Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physiological regeneration of colonic epithelium entails proliferation at the crypt base and cell loss by shedding or cell death. The aim of this study was to localise and assess the rate of apoptosis in normal and neoplastic colonic epithelium with respect to zones of proliferation. Familial adenomatous polyposis (FAP) was chosen as a model to study neoplastic transformation of colonic mucosa at an early stage. Apoptotic cells were detected in situ by TdT-mediated biotin-dUTP nick end labelling (TUNEL) in parallel to cells in cycle determined by Ki-67 immunohistochemistry using the monoclonal antibody MiB-1. By detection of genomic fragmentation, two different patterns of enterocytic apoptosis emerged: (a) apoptotic bodies being engulfed by adjacent epithelial cells, and (b) apoptotic cells with only subtle morphological changes being extruded into the gut lumen. The engulfment pattern was seen predominantly in the crypts of the normal colonic mucosa and, although very rare, was clearly confined to the basal proliferation compartment. The extrusion pattern was restricted to the luminal mucosal surface. Adenomas of FAP showed highly increased numbers of apoptotic bodies, which were scattered throughout the transformed mucosa. Both patterns of apoptosis were topographically intermingled although the extrusion pattern prevailed at the luminal adenoma surfaces. Whereas cells in cycle were somewhat more numerous in the upper parts of the crypts, apoptosis occurred with increased frequency at sites beneath the proliferation maximum suggesting an inverted direction of epithelial cell migration in adenomas. These results suggest two distinct routes towards enterocytic apoptosis in the colonic mucosa leading to engulfment or extrusion of dying cells. Adenomatous transformation of colon epithelium is associated with a considerable increase of the cellular turnover rate and with a severe disturbance of the microtopographical localisation of birth and death of enterocytes.
 ...
PMID:In situ detection of enterocytic apoptosis in normal colonic mucosa and in familial adenomatous polyposis. 853 54

A disturbance in the balance between cell proliferation and cell loss, or apoptosis, may underlie neoplastic development. Therefore, we determined spontaneous apoptotic and proliferative rates in normal, hyperplastic, adenomatous, and malignant colorectal epithelia. In paired sections, DNA strand breaks were detected using the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, and apoptotic cells were also identified in H&E-stained slides by morphological criteria. Cell proliferation, bcl-2, and p53 expression were analyzed using specific monoclonal antibodies. In normal mucosa, luminal epithelial cells demonstrated higher rates of apoptosis compared to cells in the proliferative zone. Neoplastic transformation was associated with a significant increase in rates of apoptosis and proliferation. However, apoptosis, but not proliferation, decreased at the adenoma-to-carcinoma transition coincident with expression of mutant p53. In carcinomas, both mutant p53 and bcl-2 protein levels were associated with attenuated apoptotic rates. In conclusion, apoptosis is an important regulator of growth in normal and neoplastic colorectal epithelia. Increased apoptosis and proliferation accompany neoplastic transformation, suggesting that an alteration in apoptotic rates is an important event in colorectal carcinogenesis. Furthermore, the imbalance in these processes found in carcinomas may facilitate tumor growth and progression.
 ...
PMID:Increased apoptosis accompanies neoplastic development in the human colorectum. 981 59

Caspase3/CPP32 is a member of the interleukin-1 beta-converting enzyme (ICE) or cell death effector (CED)-3 family, which is involved in the induction of apoptosis and has been considered to be correlated with apoptosis because of the most downstream enzyme in their apoptosis inducing pathway. We immunolocalized Caspase3/CPP32 in both normal and neoplastic human gastric mucosa. We then correlated the findings with cell proliferation studied by Ki67 immunostaining and apoptosis, which was tested for by DNA fragmentation in situ using TdT-mediated dUTP biotin nick end labeling (TUNEL) method in order to examine possible biological significance in cell turnover of normal and pathological human gastric tissues. Caspase3/CPP32 immunoreactivity was detected in both the cytoplasm and nuclei of glandular epithelial cells, predominantly in the Ki67 positive proliferative zone and TUNEL positive foveolar epithelium of normal non-neoplastic gastric mucosa (n = 10) and tumor cells of both adenoma (n = 17) and carcinoma (n = 33). We determined the labeling index (LI) of Ki67, Caspase3/CPP32 and TUNEL positive cells by evaluating the number of positive cells in the same areas of serial tissue sections using computer-assisted image analysis. Ki67 LI in adenocarcinoma (78.6 +/- 12.6%) was significantly [p < 0.0001] higher than that of adenoma (43.8 +/- 8.9%) and non-neoplastic gastric mucosa (24.2 +/- 9.0%). Caspase3/CPP32 LI in adenocarcinoma (17.1 +/- 10.3%) was significantly lower [p < 0.0001] than that of gastric adenoma (33.1 +/- 19.8%) and non-neoplastic gastric mucosa (42.4 +/- 15.8%). TUNEL LI in adenocarcinoma (1.9 +/- 2.1%) was significantly [p < 0.0001] lower than that of non-neoplastic gastric mucosa (6.0 +/- 3.5%), but not significantly different from that of adenoma (3.0 +/- 2.9%). These results indicate that gastric adenocarcinoma is associated with an inhibition of apoptosis and the augmentation of proliferative activity of tumor cells compared to non-neoplastic gastric mucosa. There was a tendency to a positive correlation between the Caspase3/CPP32 and TUNEL LI and an inverse correlation between the Caspase3/CPP32 and Ki67 LI, when evaluating all the specimens, although the correlation did not reach statistical significance. These results also suggest that Caspase3/CPP32 is involved in the development or regulation of apoptotic cell death in cell turnover of normal and neoplastic mucosa of the human stomach.
 ...
PMID:Immunohistochemistry of Caspase3/CPP32 in human stomach and its correlation with cell proliferation and apoptosis. 989 91

