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)

Most pancreatic adenocarcinomas are known to have ras gene (oncogene) mutations. The site of the mutations is localized in codon 12 of K-ras gene. Such high incidence and localization of the ras gene mutations have not been observed in any other human malignancies. Polymerase chain reaction and direct sequencing method enabled us to analyze DNA sequence around codon 12 of K-ras gene in small quantities of specimens obtained from needle biopsies and aspirate samples for pathological diagnosis. All the materials obtained from 12 patients with pancreatic adenocarcinoma showed the mutations, whereas those obtained from 6 patients with chronic pancreatitis showed no mutations. In several cases using the mutations of K-ras gene as a marker, this analysis supplemented conventional pathology and cytology in making the diagnosis of pancreatic adenocarcinoma. The analysis of ras-gene mutations was useful for the clinical diagnosis of pancreatic adenocarcinoma.
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PMID:Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. 198 26

We examined immunohistochemical staining with Ha-ras oncogene product in normal, benign, and malignant human pancreatic tissues. In cases of pancreatic cancer, its relation to histologic type was evaluated. Serous cystadenoma and atypical acinar cell nodules did not react with the Ha-ras oncogene product, and ductal cells and acinar cells in normal pancreas showed lower immunoreactivity than other benign or malignant lesions. However, the positive rate of islet cells in normal pancreas was almost the same in cases of pancreatic cancer. Strongest positivity was observed in cases of chronic pancreatitis, and islet cell tumors also showed high positive staining rates. In pancreatic cancer, the positive rate of well-differentiated adenocarcinomas was rather higher than that of poorly differentiated adenocarcinomas. Our study indicates that the Ha-ras oncogene p21 product does not correlate with neoplastic transformation in human pancreas, is not a useful marker for differentiating benign and malignant lesions, and cannot be used to determine the origin of differentiation in the pancreas.
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PMID:Immunohistochemical staining of Ha-ras oncogene product in normal, benign, and malignant human pancreatic tissues. 216 89

This is the first description of the detection of pancreatic adenocarcinoma peritoneal metastasis by established radiolabeled polymerase chain reaction (PCR) based Ki-ras mutational analysis. The present study evaluates both routine cytology and Ki-ras mutational analysis in the detection of peritoneal micrometastases in 24 subjects with pancreatic adenocarcinoma compared to seven control cases of chronic pancreatitis and seven control cases of cholecystitis. Locoregional extension, vascular invasion, and distal metastases were confirmed in 21/24 (88%) of the subjects with pancreatic adenocarcinoma by compute tomography, angiography, endosonography, or laparoscopy. The most common site of histologically confirmed extrapancreatic involvement was the vasculature (29%), followed by the liver (25%), duodenum (17%), peritoneum (17%), and lymph nodes (12%). Peritoneal lavage cytology was positive in 3/24 (12%) cases of pancreatic carcinoma while Ki-ras codon 12 mutational analysis was positive in 2/24 (8%). Two histologically confirmed cases of peritoneal metastases were not detected by either methodology, while peritoneal lavage cytology detected malignant cells in one case with histologically confirmed lymph node metastasis.
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PMID:Peritoneal exfoliative cytology and Ki-ras mutational analysis in patients with pancreatic adenocarcinoma. 749 64

More than 90% of tumours of the pancreas have mutations on codon 12 of the Ki-ras oncogene. Cellular DNA from pancreatic secretions and fine-needle biopsies, obtained from 69 patients (41 men, 28 women), were amplified by the polymerase chain reaction (PCR) to demonstrate this characteristic marker. All these patients had undergone endoscopic retrograde pancreatography for suspected pancreatitis or carcinoma of the pancreas. Two different methods were developed to demonstrate the mutations. With the aid of one of these methods, enrichment PCR with analysis of the restriction fragment length (FL), mutations on codon 12 of the Ki-ras gene were demonstrated in unstimulated pancreatic secretions of 29 of 33 patients with pancreatic carcinoma. All eleven fine-needle biopsies that had been cytologically examined showed the tumour-specific mutation. After direct sequencing of enrichment PCR a codon 12 mutation was demonstrated in pancreatic secretion from 21 of 24 patients and with the single strand conformation polymorphism analysis in 17 of 33 patients. In two of these 33 patients two different Ki-ras mutations were discovered. No mutations were found in acute inflammations or stone disease, while in five patients with chronic pancreatitis mutations were demonstrated only in those two patients in whom histological examination had revealed precancerous mucinous hyperplasia. This investigation indicates that codon 12 mutations of the Ki-ras gene, found after PCR in pancreatic secretion and biopsies, constitute a sensitive and specific tumour marker whose clinical value is being assessed.
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PMID:[Ki-ras mutation as a molecular tumor marker for carcinoma of the pancreas]. 778 24

