epidermal-growth-factor and Pancreatitis

Topics: Acute Disease; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Humans; Mast Cells; Nerve Growth Factors; Pancreatitis; Transforming Growth Factor beta

Epidermal growth factor (EGF) binds to pancreatic acinar cells and facilitates recovery from acute pancreatitis (AP). In animal models, EGF protects against pancreatic injury and prevents septic complications. The role of EGF in human AP is unknown.. The aim of this study was to assess EGF serum levels in AP patients and whether the EGF +61 G/A single nucleotide polymorphism (SNP) affects susceptibility and/or severity of AP.. Hospitalized AP patients were prospectively enrolled. Demographics, clinical features, DNA and early serum samples were collected when available. Patients were classified into mild (79%) and severe AP (21%) based on organ failure for >or=48 h. Early serum samples were quantitatively assayed for EGF levels. The EGF +61 G/A SNP was evaluated by restriction fragment length polymorphism analysis.. There were 179 patients ascertained with AP. EGF levels were measured in a subgroup of 60 patients with early serum samples (17 severe) and in serum from 58 healthy controls. Serum EGF levels within 48 h from the onset of pain were significantly lower in AP patients (mean 13.5 pg/ml) compared to controls (25.2 pg/ml; P=0.015). Furthermore, EGF levels were significantly lower in severe patients when compared to mild (7.8 vs. 14.3 pg/ml; P=0.026). DNA from all 179 patients and 189 healthy controls was sequenced. The EGF +61 G/A SNP did not affect susceptibility to or severity of AP.. EGF serum levels are decreased early in the course of AP and are further suppressed in severe AP. The EGF +61 G/A polymorphism has no effect on AP.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Chi-Square Distribution; Down-Regulation; Epidermal Growth Factor; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Odds Ratio; Pancreatitis; Pennsylvania; Phenotype; Polymorphism, Single Nucleotide; Prognosis; Prospective Studies; Severity of Illness Index; Time Factors; Young Adult

In both pancreatic cancer and chronic pancreatitis, there is enhanced expression of mitogenic growth factors and their tyrosine kinase receptors, which have the capacity to activate mitogen-activated protein kinase (MAPK). In view of the important role of MAPK kinase phosphatase (MKP)-1 in the regulation of MAPK activation, the expression and functional role of MKP-1 was analyzed.. Pancreatic tissues were analyzed by Northern blotting, Western blotting, and immunohistochemistry. Pancreatic cancer cells were transfected with a full-length MKP-1 antisense construct. Growth characteristics and tumorigenicity in vivo and the effects of mitogenic growth factors on cell growth and MAPK activation were determined in transfected and control cells.. MKP-1 messenger RNA (mRNA) levels were increased in pancreatic cancer and chronic pancreatitis (CP) tissues. Moderate to strong MKP-1 immunoreactivity was present in the cancer cells, ductal cells of pancreatic intraepithelial neoplasia, and in tubular complexes in CP. Down-regulation of MKP-1 resulted in decreased anchorage-dependent and -independent growth of pancreatic cancer cells, and decreased tumorigenicity in a nude mouse tumor model. MKP-1 down-regulation led to decreased proliferation and sustained MAPK activation in response to mitogens.. Suppression of MKP-1 expression reduces the tumorigenicity of pancreatic cancer cells in vivo, suggesting that MKP-1 contributes to enhanced mitogenic signaling in pancreatic cancer cells.

Topics: Adolescent; Adult; Aged; Cell Cycle Proteins; Chronic Disease; Down-Regulation; Dual Specificity Phosphatase 1; Epidermal Growth Factor; Female; Gene Expression Regulation, Enzymologic; Humans; Immediate-Early Proteins; JNK Mitogen-Activated Protein Kinases; Male; Middle Aged; Mitogen-Activated Protein Kinases; Pancreas; Pancreatic Neoplasms; Pancreatitis; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 1; Protein Tyrosine Phosphatases; RNA, Messenger; Transfection; Tumor Cells, Cultured

