Pathological characteristics and long-term prognosis of submucosal infiltrating carcinoma of the colon and rectum below 2 cm confirmed by endoscopic submucosal dissection.

The purpose of this study was to explore the correlation between additional surgery and the clinicopathological characteristics of colorectal cancer, as well as its impact on patient prognosis. A total of 119 patients with early colorectal cancer were selected and divided into an additional surgery group (28 cases) and a non-additional surgery group (91 cases). According to the tumor size, the patients were further divided into a large diameter group (54 cases, d≥1 cm and <2 cm) and a small diameter group (65 cases, d<1 cm). The clinical and pathological characteristics as well as the prognosis of the patients were statistically analyzed. The results showed that infiltration type, depth of infiltration, and tumor size were correlated with additional surgery (P<0.05). Infiltration type and depth of infiltration were closely related to additional surgery. Differentiation degree, infiltration type, and depth of infiltration were correlated with tumor diameter. Infiltration type was closely related to tumor size. Age, depth of infiltration, and tumor size were correlated with patient survival rates. Infiltration type and depth of infiltration were closely related to patient survival rate (P<0.05). They were independent risk factors affecting patient prognosis. The 5-year disease-free survival rates were 73.33% and 72.5%, respectively, with no statistically significant difference. Infiltration type and depth of infiltration were independent risk factors for recurrence in colorectal cancer patients, while depth of infiltration was an independent risk factor for the 5-year survival rate after surgery. They can be used to predict the prognosis of colorectal cancer and guide clinical treatment as a supplement to the traditional staging of colorectal cancer.

[Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine].

The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.

A deep learning-based system for identifying differentiation status and delineating the margins of early gastric cancer in magnifying narrow-band imaging endoscopy.

BACKGROUND : Accurate identification of the differentiation status and margins for early gastric cancer (EGC) is critical for determining the surgical strategy and achieving curative resection in EGC patients. The aim of this study was to develop a real-time system to accurately identify differentiation status and delineate the margins of EGC on magnifying narrow-band imaging (ME-NBI) endoscopy. METHODS : 2217 images from 145 EGC patients and 1870 images from 139 EGC patients were retrospectively collected to train and test the first convolutional neural network (CNN1) to identify EGC differentiation status. The performance of CNN1 was then compared with that of experts using 882 images from 58 EGC patients. Finally, 928 images from 132 EGC patients and 742 images from 87 EGC patients were used to train and test CNN2 to delineate the EGC margins. RESULTS : The system correctly predicted the differentiation status of EGCs with an accuracy of 83.3 % (95 % confidence interval [CI] 81.5 % - 84.9 %) in the testing dataset. In the man - machine contest, CNN1 performed significantly better than the five experts (86.2 %, 95 %CI 75.1 % - 92.8 % vs. 69.7 %, 95 %CI 64.1 % - 74.7 %). For delineating EGC margins, the system achieved an accuracy of 82.7 % (95 %CI 78.6 % - 86.1 %) in differentiated EGC and 88.1 % (95 %CI 84.2 % - 91.1 %) in undifferentiated EGC under an overlap ratio of 0.80. In unprocessed EGC videos, the system achieved real-time diagnosis of EGC differentiation status and EGC margin delineation in ME-NBI endoscopy. CONCLUSION : We developed a deep learning-based system to accurately identify differentiation status and delineate the margins of EGC in ME-NBI endoscopy. This system achieved superior performance when compared with experts and was successfully tested in real EGC videos.

Clinical outcomes of early gastric cardiac cancer treated with endoscopic submucosal dissection in patients with different indications.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been accepted as a standard treatment for early gastric cardiac cancer (EGCC). Here, we investigate the clinical outcomes of the EGCC patients who underwent ESD in different indications. METHODS: From January 2011 to October 2019, we enrolled 502 EGCC lesions from 495 patients which were resected by ESD at our center. We retrospectively analyzed the short-term and long-term clinical outcomes among different indication groups. RESULTS: The number of the patients in the absolute indication (AI), expanded indication (EI) and beyond the expanded indication (BEI) groups was 265, 137 and 93, respectively. The en bloc resection rate was 100%, 100% and 98.9% (P = 0.185). The complete resection rate was 99.3%, 98.5% and 74.5%, respectively (P < 0.001). During a median follow-up of 48.1 months, the lymph node metastasis rate was 0%, 0% and 2.3% (P < 0.001). The distant metastasis rate was 0.4%, 0% and 2.3% (P = 0.150). The five-year disease-specific survival rate in the BEI group was 96.6% (P = 0.016), compared to 99.6% in the AI group and 100% in the EI group. CONCLUSION: The efficacy for ESD patients in EI group was almost equal to the AI group. Patients in the BEI group showed generally favorable clinical outcomes and needed to be carefully checked after ESD. ESD may be an optional treatment for patients unsuitable for gastrectomy.

