silencing of MAP3K9 was seen to mimic the growth inhibitory effect of miR-23. Overexpression of MAP3K9 reversed the growth inhibition in miR-23 mimics transfected gastric cancer cells. CONCLUSION: miR-23 exerts growth inhibitory effect against gastric cancer cells and negatively regulates the cell migration and invasion along with enhancement of chemosensitivity of cancer cells.

Prediction of lymph node metastasis in superficial esophageal squamous cell carcinoma in Asia: a systematic review and meta-analysis.

A less invasive endoscopic therapy has been used as a routine treatment for superficial esophageal squamous cell carcinoma (SESCC). However, lymph node metastasis (LNM) in SESCC limits the effectiveness of this medical procedure. This meta-analysis aimed to screen the risk factors for LNM in SESCC in Asia to provide evidence for clinicians in selecting treatment. We searched the main reference databases for research involving patients who received esophagectomy (open or minimally invasive) with lymph node dissection for SESCC. Meta-analysis was performed using RevMan 5.3 software. Twenty studies including 3983 patients were obtained in this analysis. The meta-analysis showed that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular involvement are risk factors of LNM in SESCC, whereas age, sex, and tumor location showed no association with LNM. Five variables were screened as predictive factors for LNM in SESCC. The incidence of LNM in SESCC is not rare, and the physicians must be careful when making clinical decisions.

Preoperative Neutrophil Lymphocyte Ratio Can Be Used as a Predictor of Prognosis in Patients With Adenocarcinoma of the Esophagogastric Junction: A Systematic Review and Meta Analysis.

Objective: Neutrophil lymphocyte ratio (NLR), Lymphocyte mononuclear cell ratio (LMR), and Platelet lymphocyte ratio (PLR) can be used as various prognostic factors for malignant tumors, but the value of prognosis for patients with adenocarcinoma of the esophagogastric junction (AEG) has not been determined. This study used meta-analysis to assess the value of these indicators in the evaluation of AEG prognosis. Methods: Relevant literatures on the prognostic relationship between NLR, LMR, PLR, and AEG was retrieved from PubMed, Web of Science, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials, Wanfang data, and Chinese National Knowledge Infrastructure. The search time from database establishment to June 30, 2019. The language is limited to English and Chinese. Data was analyzed using Stata 15.0 software. Result: Six retrospective studies were included, five of them involved NLR and six of them involved PLR. No LMR literature that adequately satisfied the conditions was retrieved. Increased NLR was significantly associated with a significant reduction in overall survival (OS), cancer-specific survival (CSS), or disease specific survival (DSS) in patients with AEG [hazard ratio (HR) = 1.545, 95% CI: 1.096-2.179, P < 0.05]. Subgroup analysis showed that NLR had significant value in the prognosis of both Chinese and Non-Chinese patients (P = 0.009 vs. P = 0.000). NLR had significant prognostic value for ≥3 and <3 groups (P = 0.022 vs. P = 0.000). NLR has a significant prognostic value for samples ≥500 and <500 (P = 0.000 vs. P = 0.022). NLR and OS/CSS/DSS single factor meta-regression showed that regional NLR cut-off values and sample size may be the source of heterogeneity in AEG patients (all P < 0.05). There was no significant association between elevated PLR and OS in patients with AEG (HR = 1.117, 95% CI: 0.960-1.300, P > 0.05). PLR had no significant prognostic value for both Chinese and UK patients (P = 0.282 vs. P = 0.429). PLR had no significant prognostic value for ≥150 group and <150 group (P = 0.141 and P = 0.724). No significant prognostic value was found in either the 300 group and <300 group (P = 0.282 vs. P = 0.429). Conclusion: Preoperative NLR rise was an adverse prognostic indicator of AEG. High-risk patients should be treated promptly. The results showed that PLR was not recommended as a prognostic indicator of AEG.

Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing.

A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%-47.06%) and Firmicutes (35.88%-29.73%-24.27%-25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%-22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P < 0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P < 0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.

The potential role of P.gingivalis in gastrointestinal cancer: a mini review.

