Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Present diagnostic possibilities virtually do not make it possible to diagnose early stages of pancreatic cancer. Likewise, it is very difficult to differentiate between pancreatic cancer and chronic pancreatitis. The methods of visualization are insufficiently sensitive and the determination of certain genes could enrich our diagnostic opportunities. Considerable attention in this direction has been devoted to the determination and evaluation of the presence of oncogene K-ras. Our initial experience with the determination of K-ras in preparations from patients with pancreatic cancer or with chronic pancreatitis confirmed that K-ras in an oncomarker associated with adenocarcinoma of pancreas, whereas in patients with chronic pancreatitis it occurs in about 10% of the examined samples.
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PMID:[Molecular diagnosis in pancreatic carcinoma]. 1293 40

In this prospective study we evaluated the presence and importance of hepatic micrometastases at the time of operation in patients with resectable pancreatic carcinoma. In 13 patients with pancreatic carcinoma and 5 patients with chronic pancreatitis Truecut-Needle biopsies of the liver were obtained during operation. K-ras mutation analysis was done by the PCR/restriction digestion assay with HphI, followed by an ultrasound of the liver in 3 monthly intervals. Four of 13 (30%) pancreatic cancer patients had K-ras gene mutations in the liver and had a mean survival of 6 months after resection. All chronic pancreatitis patients and 8 of the 9 remaining pancreatic cancer patients without K-ras mutations in the liver biopsies are alive without evidence of liver metastases after a mean follow-up of 9 months. Detection of micrometastases in the liver by K-ras mutation analysis might be a powerful tool to identify occult clinical relevant liver metastases.
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PMID:[Detection of hepatic micrometastasis in ductal pancreatic carcinoma by K-ras mutation analysis and determination of clinical relevance]. 1451 10

Overexpression of p21WAF1/CIP1 was recently described as an early event in the development of pancreatic intraepithelial neoplasia. Since activating K-ras mutations are described in more than 80% of pancreatic cancers and are known to increase intracellular levels of p21WAF1/CIP1 in experimental models, the possible role of activating K-ras mutations in an induction of the p21WAF1/CIP1 expression was investigated in our study. We examined 71 surgical specimens, 29 of chronic pancreatitis and 42 of invasive ductal adenocarcinoma both having a large spectrum of PanIN (pancreatic intraepithelial neoplasia) lesions. Expression of p53 and p21WAF1/CIP1 was examined immunohistochemically and codon 12 K-ras mutational analysis was performed using the very sensitive mutant-enriched PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis. Our study demonstrated the overexpression of p21WAF1/CIP1 as an early event in the development of pancreatic intraepithelial neoplasia in the group of chronic pancreatitis and invasive adenocarcinoma as well. Overexpression of p21WAF1/CIP1 increased progressively from normal ducts through the spectrum of PanIN lesions to invasive carcinomas. The p53 overexpression increased again progressively according to the severity of the lesion and seems to be a later event in the development of pancreatic intraepithelial neoplasia if compared to p21WAF1/CIP1 expression. Our results confirmed also the possible p53 independent p21WAF1/CIP1 expression in some PanIN2, PanIN3 lesions and invasive carcinomas. K-ras mutations were not revealed in samples with only low grade PanIN lesions (PanIN1a and PanIN1b). K-ras mutations were detected in 69,4% adenocarcinomas and in only one case of chronic pancreatitis. Two codon 12 K-ras positive pancreatic carcinomas showed K-ras mutations in the surrounding normal pancreatic tissue. In adenocarcinomas, no statistically significant correlation was found between K-ras mutational status and p21WAF1/CIP1 and p53 expression, respectively. The possible role of activating K-ras mutations in an induction of p21WAF1/CIP1 expression was not confirmed in this study.
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PMID:Relationship between K-ras mutation and the expression of p21WAF1/CIP1 and p53 in chronic pancreatitis and pancreatic adenocarcinoma. 1462 83

