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

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.
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PMID:Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma. 749 46

beta-Lapachone, a plant product, has been shown to be a novel inhibitor of DNA topoisomerase I, with a mode of action different from camptothecin and a chemical structure distinct from those of current anti-cancer drugs. We observed that beta-lapachone, at concentrations of less than 8 microM, induces cell death with characteristics of apoptosis in human prostate cancer cell lines. This effect of beta-lapachone was also observed in a human promyelocytic leukemia cell line (HL-60). beta-Lapachone-induced apoptosis is independent of p53 expression, and ectopic overexpression of bcl-2 did not confer significant resistance to beta-lapachone. Among other human carcinoma and adenoma cell lines tested, human breast and ovary carcinoma showed sensitivity to the cytotoxic effect of beta-lapachone without manifesting signs of apoptosis. These results suggest that beta-lapachone is a potential compound to be added to cancer chemotherapy, particularly for prostate cancer.
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PMID:Induction of apoptosis by beta-lapachone in human prostate cancer cells. 764 Nov 81

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

The bcl-2 gene is an oncogene that inhibits programmed cell death (apoptosis). We investigated by immunocytochemistry bcl-2 expression in normal colonic mucosa, hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel. The purpose of the investigation was twofold; to assess the possible role of bcl-2 in colorectal tumorigenesis and to evaluate its clinical significance. The cases studied included 24 hyperplastic polyps, 49 adenomas, and 205 colorectal carcinomas. In both normal mucosa and hyperplastic polyps bcl-2 immunoreactivity was detected only in the proliferative cells of the colonic crypts. Conversely, bcl-2 immunoreactivity was noted in all adenomas irrespective of the degree of dysplastic change; it was diffuse in 84% of adenomas and focal in the remaining cases. In colorectal carcinomas bcl-2 expression was undetectable in 50% and focal (less than 50% immunostained neoplastic cells) in 38% of tumors. The remaining 12% of the carcinomas displayed diffuse (more than 50% immunostained neoplastic cells) bcl-2 immunoreactivity. In colorectal carcinomas bcl-2 expression was not correlated with relevant clinicopathologic parameters, including disease stage, tumor location and growth fraction, DNA ploidy, and p53 protein accumulation, and had no prognostic significance by univariate or multivariate analysis. These results suggest that bcl-2 oncoprotein may play a role in colorectal tumorigenesis, probably in the early phases of the adenoma-carcinoma sequence. bcl-2 expression in established tumors has no prognostic significance.
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PMID:bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. 775 Sep 37

The bcl-2 product has been related to the block of programmed cell death (apoptosis) both in lymphoid and in epithelial cells. The pathological expression of bcl-2 has been investigated mainly in haematological malignancies. Here we have investigated bcl-2 expression in a model of epithelial tumours represented by the spectrum of carcinomas arising from the follicular epithelium of the human thyroid gland. The analysis was carried out by immunocytochemistry on archival material using monoclonal antibodies against bcl-2 and thyroglobulin (Tg) on consecutive sections of 94 well-differentiated carcinomas (WDCs), 19 poorly differentiated carcinomas (PDCs), and 22 undifferentiated carcinomas (UCs) of the thyroid gland. In a subset of 5 cases of UC showing a differentiated component (UC-D), the expression of p53 protein was also investigated. As controls, fetal and adult normal thyroid glands and adenomas were analysed. bcl-2 expression was detected in 74 of 94 cases (78.7 per cent) of WDC, 16 of 19 cases (84.2 per cent) of PDC, and 3 of 22 cases (13.6 per cent) of UC. Simultaneous expression of bcl-2 protein and Tg was observed in 74 of 94 cases (78.7 per cent) of WDC, 13 of 19 cases (68.4 per cent) of PDC, and in no case of UC. bcl-2 and Tg immunostaining was detected in all fetal and normal thyroid glands as well as in the adenoma specimens examined. In the subset of UC-D, mutual exclusion of bcl-2 and p53 expression was observed in the undifferentiated and differentiated components (p53 but not bcl-2 expressed in the former).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bcl-2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland. 820 14