Acute pancreatitis is accompanied by the enhanced expression of EGF in the pancreas and the administration of EGF was found to exhibit the beneficial effect on edematous cerulein-induced pancreatitis. Therefore, we decided to determine the influence of EGF on necro-hemorrhagic pancreatitis induced by ischemia and reperfusion (I/R). Acute pancreatitis was induced in rats by restricting the pancreatic blood flow (PBF) in the inferior splenic artery for 30 min using microvascular clips. EGF was administered three times daily (10 microg/kg per dose s.c.) starting immediately after the clips removal. Rats were sacrificed on day 1, 3, 5, 10 and 21 following ischemia. PBF was measured using a laser Doppler flowmeter. Morphological signs of pancreatitis, as well as the levels of plasma amylase, lipase, interleukin-1beta and interleukin-10 concentration and pancreatic cell proliferation were examined.. Ischemia with reperfusion caused acute necro-hemorrhagic pancreatitis with a histological and biochemical manifestation of pancreatic damage, followed by a spontaneous regeneration. The administration of EGF caused the reduction in the histological signs of pancreatic damage, such as necrosis, edema and leukocyte infiltration, and accelerated the pancreatic repair. Also, EGF treatment significantly attenuated the reduction in pancreatic blood flow and DNA synthesis. The activity of plasma amylase and lipase, as well as plasma interleukin-1beta and interleukin-10 concentrations were decreased in EGF treated animals.. EGF exerts beneficial influence on the course of I/R induced pancreatitis and this effect seems to be related to the reduction in the activation of pro-inflammatory interleukin cascade, the improvement of PBF, and the increase in pancreatic cell growth.

Topics: Amylases; Animals; DNA; Epidermal Growth Factor; Interleukin-1; Interleukin-10; Ischemia; Lipase; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regional Blood Flow; Reperfusion Injury

Studies have revealed that emodin is a potent agent in the management of clinical and experimental acute pancreatitis, but the molecular mechanisms by which emodin produces its biologic effects, especially on pancreatic regeneration after acute pancreatitis, remain unknown. Numerous experimental and clinical studies have shown that somatostatin analogs have favorable effects on acute pancreatitis, but their role in the management of acute pancreatitis remains controversial.. To investigate mechanisms of the Chinese herb emodin and somatostatin analogs (SSa; Sandostatin) in acute pancreatitis of rats by analyzing the changes in pancreatic tissue cytokine transforming growth factor beta1 (TGFbeta1) and epidermal growth factor (EGF) gene expression, DNA synthesis, total protein content, and the relations between them.. Acute pancreatitis was induced by intraperitoneal infusion of cerulein in rats. Emodin was administered intravenously and Sandostatin was administered subcutaneously at the time of induction of pancreatitis and 24, 48, and 72 hours afterward. Rats were killed at 6, 24, 48, 72, and 96 hours after the operation. The mRNA expression of TGFbeta1 and EGF were evaluated by reverse transcription polymerase chain reaction, and pancreatic tissue DNA synthesis was measured by the 3H-thymidine incorporation method in vitro. Total protein content was detected by Lowry's method.. The serum amylase level was decreased significantly in the emodin-treated and Sandostatin-treated groups in comparison with the nontreated group. Pancreatic tissue DNA synthesis was significantly decreased at 72 hours after the induction of pancreatitis, and a marked increase was observed at 96 hours after treatment with emodin and Sandostatin. Within 48 hours of the induction of pancreatitis, the total protein content in pancreatic tissue declined, but there was a remarkable increase in the emodin-treated group at 96 hours and Sandostatin-treated group at 48 hours. Expression of TGFbeta1 mRNA and EGF mRNA were undetectable in normal pancreas and the nontreated group at 6 hours but was observed from 24 hours to 96 hours after the induction of pancreatitis and reached its maximum at 72 hours. TGFbeta1 mRNA could be detected 6 hours after treatment with emodin and Sandostatin, and its expression was significantly higher in the emodin-treated and Sandostatin-treated groups than in the nontreated group at 24 and 48 hours. The expression of EGF mRNA was significantly higher in the emodin-treated and Sandostatin-treated group than in the nontreated group at 48 hours.. It was concluded that mechanisms of the Chinese herb emodin and somatostatin analogs in the management of acute pancreatitis in rats might be ascribed to the upregulation of TGFbeta1 and EGF gene expression, which subsequently increases DNA synthesis and protein content and thus accelerates pancreatic repair and regeneration.