Bacterial infection may be involved in the entire process of tissue carcinogenesis by directly or indirectly affecting the occurrence and development of tumors. Porphyromonas gingivalis (P.gingivalis) is an important pathogen causing periodontitis. Periodontitis may promote the occurrence of various tumors. Gastrointestinal tumors are common malignant tumors with high morbidity, high mortality, and low early diagnosis rate. With the rapid development of molecularbiotechnology, the role of P.gingivalis in digestive tract tumors has been increasingly explored. This article reviews the correlation between P.gingivalis and gastrointestinal cancer and the pathogenesis of the latter. The relationship among P.gingivalis, periodontal disease, and digestive tract tumors must be clarifiedthrough a multi-center, prospective, large-scale study.

Serum pepsinogen assay is not recommended for the diagnosis of esophageal squamous cell carcinoma: a systematic review and meta-analysis.

Background: Serum pepsinogen I (PGI) concentration and PGI/PGII ratio (PGR) are often used as serological markers for gastric fundus atrophy (AGA) and gastric carcinoma. However, their diagnostic value in esophageal carcinoma (EC) is inaccurate. Methods: This study evaluated the diagnostic value of PGI and PGR in EC by searching the PubMed, Web of Science, Embase, Cochrane Library and Cochrane Central Register of Controlled Trials databases for literature on the diagnosis of EC with PGI and PGR from January 1, 2000 to October 2, 2018. The included literature were systematically evaluated using QUSDAS-2 software. Meta-analysis was conducted using STATA 15.0 software. The summary receiver operating characteristic curve (SROC) accuracy was plotted, the area under the curve was calculated. Results: A total of 84 papers were selected, and after screening, nine papers on esophageal squamous cell carcinoma (ESCC) were finally included. Results showed low an ESCC-specific diagnostic sensitivity (0.27), high specificity (0.85), and 0.63 AUC of SROC when PGI≤70 ng/mL. When PGR≤3, the ESCC-specific diagnostic sensitivity was low (0.29), the specificity was high (0.83), and the AUC of SROC was 0.63. Conclusion: According to the current research results, PGI≤70 ng/mL or PGR≤3 diagnostic ESCC sensitivity is low, and specificity is high. These findings indicate that neither PGI≤70 ng/mL nor PGR≤3 can be used as an ESCC-screening index.

Octamer binding transcription factor-4 expression is associated with cervical cancer malignancy and histological differentiation: a systematic review and meta-analysis.

Objective: In this work, the relationship between octamer binding transcription factor 4 (OCT-4) expression and the clinicopathological features of cervical cancer (CC) is evaluated in detail.Methods: The library databases Pubmed, Embase, Cochrane library, Wan Fang and Chinese National Knowledge Infrastructure (CNKI) were searched for research related to these concepts published from the time the databases were established until May 2018. The obtained studies are screened, extracted, and evaluated according to the inclusion and exclusion criteria, and meta-analysis is carried out via RevMan 5.3.Results: Ten case-control studies, including 408 cases of CC, 164 cases of cervical intraepithelial neoplasia (CIN), and 148 cases of normal cervix, are included in the analysis. Results show that OCT-4 levels are statistically significantly different between the CC and normal cervical tissue groups (odds ratio (OR) = 15.59, 95% confidence interval (CI): 8.70, 27.94), the CC and CIN groups (OR = 5.64, 95% CI: 3.23, 9.86), the CIN and normal cervical tissues groups (OR = 7.13, 95% CI: 2.41, 21.05), and the CC well/moderately differentiated and poorly differentiated groups (OR = 0.44, 95% CI: 0.24, 0.81). OCT-4 is not statistically significantly different between CIN I + II and CIN III tissues (OR = 0.40, 95% CI: -0.02, 0.81), the CC lymphatic and non-lymphatic metastasis groups (OR = 1.93, 95% CI: 0.83, 4.47), the FIGO I and FIGO II groups (OR = 0.79, 95% CI: 0.29, 2.13), and the adenocarcinoma and squamous cell carcinoma groups (OR = 1.55, 95% CI: 0.70, 3.44).Conclusions: The available evidence suggests that OCT-4 expression is associated with CC malignancy and histological differentiation. This finding, however, is subject to quantitative studies and quality tests.

An improved surgical procedure to establish a gastroesophageal reflux model with a high incidence of Barrett's esophagus in rats.

Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease and is a precursor lesion of esophageal adenocarcinoma. In existing BE models, the incidence of BE is typically low and induction is usually time consuming. In the present study, a gastroesophageal reflux model with a high incidence of BE in rats. Rats were divided into a model group and a sham operation group, and anesthetized with an inhalation anesthesia machine. Stomach-jejunal anastomosis (SJA) and esophagus-jejunal anastomosis (EJA) were simultaneously performed in the model group. The distance between the Treitz ligament and the gastro-jejunal anastomosis was shortened to 3 cm. The distance between the SJA and the EJA was prolonged to 1-1.5 cm. However, 15/40 rats in the model group succumbed to post-surgical complications (mortality rate was 37.5%). The weight of surviving rats in the model group was significantly lower compared with the sham group rats post-surgery. Erosions and ulcers were common of the surviving rats in the model group, with an incidence of 80% (20/25). Squamous cell dysplasia was identified in 40% (10/25) of rats in model group. The modified model was well established within 16 weeks. Notably, the modified surgical procedure used enhanced the incidence of BE in rats from 47% in the EJGJ model (as establish by Zhang) to 100%. To conclude, this model can be used as a reliable animal model for basic research on BE.

Combined detection of IL-6 and IL-8 is beneficial to the diagnosis of early stage esophageal squamous cell cancer: a preliminary study based on the screening of serum markers using protein chips.

BACKGROUND: The diagnosis rate of early stage esophageal squamous cell carcinoma (ESCC) is low due to the lack of specific tumor markers. Seeking for these markers is beneficial to improve the early diagnosis rate and the prognosis of patients. This study profiles the differentially expressed proteins of early stage ESCC patients via the AAH-BLG-507 protein chip, which further consolidates the clinical evidence of ESCC diagnosis. MATERIALS AND METHODS: In this study, 20 serum samples were collected from Taihe Hospital between August 2016 and June 2017. Ten of them carried ESCC, while the rest were healthy controls. To profile the proteins' expression level, the AAH-BLG-507 protein chip was used, and both highly expressed and lowly expressed proteins were fished out. Meanwhile, their biological roles were examined by using Gene Ontology (GO) database and String database, and they were further verified by ELISA. RESULTS: Results showed that the expression levels of AXL, ARTN, Ang2, BDNF, BMP7, cripto-1, CCL28, E-selectin, IL-6, IL-8 and SHH in the serum of early ESCC were significantly upregulated (P<0.05), particularly IL-6 and IL-8. The expression levels of TSP1 and MMP-8 were markedly downregulated (P<0.05). Analysis showed that these proteins were mainly involved in angiogenesis, signal transduction, cell proliferation and migration, indicating the close relationship with the development of ESCC. CONCLUSION: It suggested that IL-6 and IL-8 proteins could be considered as the markers for ESCC diagnosis.

DEPTOR suppresses the progression of esophageal squamous cell carcinoma and predicts poor prognosis.

As a naturally occurring inhibitor of mTOR, accumulated evidence has suggested that DEPTOR plays a pivotal role in suppressing the progression of human malignances. However, the function of DEPTOR in the development of esophageal squamous cell carcinoma (ESCC) is still unclear. Here we report that the expression of DEPTOR is significantly reduced in tumor tissues derived from human patients with ESCC, and the downregulation of DEPTOR predicts a poor prognosis of ESCC patients. In addition, we found that the expression of DEPTOR negatively regulates the tumorigenic activities of ESCC cell lines (KYSE150, KYSE510 and KYSE190). Furthermore, ectopic DEPTOR expression caused a significant suppression of the cellular proliferation, migration and invasion of KYSE150 cells, which has the lowest expression level of DEPTOR in the three cell lines. Meanwhile, CRISPR/Cas9 mediated knockout of DEPTOR in KYSE-510 cells significantly promoted cellular proliferation, migration and invasion. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic DEPTOR expression as compared to untreated KYSE150 cells, and was markedly enhanced in DEPTOR knockout KYSE-510 cells. Biochemical studies revealed that overexpression of DEPTOR led to the suppression of AKT/mTOR pathway as evidenced by reduced phosphorylation of AKT, mTOR and downstream SGK1, indicating DEPTOR might control the progression of ESCC through AKT/mTOR signaling pathway. Thus, these findings, for the first time, demonstrated that DEPTOR inhibits the tumorigenesis of ESCC cells and might serve as a potential therapeutic target or prognostic marker for human patients with ESCC.