The occurrence of apoptosis and cell proliferation in hereditary intestinal diseases was analyzed for possible diagnostic markers that could discriminate the formation of tumors that would develope into cancer. In all, 15 adenomas in familial adenomatous polyposis, 3 juvenile polyposis, 5 Peutz-Jeghers syndrome, 14 sporadic adenomas, and 46 colorectal carcinomas were investigated. Tissue specimens were examined for apoptotic cells by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and proliferating cells by immunohistochemistry of proliferating cells nuclear antigen (PCNA). In hereditary intestinal diseases, the apoptotic and proliferating indexes were significantly lower than those in colorectal carcinoma, and higher apoptotic and proliferating indexes were observed in poorly differentiated colorectal adenocarcinoma and in subserosal stages of invasion. There were no significant differences in proliferating and apoptotic indexes between adenoma in FAP and sporadic adenoma. No apoptotic and proliferating cells were observed in juvenile polyposis, and only occasional proliferating cells were seen in Peutz-Jeghers syndrome. These findings demonstrated that TUNEL and PCNA staining are useful in correctly reflecting disease progression in hereditary intestinal diseases.
 ...
PMID:Histochemical study of apoptosis and cell proliferation in hereditary intestinal diseases. 1118 3

The expression of COX-2 participates strongly in polyp formation of adenomatous polyposis coli (APC)-mutated mice. However, the mechanism of growth inhibition by COX-2 inhibition remains unclear. The aims of this study were to assess the role of COX-2 during the process of polyp formation in APC(Delta474) knockout mice. Starting at 4 weeks of age, the treated group (T group) were given a diet containing JTE-522, a selective COX-2 inhibitor, and the control group (C group) were given a control diet. At 12 weeks of age, mice were killed and polyps located in a proximal 10 cm of the small intestine were classified into two morphological stages: large adenomas (>300 microm in diameter) which lacked normal villous structure, and small adenomas (</=300 microm) covered with normal villous epithelia. In both classes, after counting the incidence, adenomas were examined for vascularity, expression of COX-2 and VEGF protein, labeling proliferating cell nuclear antigen (PCNA) and apoptosis with the TdT-mediated dUTP nick end labeling method, including expression of Bcl-2 and Bcl-X. JTE-522 significantly reduced the incidence of large adenomas, but not of small adenomas. Although it did not affect the proliferating potential of adenomas, the apoptosis index increased significantly in the T group accompanied by a reduction in Bcl-X expression in both small and large adenomas. In the C group, macrophages with both COX-2 and VEGF expression were observed in the submucosa of large adenomas, where some large vessels were also observed. JTE-522 inhibited the VEGF expression of these macrophages, resulting in a decrease in vascular area. In conclusion, macrophages with COX-2 and VEGF expression in the submucosal layer are responsible for angiogenesis in large adenomas, and a selective COX-2 inhibitor reduced the growth of adenoma mainly by its inhibitory effect on angiogenesis.
 ...
PMID:The role of cyclooxygenase-2 (COX-2) in two different morphological stages of intestinal polyps in APC(Delta474) knockout mice. 1215 54

The development of colorectal cancer is known to be characterized by a sequence of events during which normal colonic epithelium gradually transforms to carcinoma, the adenoma-carcinoma sequence. Apoptosis plays an important role in the development and maintenance of tissue homeostasis. Currently, there is no agreement in the literature about the prognosis of apoptosis in colorectal cancer. The number of studies examining the expression of caspases in colorectal cancer is very limited, and they have not examined any correlation between expression and patient survival. This study included histologic samples from 179 patients diagnosed with colon cancer. We used the TdT-mediated X-dUTP nick end labeling method and caspase-3 labeling to identify the degree of apoptosis. Our results show that lower apoptotic index measured by TdT-mediated X-dUTP nick end labeling method and lower immnuhistochemical expression of caspase-3 is associated with shorter disease-free survival and overall survival. However, only apoptotic index is proven to be an independent survival indicator. The results of our study are consistent with the proposed models of carcinogenesis of colorectal cancer that emphasize resistance to apoptosis as a decisive factor in the progression of the disease and resistance to treatment.
 ...
PMID:Apoptosis as a Prognostic Factor in Colorectal Carcinoma: Comparison of TUNEL Method and Immunohistochemical Expression of Caspase-3. 2948 4