Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of acute and recurrent pancreatitis was investigated in pancreatic cancer induction by N-nitrosobis(2-oxopropyl)amine (BOP) in Syrian golden hamsters. For the correlation of the cellular alteration with carcinogenesis, BOP (20 mg/kg body wt) was injected once sc into hamsters at day 3 (group 2), week 1 (group 3), and week 8 (group 4), corresponding to cellular degeneration, regeneration, and healing, respectively. Additional groups received BOP 30 minutes before common duct ligation for 48 hours (group 1) or before repeated induction of pancreatitis at 4 weekly intervals for 4 weeks (group 5). Group 6 was a pancreatitis control. Two groups of hamsters received BOP only, at the age of 8 weeks (group 7, which served as a BOP control for groups 1-3 and 5) or at the age of 16 weeks (group 8, the control for group 4). Hamsters were killed 46 weeks after BOP injection (with the exception of group 1 animals, which were killed 52 wk after BOP) to guarantee the same postcarcinogen exposure time in each group. The results showed that BOP, when given during cellular degeneration (group 2) and healing (group 4), induced significantly fewer carcinomas than in the control groups, whereas the tumor pattern was not affected when BOP was given before pancreatitis induction (group 1) or at the time of cellular regeneration (group 3). Recurrent pancreatitis (group 5), however, resulted in carcinomas significantly larger in number and size than those in control group 8. A significantly higher incidence of carcinomas occurred in group 8 controls (treated with BOP at the age of 16 wk) compared to the incidence in group 7 controls (treated with BOP at the age of 8 wk).
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PMID:Modification of pancreatic carcinogenesis in the hamster model. IX. Effect of pancreatitis. 657 34

In 21 patients who had undergone total pancreatectomy for pancreatic head carcinoma, the uninvolved pancreas was examined with regard to the type, incidence and regional distribution of duct epithelial proliferation. The results were compared with those in 37 operative specimens from patients with chronic pancreatitis, in 46 normal pancreases from autopsies and with findings in experimental pancreatic carcinogenesis. While the incidence of squamous metaplasia and non-papillary epithelial hypertrophy varied little in the different groups, papillary epithelial hyperplasia was found three times more often in cases of carcinoma, with associated mild duct obstruction. Atypical epithelial proliferation was only detected in the vicinity of carcinomas. Unequivocal transition from papillary hyperplasia to atypical proliferation was not observed. In hamsters treated with dihydroxy-di-n-propylnitrosamine (DHPN) for induction of pancreatic duct carcinomas, the early duct lesions closely resembled atypical epithelial proliferation of human pancreas. It is concluded that (1) papillary epithelial hyperplasia is probably only indicative of early duct obstruction and/or a general neoplastic stimulus, (2) intraductal epithelial proliferation with atypia is a true precursor of duct carcinoma, and (3) chronic pancreatitis lacks atypical duct lesions.
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PMID:Intraductal proliferation in the pancreas and its relationship to human and experimental carcinogenesis. 745 11

To establish an adequate statistical classification of epithelial atypia in the pancreatic duct, a total of 78 areas of duct epithelia with varying grades of atypia were subjected to nine-parameter morphometry and nine-dimensional multivariate cluster analysis. The material was derived from 53 pancreases resected for various epithelial tumors or acute or chronic pancreatitis. The result was correlated with immunohistochemical findings in which the pattern of intraepithelial distribution of carcinoembryonic antigen changed with the degree of ductal atypia. Finally, atypical cells classified by cluster analysis and immunohistochemistry were subjected to computer-aided three-dimensional mapping to visualize their distribution in the ductal tree. Cluster analysis demonstrated that the various epithelial forms were classifiable into Clusters 1, 2, and 3, representing ordinary epithelia and mild and severe dysplasias, respectively. The last category was created so as to include not only in situ and invasive carcinoma but the so-called borderline atypical lesions. The reproducibility of this classification was proved by two sorts of discriminant analyses. Also, the grades of atypia shown by the clustering proved to correlate with the reaction patterns for carcinoembryonic antigen. In the computer-aided three-dimensional mapping, severely dysplastic areas were shown surrounded by zones of mild dysplasia, justifying the assumption of a stepwise carcinogenesis in the pancreatic ducts.
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PMID:Varying grades of epithelial atypia in the pancreatic ducts of humans. Classification based on morphometry and multivariate analysis and correlated with positive reactions of carcinoembryonic antigen. 813 24