Differential diagnosis of pancreatic cancer and chronic pancreatitis is sometimes difficult and cytological examination of brushings or aspirated material collected during endoscopic retrograde cholangiopancreatography (ERCP) remains disappointing. As point mutations in codon 12 of the c-Ki-ras 2 gene are found in most pancreatic adenocarcinoma and not in chronic pancreatitis, this study analysed prospectively the presence of these mutations in brushing samples collected during ERCP in 45 patients (26 males, 19 females) showing a dominant stricture of the main pancreatic duct at pancreatography: 24 with pancreatic adenocarcinoma, 16 with chronic pancreatitis, and five intraductal mucin hypersecreting neoplasms. Twenty of 45 patients presented equivocal ERCP findings that did not permit a definite diagnosis. Ki-ras mutations at codon 12 were detected using a rapid and sensitive method based on polymerase chain reaction mediated restriction fragment length polymorphism analysis and confirmed by direct sequencing of polymerase chain reaction products. Results were compared with those provided by routine brush cytology. A definitive diagnosis was established for each patient. Mutations were detected in 20 of 24 patients with pancreatic adenocarcinoma (83%), but in none of the chronic pancreatitis patients and intraductal mucin hypersecreting neoplasms, irrespective of their location. By contrast, only 13 of 24 pancreatic adenocarcinoma (54%) were detected by conventional cytological examination, which yielded four false negative and seven non-contributive results. Sensitivity, specificity, and accuracy of molecular biological and cytological methods were 83%-76%, 100-83%, and 90%-58%, respectively. Notably the mutations could be detected in six patients with small tumour size (< or = 2 cm). In conclusion, Ki-ras analysis performed on pancreatic brushing samples is an efficient procedure, more accurate than cytology in the diagnosis of pancreatic adenocarcinoma, and highly specific in the differentiation between neoplastic and chronic inflammatory ductal changes, especially in patients showing inconclusive ERCP findings.
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PMID:Detection of c-Ki-ras gene codon 12 mutations from pancreatic duct brushings in the diagnosis of pancreatic tumours. 779 31

Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to analyze c-Ki-ras codon 12 mutation in 27 fine needle aspiration biopsy (FNAB) specimens of the pancreas and its adjacent organs for the diagnosis of pancreatic adenocarcinoma. C-Ki-ras codon 12 mutation was present in 14 out of 15 cases of pancreatic adenocarcinoma, the positive rate was 93.33% (14/15); whereas no mutation was detected in those obtained from 12 patients with chronic pancreatitis, pancreatic cyst, gallbladder carcinoma, carcinoma of ampulla of Vater and gastric lymphoma. The results of this study verifies the PCR-RFLP technique as a practical, sensitive, rapid and reliable method for the detection of c-Ki-ras codon 12 mutation in the diagnosis of pancreatic adenocarcinoma.
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PMID:[Gene diagnosis of pancreatic adenocarcinoma]. 787 57