Topics: Acute Disease; Amylases; Animals; DNA; Drugs, Chinese Herbal; Emodin; Enzyme Inhibitors; Epidermal Growth Factor; Gene Expression Regulation; Hormones; Male; Microscopy, Electron; Octreotide; Pancreas; Pancreatitis; Protein Biosynthesis; Proteins; Rats; Rats, Wistar; Regeneration; RNA, Messenger; Time Factors; Transforming Growth Factor beta; Transforming Growth Factor beta1

To evaluate the effects of epidermal growth factor (EGF) on intestinal permeability and bacterial translocation in rats with acute pancreatitis during total parenteral nutrition (TPN).. Thirty-two male Sprague-Dawley rats that underwent injection of 3.5% sodium taurocholate solution into the pancreatic duct were randomly divided into one of the following two groups: (1) received only TPN (control group) or (2) received TPN with EGF at a dose of 0.2 mg x kg(-1) x day(-1) (Egf group). On fifth day of total parenteral nutrition, samples from mesenteric lymph nodes, pancreas, liver and spleen were harvested for cultures. Water, protein and DNA content in jejunal mucosa were determined. D-xylose and fluorescein isothiocyanate (FTC)-dextran were instilled into the lumen of a ligated segament of small intestine. Thirty minutes later, superior mesenteric vein D-xylose and plasma FITC-dextran concentration were measured.. Positive cultures in liver and spleen, as well as FITC-dextran concentration in the Egf group were significantly lower than in the control group. Protein and DNA content in jejunal mucosa in the Egf group were significantly higher than in the control group.. The results indicate that EGF may prevent increased intestinal permeability and bacterial translocation in rats with acute pancreatitis during TPN.

Topics: Acute Disease; Animals; Bacterial Translocation; Epidermal Growth Factor; Intestinal Mucosa; Male; Pancreatitis; Parenteral Nutrition, Total; Permeability; Rats; Rats, Sprague-Dawley

We examined the influence of endogenous and exogenous epidermal growth factor (EGF) on pancreatic repair after acute pancreatitis. Caerulein-induced pancreatitis was evoked in rats with intact or removed salivary glands and EGF (10 microg/kg) was administered starting 24 h after cessation of caerulein infusion. The dose of EGF 10 microg/kg was chosen because it was the most effective in preliminary experiments when 1, 10 or 50 microg/kg of EGF was used. Caerulein administration caused acute edematous pancreatitis with biochemical and histological manifestation of pancreatic damage, followed by spontaneous regeneration. The effect of salivectomy on the course of acute pancreatitis was slight, resulting in additional reduction in pancreatic blood flow, DNA synthesis and in an increase in plasma interleukin 1beta level. Treatment with EGF accelerated the healing of pancreatic damage, causing an increase in pancreatic blood flow and DNA synthesis. EGF caused faster normalization of plasma amylase and lipase activity and plasma interleukin 1beta concentration, as well as, this peptide accelerated the restoration of pancreatic amylase activity. On histological examination, EGF caused reduction of pancreatic damage and acceleration of tissue repair. We conclude that EGF reduces the severity of pancreatic damage evoked by caerulein-induced pancreatitis-related pancreatic damage and accelerates tissue repair. The beneficial effects of EGF appear to depend, at least in part, on the improvement of pancreatic blood flow, as well as on an increase of pancreatic cell growth and limitation of the activation cytokine release.

Topics: Amylases; Animals; Ceruletide; DNA; Dose-Response Relationship, Drug; Epidermal Growth Factor; Interleukin-1; Lipase; Male; Organ Size; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regional Blood Flow; RNA; Time Factors

The results of this study show that routine measurements of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) cannot improve screening for pancreatic cancer despite the frequently present tissue overexpression. Both values fail to reveal this malignancy in a serum test. Patients with chronic pancreatitis exhibit no or very low concentrations of EGF. In cases where preoperative diagnosis is difficult the noninvasive EGF and EGF-R serum measurements may be helpful in discriminating between pancreatic cancer and chronic pancreatitis.. EGF and EGF-R are frequently overexpressed in the tissue of patients suffering from ductal pancreatic cancer and to lesser degree in patients with chronic pancreatitis. The aim of this study was to determine the value of serum measurements in these patients to detect malignant pancreatic disease. In cases of pancreatic cancer, the tissue expression of EGF and EGF-R was evaluated by immunohistochemistry.. Thirty-five patients with chronic pancreatitis and 31 patients with pancreatic cancer were evaluated; 71 patients admitted for routine surgery (hernia repair, cholecystectomy, goiter surgery) served as controls.. EGF and EGF-R values were not significantly different in pancreatic cancer as compared to controls and did not correlate with other tumor markers (CA 19-9, carcinoembryonic antigen [CEA], tumor polypeptide antigen [TPA]) or with the stage of the disease. Fourteen patients (67%) with pancreatic cancer displayed tissue overexpression for EGF and 11 patients for EGF-R (52%). These patients, however, also failed to exhibit any significant pathological changes in serum concentration. In chronic pancreatitis, EGF and EGF-R were significantly decreased as compared to pancreatic cancer and controls. This was an unexpected finding. There was a positive correlation to clinical exocrine insufficiency.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunohistochemistry; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis

Overexpression of transforming growth factors (TGF) in acute pancreatitis (AP) suggested that these substances play an important role in pancreatic repair and remodeling but the contribution of epidermal growth factor (EGF), that is well known to promote cell growth and regeneration, has not been investigated. The aim of this study was to compare the gene and immunohistochemical expression of EGF and TGF-beta1, cell proliferation, and biochemical parameters in AP induced by infusion of a supramaximal dose of caerulein in rats. The rats were sacrificed at 0, 12, 24, 48, 72 h, 5 and 10 days after the termination of caerulein infusion. Pancreatic tissue DNA synthesis, cell proliferation, histological and immunohistochemical assessments and plasma amylase were estimated following induction of AP. The mRNA expression for EGF and TGF-beta1 was evaluated by reverse transcription-polymerase chain reaction. During 10 days of the study after induction of AP a gradual normalization of biochemical and histological parameters was observed. DNA synthesis and cell proliferation which were significantly decreased at 0 and 24 h, increased significantly at 48 and 72 h, and then gradually decreased reaching at day 10 the values similar to those of vehicle-treated control rats. In these control rats the EGF mRNA or immunohistochemical expression was not detected, while the TGF-beta1 expression was weak. After induction of AP, the mRNA and immunohistochemical expression of EGF showed an increase during the initial 5 days, while those of TGF-beta1 showed a marked increase between 0 and 48 h and then again at day 10. We confirm that: (1) the expression of TGF-beta1 during AP is biphasic with an initial increase probably related to pancreatic damage and inhibition of cell proliferation and with the later phase of increase accompanied by the stimulation of the synthesis of extracellular matrix components and (2) AP is accompanied by an induction of synthesis of EGF that occurs in the initial phase of AP, probably limiting the extent of AP, and enhancing the stimulation of the pancreatic repair and regeneration.

Topics: Acute Disease; Animals; Biomarkers; Cell Division; Ceruletide; DNA; Epidermal Growth Factor; Gastrointestinal Agents; Gene Expression; Immunohistochemistry; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; RNA, Messenger; Transforming Growth Factor beta

Growth factors such as TGF-beta 1 and EGF are known to modulate the deposition of extracellular matrix components and tissue repair and to affect the cellular growth but their expression in the course of pancreatitis has not been studied. In this study we investigated the gene expression of TGF-beta 1 mRNA and EGF mRNA and other parameters of the pancreas including DNA synthesis, blood flow (PBF), tissue protein content and plasma amylase during the induction of acute pancreatitis. Supramaximal dose of cearulein (10 mg/kg/h s.c.) was infused for 5 h to induce pancreatitis. Animals were killed after 1, 2, 3, 4 and 5 h of infusion. The PBF was measured, blood samples were withdrawn to determine serum amylase concentration, biopsy samples were taken to measure the protein content and DNA synthesis. Expression of TGF-beta 1 and EGF mRNA was studied by reverse-transcription of polymerase chain reaction (RT-PCR). Caerulein infused caused a time-dependent decrease in DNA synthesis accompanied by gradual decrease of PBF and significant increase in pancreatic weight. The pancreatic protein content and plasma amylase showed progressive rise during 5 h of cearulein infusion. Histology revealed tissue edema, cellular vacuolization and prominent leukocyte infiltration after 3 h of cearulein infusion. TGF-beta 1 mRNA was strongly expressed at each time interval beginning from the 1 h after the start of cearulein infusion. In contrast, EGF mRNA was detected only at 5 h after induction of pancreatitis. We conclude that 1) the development of caerulein-induced pancreatitis results in the inhibition of pancreatic growth and the reduction in PBF accompanied by enhanced expression of TGF-beta 1; 2) The expression of EGF that was observed at the end of the induction of pancreatitis may indicate the initiation of pancreatic repair; 3) TGF-beta 1 seems to lead to subsequent induction of EGF that may stimulate the regeneration of injured pancreas.