Recent studies on genetic abnormalities in pancreatic ductal cancer have led to the investigation of tumor markers and genetic markers in both serum and pancreatic juice (PJ). Serum type 1 chain carbohydrate antigens such as CA19-9 are positive in nearly 80% of patients with pancreatic cancer (PCa), of which most are in advanced stage, whereas false-positive rates are relatively high at 20%-30% in benign hepatobiliary and pancreatic diseases. Although the prevalence of type 2 chain carbohydrate antigens, such as SLX, is relatively low, cancer specificity of these antigens is high. However, serum tumor markers have limited diagnostic value for early detection of PCa. In PJ collected endoscopically from patients with PCa, K-ras mutations (KRM) are detectable in > 80%, whereas KRM are observed in 20%-30% of PJ from patients with chronic pancreatitis (CP), reflecting benign mucous cell hyperplasia harboring KRM. Thus, a qualitative analysis of KRM in PJ is unsuitable for diagnosis of PCa. On the other hand, using an hybridization protection assay that can quantitatively determine KRM, KRM were positive in 66% of PCa but only in 40% of CP cases, indicating that qualitative analysis of KRM in PJ may be useful for differentiating PCa from CP. p53 Mutations are found in 4%-50% in PJ from patients with PCa but are not detectable in PJ from CP, suggesting that the specificity of p53 mutations is very high for PCa. Furthermore, p53 mutations were detected in 7 of 15 (47%) patients with PCa in which the PJ cytologic diagnosis was negative. Telomerase (TE) activity or its catalytic subunit, h-TERT, was reportedly positive >80% in PJ from PCa but was detected in <20% of PJ from CP. TE activity in PJ from CP originates from lymphocytes. The development and application of these new genetic and epigenetic markers with high specificity and sensitivity for PCa in serum and PJ will significantly improve our diagnostic accuracy.
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PMID:Serum tumor markers and molecular biological diagnosis in pancreatic cancer. 1508 68

Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies published between 1988 and 2003 that provide information on K-ras mutations in hyperplastic and dysplastic duct lesions in the pancreas. The described duct lesions were reclassified according to the nomenclature for pancreatic intraepithelial neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed. In PanIN lesions from pancreata of patients with PDAC, there was a stepwise increase in K-ras mutations that correlated with the grade of dysplasia of the PanIN lesion. K-ras mutations were found in 36%, 44%, and 87% of PanIN-1a, 1b, and 2-3 lesions, respectively (trend statistic P <.001). Mutation-enriched polymerase chain reaction (PCR) resulted in higher rates of K-ras mutations in PanIN than plain PCR did. The incidence of K-ras mutations in PanIN lesions associated with chronic pancreatitis (CP) or normal pancreas was low (around 10%). In CP, K-ras mutations were only found after a disease duration of 3 years. The correlation of the incidence of K-ras mutations with the grade of dysplasia in PanIN and the occurrence of these mutations in CP with a duration of more than 3 years underlines the importance of this genetic change for the development of PDAC.
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PMID:Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis. 1572 Aug 14

Pancreatic ductal carcinomas are thought to arise from precursor ductal lesions called pancreatic intra-epithelial neoplasias or PanINs. We report the case of a woman suffering from idiopathic chronic pancreatitis associated with PanINs lesions who developed six years later an invasive ductal carcinoma. Immunohistochemistry for p53, HER-2/neu and genetic analysis of K-ras oncogene were performed at different stages of disease and revealed that the PanINs and the carcinoma did not express p53 and HER-2/neu gene products whereas a K-ras mutation was present at the carcinoma stage. The relationship between cancer and chronic pancreatitis and the main difficulties concerning the early diagnostic of pancreatic cancer are discussed.
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PMID:From pancreatic intraepithelial neoplasia to cancer: a dramatic progression with K-ras status analysis. 1586 14

Chronic inflammatory processes induce oxidative stress and lipid peroxidation (LPO), hereby generating DNA-reactive aldehydes such as trans-4-hydroxy-2-nonenal (HNE). Etheno-modified DNA bases are inter alia generated by reaction of DNA with HNE. Using an immunoaffinity-(32)P-postlabeling method, the authors have investigated etheno-DNA adduct levels 1,N (6)-ethenodeoxyadenosine (epsilondA) and of 3,N (4)-ethenodeoxycytidine (epsilondC) in the pancreas of chronic pancreatitis patients and in the colon of patients with inflammatory bowel disease. Both epsilondA and epsilondC levels were found to be significantly, 3 and 28 times, respectively, elevated in the inflamed pancreatic tissue. In contrast, only epsilondC was found to be increased in affected colonic mucosa of Crohn's disease (19 times) and of ulcerative colitis patients (4 times) when compared to asymptomatic tissues. In all three cancer-prone diseases, the mean epsilondC-levels in tissues were five- to ninefold higher than those of epsilondA. Differential or impaired DNA repair pathways of these adducts, known to occur by two different glycosylases are implicated. K-ras in pancreatic tumors and K-ras and p53 in colon mucosa in long-standing inflammatory bowel disease are known to be highly mutated. The conclusion is that promutagenic etheno-DNA adducts are generated as a consequence of chronic inflammation, acting as a driving force to malignancy in cancer-prone inflammatory diseases.
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PMID:Increased etheno-DNA adducts in affected tissues of patients suffering from Crohn's disease, ulcerative colitis, and chronic pancreatitis. 1677 90

