摘要:

Two human pancreatic adenocarcinoma cell lines (PANC 1 and MIA PACA 2) were examined for expression of growth factors that could potentially play a role either in growth regulation of the tumor cells, or in cells that comprise the stromal elements of tumors. Both cell lines expressed transforming growth factor-α (TGFα), basic fibroblast growth factor (bFGF), c-sis (PDGF B chain), TGFβ1, and TGFβ3 mRNA by Northern blot analysis. Only the PANC 1 cells, however, expressed the TGFβ2 transcript. TGFP-like competing activity was found in medium conditioned by either cell line, but TGFα-like [epidermal growth factor (EGF)-competing] activity was not detected in the medium from either cell line by radioreceptor assay. TGFα and EGF caused concentration-dependent stimulation of soft agar colony growth of the MIA PACA 2 cells, while only TGFα caused a significant but less dramatic stimulation of soft agar growth of the PANC 1 cells. Insulin stimulated the anchorage-independent growth of MIA PACA 2 but not PANC 1 cells. Likewise, bFGF also caused a concentration-dependent stimulation of MIA PACA 2 but not PANC 1 growth in soft agar, and PDGF had no effect on the growth of either cell line. TGFβ had no inhibitory or stimulatory effect on soft agar colony growth of either the PANC 1 or the MIA PACA 2 cells, although both cell lines exhibited high affhity, saturable TGFβ binding sites, and TGFβl was capable of autoinduction of TGFβ1 mRNA expression in PANC 1 cells. The ability to continue to respond to positive growth regulatory factors coupled with the loss of responsiveness to negative growth factors may be important in the pathogenicity of these aggressive tumors.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Monoclonal antibodies specific for luminal plasma membranes of acinar and duct cells of the exocrine pancreas were used to investigate changes in antigen expression during regeneration of the pancreas after acute pancreatitis and during fetal pancreatic development in mice. During regeneration after acute pancreatitis induced by supramaximal injections of cerulein or by a choline-deficient, ethionine-supplemented diet, morphologically identifiable acinar cells expressed the ductal antigen on their luminal surface, but at a lower level than this antigen is expressed on duct cells. As the pancreas regenerated, the ductal antigen was lost from acinar cells and was found only on duct cells. Characteristic tubular complexes formed in both pancreatitis models and were positive for the acinar antigen, demonstrating their acinar origin. In fetal pancreas, acinar cells between prenatal days 3 through 1, when zymogen granules were already abundant, expressed the duct-cell antigen on their luminal surface. By birth duct antigen was mostly present on ducts with only occasional label on acinar cells. The presence of a ductal antigen on acinar cells is associated with acinar-cell growth during regeneration and during fetal development and may reflect a less differentiated state.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effects of cyclosporine (CsA), an immunosuppressive agent, on azaserine-induced pancreatic carcinogenesis in rats were investigated using the short-term assays of the quantitation of atypical acinar cell foci. Male Lewis rats at 14 days of age were given a single intraperitoneal injection of azaserine (30 mg/kg). At 25 days of age, the treated rats were weaned and divided into two groups fed either basal diet or the same diet containing 0.011% CsA. Saline-injected rats were also fed the CsA diet. Rats were killed 4 months after azaserine injection and acidophilic and basophilic foci in the pancreas were quantified. The pancreas of the rats given saline injection and maintained on the CsA diet showed no significnt histological alterations. The dietary CsA after the injection of azaserine markedly reduced the number of both acidophilic and basophilic foci. It is concluded that addition of CsA to the diet inhibits the growth of initiated cells to form foci in the pancreas of azaserinetreated rats. The experimental model is useful in analyzing the modifying role of this immunosuppresant in the induction and growth of epithelial cell tumors.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The routes by which secretory proteins leave the pancreas have been studied during single-pass perfusion of the isolated cat pancreas with a physiological salt solution. The amounts of amylase and total protein appearing in pancreatic juice, venous effluent, and the exudate escaping from the surface of the gland (probably representing lymph) were measured during stimulation with secretin alone and together with bolus injections of acetylcholine. During stimulation with secretin alone, the amylase output in venous effluent was four times greater than in pancreatic juice or exudate. In contrast, most protein appeared in exudate, some in the venous effluent, and a very small amount in pancreatic juice. Acetylcholine transiently increased the output of both amylase and total protein in pancreatic juice to values that greatly exceeded those in venous effluent and exudate. After a delay of 10 min, it also increased the output of amylase and total protein in exudate, but had no effect on venous effluent. In conclusion, secretory proteins enter the venous circulation at a constant rate (i.e., not influenced by acetylcholine stimulation). Some also appear in exudate (lymph), the proportion of which is determined by stimulation. Whether the proteins in these two fluids and in pancreatic juice are derived from the same intracellular pool remains to be determined.