Topics: Acute Disease; Amylases; Animals; Ceruletide; DNA; DNA Primers; Epidermal Growth Factor; Gene Expression Regulation; Male; Organ Size; Pancreas; Pancreatitis; Polymerase Chain Reaction; Protein Biosynthesis; Rats; Rats, Wistar; Regional Blood Flow; RNA; Transforming Growth Factor beta

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLN) and other extraintestinal organs is an important source of infection in acute pancreatitis (AP). Epidermal growth factor (EGF), a peptide hormone with trophic effects on gut mucosa, has decreased intestinal mucosal injury in septic rats and decreased burn-induced BT in mice. The purpose of this study is to examine whether EGF could affect BT in acute necrotizing pancreatitis. Forty-eight male Sprague-Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the biliopancreatic duct (1 ml/kg of body weight). Group III and Group IV underwent laparotomy without induction of acute pancreatitis. Group I rats received human recombinant EGF (100 micrograms/kg, subcutaneously twice daily) and Group II rats received a similar volume of 0.1% bovine serum albumin as a placebo postoperatively. Group III and Group IV received EGF and placebo, respectively. At 48 hr postoperatively, blood was drawn for culture and amylase determinations. Jejunum and ileum were obtained to measure mucosal protein content, mucosal thickness, villus height, and crypt depth. Specimens from MLN, spleen, liver, pancreas, and cecum were harvested for pathology and culture of gram positive (G+), gram negative (G-), and anaerobic bacteria. Ileal mucosal protein levels were increased significantly in Group I (1.96 +/- 0.14 mg/cm) compared to Group II (0.95 +/- 0.15 mg/cm intestinal segment) (P < 0.01). Jejunal and ileal mucosal thickness, villus height, and crypt depth in Group I were significantly increased when compared to Group II (P < 0.05). All 12 rats in Group II had BT to MLN compared to 58% (7 of 12 rats) in Group I (P < 0.05). Thirty-three percent (4 of 12 rats) had BT to distant sites such as pancreas, spleen, liver, and/or blood in Group I vs 83% (10 of 12 rats) in Group II (P < 0.05). EGF treatment minimizes intestinal damage, decreases BT to MLN and bacterial spread to distant sites, and may be beneficial in preventing septic complications in AP.

Topics: Acute Disease; Animals; Bacterial Translocation; Epidermal Growth Factor; Humans; Ileum; Infections; Intestinal Mucosa; Laparotomy; Lymph Nodes; Male; Mesentery; Pancreatitis; Proteins; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Serum Albumin, Bovine

The expression of cripto gene product was examined immunohistochemically in 45 surgically resected pancreatic tumors, including 32 invasive ductal carcinomas, 4 intraductal papillary adenocarcinomas, 4 intraductal papillary adenomas, 2 mucinous cystadenomas, 2 islet cell tumors, and one solid and cystic tumor, and compared with that in 32 areas of accompanying chronic pancreatitis present in the cases of invasive ductal carcinomas and 5 non-tumorous areas of pancreas without pancreatitis. All pancreatic ductal tumors including adenomas and carcinomas showed positive staining with no difference in terms of staining intensity among intraductal tumors and invasive carcinomas with or without mucin hypersecretion. Islet cell tumors were positively stained but the solid and cystic tumor was negative. Duct epithelial cells and acinar cells were negative but islet cells were positive in the pancreas tissues without pancreatitis. Cells arranged in duct-like structures in areas of accompanying chronic pancreatitis were positively stained. The results suggest that cripto expression might be associated with a growth advantage of tumor cells and also with differentiation to form duct-like structures.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Islet Cell; Cell Transformation, Neoplastic; Cystadenoma, Mucinous; Epidermal Growth Factor; Gene Expression; GPI-Linked Proteins; Humans; Intercellular Signaling Peptides and Proteins; Islets of Langerhans; Membrane Glycoproteins; Neoplasm Proteins; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatitis

Cripto is a 188 amino-acid protein containing a central segment that shares amino-acid sequence homology with epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). The EGF receptor, EGF and TGF-alpha are expressed in the normal human pancreas, and are over-expressed in human pancreatic cancer. Therefore, in the present study we sought to determine whether cripto is found in the normal human pancreas and whether its expression is altered in pancreatic cancer. Because chronic pancreatitis (CP) is associated with interstitial fibrosis similar to that observed in pancreatic cancer, we also examined cripto expression in pancreatic tissues from patients with CP. In the normal pancreas, cripto immunoreactivity was found at moderate levels in most ductal cells and was present very faintly in a rare acinar cell. In 26 of 58 pancreatic cancers, cripto immunoreactivity was present in many cancer cells. Its presence was associated with advanced tumor stage, but not with shorter post-operative survival. Cripto was also present in acinar and ductal cells adjacent to the cancer cells, and in many ductal atrophic acinar cells in the CP samples. Northern blot analysis revealed a marked increase in cripto mRNA levels in the cancer and CP samples. By densitometry, there was a 11- and 4-fold increase in cripto mRNA levels in pancreatic cancer and CP respectively. Southern blot analysis did not reveal an increase in gene copies encoding cripto either in cancer or in CP. These findings indicate that cripto expression may contribute to disease progression in pancreatic cancer, and implicate cripto in the histopathological alterations that occur in the pancreas both in cancer and in CP.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Blotting, Northern; Blotting, Southern; Chronic Disease; Epidermal Growth Factor; Female; GPI-Linked Proteins; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Male; Membrane Glycoproteins; Middle Aged; Neoplasm Proteins; Pancreas; Pancreatic Neoplasms; Pancreatitis

The expressions of epidermal growth factors (EGF), epidermal growth factor receptors (EGFR), and the c-erbB-2 oncoprotein were immunohistochemically examined in 25 cases of human pancreatic carcinoma and epineoplastic pancreatitis and in 10 non-cancerous/non-inflammatory pancreatic tissues. The positive rates of EGF, EGFR, and the c-erbB-2 oncoprotein in cancer tissues were 72%, 36%, and 28%, respectively. EGF was stained mainly in the cytoplasm and partly on the surfaces of the cancer cells. EGFR and the c-erbB-2 oncoprotein were stained mainly on the surfaces of the cancer cells and partly in the cytoplasm. The expressions of these 3 products correlated significantly with tumor invasion into the anterior and posterior areas surrounding the pancreas. In the EGF, EGFR, and c-erbB-2 positive cancer tissues, some stromal cells, that is fibroblasts and endothelial cells, were also positive. In the adjacent pancreatic tissues with inflammation, these products were noted in some ductal cells, acinar cells, fibroblasts and endothelial cells. No distinct staining was detected in non-cancerous/non-inflammatory tissues. The survival period for patients who tested positive for these three proteins was statistically shorter than for those who tested negative. These results suggest that the coexpression of EGF and EGFR and the expression of the c-erbB-2 oncoprotein are related to the existence of the invasion of human pancreatic cancer. Furthermore, an immunohistochemical examination of these three products is useful in forming a prognosis for pancreatic cancer patients.

Topics: Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunohistochemistry; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Oncogene Proteins v-erbB; Pancreas; Pancreatic Neoplasms; Pancreatitis; Prognosis; Retroviridae Proteins, Oncogenic

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.

Topics: Adenocarcinoma; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Fetus; Humans; Immunoenzyme Techniques; Pancreas; Pancreatic Neoplasms; Pancreatitis; Staining and Labeling; Transforming Growth Factor alpha

The pS2 gene encodes for a small cysteine-rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF-7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5-cysteine domain is tandemly repeated. The 5' flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally-derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co-expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.

Topics: Cell Line; Crohn Disease; Epidermal Growth Factor; Estrogens; Gastric Mucosa; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins; Intestinal Mucosa; Intestine, Small; Mucins; Muscle Proteins; Neoplasm Proteins; Neuropeptides; Pancreatic Ducts; Pancreatitis; Peptic Ulcer; Peptide Biosynthesis; Peptides; Proteins; RNA, Messenger; Trefoil Factor-1; Trefoil Factor-2; Trefoil Factor-3; Tumor Suppressor Proteins