Despite scientific efforts and significant progress in understanding the basic cellular event in pancreatic adenocarcinoma (PA), survival rates have not changed much during the last 20 years. Prognosis in pancreatic cancer remains unsatisfactory due to its late clinical presentation, low surgical resectability rates, and resistance to chemotherapy. Novel therapeutic strategies are needed in order to improve the prognosis of patients with PA. Improvement of our knowledge of the molecular biology of pancreatic cancer may have important clinical implications in pancreatic cancer risk assessment, early diagnosis, and management. In human pancreatic cancer, a specific sequence of oncogene and tumor suppressor gene alterations is observed, including K-ras, HER-2/neu, p16, p53, and DPC4. The prevalence of these genetic alterations rises with increasing severity of dysplasia of the ductal mucosal lesions. Drugs that target these molecular abnormalities hold great promise for PA treatment in the near future. The focus of this review is to evaluate the gene mutations in pancreatic cancer, with emphasis on those studies that are most important to the clinical practice. Our review also summarizes current aspects of PA treatment and the differential diagnosis of pancreatic cancer and chronic pancreatitis.
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PMID:Molecular pathogenesis of pancreatic adenocarcinoma: potential clinical implications. 1694 Sep 43

Morphologic, clinical, and genetic evidence suggests that pancreatic intraepithelial neoplasia (PanIN) is a precursor to ductal adenocarcinoma. But understanding precursor lesions in a pancreas with existing tumor is hampered by the fact that chronic pancreatitis often accompanies carcinoma, and the possible interactions between tumor, chronic pancreatitis, and PanIN are complex. Furthermore, cancerization of ducts can mimic high-grade PanIN. Heterotopic pancreas has a genetic make-up, physiologic function, and local environmental exposure similar to that of the pancreas. It offers an opportunity to study putative precursor lesions in a setting with fewer confounding factors. We identified 6 pancreatic cancer patients who had heterotopic pancreas removed at the time of surgery. All 6 cases were immunostained for p53, cyclin D1, and p16. Molecular analysis of K-ras mutation was also done. All 6 cancer-associated heterotopias had PanIN-1A or 1B; 5 had PanIN-2 and 1 had PanIN-3. Three of 6 cases harbored the same K-ras codon 12 mutation as the PanINs in orthotopic pancreas, and a similar pattern of p53, cyclin D1, and p16 expression was observed between heterotopic and orthotopic pancreas in all 6 cases. There was no chronic pancreatitis in the cancer-associated heterotopias, but chronic pancreatitis was seen adjacent to carcinoma in 5 of 6 cases. The presence of PanIN in heterotopic pancreas from patients with ductal adenocarcinoma supports the progression model.
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PMID:Pancreatic intraepithelial neoplasia in heterotopic pancreas: evidence for the progression model of pancreatic ductal adenocarcinoma. 1766 42

The understanding of the biology of pancreatic carcinoma has greatly benefited from studies of genetic alterations and molecular expression in experimental models as well as in pre-cancerous and cancerous tissues by mean of molecular amplification and large scale transcriptome analysis. P16, TP53, DPC4/Smad4 tumor suppressor pathways are genetically inactivated in the majority of pancreatic carcinomas, whereas oncogenic k-ras is activated. The activating mutation of the K-ras oncogene on codon 12 seems to occur early in pancreatic carcinogenesis and detecting its mutation in tumor samples could have a clinical relevance in term of positive (improvement of current histological diagnosis) and differential diagnosis (versus chronic pancreatitis) of pancreatic cancer. At a late stage of tumor development, an increase of telomerase activity, an over expression of growth factors and/or their receptors (EGF, nerve growth factor, gastrin, bombesin), of proangiogenic factors (VEGF, FGF, PDGF), of invasiveness factors (metalloproteinases, E-cadherin, beta integrin, urokinase and tissue plasminogen activator) occur. All these molecular events contribute to the progression and to the metastatic potential of this carcinoma. New markers and targets are currently studied among microRNA and epigenetics events such as methylation and acetylation. Among all these molecular markers, some are now tested for their potential clinical interest in term of diagnosis or therapeutic target.
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PMID:[New molecular targets in pancreatic cancer]. 1854 14


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