Factors influencing development of non-cardiac chest pain after endoscopic submucosal dissection for esophageal neoplasms: a retrospective case-control study of 309 patients from a single center.

Endoscopic submucosal dissection (ESD) is widely used for early stage esophageal cancer and precancerous lesions. Non-cardiac chest pain (NCCP) is a frequent complication of ESD. However, little is known about its incidence and associated factors. This study investigated the pain incidence and predictive factors for pain development after ESD for esophageal neoplasms. We enrolled a total of 309 patients with esophageal neoplasms, who underwent ESD in our center from January 2018 to June 2019. Sociodemographic and clinicopathological information for all patients was collected, and patients were divided into either a pain-free group (n = 156) or a pain group (n = 153) according to whether there was onset of NCCP 24-48 hours after surgery. We made comparisons between groups using Student's t test or the χ2 test. Logistic-regression analysis was used to screen for risk factors. There were statistically significant differences in histories of previous surgery (P = 0.039), lesion size (P = 0.026), operation time (P = 0.009), and postoperative fever (P = 0.001). History of previous surgery (P = 0.043) and postoperative fever (P = 0.007) were independent risk factors for chest pain after esophageal ESD treatment. Chest pain and fever prolonged postoperative hospitalization time (P = 0.005, P = 0.001) and increased hospitalization cost (P = 0.034, P < 0.001). A history of previous surgery and postoperative fever was associated with the occurrence of NCCP after ESD in patients with esophageal neoplasms. NCCP and fever after esophageal ESD increased both hospitalization time and cost.

Crosstalk of mTOR/PKM2 and STAT3/c-Myc signaling pathways regulate the energy metabolism and acidic microenvironment of gastric cancer.

Cancer cells consume large amounts of glucose to produce lactate, even in the presence of ample oxygen. This phenomenon is called the Warburg effect. c-Myc is an important member of the Myc gene family and is involved in the development of various tumors. It plays an important role in the regulation of tumor energy metabolism, which can regulate glycolysis to promote the Warburg effect in a tumor. Our study aimed to improve the malignant biological behavior by controlling the energy metabolism of gastric cancer through the mTOR/PKM2 and signal transduction and activator 3 (STAT3)/c-Myc signaling pathways through a series of in vitro experiments. Human gastric cancer AGS and HGC-27 cells were treated with PKM2 and c-Myc lentivirus, and the effects of the knockdown of PKM2 and/or c-Myc were analyzed on cell proliferation, cell apoptosis, the ability of cell migration, and the growth signaling pathway in vitro. The expressions of PKM2, c-Myc, LDHA, STAT3, P-STAT3, GLUT-1 gene were identified by the quantitative real-time polymerase chain reaction and Western blot analysis. Lactate and glucose levels were tested by the corresponding kit. Our findings showed that PKM2 and c-Myc were upregulated in human gastric cancer. Knockdown of c-Myc in gastric cancer cells suppressed cell proliferation capacity and glycolysis level, and the inhibitory effects on gastric cancer cells upon co-knockdown of PKM2 and c-Myc were more obvious compared with knockout of PKM2 or c-Myc alone. And there was a correlation between the mTOR/PKM2 and the STAT3/c-Myc signaling pathways. Our results suggested that c-Myc might be considered a potential therapeutic target for gastric cancer and PKM2 combined with c-Myc could better inhibit the malignant biological behaviors of gastric cancer.

A deep neural network improves endoscopic detection of early gastric cancer without blind spots.