Gene changes in multiple oncogenes, multiple growth factors and multiple tumor-suppressor genes are observed in stomach cancer. Among them, those most commonly implicated in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma are inactivation (mutations and allele loss) of the p53 gene, and activation (abnormal expression and amplification) of the c-met gene. Moreover, they occur at an early stage of stomach carcinogenesis. In addition, loss of heterozygosity (LOH) on chromosome 5q (APC locus) is frequently associated with well-differentiated adenocarcinoma. LOH on chromosome 18q (DCC locus) and LOH of the bcl-2 gene also are common events of well-differentiated adenocarcinoma. LOH on chromosomes 1q and 7q may be involved in the progression of well-differentiated adenocarcinoma. Conversely, the development of poorly differentiated adenocarcinoma, in addition to changes in p53 and c-met genes, requires reduction or dysfunction of cadherin. Overexpression of bcl-2 protein is observed in poorly differentiated adenocarcinoma or signet-ring cell carcinoma. Moreover, the K-sam gene is amplified preferentially in poorly differentiated adenocarcinoma of scirrhous carcinoma. K-sam amplification in scirrhous carcinoma often occurs independently of c-met gene amplification. LOH on chromosome 1p also is relatively common in poorly differentiated adenocarcinoma. Exceptionally, signet-ring cell carcinoma shares APC mutations. There are some differences in expression of the growth-factor/receptor system between well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma. Moreover, interaction between cell-adhesion molecules in tumor cells expressing c-met and hepatocyte growth factor (HGF) from stromal cells is linked with morphogenesis of two histological types of stomach cancer. Intestinal metaplasia and adenoma of the stomach also contain p53 mutations and K-ras mutations or tpr-met rearrangement. Taken together, different genetic pathways of stomach carcinogenesis may exist for poorly differentiated and well-differentiated stomach cancers. Some of the latter may develop by a cumulative series of gene alterations similar to those of colorectal cancer.
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PMID:Molecular mechanism of stomach carcinogenesis. 844 Jul 43

Colorectal polyps were analyzed from the standpoint of cell death by using the in situ 3'-tailing reaction (ISTR), which identifies cell death-associated DNA double strand breaks, and immunohistochemistry for bcl-2 oncoprotein (BCL-2) and for Ki-67. There were few ISTR-positive cells in the non-neoplastic glands, whereas 38% of non-neoplastic mucosa just adjacent to the adenoma had many labeled nuclei, suggestive of cell death associated with replacement by tumor. The neoplastic glands contained variable number of ISTR-positive nuclei, mostly showing the morphological feature of apoptotic bodies. In the representative glands with the most prominent ISTR-labeling, their indices did not have a significant relationship to the grade of atypia, to the proliferative activity (Ki-67 labeling indices) of neoplastic glands, or to BCL-2 stainability. In each case, however, the neoplastic glands with no or few ISTR-labeled nuclei tended to express BCL-2 intensely, and all lesions of adenoma or carcinoma with more than 15% of ISTR-labeling indices showed weak BCL-2 immunoreactivity. In general, BCL-2 expression was significantly stronger in the adenoma than in non-neoplastic mucosa and carcinoma, although there was no significant difference of ISTR-labeling between adenoma and carcinoma. These results indicate that cell death in colorectal neoplastic polyps does not have a significant influence on their growth rate, and that BCL-2 plays some role, at least in part, in the regulation of apoptosis.
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PMID:Cell death in colorectal polyps as evaluated by in situ 3'-tailing reaction and its relationship to BCL-2 expression. 856 32