Growing evidence indicates that lysosomal Cathepsins D (CD), B (CB) and L (CL) may promote carcinogenesis and tumor progression. Therefore, we evaluated their potential value as biochemical parameters of malignant progression in patients with benign diseases which may undergo malignant transformation, such as liver cirrhosis (LC) and chronic pancreatitis (CHP) as well as in hepatocellular carcinoma (HCC) and pancreatic cancer (DPC). CD, CB and CL serum levels were determined by immunoenzymatic assays in LC, CHP, HCC or DPC patients and correlated with a number of biochemical and clinical parameters of these diseases. CD serum levels were increased in LC, CHP and HCC, but not in the DPC group as compared to normal subjects (NS) (P < 0.01). Interestingly, higher levels of this enzyme were observed in LC patients compared to HCC patients ( P < 0.01). CB serum concentrations were increased in all patient groups (P < 0.01). However no difference was evidenced between benign and malignant diseases. CL serum levels were significantly increased only in DPC as compared to NS (P < 0.01) or CHP patients (P < 0.02) and in HCC as compared to NS (P < 0.01). The evaluation of CD, CB and CL serum pattern in LC, CHP, HCC and DPC patients may be useful as additional biochemical parameters in the differential diagnosis and therapeutic monitoring of these diseases. Prospective clinical investigations to assess the potential value of these enzymes as biochemical markers of malignant progression of LC or CHP are warranted by the present data.
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PMID:Cathepsin D, B and L circulating levels as prognostic markers of malignant progression. 869 62

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions.
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PMID:Expression of cathepsin E in pancreas: a possible tumor marker for pancreas, a preliminary report. 875 6

The epithelial expression of apomucins MUC1, MUC2, MUC3, and MUC5/6 was examined in normal pancreas and in pancreatic lesions, using immunohistochemical methods. In normal pancreas (n = 5), MUC1 apomucin was expressed in ducts and some acini, but there was no expression of MUC2, MUC3, or MUC5/6. In chronic pancreatitis (n = 5), MUC1 apomucin was expressed, but expression of the other apomucins was not noted. However, mucous hyperplastic foci of pancreatic ducts expressed MUC5/6 apomucin in 2/5 cases (40 percent). In intraductal papillary-mucinous neoplasm (IPMN) of the pancreas (n = 9), MUC1, MUC2, MUC3, and MUC5/6 apomucins were expressed in 8/9 (89 percent), 0/9 (0 per cent), 4/9 (44 per cent), and 9/9 (100 per cent) case, respectively. In pancreatic mucinous cystadenoma (n = 8), MUC1, MUC2, MUC3, and MUC5/6 apomucins were expressed in 7/8 (88 percent), 0/8 (0 percent), (25 percent), and 3/8 (38 percent) cases, respectively. In invasive ductal adenocarcinoma of the pancreas (n = 25), expression of MUC1, MUC2, MUC3, and MUC5/6 apomucins was found in 25/25 (100 percent), 1/25 (4 percent), 20/25 (80 percent), and 24/25 (96 percent) cases, respectively. Atypical mucous duct hyperplasia near cancer cells consistently expressed MUC1 apomucin and occasionally expressed MUC3 and MUC5/6. In positive cases, MUC1 apomucin expression was noted in the cell membrane facing the ductal or neoplastic lumina, while expression of MUC2, MUC3, and MUC5/6 apomucins was found in the cytoplasm. These results suggest that MUC3 and MUC5/6 apomucins newly emerge during the neoplastic transformation of pancreatic mucinous cystadenoma and IPMN and during pancreatic ductal carcinogenesis, while MUC1 apomucin remains positive and MUC2 apomucin remains almost negative during neoplastic transformation.
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PMID:Expression of MUC apomucins in normal pancreas and pancreatic tumours. 897 74