BACKGROUND: Gastric cancer is the third most lethal malignancy worldwide. A novel deep convolution neural network (DCNN) to perform visual tasks has been recently developed. The aim of this study was to build a system using the DCNN to detect early gastric cancer (EGC) without blind spots during esophagogastroduodenoscopy (EGD). METHODS: 3170 gastric cancer and 5981 benign images were collected to train the DCNN to detect EGC. A total of 24549 images from different parts of stomach were collected to train the DCNN to monitor blind spots. Class activation maps were developed to automatically cover suspicious cancerous regions. A grid model for the stomach was used to indicate the existence of blind spots in unprocessed EGD videos. RESULTS: The DCNN identified EGC from non-malignancy with an accuracy of 92.5 %, a sensitivity of 94.0 %, a specificity of 91.0 %, a positive predictive value of 91.3 %, and a negative predictive value of 93.8 %, outperforming all levels of endoscopists. In the task of classifying gastric locations into 10 or 26 parts, the DCNN achieved an accuracy of 90 % or 65.9 %, on a par with the performance of experts. In real-time unprocessed EGD videos, the DCNN achieved automated performance for detecting EGC and monitoring blind spots. CONCLUSIONS: We developed a system based on a DCNN to accurately detect EGC and recognize gastric locations better than endoscopists, and proactively track suspicious cancerous lesions and monitor blind spots during EGD.

The fourth space surgery: endoscopic subserosal dissection for upper gastrointestinal subepithelial tumors originating from the muscularis propria layer.

BACKGROUND AND AIMS: We developed a novel method of endoscopic subserosal dissection (ESSD) for removal of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the upper gastrointestinal (GI) tract. The aim of this study was to evaluate the efficacy, safety, and clinical outcome of this method. METHODS: Eleven patients with upper GI SETs originating from the MP layer were treated by ESSD between October 2016 and March 2017. ESSD technique consists of six major procedures: (1) incising the mucosal and submucosal layer around the lesion and exposing MP layer; (2) continuous injection was performed while the injection needle slowly moved from the MP layer toward the subserosal layer; (3) incising MP layer; (4) subserosal injection was performed to further separate the serosa from the MP layer; (5) the mucosa, submucosa, and MP layer including SET were carefully dissected en bloc; and (6) closure of the gastric-wall defect with endoscopic techniques. Primary outcome including clinical procedural success and procedure-related adverse events were documented. RESULTS: ESSD was successfully performed in 11 patients. The complete resection rate was 100%, and the mean operation time was 51 (range 22-76) min. The mean resected lesion size was 27 (range 15-40) mm. Pathological diagnosis of these lesions included gastrointestinal stromal tumors (8/11), heterotopic pancreas (1/11), hamartoma (1/11), and leiomyoma (1/11). The small perforations occurred in two patients (4 × 4 and 5 × 5 mm, respectively) during the operation. All perforations and defects were closed successfully by endoscopic techniques. No GI bleeding, peritonitis, abdominal abscess, and other adverse events were observed. No lesion residual or recurrence was found during the follow-up period (mean 18 weeks; range 10-29 weeks). CONCLUSION: ESSD seems to be an efficacious, safe, and minimally invasive treatment for patients with upper GI SETs originating from the MP layer, making it possible to resect deep lesions, provide precise pathological diagnosis, and maintain the integrity of serosa.

Risk factor analysis of post-ERCP cholangitis: A single-center experience.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) may have complications. Our study aimed to investigate the risk factors and prevention of post-ERCP cholangitis. METHODS: We retrospectively analyzed 4234 cases undergone ERCP in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2008 to December 2013. Patient-related factors and procedure-related factors were analyzed to find the risk factors of post-ERCP cholangitis. The time point of post-ERCP cholangitis was also analyzed. Univariate and multivariate analyses were performed to define the independent risk factors of post-ERCP cholangitis. RESULTS: The success rate of ERCP was 96.8% (4099/4234). The overall complication rate was 9.4% (399/4234). Post-ERCP cholangitis occurred in 102 cases (2.4%, 102/4234). The most dangerous time of post-ERCP cholangitis was from 24 h-48 h after ERCP (45.1%, 46/102). Univariate analysis revealed that age, hypertension, diabetes, previous ERCP history, biliary stent insertion, pancreatography, endoscopic sphincterotomy, balloon dilation and hilar obstruction were risk factors of post-ERCP cholangitis (P < 0.05). Multivariate analysis indicated that age, previous ERCP history and hilar obstruction were independent risk factors (P < 0.05). While endoscopic stone extraction was the potential protective factor. CONCLUSIONS: Many risk factors are involved in post-ERCP cholangitis. Among them, old age, previous ERCP history and hilar obstruction were independently related to this post-ERCP complication.

Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients.

Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC.