Evidence of accumulating for the failure of apoptosis as an important factor in the evolution of colorectal cancer and its poor response to adjuvant therapy. The proto-oncogene bcl-2 suppresses apoptosis. Its expression could provide an important survival advantage permitting the development of colorectal cancer. The expression of bcl-2 and p53 was determined by immunohistochemistry in 47 samples of histologically normal colonic mucosa, 19 adenomas and 53 adenocarcinomas. Expression of bcl-2 in colonic crypts > 5 cm from the tumours was confined to crypt bases but was more extensive and intense in normal crypts < 5 mm from cancers. A higher proportion of adenomas (63.2%) than carcinomas (36.5%) expressed bcl-2 (P < 0.05). A lower proportion of adenomas (31.6%) than carcinomas (62.3%) expressed p53 (P < 0.02). A total of 26.3% of adenomas and 22% of carcinomas expressed both bcl-2 and p53. To determine whether these samples contained cells which expressed both proteins, a dual staining technique for bcl-2 and p53 was used. Only 1/19 adenomas and 2/53 carcinomas contained cells immunopositive for both bcl-2 and p53. Moreover there was evidence of reciprocity of expression of bcl-2 and p53 in these three double staining neoplasms. We suggest that bcl-2 provides a survival advantage in the proliferative compartment of normal crypts and colorectal neoplasms. However, its expression is lost during the evolution from adenoma to carcinoma, whereas p53 expression is increased, an event generally coincident with the expression of stabilised p53, which we presume to represent the mutant form.
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PMID:Evidence of reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas. 861 22

In order to cast light on the possible role of bcl-2 protein (Bcl-2) expression in gastric tumorigenesis, 33 cases of gastric adenomas and carcinomas originating from the same stomachs were immunohistochemically investigated for Bcl-2 protein (Bcl-2) expression, accumulation of p53 protein and cell proliferation as determined by the Ki-67 labeling index (LI). Bcl-2 expression was detected in 24/33 (72.7%) adenomas and in 6/33 (18.2%) carcinomas, the difference being statistically significant (P = 0.0001). Only 4 of 33 (12.1%) cases exhibited expression in both adenoma and carcinoma lesions in the same stomachs. Immunoreactivity was decreased in areas of cellular and structural atypia in adenoma lesions (P < 0.008), and appeared to be positively linked to the tumor progression and the degree of differentation in carcinomas, although it did not reach statistical significance. Accumulation of p53 protein was rare in the adenomas but was found in 15/33 (45.5%) of carcinoma lesions, with a significant dissociation from Bcl-2 immunoreactivity. No apparent relation between Ki-67 LI and either adenoma grading or carcinoma typing was noted, although average Ki-67 LI of the highest labeling areas in carcinomas was statistically higher than in adenomas (P = 0.0001). These results indicate that the regulation of Bcl-2 expression may differ between gastric adenomas and carcinomas, may be correlated with tumor differentiative features. In addition, p53 accumulation may play an important role in the onset of malignancy.
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PMID:Different expression of Bcl-2 protein in gastric adenomas and carcinomas. 872 51

The development of colorectal carcinoma from adenomas is recognized as the dominant mechanism of colon carcinogenesis. However, early colon carcinomas are being increasingly detected which have no adenomatous elements in their vicinity, and which, despite their small size, already show submucosal invasion. Such tumours (so-called 'de novo' carcinomas) have renewed consideration of the de novo colorectal carcinogenesis pathway. The goal of this study was to evaluate the expression of tumour suppressor gene p53 and apoptosis control gene bcl-2 in de novo carcinomas, compared with early carcinomas developing in the background of an adenoma (ex-adenoma). Fifty cases each of de novo and ex-adenoma carcinomas (pT1) were studied. p53 expression was significantly higher in the de novo carcinomas than in the ex-adenoma carcinomas (62 per cent vs. 42 per cent), while bcl-2 tended to be weaker in the de novo than in the ex-adenoma carcinomas. These differences' support the concept that de novo carcinomas are a unique pathological entity, with a phenotype reflecting their more aggressive behaviour.
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PMID:Expression of bcl-2 and p53 in de novo and ex-adenoma colon carcinoma: a comparative immunohistochemical study. 895 2


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