Therapeutic effect of total triterpenoids of Chaenomeles speciosa combined with omeprazole on gastric ulcer induced by indomethacin in rats / 中国中药杂志

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1β, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1β, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1β and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.

Associations between the Expression of Mucins (MUC1, MUC2, MUC5AC, and MUC6) and Clinicopathologic Parameters of Human Breast Ductal Carcinomas / 한국유방암학회지

PURPOSE: Mucins are members of the glycoprotein family expressed in benign and malignant epithelial cells. The aim of this study is to evaluate the relationships between the expression of mucins in breast ductal carcinoma and clinicopathologic parameters. METHODS: We constructed tumor microarrays based on 240 cases of invasive ductal carcinoma and 40 cases of ductal carcinoma in situ (DCIS) using formalin fixed, paraffin embedded tissues. We examined the expressions of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. RESULTS: MUC1 demonstrated cytoplasmic, membranous, apical, and combinative expressions. Other mucins demonstrated cytoplasmic expression. In invasive ductal carcinoma, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 93.6%, 6.2%, 4.8%, and 12.4% of cases, respectively; these rates were slightly, but not significantly, higher than observed in cases of DCIS. MUC1 expression was associated with estrogen receptor (ER) expression and negative MUC1 expression was associated with triple negativity. MUC6 expression was correlated with higher histologic grade, lymphatic invasion, lymph node metastasis, and HER2 positivity. No associations with any other clinicopathologic parameters were observed. CONCLUSION: Most invasive ductal carcinomas of the breast express MUC1, and this expression is associated with ER expression. MUC6 expression is correlated with some clinicopathologic parameters that are indicators of poor prognosis. To evaluate the role of MUC6 as a potential biomarker, further studies are warranted.

Expression of MUC2 and MUC6 in Colorectal Adenomas and Adenocarcinomas

PURPOSE: Although the expression of MUC2 is seen in colorectal tumors, there have been few reports about the expression of MUC6 in colorectal tumors. The aim of this study was to investigate the expressions of MUC2 and MUC6 in normal colorectal tissues and in tumors, as well as the association of MUC2 and MUC6 expressions with prognostic factors. METHODS: Twenty (20) cases of colorectal adenomas treated by using a endoscopic polypectomy and 30 cases of colorectal carcinomas treated by using a resection were collected. Ten (10) normal tissue samples were obtained apart from the carcinomas. Sections were used for MUC2 and MUC6 immunostaining. The expressions of MUC2 and MUC6 were scored by using the sum of the percentages of the stained cells and the intensity of staining. RESULTS: All of the ten normal colorectal tissues expressed MUC2 and MUC6. Of the 20 adenomas, 19 cases (95%) were MUC2 positive, and 17 cases (85%) were MUC6 positive. Adenomas with severe atypia tended to express lower levels of MUC2 and MUC6 than those with mild or moderate atypia. Of the 30 carcinomas, 28 cases (93%) were MUC2 positive and 19 cases (63.3%) were MUC6 positive. Colorectal mucinous carcinomas differed significantly from non-mucinous carcinomas in strong MUC6 expression. MUC2 expression showed a significant association with lymph-node metastasis. CONCLUSIONS: The results suggest that MUC6 is expressed in normal colorectal tissues and tumors, that MUC6 expression is especially strong in mucinous carcinomas, and that MUC2 expression is associated with lymph-node metastasis, among the prognostic factors.

Expression of MUC Gene Proteins in Cholecystitis, Adenoma and Adenocarcinoma of the Gallbladder

PURPOSE: Normal gallbladder mucosa shows unique and diverse patterns of mucin genes, and altered mucin expressions have been noted in the gallbladders with stones, dysplasia or carcinomas. The aim of this study was to characterize the expressions of MUC gene proteins in cholecystitis, adenoma and adenocarcinoma of the gallbladder. Differences of MUCs expressions according to the histopathologic parameters in gallbladder carcinomas were also studied. METHODS: Three tissue microarray blocks were made from 23 cases of cholecystitis, 40 cases of gallbladder adenoma, and 66 cases of gallbladder adenocarcinoma. Immunohistochemical stains for MUC1, MUC2, MUC4, MUC5AC and MUC6 were performed, and staining intensity and patterns were evaluated. RESULTS: MUC1, MUC2, MUC4, MUC5AC and MUC6 were overexpressed in 86 (66.7%), 20 (15.5%), 68 (52.7%), 74 (57.4%) and 47 (36.4%) of gallbladder lesions, respectively. MUC1 and MUC2 overexpression rates were higher in gallbladder carcinoma than in cholecystitis and gallbladder adenoma (P<0.05). MUC6 overexpression rate was higher in gallbladder adenoma than in cholecystitis and gallbladder carcinoma (P<0.05). Overexpression of MUC4 and MUC5AC showed no significant differences in cholecystitis, gallbladder adenoma and gallbladder carcinoma. In gallbladder carcinomas MUC1 overexpression rate was high in cases with deeper tumor invasion (P<0.05). MUC6 overexpression rate decreased in cases with larger tumor (P<0.05), higher histologic grade (P=NS), and deeper invasion (P=NS). MUC2, MUC4 and MUC5AC overexpression rates had no relations to the histopathologic parameters. CONCLUSION: Carcinomatous change of gallbladder may be related to MUC1 and MUC2 overexpressions. MUC1 overexpression seems to be related to aggressive biologic behavior of gallbladder carcinoma. MUC6 overexpression acts as a good prognostic factor.

Expression of MUC3, MUC5AC, MUC6 and Epidermal Growth Factor Receptor in Gallbladder Epithelium according to Gallstone Composition / 대한소화기학회지

BACKGROUND/AIMS: Gallbladder (GB) mucin is one of the key factors in the gallstone formation. However, there is little information about the diversity of mucin secretion according to the stone composition. Epidermal growth factor receptor (EGFR) functions in proliferation including mucin secreting goblet cell hyperplasia. We compared the expressions of MUC3, MUC5AC, MUC6 and EGFR in the GB epithelium with cholesterol gallstones (GB-chol) group and pigment gallstones (GB-pig group). METHODS: GBs from elective laparoscopic cholecystectomy for the gallstone disease were studied. Stone composition was analyzed by the spectrophotometer. Immunohistochemical stain was performed using each monoclonal antibody. The percentage of stained proportion was scored by the NIH image program and the results were compared between both groups. RESULTS: Total 20 patients were enrolled (10 patients with cholesterol gallstones, 10 patients with pigment gallstones). The percentages of stained proportion for MUC3, MUC5AC, and MUC6 were 42+/-27%, 31+/-15%, and 17+/-9%, respectively in GB-chol group and 32+/-22%, 33+/-23%, and 15+/-10%, respectively in GB-pig group (p>0.05). The expression of EGFR was 50% (5/10) in the GB-chol group and 80% (8/10) in the GB-pig group respectively. CONCLUSIONS: There was no difference in the expressions of MUC3, MUC5AC, and MUC6 between the two groups. Further studies are needed to elucidate the role of EGFR in the gallstore formation.