Point mutations in K-ras codon 12 were detected in 7 of 10 specimens (70%) of frozen tissues. To determine when point mutations appear in the oncogenic stage, paraffin-embedded tissues of pancreatic cancer, hyperplastic ductal lesions in pancreatic cancer and in chronic pancreatitis were used. DNA extracted from the paraffin-embedded tissues classified as cancer, atypical and nonatypical hyperplasia of the pancreatic duct epithelium, and normal tissue from pancreatic cancer patients and those classified as atypical hyperplasia of the pancreatic duct epithelium and normal tissue from chronic pancreatitis patients were amplified by the polymerase chain reaction (PCR) method. Point mutations were detected in 8 of 17 cancer cases (47.0%). In 5 of 8 point mutation positive cases, atypical hyperplasias were found in the surrounding tissues. In all 5 of these atypical hyperplasia, point mutations, that is, GGT-GTT (Gly-Val) and GGT-GAT (Gly-Asp), were detected. The same transitions were observed in the cancer of these 5 cases. These results suggest a strong relationship between cancer and atypical hyperplasia surrounding cancer. Although atypical hyperplasia around cancer was histologically very similar to that found in chronic pancreatitis, all 5 atypical and 5 nonatypical hyperplasias in chronic pancreatitis were negative for ras point mutation. Thus, the result argues against an association between chronic pancreatitis and pancreatic cancer.
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PMID:The role of Ras mutation in pancreatic cancer, precancerous lesions, and chronic pancreatitis. 811 25

In order to scrutinize the possible significance of (nonatypical) mucous cell hyperplasia of the pancreas to neoplasia, we analyzed these lesions in terms of c-Ki-ras activation, which is known to be very frequent in pancreatic carcinomas. A total of 16 such mucous cell hyperplasias were collected from 10 pancreases resected for chronic pancreatitis. Tiny tissue fragments were taken from hematoxylin-stained sections by microdissection, and DNA analysis was carried out by the polymerase chain reaction amplification and oligonucleotide hybridization methods. Activating mutations of c-Ki-ras oncogene at codon 12 were detected in 10 of the 16 lesions (62.5%), a high rate as seen in carcinomas. The results indicated a clonal origin of cells comprising the mucous cell hyperplasia suggesting a neoplastic and/or precancerous nature.
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PMID:Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. 843 69

Pancreatic adenocarcinomas are known to have a high incidence of K-ras gene mutations. Differential diagnosis of pancreatic cancer and chronic pancreatitis sometimes presents a clinical dilemma. We recently developed a highly sensitive and specific polymerase chain reaction capable of detecting 3-30 copies of mutant K-ras genes harboring codon 12 single base changes in the presence of 300,000 normal copies. Mutant ras genes were detected in DNA purified from pancreatic juice from all 6 cases of pancreatic adenocarcinoma and 1 case of intraductal papillary neoplasms of the pancreas. In 2 of 6 other cases with pancreatic adenocarcinoma, circulating metastatic cells were detected in DNA purified from peripheral blood. Activated ras genes were not found in pancreatic juice of three control cases (chronic pancreatitis and choledocholithiasis) or in the peripheral blood of two patients with insulinomas. Notable conclusions of this study are that there can be significant levels of shed tumor cells in peripheral blood and an even higher number in pancreatic juice. In addition, two different K-ras mutations were found in some patients.
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PMID:Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. 849 7

There are approximately 27,000 new cases of carcinoma of the pancreas each year and most afflicted patients will die of the disease. Although smoking is a common denominator, chronic pancreatitis is considered an important precursor lesion in a smaller number of cancers. Pancreatic cancer is primarily a disease of the pancreatic ducts. The molecular events are under intense study, but c-K-ras mutation is involved in approximately 80% of the cases and p53 to a slightly lesser degree (60-80%). Early manifestations are usually occult, but jaundice is a common manifestation in patients with cancers of the pancreatic head. Thin-slice computed tomography, portography, and endoscopic retrograde cholangiopancreatography are currently the most sensitive detection techniques. The developing use of endoscopic ultrasound and laparoscopy appear to enhance detection and are under evaluation. In many patients with advanced disease, endoscopic bypass may eliminate the need for unnecessary surgery, although gastrointestinal bypass is still required in some patients (10-15%). Curative resection is possible in selected patients (perhaps 10-15%), with expectation of extended survival ranging from 6->20% in some series. The survival differences may be related to stage, patient selection, and the expertise of the operative team. Preoperative chemotherapy/radiation is under study and may improve outcome. Clinical trial participation is essential for improvement in treatment outcomes.
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PMID:Pancreatic carcinoma in perspective. A continuing challenge. 868 Dec 96


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