Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients: a multicenter randomized-controlled trial.

BACKGROUND: Data from single-center experience or small sample-sized studies have shown that chromoendoscopy (CE) might be superior to white-light endoscopy (WLE) for dysplasia surveillance in ulcerative colitis (UC) patients. We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies (WLT), WLE with random biopsies (WLR), and dye-based CE with targeted biopsies (CET) in UC patients. METHODS: Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms (WLT, WLR, and CET). Only high-definition endoscopy was used in all three groups. The patients were followed up by annual endoscopy with biopsies through December 2017. RESULTS: With a median follow-up time of 55 months, a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set: WLT (n = 43), WLR (n = 40), and CET (n = 39). A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients. WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT (8.1% and 9.7% vs 1.9%; P = 0.014 and 0.004, respectively). WLR obtained more biopsied samples than WLT and CET (16.4 ± 5.1 vs 4.3 ± 1.4 and 4.3 ± 1.4; both P < 0.001). During the second half of the follow-up (37 - 69 months), CET could identify more colonoscopies that diagnosed dysplasia than WLT (13.3% vs 1.6%, P = 0.015) and showed a trend for increasing the detection rate compared with WLR (13.3% vs 4.9%, P = 0.107). CONCLUSIONS: For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC, CET appeared to be more effective than WLT and less tedious than WLR. CET was found to be particularly useful when a long-term (>3 years) follow-up was conducted for dysplasia surveillance. The trial was registered on www.chictr.org.cn (ChiCTR1900023689).

Aldolase A-HBsAg interaction and its effect on ultraviolet radiation induced apoptosis in 293FT cells.

BACKGROUND AND AIM: Hepatitis B virus (HBV) infection poses great challenges to humans, claiming one million lives annually worldwide. Solid data have related HBV to hepatocellular carcinoma. METHODS: In the present research, we verified the interaction between surface protein (HBs) encoded by HBV and aldolase A (ALDA) using yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation, GST pull-down and laser scanning confocal. RESULTS: Anti-ALDA antibody precipitated Gal4-HBs fusion protein in the presence of HBs. Anti-HBs antibody precipitated p65ΔN-ALDA only in the presence of ALDA. Small HBs could be pulled down by GST-ALDA. Cells transfected with pCMV-AD-ALDA showed a protection from ultraviolet radiation-induced apoptosis (21.3% ± 1.3% for ALDA, 35.4% ± 2.1% for control, P < 0.05). CONCLUSIONS: An interaction does exist between ALDA and HBs. The S region within HBs is sufficient for binding ALDA. In addition, ALDA conferred protection to ultraviolet radiation-induced apoptosis, and this effect was enhanced by the interaction between HBs and ALDA.

Interacting with HBsAg compromises resistance of jumping translocation breakpoint protein to ultraviolet radiation-induced apoptosis in 293FT cells.

Jumping translocation breakpoint protein (JTB) is suppressed in many cancers, implying it plays a role in the neoplastic transformation of cells. In order to explore the role of JTB in the carcinogenesis of liver, we used mammalian two-hybrid, co-immunoprecipitation, GST pull-down and laser scanning confocal to verify the interaction between HBs and JTB. According to the results, HBs interacts with JTB. In addition, we further determined that S region within HBs is sufficient for binding JTB. Overexpression of JTB conferred resistance to apoptosis induced by ultraviolet radiation, whereas this effect was compromised by the co-overexpression of HBs.

Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues.

AIM: To study the molecular forms of trefoil factor 1 (TFF1) in normal gastric mucosa and its expression in normal and abnormal gastric tissues (gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa) and the role of TFF1 in the carcinogenesis and progression of gastric carcinoma and its molecular biological mechanism underlying gastric mucosa protection. METHODS: The molecular forms of TFF1 in normal gastric mucosa were observed by Western blot. The expression of TFF1 in normal and abnormal gastric tissues (gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa) was also assayed by immunohistochemical method. The average positive AO was estimated by Motic Images Advanced 3.0 software. RESULTS: Three patterns of TFF1 were found in normal gastric mucosa: monomer, dimmer, and TFF1 compound whose molecular weight is about 21 kDa. The concentration of TFF1 compound was the highest among these three patterns. TFF1 was expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum, especially around the nuclei. The closer the TFF1 to the lumen, the higher the expression of TFF1. The expression of TFF1 in peripheral tissue of gastric carcinoma (0.51 +/- 0.07) was higher than that in normal gastric mucosa (0.44 +/- 0.06, P < 0.001). The expression of TFF1 in gastric adenocarcinoma was positively related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma was, the weaker the expression of TFF1. No TFF1 was expressed in poorly-differentiated adenocarcinoma. The expression of TFF1 in moderately-well differentiated adenocarcinoma (0.45 +/- 0.07) was a little lower than that in normal mucosa (P > 0.05). The expression of TFF1 in gastric mucosa with atypical hyperplasia (0.57 +/- 0.03) was significantly higher than that in normal gastric mucosa (P < 0.001). No TFF1 was expressed in intestinalized gastric mucosa. There was no statistically significant difference between the expressions of TFF1 in gastric mucosa around the intestinalized tissue (0.45 +/- 0.07) and normal gastric mucosa (P > 0.05). CONCLUSION: TFF1 is expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum. Its main pattern is TFF1 compound, which may have a greater biological activity than monomer and dimer. The expression of TFF1 in peripheral mucosa of gastric ulcer is higher than that in mucosa 5 cm beyond the ulcer, indicating that TFF1 plays an important part in protection and restitution of gastric mucosa. The expression of TFF1 is increased in peripheral tissues of gastric carcinoma and gastric mucosa with atypical hyperplasia, but is decreased in cancer tissues, implying that TFF1 may be related to suppression and differentiation of carcinoma. The weaker expression of TFF1 in poorly-differentiated carcinoma may be related to the destruction of glands and cells in cancer tissues and the decrease in secretion of TFF1.