Variations in NAG-1 expression of human gastric carcinoma and normal gastric tissues.

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a member of the transforming growth factor ß (TGF-ß) superfamily, has been demonstrated to possess antitumorigenic and proapoptotic activities in gastric cancer cells. In the present study, the expression of NAG-1 was assessed in human gastric carcinoma, tumor-adjacent normal tissues and normal gastric mucosa, with the aim to investigate the role of NAG-1 in the carcinogenesis and development of gastric carcinoma. NAG-1 protein expression was evaluated using immunohistochemical staining, while the expression of NAG-1 mRNA was evaluated using reverse transcription-polymerase chain reaction. It was observed that adenocarcinoma tissues had a lower expression of NAG-1 than normal gastric tissues. Furthermore, moderately and well-differentiated adenocarcinoma tissues expressed more NAG-1 protein than the poorly differentiated adenocarcinoma tissues. The expression of NAG-1 protein in adenocarcinoma tissues did not correlate with tumor-node-metastasis staging, infiltration degree or tumor size. The NAG-1 mRNA expression in adenocarcinoma tissues was also lower than that in normal gastric tissues. In conclusion, NAG-1 was poorly expressed in adenocarcinoma tissues and inversely correlated with the degree of tumor differentiation. These results indicate that NAG-1 may have an anti-oncogenic function in the carcinogenesis and development of gastric carcinoma, and that its attenuated or absent expression may lead to gastric carcinogenesis.

Up-regulation of P-glycoprotein is involved in the increased paclitaxel resistance in human esophageal cancer radioresistant cells.

OBJECTIVE: Development of drug and radiation resistance is one of the major causes of cancer treatment failure with chemoradiotherapy. Whether radiotherapy affects drugs resistance in esophageal cancer cells remain to be determined. The purpose of the study was to investigate the change of drug-sensitivity and P-glycoprotein (P-gp) expression in ionization radiation-induced human esophageal cancer radioresistant cells. MATERIALS AND METHODS: Radioresistant cells were established by means of continuous fractionated gamma-ray irradiation on human esophageal squamous cancer cell line EC9706. The radiosensitivity and drug-sensitivity between established radioresistant cells and parental cells were detected by a colony-forming assay and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, respectively. The expressions of multidrug resistance type 1 gene (MDR1) mRNA and protein for P-gp were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot methods. The roles of P-gp activity in irradiation-induced drugs resistance were studied by using verapamil, an inhibitor of P-gp activity. RESULTS: The esophageal cancer radioresistant cells showed an increased cisplatin or paclitaxel resistance. Compared with their parental cells, the expressions of MDR1 mRNA and protein for P-gp were increased significantly in radioresistant cells. Verapamil reduced paclitaxel resistance but had no effect on cisplatin resistance in human esophageal cancer radioresistant cells. CONCLUSIONS: These results suggested that up-regulation of P-gp is involved in the increased paclitaxel resistance but not cisplatin resistance in ionization radiation-induced human esophageal squamous cancer radioresistant cells.

A cyclooxygase-2 inhibitor NS-398-enhanced apoptosis of esophageal carcinoma cell EC9706 by adjusting expression of survivin and caspase-3.

The aim of this study is to examine the effect and mechanism of a selective cyclooxygenase-2 (COX-2) inhibitor NS-398 on inducing apoptosis of esophageal cancer cells. After the treatment with NS-398 on esophageal carcinoma EC9706 cell, MTT assay was used to observe the inhibition of EC9706 cell growth and apoptosis was determined by electronic microscopy and flow cytometry. The expression of survivin and caspase-3 was examined using immunocytochemical technique. The dose of 0.01­0.1 mM NS398 showed the inhibitory effect on growth of EC9706 cell lines and induce apoptosis in a dose- and time-effective manner; moreover, NS-398 also downregulated the level of expression of survivin and elevated the expression of capase-3. NS-398 can induce apoptosis of the esophageal carcinoma EC9706 cells by means of adjusting expression of survivin and caspase-3.