Endoscopic ultrasonography for staging depth of invasion in early gastric cancer: A meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasonography (EUS) is a widely used imaging modality for detecting the depth of early gastric cancer (EGC) invasion. However, the studies pertaining to EUS for staging early gastric cancer have reported widely varied sensitivities and specificities. This study was conducted to estimate the overall diagnostic accuracy of EUS for staging the depth in EGCs. METHODS: The literatures were identified by searching in PubMed, Embase, and Web of Knowledge databases. Two reviewers independently extracted the information from the literatures for constructing 2 × 2 table. A random-effect model or a fixed-effect model was used to estimate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. A summary receiver operating characteristic curve also was constructed. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. RESULTS: The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of EUS for M staging were 76% (95% confidence interval [CI], 74-78%), 72% (95% CI, 69-75%), 3.67 (95% CI, 2.48-5.44), and 0.31 (95% CI, 0.24-0.40), respectively. For SM staging, these results were 62% (95% CI, 59-66%), 78% (95% CI, 76-80%), 2.99 (95% CI, 2.26-3.96), and 0.43 (95% CI, 0.32-0.57), respectively. For M/SM1 staging, they were 90% (95% CI, 88-92%), 67% (95% CI, 61-72%), 3.14 (95% CI, 2.08-4.73), and 0.12 (95% CI, 0.07-0.22), respectively. The area under the curve for mucosal, submucosal, and mucosal/minimal submucosal invasion staging were 0.85, 0.82, and 0.81, respectively. CONCLUSIONS: Endoscopic ultrasonography only has a relatively low accuracy for staging the depth of invasion in EGCs. Accordingly, EUS may be not indispensable in the staging of EGCs.

[Expression of FBXW7 in esophageal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To evaluate the expression of FBXW7 in esophageal squamous cell carcinoma (ESCC) and to explore the correlation of FBXW7 expression with clinicopathologic features and prognosis of ESCC. METHODS: Ninety cases of ESCC and twenty cases of tumor-adjacent normal tissues and forty intraepithelial neoplasia tissues were detected by immunohistochemistry methods. The expression of FBXW7 in 40 surgical ESCC tissues and tumor-adjacent normal tissues was detected by Western blotting and RT-PCR. The relationship between the expression of FBXW7, clinicopathological characteristics and prognosis was analyzed. RESULTS: The positive rate of FBXW7 protein was significantly lower in the ESCC and high-grade intraepithelial neoplasia tissues than in the tumor-adjacent normal tissues and low grade intraepithelial neoplasia tissues (40.0% and 33.3% vs. 85.0% and 77.3%, χ² = 21.923, P < 0.001). The FBXW7 protein was down-regulated in ESCC tissues (P < 0.05), whereas the FBXW7 mRNA was down-regulated in ESCC tissues compared with that in the paracancerous tissues. The expression of FBXW7 was significantly correlated with TNM stage, degree of differentiation, invasion depth and lymph node metastasis (χ² =9.643, 14.908, 16.294, 10.222, respectively, P = 0.002, 0.001, 0.000, 0.001). In the ninety patients, the 5-year survival rates of cases with positive and negative expression of FBXW7 protein was 67.6% and 39.3%, respectively (χ² =6.699, P = 0.01). CONCLUSIONS: The results of this study demonstrate that FBXW7 expression is significantly declined in ESCC and high grade intraepithelial neoplasia tissues, and is closely correlated with poor prognosis of this disease. FBXW7 as a tumor suppressor gene may play an important role in the carcinogenesis, development and metastasis of ESCC. These results suggest that FBXW7 may become a valuable marker for the severity and prognosis in ESCC.

Effect of peroral endoscopic myotomy in achalasia patients with failure of prior pneumatic dilation: a prospective case-control study.