cDNA representational difference analysis (cDNA-RDA) is a polymerase-chain-reaction-coupled subtractive and kinetic enrichment procedure for the isolation of differentially expressed genes. In this study, the technique was used to isolate novel genes specifically expressed in pancreatic cancer. cDNA-RDA was done on cDNA reverse transcribed from a poly(A)+ mRNA pool made from 10 cancer tissues (tester) by using as a driver a cDNA from a poly(A)+ mRNA pool made from a combination of 10 tissues of chronic pancreatitis and 10 healthy pancreatic tissues. The use of chronic pancreatitis in addition to healthy pancreas mRNA in the driver preparation eliminated the influence of stromal tissue components present as contamination in the cancer-specific preparations. Such cDNA-RDA led to the isolation of 16 distinct, cancer-specific gene fragments. These were confirmed to be overexpressed in pancreatic cancer tissues by Northern blot analysis. Sequence analysis revealed homologies to five genes previously implicated in the carcinogenesis of the pancreas or other tissues. Eleven fragments had no significant homology to any known gene and thus represent novel candidate disease genes. The experiments demonstrate that cDNA-RDA is a reproducible and highly efficient method for the identification of novel genes with cancer-specific expression.
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PMID:Identification of genes with specific expression in pancreatic cancer by cDNA representational difference analysis. 917

Genetic alterations such as K-ras mutation, inactivation of the p53, p16 and DPC4 genes and frequent chromosomal loss of the 17p, 9p, 18q and 1p are thought to play a crucial role in the carcinogenesis of pancreatic cancer. Mutations of K-ras oncogene could be detected frequently in pancreatic juice samples from patients with pancreatic carcinoma and intraductal papillary neoplasm (IPN), although they could be detected in some of the samples from patients with chronic pancreatitis and pancreatic cyst. This suggests that K-ras mutation is an early event in the carcinogenesis of the exocine pancreas. In IPN, analysis of other genetic alteration would be available, since pancreatic juice samples from the patient are relatively rich in the proportion of the tumor cells. A new diagnostic modality of sensitive allelotyping would be useful for evaluating malignant potential of these borderline lesions.
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PMID:[Molecular diagnosis of pancreatic cancer]. 927 65

The centrosome plays an important role in microtubule nucleation and organization, ensuring the establishment of cell polarity and balanced chromosome segregation. Recent studies have suggested that the loss of cell polarity and/or chromosome missegregation (aneuploidy) in human malignant tumors could result from defects in centrosome function. Using immunofluorescence analysis with an antibody to gamma-tubulin (a well-characterized centrosomal component), we examined surgically resected human pancreatic tissues for centrosome abnormalities. The tissues included ductal carcinomas (n = 13), adenomas (n = 3), endocrine tumors (n = 3), chronic pancreatitis (n = 5), and normal pancreatic tissues (n = 12). We found that most (85%) carcinomas and some adenomas displayed abnormal centrosome profiles, characterized by an increase in size and number of centrosomes, and by their irregular distribution. In contrast, none of normal ductal and stromal tissues showed these abnormalities. These findings suggest that centrosome abnormalities may develop at a relatively early stage of pancreatic ductal carcinogenesis.
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PMID:Centrosome abnormalities in pancreatic ductal carcinoma. 1035 27

Matrix metalloproteinases (MMPs) have been implicated in the invasion and metastasis of tumor cells. To elucidate the involvement of MMP-1 in human pancreatic ductal adenocarcinoma, we performed immunohistochemical analysis on tissues from 2 fetal pancreases, 5 normal pancreases, 6 cases of chronic pancreatitis, and 46 pancreatic ductal adenocarcinomas. In addition, among the pancreatic carcinomas, we compared MMP-1 expression in relation to the degree of differentiation, lymph node metastasis, and depth of invasion of the carcinoma. MMP-1 was expressed faintly in fetal and normal pancreatic tissues. Among the 46 pancreatic carcinomas, 33 (72%) showed positive staining for the MMP-1 protein. There was no difference in the degree of differentiation. In situ hybridization confirmed the presence of MMP-1 mRNA in the pancreatic carcinomas. Expression of MMP-1 mRNA was also detected in two human pancreatic carcinoma cell lines and three pancreatic carcinoma tissues by the reverse transcription polymerase chain reaction method. MMP-1 was expressed in the carcinoma cells themselves and in stromal fibroblasts. Patients with MMP-1 positivity in the primary site had a significantly poorer prognosis than patients who were MMP-1 negative (P < .05). MMP-1 expression, however, had no relation to the presence of lymph node metastasis, tumor size, or tumor-node-metastasis stage in pancreatic carcinomas. These findings suggest that MMP-1 expression is related to the carcinogenesis and prognosis of human pancreatic ductal adenocarcinoma.
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PMID:Expression of the MMP-1 in human pancreatic carcinoma: relationship with prognostic factor. 1043 Feb 70


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