ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Fine structural analysis of a series of 51 adenocarcinoma in the human pancreas revealed their composition of one major cell type, a mucoprotein secreting cell which has a number of structural features resembling the cells of the larger interlobular ducts in the normal pancreas. In addition to mucus secretion, the tumor cells released large quantities of membrane material, both as vesicles pinched off from microvilli and as blebs sequestered from the plasma membrane. At the ultrastructural level the subdivision of tumors into three major grades of malignancy was manifested by a progressive loss in cell polarity and a reduction in the association of tumor cells with elements of the extracellular matrix (basal lamina). The highest grade of differentiation grew as tubular structures with a common luminal space, while with progressive dedifferentiation and loss of cell polarity secretion occurred into both luminal and interstitial spaces. This release pattern of tumor cell products, which constitute a complex mixture of exportable and constitutive proteins, will lead to their appearance in both pancreatic juice and blood circulation. Tumor cell spreading occurred along perineural sheaths and was combined with nerve fiber destruction. Primary tumors and lymph node or liver metastases did not differ significantly in their respective grading.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Affinity-purified antibodies to major components of the extracellular matrix (fibronectin and collagen type I) and basal lamina (laminin) were used in indirect immunofluorescence studies on frozen sections of 12 pancreatic ductal adenocarcinoma of the human and on sections of normal and inflamed pancreatic tissue of the same patients. Laminin-specific immunoreactivity was distributed in close correlation to the grade of differentiation of the tumor tissue. Intact basement membranes, also with some structural irregularities were found only in the highest grade of differentiation where tumor cells grew as tubular structures. With progressive dedifferentiation basal laminae were either absent or the laminin-positive material was focally distributed without spatial association with tumor cells. In all cases of pancreatic tumors a remarkable increase in interstitial connective tissue was observed, as demonstrated by antibodies specific for human collagen type I and for human serum fibronectin. Tumor extracts contained high amounts of collagen type I and V but no significant amount of collagen type I11 as visualized by analytical SDS gel electrophoresis. A similar distribution of collagen types was observed in lymph node and liver metastases, and in tumors xenografted into nude mice. Since previously a close correlation between grading and growth kinetics of primary tumors had been observed, in vitro experiments were performed analyzing the effect of purified extracellular matrix proteins on tumor cell proliferation. In vitro cultivation of two established cell lines of pancreatic carcinoma on collagen type I or on laminin resulted in an arrest of proliferation on laminin substrates, while normal proliferation comparable to growth on regular culture dishes was found using collagen type I and fibronectin as substrates. Fine structural studies demonstrated a higher degree of cell differentiation in the presence of laminin, as compared to collagen type I or fibronectin.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The effects of butyrate (a biological response modifier) on cellular morphologic features and carcinoembryonic antigen (CEA) expression of human pancreatic carcinoma cells were studied and compared in a well-differentiated, CEA-producing cell line (CAPAN-1), and a poorly differentiated cell line (PANC-1). Butyrate treatment resulted in the acquisition of phenotypic traits commonly attributed to increased “differentiation,” including a twofold increase in doubling time, decreased saturation densities, and ∼50% reduction in colony forming efficiency in both cell lines. Elongation and flattening of cells with extending cellular processes were seen by light microscopy. Significant ultrastructural changes were seen only in the PANC-1 cells, including an increased number of intercellular desmosomes, tonofilaments, and lipid droplets. In contrast, to the coarsely clumped nuclear chromatin (heterochromatin) of untreated PANC-1 cells, the nuclei of the butyrate-treated cells consisted of finely dispersed chromatin (euchromatin). CAPAN-1 cells responded to butyrate with increased CEA synthesis and release. This effect was greatest in the stationary growth phase. Butyrate had no effect on the already low rate of CEA synthesis by PANC-1 cells. These studies suggest that CEA synthesis and state of differentiation are affected independently by butyrate treatment and that the original tumor phenotype plays an important role in response to such treatment.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The diagnostic value of the tumor-associated antigens Ca 19–9 and Ca 12–5 was tested in 130 subjects (38 healthy controls, 37 carcinomas of the pancreas, 23 chronic pancreatitis, 23 extrapancreatic gastrointestinal cancers, 9 endocrine pancreatic tumors). Ca 19–9 levels above 37 U/ml were obtained in 67.6% and Ca 12–5 levels above 39 U/ml in 45.9% of carcinomas of the pancreas, 4.3 and 8.796, respectively, of chronic pancreatis, 21.7 and 17.4% of extrapancreatic gastrointestinal tumors, and 0 and 11.1% of endocrine pancreatic tumors and in none of the healthy controls. Results of preoperative determination of Ca 19–9 and Ca 12–5 gave a sensitivity of 67.6 and 45.9%, a specificity of 91.8 and 90.9%, a predictive value of a positive test of 80.6 and 70.8%. When elevation of both antigens was required, sensitivity decreased to 32.4% but specificity rose to 97.3%. All but one of the pancreatic cancer patients were at stage 3 and 4. The only patient with pancreatic cancer in stage 1 had normal levels of both markers. Ca 19–9 and Ca 12–5, whether alone or associated, represent a good diagnostic test for differentiating pancreatic cancer from chronic pancreatitis. Due to the low sensitivity of both markers, the tests are of limited value when any other diagnostic evidence of pancreatic cancer is absent.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The incidence of carcinoma of the pancreas is higher among men than women. It is also higher among male than female carcinogen-treated rats. The role of testosterone in this preferential induction of pancreatic cancer was evaluated in a rat model of pancreatic carcinogenesis. Two-week-old Lewis rats were treated with a single injection of azaserine. At weaning (3 weeks), rats were divided into five groups as follows: (1) females; (2) intact males; (3) sham-operated males; (4) orchiectomized males; and (5) orchiectomized males plus testosterone. Four months after administration of azaserine, quantitative histologic analysis of atypical acinar cell foci and nodules of the pancreas showed that in female and orchiectomized male rats, foci and nodules were smaller and less numerous than in intact males. Testosterone treatment partly reversed the effect of orchiectomy. This suggests that the susceptibility of male rats to induction of pancreatic carcinomas by azaserine is at least partially mediated by testosterone. Estrogen and testosterone receptors were assayed, but high-affinity receptors characteristic of gonadal tissues were not detected in normal pancreas or in a transplantable azaserine-induced acinar cell carcinoma. Thus, the effect of testosterone in the pancreas may depend on steroid-binding proteins of another type, or may be indirectly mediated.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The bentiromide test reliably detects exocrine pancreatic insufficiency. The synthetic peptide attached to p-aminobenzoic acid (PABA) is cleaved by chymotrypsin, PABA is absorbed in the small intestine, partially conjugated in the liver, and excreted in the urine. It has been claimed that the bentiromide test is abnormal not only in patients with pancreatic insufficiency but also in patients with small bowel or liver disease because of impaired PABA absorption or conjugation, respectively. This study prospectively evaluates the bentiromide test in 12 patients with small bowel disease and 18 patients with biopsy-proven liver disease. One of 30 patients had an abnormal bentiromide test. Cumulative 6-h urinary arylamine excretion and plasma PABA concentration, 2 h after administration, were in the same range as healthy controls. We conclude that the bentiromide test is not affected by small bowel or liver disease. An abnormal test is virtually diagnostic for exocrine pancreatic insufficiency.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The presence of macroamylasemia can be suspected when a patient has low renal clearance of amylase relative to creatinine (Cam/Ccr). However, the Cam/Ccr is seldom reduced to the extent expected given the fraction of amylase that appears to be bound in the macroamylase complex by gel filtration studies at 3°C. Therefore, we tested the possibility that the binding of amylase in macroamylase complexes was temperature dependent and that binding at physiological temperatures might be less than at 3°C. Gel filtration of five macroamylase-containing sera was carried out at temperatures of 3°, 25°, 37°, 43°, and 49°C. Binding of amylase in the complex decreased as the temperature increased with virtually all amylase bound at 3°C and virtually no amylase bound at 49°C. The fraction of the amylase that bound at 37°C was approximately what would have been predicted from the Cam/Ccr of each of the five subjects. We conclude that amylase binding in macroamylase complexes is extremely temperature sensitive and appreciable changes in binding may occur over the physiological temperature range of 37–41°C.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The value of a modified fluorescein dilaurate (FDL) serum test for the detection of pancreatic exocrine insufficiency was investigated in 89 patients with and without pancreatic disease. This test modification with fluorescein serum determination following metoclopramide (10 mg) and secretin (1 U/kg) i.v. injection appeared efficacious in a pilot study in six healthy volunteers. Individual peak fluorescein serum concentration was achieved within 180 min after the test meal in 96% of all subjects studied. Peak fluorescein serum concentration within this time period allowed the best discrimination between normal and abnormal pancreatic function. Sensitivity in detection of chronic pancreatitis was 86% (38 of 44 patients) when the lower normal fluorescein serum concentration was considered 4.5 μg/ml (this value corresponds to mean – 2 SD). The specificity of this test in detecting chronic pancreatitis was 100% when healthy controls were considered, but fell to 78% when patients with different gastrointestinal disorders, including those with secondary pancreatic insufficiency, were included. The correlation between serum and urinary fluorescein determination was significant (r = 0.61; p <0.01). Duodenal bicarbonate output/h after secretin also showed a significant correlation with peak fluorescein serum concentration (r = 0.79; p <0.001).