[Molecular forms of TFF1 in normal gastric mucosa and its relationship with canceration].

OBJECTIVE: To study the molecular forms of TFF1 in normal gastric mucosa and its expression in normal, gastric carcinoma, atypical hyperplasia, and intestinalized gastric mucosa. METHODS: The molecular forms of TFF1 in normal gastric mucosa was observed by western blotting. The expression of TFF1 in normal, gastric carcinoma, atypical hyperplasia, and intestinalization gastric mucosa was assayed immunohistochemically. RESULTS: TFF1 existed in normal gastric mucosa in forms of monomer, dimer and 21-kD TFF1 complex, with the last being the richest. TFF1 was expressed mainly in the epithelial cytoplasm of the mucosa in the gastric body and antrum, especially around the nucleus, and the closer to the lumen, the higher the expression. TFF1 expression in the tissues adjacent to gastric carcinoma was higher than that in normal gastric mucosa (P<0.001), and the expression in gastric adenocarcinoma was positively correlated to differentiation of adenocarcinoma. No TFF1 was expressed in poorly differentiated adenocarcinoma. The expression of TFF1 in moderate and well differentiated adenocarcinoma was a little lower than that in normal mucosa (P>0.05). The gastric mucosa with atypical hyperplasia had significantly higher TFF1 expression than normal gastric mucosa (P<0.001), and TFF1 was not detected in intestinalized gastric mucosa. There was no significant difference in TFF1 expression between gastric mucosa around the intestinalized tissues and normal gastric mucosa (P>0.05). CONCLUSIONS: TFF1 plays an important part in protection and restitution of the gastric mucosa, and TFF1 may be related to suppression and differentiation of carcinoma.

[Association of trefoil factor 1 expression with gastric mucosa injuries and gastric cancer].

OBJECTIVE: To investigate the role of trefoil factor 1 (TFF1) expression in gastric mucosa healing and carcinoma suppression. METHODS: TEF1 expressions in normal and pathological gastric mucosa tissues were detected by immunohistochemical analysis, and the average optical density (OD) was estimated by Motic Images Advanced 3.0 software. RESULTS: Increased TFF1 expression was detected in gastritis, gastric ulcer and duodenal ulcer tissues as compared with that in normal gastric mucosa. TFF1 expression was increased in multiple and compound ulcer in comparison with simple ulcer, but there was no significant difference between gastric ulcer and duodenal ulcer, or between gastritis and simple ulcer tissues. Increased TFF1 was also detected in the mucosa adjacent to the gastric adenocarcinoma, and adenocarcinoma with poorer differentiation had lower TFF1 expression. CONCLUSIONS: TFF1 expression is increased in gastritis, gastric ulcer and duodenal ulcer, and multiple and compound ulcer has higher TFF1 expression than simple ulcer, suggesting the protective role of TFF1 in gastric mucosa and epithelial restitution. TFF1 may directly contribute to the differentiation of adenocarcinoma, and the poorer the differentiation, the lower the expression of TFF1.

Relationship between trefoil factor 1 expression and gastric mucosa injuries and gastric cancer.

AIM: To determine whether trefoil factor 1 (TFF1) is associated with mucosa healing and carcinoma suppression, we assess the expression of trefoil factor 1 in normal and pathologic gastric mucosa. METHODS: TFF1 in normal and pathologic gastric mucosa was assessed by immunohistochemical method, and the average positive A was estimated by Motic Images Advanced 3.0 software. RESULTS: Increased TFF1 was detected in gastritis, gastric ulcer and duodenal ulcer compared with normal mucosa. The same result could be seen in multiple and compound ulcer compared with simple ulcer. There was no significant difference between gastric ulcer and duodenal ulcer, gastritis and simple ulcer respectively. Increased TFF1 was detected in the peripheral mucosa of the gastric adenocarcinoma compared with normal mucosa. The expression of TFF1 in gastric adenocarcinoma was related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma, the weaker the expression of TFF1. There was no TFF1 expressed in low-differentiated adenocarcinoma. The expression of TFF1 in middle and highly differentiated adenocarcinoma was a little lower than that in normal mucosa. But there was no significant difference. No TFF1 was assessed in esophageal squamous carcinoma and peripheral tissue. There was no significant difference between male and female. CONCLUSION: The expression of TFF1 was higher in gastritis and peptic ulcer than that in normal mucosa, and was also higher in multiple and compound ulcer than in simple ulcer. It seems that TFF1 plays a role in gastric mucosa protection and epithelial restitution. Increased expression of TFF1 in peripheral tissue suggests that TFF1 is associated with mechanism of carcinoma suppression and differentiation. Decreased expression of TFF1 in carcinoma and its relativity to the differentiation suggests that TFF1 is related to gland and cell destruction of carcinoma.