BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be involved in the process of invasion, growth and apoptosis in colorectal carcinoma and in the growth and tumorigenesis in familial adenomatous polyposis. This study was conducted to determine the significance of the expression of COX-2 in gastric and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty-seven samples of colorectal adenoma were obtained by endoscopic mucosal resection or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression was determined by immunohistochemistry. Correlation between COX-2 expression and several clinical factors were compared in each gastric and colorectal adenomas. RESULTS: The expression of COX-2 in epithelial cells was significantly higher in the group with large adenoma (>1 cm) compared with the group with small adenoma (adenoma (64.3% vs. 37.9%, p=0.047). CONCLUSIONS: COX-2 was expressed in a size-dependent manner in gastric and colorectal tubular adenomas. The expression of COX-2 was different according to the location of colorectal adenoma. The association of COX-2 expression with the size of adenoma may suggest that the role of COX-2 is not related to the early development of adenoma, but related to the progression of adenoma.
Adenoma/enzymology/*pathology ; Aged ; Colorectal Neoplasms/enzymology/*pathology ; English Abstract ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prostaglandin-Endoperoxide Synthase/*analysis ; Stomach Neoplasms/enzymology/*pathology

OBJECTIVETo investigate the expression of PI3K p85alpha in normal colorectal tissue, colorectal adenoma and primary colorectal carcinoma and explore its significance in the progression of colorectal cancer.

METHODSThe expression of PI3K p85alpha was detected in 116 normal colorectal tissue, colorectal adenoma and primary colorectal carcinoma specimens using immunohistochemical staining, and the relationship between the expression of PI3K p85alpha protein and the clinicopathological factors was analyzed.

RESULTSThe positivity rates of the expression of PI3K p85alpha protein increased gradually in the progression of colorectal cancer and showed significant differences between the tissues (P<0.05). A significant difference was also noted in the positivity rates of the PI3K p85alpha expression in colorectal carcinoma tissues at different Dukes' stages (P<0.05). No obvious correlation was found between PI3K p85alpha expression and the degree of the tumor differentiation.

CONCLUSIONSAbnormal PI3K p85alpha expression occurs in the progression of colorectal cancer in close relation to the clinical stage, and the PI3K/AKT pathway plays an important role in the progression of colorectal cancer.

Adenoma ; enzymology ; pathology ; Adult ; Aged ; Carcinoma ; enzymology ; pathology ; Colorectal Neoplasms ; enzymology ; pathology ; Disease Progression ; Humans ; Immunohistochemistry ; Middle Aged ; Phosphatidylinositol 3-Kinases ; metabolism ; Signal Transduction ; Young Adult

BACKGROUND: Cyclooxygenase (COX) -2 is the rate-limiting enzyme in prostaglandin synthesis. An increased expression has been implicated in the development and progression of human gastric cancers and colorectal adenomas and cancers. This study aimed to determine the involvement and association of COX-2 and Bcl-2 in precancerous gastric adenomas. METHODS: Seventy-nine gastric polyps were obtained by endoscopic mucosal resection or polypectomy from January, 2000 to July, 2003. Immunohistochemical expression of COX-2 and Bcl-2 was observed, and their relationships with various clinicopathological factors were analyzed. RESULTS: Histologically, 13 hyperplastic polyps and 66 tubular adenomas, of which 17 showed high-grade dysplasia, were observed. Increased COX-2 expression was observed in low-grade and high-grade tubular adenomas compared to hyperplastic polyps (p=0.004 and p=0.001, respectively). COX-2 expression was significantly higher in larger (> 1 cm) compared with smaller (< or=1 cm) tubular adenomas (p=0.034), but no relation was observed in hyperplastic polyps. While Bcl-2 expression differed significantly according to histology, increased Bcl-2 expression was observed especially in COX-2 positive low-grade tubular adenomas. CONCLUSION: COX-2 expression increased in a size-dependent manner in tubular adenomas, suggesting a role in polyp growth. The increased expression of Bcl-2 in tubular adenomas, especially in COX-2 positive tubular adenomas, suggests that COX-2 action may be related to Bcl-2 expression.
Stomach Neoplasms/*enzymology/pathology ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Middle Aged ; Male ; Immunohistochemistry ; Humans ; Disease Progression ; Cyclooxygenase 2/*metabolism ; Adenoma/*enzymology/pathology

BACKGROUNDIndoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer.

METHODSWe evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ). We performed immunohistochemical staining and Western blot analysis for IDO expression in both pancreatic cancer and normal pancreas tissues obtained from Chinese PLA General Hospital from July 2012 to December 2013. Survival analysis was performed to correlate IDO expression and histopathologic parameters with overall survival. The Kaplan-Meier method and Cox proportional hazards regression model were conducted.

RESULTSPANC-1, CFPAC-1, and BxPC-3 cell lines expressed IDO at the protein level, and the relative expression amount increased after stimulation with 500 U/ml IFN-γ. Immunohistochemical analysis results revealed that high IDO expression was observed in 59% of pancreatic adenocarcinoma tissues. Compared with normal pancreatic tissues, pancreatic adenocarcinoma showed significantly higher IDO expression levels, especially among patients with high tumor node metastasis (TNM) stages (χ2 = 4.550, P = 0.030), poor histological differentiation (χ2 = 5.690, P = 0.017), and lymph node metastasis (χ2 = 4.340 P = 0.037). Kaplan-Meier survival curves showed that high IDO expression was correlated with low survival rates (hazard ratio [HR] = 0.49 P = 0.009). Multivariate analysis using Cox proportional hazards model indicated that lymph node metastasis (HR = 0.35 P = 0.010) and IDO expression (HR = 0.42 P = 0.020) were two independent prognostic predictors of pancreatic adenocarcinoma.

CONCLUSIONSThe study confirmed that high IDO expression in pancreatic adenocarcinoma was related to poor prognosis of patients. These findings provided evidence that IDO was involved in pancreatic adenocarcinoma progression and might serve as a relevant therapeutic target.

Adenoma ; enzymology ; mortality ; pathology ; Blotting, Western ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Pancreas ; enzymology ; metabolism ; pathology ; Pancreatic Neoplasms ; enzymology ; mortality ; pathology ; Prognosis ; Survival Rate