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The proliferation of pancreatic extracellular matrix, which characterizes chronic pancreatitis, has been analysed using immunohistochemistry. The relationship of matrix components to intraductal precipitates and the presence of serum proteins in precipitates were also studied to investigate the suggestion that ductal permeability increases in chronic pancreatitis. Pancreatic tissue from organ donors was compared with that from patients with chronic calcifying or chronic obstructive pancreatitis. Frozen sections were labeled with monospecific antibodies to collagen types I, III, pro-III and IV, laminin, fibronectin, IgG, IgA, and IgM and then visualized by indirect immunofluorescence. In chronic pancreatitis, interstitial collagens and fibronectin appeared increased and disorganized in both fibrous tissue and areas that appeared histologically normal. Type IV collagen distribution was abnormal and in some sites was present with interstitial collagen. In addition, intraductal precipitates were shown to contain immunoglobulins, and defects were identified in the duct basal lamina associated with precipitates. These results demonstrate that in chronic pancreatitis interstitial collagens are extensively disorganized, the fibrosis possibly being relatively labile. The presence of serum proteins in intraductal precipitates confirms an increase in ductal permeability, and associated defects in the basal lamina appear to define a route via which serum proteins may enter the intraluminal compartment.

ISSN:0885-3177    

出版商:OVID    

年代:1987

数据来源: OVID