Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis.

Background And Study Aims: Differential diagnosis between pancreatic adenocarcinoma (PADC) and pseudotumoral forms of chronic pancreatitis remains difficult. Mutation of KRAS oncogene is present in 75% to 95% of PADC. This study aimed to evaluate whether the combined analysis of KRAS mutation with cytopathological findings from endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) might improve discrimination between PADC and chronic pancreatitis.

let-7 MicroRNA transfer in pancreatic cancer-derived cells inhibits in vitro cell proliferation but fails to alter tumor progression.

Pancreatic ductal adenocarcinoma (PDAC) is still the fourth leading cause of cancer-related deaths in Western countries, with increasing incidence. Neither effective prognostic markers nor therapies exist for this cancer. MicroRNAs are potent inhibitors of protein translation, and aberrantly expressed in many cancers.

Expression of the transcription factor Klf6 in cirrhosis, macronodules, and hepatocellular carcinoma.

Background And Aims: Macronodules (MN) occurring in cirrhosis are considered to be precursor lesions for hepatocellular carcinoma (HCC). However, early molecular events in hepatocellular carcinogenesis are poorly understood. The aim of this study was to compare gene expression profiling between cirrhotic tissues, MN, and HCC, to identify genes early involved in liver carcinogenesis.

Replication-deficient rSV40 mediate pancreatic gene transfer and long-term inhibition of tumor growth.

Pancreatic cancer is one of the most aggressive and devastating human malignancies. There is an urgent need for more effective therapy for patients with advanced disease. In this context, genetic therapy potentially represents a rational new approach to treating pancreatic cancer, which could provide an adjunct to conventional options.

Identification of biomarkers of human pancreatic adenocarcinomas by expression profiling and validation with gene expression analysis in endoscopic ultrasound-guided fine needle aspiration samples.

Aim: To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens.

Methods: Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used.

Clinical utility of telomerase for the diagnosis of malignant well-differentiated endocrine tumours.

Objective: The distinction between benign and malignant well-differentiated endocrine tumours is hard to achieve. The aim of the present study was to determine whether detection of telomerase or quantification of human telomerase reverse transcriptase protein subunit (hTERT) differ between benign and malignant endocrine tumours.

Patients And Methods: This retrospective study investigated 31 well-differentiated primary endocrine tumours.

Frequent deletions of tumor suppressor genes in pure pancreatic juice from patients with tumoral or nontumoral pancreatic diseases.

Background/aims: K-ras codon 12 mutation is the most frequent genetic alteration in pancreatic cancer. Sensitivity and specificity of K-ras are not high enough to detect all pancreatic cancers, especially at early stage. This study investigated whether detection of p16 and/or DPC4 deletions along with K-ras mutation in DNA samples could improve the definition of patients at risk of pancreatic cancer.

Expression of CCK2 receptors in the murine pancreas: proliferation, transdifferentiation of acinar cells, and neoplasia.

Background & Aims: To explore the pancreatic function of CCK2/gastrin receptor, we created ElasCCK2 transgenic mice expressing the human receptor in pancreatic exocrine cells. In previous studies, the transgenic CCK2/gastrin receptor was demonstrated to mediate enzyme release and protein synthesis. We now report results of phenotypic and long-term studies.

Transcription of SST2 somatostatin receptor gene in human pancreatic cancer cells is altered by single nucleotide promoter polymorphism.

Background & Aims: The somatostatin receptor SST2 mediates the antiproliferative effect of stable somatostatin analogues. SST2 gene expression is lost in most human pancreatic carcinomas. We investigated the mechanisms that could be involved in this defect.

Arginine 197 of the cholecystokinin-A receptor binding site interacts with the sulfate of the peptide agonist cholecystokinin.

The knowledge of the binding sites of G protein-coupled cholecystokinin receptors represents important insights that may serve to understand their activation processes and to design or optimize ligands. Our aim was to identify the amino acid of the cholecystokinin-A receptor (CCK-AR) binding site in an interaction with the sulfate of CCK, which is crucial for CCK binding and activity. A three-dimensional model of the [CCK-AR-CCK] complex was built.

Evidence for a direct interaction between the penultimate aspartic acid of cholecystokinin and histidine 207, located in the second extracellular loop of the cholecystokinin B receptor.

Recently, we reported that the mutation of His(207) to Phe located in the second extracellular loop of the cholecystokinin B receptor strongly affected cholecystokinin (CCK) binding (Silvente-Poirot, S., Escrieut, C., and Wank, S.

Gastrin induces phosphorylation of eIF4E binding protein 1 and translation initiation of ornithine decarboxylase mRNA.

Gastrin via its G-protein coupled specific receptor induces transcription of c-fos and c-jun genes through a ras-MAPK pathway. Ornithine Decarboxylase (ODC), a growth regulated proto-oncogene, was chosen to investigate gastrin effects on translation initiation of mRNAs exhibiting a 5'UnTranslated Region (5'UTR) responsible for translation repression in quiescent cells. In AR4-2J tumoral cells, we first demonstrated that gastrin increases ODC mRNA translation.

Intraduodenal free fatty acids rather than triglycerides are responsible for the release of CCK in humans.

Exocrine pancreas from different species behaves differently in response to the presence of intact or digested nutrients in the duodenum. A failure of cholecystokinin (CCK) release after a meal has been shown among patients with exocrine pancreatic insufficiency. This abnormality could be restored by the administration of pancreatic extracts, suggesting that digested rather than intact nutrients are responsible for the release of CCK and subsequently gallbladder contraction in humans.

AR4-2J cell line coexpresses dihydropyridine and omega-conotoxin sensitive Ca2+ channels.

