Adenocarcinoma, Mucinous ; enzymology ; pathology ; Cathepsin B ; metabolism ; Cathepsin D ; metabolism ; Colorectal Neoplasms ; enzymology ; pathology ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness

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 (colorectal adenomas (75% vs. 41.5%, p=0.023). Moreover, increased COX-2 expression was shown in distal compared to proximal colorectal 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 explore the expression of manganese superoxide dismutase (MnSOD) in colorectal carcinoma and its relationship with the clinicopathological findings.

METHODSThe expressions of MnSOD in colorectal carcinoma, adenoma, and adjacent corresponding intestinal mucosal tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between MnSOD expression level in colorectal adenoma and clinical parameters was analyzed.

RESULTSThe expression of MnSOD was negative in adjacent corresponding colorectal tissues. The positive expression rate of MnSOD was 44% (11/25) in colorectal adenoma and 76% (19/25) in colorectal carcinoma (P < 0.05 when compared with the colorectal adenoma and its adjacent tissues). The expression of MnSOD was positively correlated with histopathological grades (P < 0.05) but not with other clinicopathological findings (P > 0.05).

CONCLUSIONThe expression of MnSOD may be associated with the carcinogenesis and progression of colorectal carcinoma, and therefore may be used as a new biomarker.

Adult ; Aged ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the thymidine phosphorylase (TP) expression in different types of cancer and its correlation with tumor microvessel density (MVD).

METHODSThe expression of TP and MVD was detected by immunohistochemistry method. In a series of 251 cancer patients there were 48 patients with gastric cancer, 53 with colorectal cancer, 47 with breast cancer, 56 with cervical cancer, 47 with lung cancer. Normal gastric (n = 25), colorectal (n = 25), cervical (n = 17) and lung (n = 25) tissues around the cancer were also examined.

RESULTSThe TP expression rate was 64.6% in gastric cancer, 67.9% in colorectal cancer, 80.9% in breast cancer, 82.1% in cervical cancer, and 63.8% in lung cancer, which was significantly higher than that in normal tissues (P = 0.0000). TP expression was positively correlated with MVD in gastric, colorectal, breast, and cervical cancers. The correlation was not statistically significant in lung cancer.

CONCLUSIONThis study indicates that TP overexpression in cancer may be associated with tumor angiogenesis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; blood supply ; enzymology ; Colorectal Neoplasms ; blood supply ; enzymology ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Stomach Neoplasms ; blood supply ; enzymology ; Thymidine Phosphorylase ; metabolism ; Uterine Cervical Neoplasms ; blood supply ; enzymology

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/AIMS: Telomeres are simple repeat elements located at each chromosome end of eukaryotic cells. The main function of telomeres is to cap the chromosome end and protect it from enzymatic attack. Telomerase that facilitates the synthesis of telomere has been detected in not only cancer but also precancerous lesion. In this study, we compared the telomerase expression between low grade and high grade colorectal tubular adenoma. METHODS: Among thissues from forty eight patients with colorectal tubular adenoma (23 low grade and 25 high grade colorectal dysplasia), telomerase expressions were evaluated by immunohistochemical staining. RESULTS: We classified 48 patients into two groups by the extent of nuclei staining pattern. High telomerase expression was a group which showed staining nucleus pattern above 50% in tubular adenoma. Low telomerase expression was a group which showed staining pattern nucleus below 50%. Twelve in 25 high grade colorectal dysplasia showed high telomerase expression (48%). Only one in 23 low grade colorectal dysplasia showed high telomerase expression (4%). Telomerase expression was much higher in the tissues from the patients with high grade than in those with low grade colorectal dysplasia (p<0.05). CONCLUSIONS: Activation of telomerase may be related to the malignant potential in colorectal epithelial cells. Further studies are needed to define the role of telomerase in colorectal tumorigenesis.
Adenocarcinoma/*enzymology/pathology ; Adult ; Aged ; Colorectal Neoplasms/*enzymology/pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Telomerase/immunology/*metabolism

MUTYH, one of base-excision repair enzymes, is associated with human genetic disorders. Inherited biallelic mutations in the human MUTYH gene are responsible for an autosomal recessive syndrome-adenomatous colorectal polyposis (MUTYH associated polyposis, MAP), which significantly increases the risk of colorectal cancer (CRC). In this article we review the relationship between BER and the oxidative damage to DNA, the functional overlap of BER with other repair proteins, the molecular mechanism of tumourigenesis in MAP, and delineate the MUTYH polyposis phenotype and its prevention.
Adenomatous Polyposis Coli ; complications ; enzymology ; genetics ; Colorectal Neoplasms ; enzymology ; etiology ; genetics ; DNA Damage ; DNA Glycosylases ; genetics ; Germ-Line Mutation ; Humans ; Mutation ; Risk Factors

OBJECTIVETo investigate the association between metabolic enzymes polymorphisms and the risk of colorectal cancer(CRC).

METHODSMethods of detection used were based on polymerase chain reaction(PCR) including PCR-restriction fragment length polymorphism (PCR-RFLP), allele specific-PCR (AS-PCR) and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls.

RESULTSThe allele frequencies of CYP1A1 6235C, CYP1A2 734A, CYP2E1 -1259C, CYP2E1 -1019T, GSTM1 and T1 null type, NAT1* 10 and NAT2 Mx (x = 1,2,3) alleles were 31.65%, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the case group and 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk (OR = 0.79, 95% CI: 0.63-0.99) and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect (OR = 0.53, 95% CI: 0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk (OR = 4.41, 95% CI: 1.21-16.10).

CONCLUSIONCYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.

Alleles ; Case-Control Studies ; Colorectal Neoplasms ; enzymology ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Homozygote ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic

OBJECTIVETo investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance.

METHODSThe expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed.

RESULTSThe rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis.

CONCLUSIONSPyk2 expression can be a prognostic factor to the CRC patients together with other predictors.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Focal Adhesion Kinase 2 ; metabolism ; Humans ; Male ; Middle Aged ; Prognosis

OBJECTIVETo evaluate the clinical significance of blood and fecal expression of tumor M2-pyruvate kinase (Tumor M2-PK) in patients with colorectal cancer.

METHODSWith 22 healthy subjects as controls, 44 patients with CRC were examined for tumor M2-PK in serum and fecal samples using a sandwich enzyme immunoassay.

RESULTSThe sensitivity of serum and fecal tumor M2-PK for detecting CRC was 59.1% and 63.6% with a specificity of 86.4% and 81.8%, respectively. The serum and fecal levels of tumor M2-PK showed a significant correlation in CRC patients.

CONCLUSIONTumor M2-PK has good sensitivity and specificity in the diagnosis of CRC.

Biomarkers, Tumor ; metabolism ; Case-Control Studies ; Colorectal Neoplasms ; blood ; metabolism ; Feces ; enzymology ; Female ; Humans ; Male ; Pyruvate Kinase ; blood ; metabolism