BACKGROUND AND AIM: To investigate the effectiveness of peroral endoscopic myotomy (POEM) surgery in achalasia patients with failure of prior pneumatic dilation (PD). METHODS: Twenty-one patients with a history of failed PD were prospectively recruited as the case group, and 30 patients with no history of prior treatment for achalasia were included as the control group. Outcome of POEM procedures was evaluated through esophageal manometry, timed barium esophagogram and short form 36 (SF-36) questionnaires, which were performed before surgery, at 5 days after surgery and at the last follow-up, respectively. Relief of patients' symptoms was considered as the primary outcome. Secondary outcomes included lower esophageal sphincter pressure, esophageal emptying, quality of life of the patient, and procedure-related complications. RESULTS: The two groups were matched in terms of age, gender, body mass index, and results of preoperative examinations. For patients with failed PD, it was observed that Eckardt score, lower esophageal sphincter pressure, and height of the barium column were significantly decreased after POEM surgery. Besides, the mean physical component summary and mental component summary of patients at the final follow were significantly higher than those before surgery. Complications that occurred during the surgery included three cases of subcutaneous emphysema (14.3%) and one case of pneumothorax (4.8%). Patients with failed PD were found to have the significantly longer operation time than the control group. There was no significant difference between the two groups in terms of surgical outcome at the final follow-up. CONCLUSIONS: POEM is a promising therapeutic modality for achalasia patients who have failed to respond to PD therapy. Previous dilation procedures might have no obvious influence on the efficacy of POEM surgery.

Efficacy and safety of Shenbai Granules for recurrent colorectal adenoma: A multicenter randomized controlled trial.

BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.

[Effect of Akt on the function of esophageal squamous cancer cell Eca109 and the expression of vasculogenic mimicry-related genes].

OBJECTIVE: To investigate the inhibitory effect of siRNA targeting Akt on the biological behavior of esophagus squamous cell carcinoma cell line in vitro and to explore the relationship between Akt and vasculogenic mimicry (VM)-related genes in esophageal squamous cell carcinoma. METHODS: The plasmid-harboring small interfering RNA targeting Akt was introduced into Eca109 cells by liposome-mediated transfection. The proliferation of Eca109 cell was determined by colony formation assay. The cellular migration was evaluated by Transwell migration assay. And three dimensional cell culture was employed to observe and count the number of capillary structure for each cell group. Flow cytometry (FCM) was used to detect the apoptotic rate of Eca109, Eca109/Neo and Eca109/siRNA Akt cells under normoxia exposure. The apoptotic rate was assessed by Annexin V/7-AAD double labeling. And the expressions of Akt and matrix metalloproteinase-2 (MMP-2) protein were detected by Western blotting. RESULTS: The results of Western blotting showed that the expression of Akt in stably transfected group were significantly lower than empty carrier and untransfected groups (0.03 ± 0.01 vs 1.49 ± 0.39 and 1.47 ± 0.41, both P < 0.05). Transwell migration assay showed that fewer Eca109/8 cells could move through the artificial basement membrane as compared with untransfected and empty carrier groups (48 ± 9 vs 128 ± 10 and 122 ± 11, both P < 0.05). Clone formation number of stably transfected group was significantly lower than empty carrier and untransfected groups (63 ± 7 vs 148 ± 11 and 163 ± 15, both P < 0.05). Annexin V/7-AAD double standard method demonstrated that the apoptotic rate of stably transfected group was much more than those of untransfected and empty carrier groups (12.2% ± 1.6% vs 4.8% ± 0.8% and 4.2% ± 0.8%, both P < 0.05). Eca109 and Eca109/Neo cells were capable of forming the in vitro structures of VM. And the number of tube-shaped structure in stably transfected group was markedly less than those of untransfected and empty carrier groups (14.0 ± 1.2 vs 30.0 ± 1.2 and 27.7 ± 1.5, both P < 0.05). MMP-2 protein expression in stably transfected group was less than those of untransfected and empty carrier groups (both P < 0.05). CONCLUSIONS: The PI(3)K/Akt pathway is involved in the regulation of VM formation in esophageal squamous cell carcinoma through the action of MMP-2. Blockade of this pathway may provide a new therapeutic approach to human esophagus squamous cell carcinoma.

Effects of YC-1 targeting hypoxia-inducible factor 1 alpha in oesophageal squamous carcinoma cell line Eca109 cells.

HIF-1α (hypoxia-inducible factor 1 alpha) is believed to promote oesophageal squamous tumour growth. Thus, an HIF-1α inhibitor is viewed as a therapeutic target in treating oesophageal cancer. Recently, YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] has been widely used as a potential HIF-1α inhibitor and is being developed as a novel anticancer drug. However, little is known about the effects of YC-1 in human oesophageal cancer. In the present study, we aimed to investigate these effects in an esophageal squamous cancer cell line; i.e. Eca109 cells. We found that YC-1 abolished the hypoxia-induced up-regulation of HIF-1α. YC-1 arrested cell growth and inhibited cell migration activities in Eca109 cells. These results suggest that YC-1 may be a chemotherapy candidate against oesophageal squamous cancers.