For the first time, we have demonstrated in AR4-2J cells, an experimental model of azaserine-induced carcinoma in the rat exocrine pancreas, the co-expression of alpha 1 subunit of dihydropyridine-sensitive Ca2+ channel and the alpha 1 sub-unit of omega-conotoxin-sensitive Ca2+ channel RNA messengers which share homologous sequences with, respectively, rbC II and rbB I sub-types described in the rat brain. These two types of voltage-dependent Ca2+ channels which are functionally expressed, emphasize the acquisition during carcinogenesis of neuroendocrine features of AR4-2J cells. Additionally, using antisense phosphorothioate oligodeoxynucleotide, we demonstrated clearly the involvement of dihydropyridine-sensitive Ca2+ channels in the control of AR4-2J cell proliferation.

Autocrine stimulation of AR4-2J rat pancreatic tumor cell growth by glycine-extended gastrin.

Glycine-extended gastrin (gastrin-Gly) stimulates proliferation of AR4-2J pancreatic tumor cell line through a specific receptor, different from the gastrin-cholecystokinin B receptor. Our purpose was to determine whether AR4-2J cells produced gastrin-Gly and then whether the peptide was involved in an autocrine loop. First, proliferation of AR4-2J cells in serum-free medium was inhibited by a gastrin anti-sense oligodeoxynucleotide phosphorothioate and by antibodies specific for gastrin-Gly.

Relief of ornithine decarboxylase messenger RNA translational repression induced by alternative splicing of its 5' untranslated region.

The ornithine decarboxylase enzyme (ODC) is the key regulator of polyamine synthesis and is a member of the cellular proto-oncogene family. Its expression becomes constitutively activated by carcinogens, viruses, and oncogenes. ODC mRNA has a long 5' untranslated region that could be important in the regulation of enzyme levels by affecting translation.

Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer.

Objective: To develop an early diagnostic test for pancreatic cancer based on the identification of K-ras mutations in pure pancreatic juice collected during endoscopic retrograde pancreatography.

Design: Prospective study with masked comparison. The standard criteria for the diagnosis of pancreatic cancer were pancreatography or surgery (or both) and histopathology, with follow-up ranging from 6 to 40 months.

Photoaffinity labeling of rat pancreatic cholecystokinin type A receptor antagonist binding sites demonstrates the presence of a truncated cholecystokinin type A receptor.

During the past few years, several antagonist ligands for cholecystokinin (CCK) receptors have been discovered, but the mechanism of action of these candidate drugs, as well as the nature of their molecular targets, remains poorly documented. In a previous study, we developed a new antagonist radioligand, 125I-Bolton-Hunter-labeled JMV-179, for the CCK-A receptor (CCK-AR), to analyze CCK antagonist binding sites in pancreatic plasma membranes. We found that 125I-Bolton-Hunter-labeled JMV-179 identified 4 times as many sites as did an agonist radioligand, although agonists were able to interact competitively with the entire population of antagonist sites.

Postprandial cholecystokinin secretion in elderly with protein-energy undernutrition.

Objective: Malnutrition is currently observed in aged people, and cholecystokinin is an important peripheral satiety signal. The aim of this study was to examine the effect of aging and protein-energy malnutrition on postprandial cholecystokinin (CCK) release.

Design: Non-randomized, cross-sectional comparison by age group.

Gastric lipase in alcoholic pancreatitis. Comparison of secretive profiles following pentagastrin stimulation in normal adults and patients with pancreatic insufficiency.

The aims of this study were to evaluate the amount of gastric lipase secreted by the stomach in normal adults and to elucidate a possible adaptative secretion of this enzyme in response to pancreatic insufficiency secondary to alcoholic chronic pancreatitis. Forty-one subjects underwent a gastric intubation. Pentagastrin (6 micrograms.

Protective effect of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced acute pancreatitis in rats.

This study was performed to assess the effects of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced pancreatitis. Per group of 10 each, male Wistar rats received either cerulein (2.5 micrograms/kg/h subcutaneously), cerulein and misoprostol (500 micrograms/kg intraperitoneally at 0 and 4 h), or saline.

Protective effect of misoprostol, a synthetic prostaglandin E1 analog, on experimental pancreatitis induced by pancreatic duct ligation in rat.

This study was performed to assess the effects of misoprostol (M), a synthetic prostaglandin E1 analog, on experimental pancreatitis in rat. Pancreatitis was induced by ligation of the main pancreatic duct of 3-month-old male Wistar rats. Pancreatic lesions were observed at 6, 12, 24, 48, and 96 h after pancreatic duct ligation (PDL).

Exocrine pancreatic secretion in the elderly.

In order to evaluate impairment of exocrine pancreatic function during aging, 27 subjects (mean age: 36 years +/- 7.8) and 28 subjects (mean age: 72 years +/- 3.2), with no clinical or radiological evidence of digestive disease, were selected.

[Aging of the pancreas. Its implication in malnutrition states in elderly persons].

The influence of ageing on exocrine pancreatic function was investigated in rats and in men. Young rats (3-months old, 150-200 g) and old rats (24-month old, 400-500 g) were killed after fasting overnight. Small pancreatic fragments were removed and kept for stereological analysis both in light and electron microscopy; in addition, levels of tritium-labelled leucine uptake and protein synthesis were measured by quantitative histoautoradiography on isolated acini in vitro.

[Comparison of fungal lipase and pancreatic lipase in exocrine pancreatic insufficiency in man. Study of their in vitro properties and intraduodenal bioavailability].

Assuming that acidic degradation of lipase was the major cause of failure for the correction of steatorrhea by pancreatic extracts, we compared the in vitro and in vivo activities of a fungal lipase (FL) (Rhizopus arrhizus) with classical porcine pancreatic extract (Eurobiol). The choice of FL was determined by its two optimum pH (3.5 and 7.