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Although fat accumulation in acinar cells is the earliest histopathological change in the pancreas of patients and experimental animals, there are few long-term studies regarding lipid composition of the pancreas in alcoholism. In the present study, female Sprague-Dawley rats were divided into three groups each fed Wayne Rodent-Blox ad libitum or Lieber-DeCarli diet with 36% of maltose dextrin calories replaced with ethanol ad libitum, or isocaloric amounts of liquid diet for a period of 21 months resulting in changes of chronic pancreatitis in ethanol-fed rats. A low level of triglycerides, a high level of cholesterol ester and moderately elevated phospholipids, low incorporation of [14C]palmitoyl in triglycerides, increased14C activity in phospholipids, and cholesterol ester were found by thin-layer chromatography in ethanol-fed rats. These data indicate that the pancreas synthesized triglycerides and other lipid components in the same way as liver and fat cells. Chronic ethanol ingestion caused marked changes in pancreatic lipid metabolism due to altered enzyme activities involved in the lipid pathways.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Two novel neuromedin C analogs [D-Ala1, Leu9-ψ-CH2NH-Leu10]neuromedin C and [Leu9-ψ-CH2NH-Leu10]neuromedin C, were synthesized by rapid solid phase methods and examined for their abilities to inhibit neuromedin C-stimulated amylase release by isolated rat pancreatic acini. Both analogs significantly inhibited maximally stimulated amylase release by neuromedin C in a dose-dependent manner with maximal inhibition seen at concentrations of 100 and 300 μM of [D-Ala1, Leu10-ψ-CH2NH-Leu10]neuromedin C and [Leu9-ψ-CH2NH-Leu10]neuromedin C, respectively. The IC50(concentration required to half-maximally inhibit neuromedin C-stimulated amylase release) was 1.5 μM for [D-Ala1, Leu9-ψ-CH2NH-Leu10]neuromedin C compared to a 13.4 μM IC50for [Leu9-ψ-CH2NH-Leu10]neuromedin C. The [D- Ala1, Leu9-ψ-CH2NH-Leu10]neuromedin C analog produced a parallel rightward shift in the neuromedin C dose-response curve and Schild plots of the inhibition data gave a slope of 0.969 ± 0.121 and a PA, (apparent affinity for the acinar cell receptor in terms of neuromedin C receptor-stimulated amylase release) of 100 nM. While ID-Ala', Leu9-+-CH2NH-Leu9olneuromedin C significantly inhibited both neuromedin B- and gastrin releasing peptide stimulated amylase release, the analog did not inhibit amylase release in response to either cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, carbamylcholine, the Ca2+ionophore A23187, forskolin, or 8-bromo-cyclic AMP. The results demonstrate that [D-Ala1, Leu9-ψ-CH2NHL10] neuromedin C is a potent, specific, and competitive antagonist for neuromedin C and peptides of the gastrin releasing peptide family and may serve as a useful molecule for exploring the physiological role of these peptides.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In an attempt to study the mechanisms leading to fibrosis in chronic pancreatitis, an in situ immunohistochemical investigation of lymphocytes and of class II major histocompatibility complex expression (HLA-DR) by epithelial cells has been designed. Samples of normal pancreas (n= 8), chronic calcifying pancreatitis (n= 4), chronic obstructive pancreatitis (n= 6), and diffuse fibrosing pancreatitis (n= 6) have been studied. In normal pancreas, T-lymphocytes were rare and were located in the epithelial layer of pancreatic ducts and in the penductal connective tissue. Duct cells were constantly HLADR negative. In chronic calcifying pancreatitis and chronic obstructive pancreatitis, T cells were numerous and were located around ducts and in the spreading areas of fibrous septa. In chronic obstructive pancreatitis, the duct cells strongly expressed the HLA-DR antigen. In diffuse fibrosing pancreatitis, fibrous tissue was devoid of lymphocytes and duct cells never expressed the HLA class II antigen. These results suggest that lymphocytes are involved in the fibrosing process occurring in chronic calcifying pancreatitis and chronic obstructive pancreatitis but not in diffuse fibrosing pancreatitis. The significance of de novo expression of HLA-DR antigen by duct cells is discussed.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Changes in pancreatic growth and in mRNA concentrations in rat pancreas were monitored by dot-blot hybridization with cloned cDNAs of rat amylase, chymotrypsinogen B, proinsulin I, and actin during the pre- and postnatal period in the rat. Wistar rats were killed at the 18th day of gestation and at the 1st, 10th, 20th, 35th, and 87th day of postnatal life. It was concluded from the ratio of pancreatic weight/body weight that pancreatic growth preceded body growth. Pancreatic protein and total RNA concentration increased 2.9 times during the period studied. All studied mRNAs increased in concentration during the postnatal development period. Messenger RNA for chymotrypsinogen B and proinsulin I exhibited a significant increase after birth, decreased by the 10th day of life, and increased thereafter. For amylase mRNA, no significant changes were observed around birth, a progressive increase occurring thereafter up to the 87th day of life. The mRNA for actin showed a progressive increase between the 18th day of gestation and the 20th postnatal day, after which it remained stable. We concluded that each mRNA showed a singular profile of increase during postnatal development.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effect of aclatonium napadisilate, a newly synthesized choline ester, on pancreatic exocrine function was compared with that of the muscarinic agonist carbamylcholine in isolated rat pancreatic acini. Both compounds increased amylase release and45Ca2+efflux in a dose-dependent fashion, and similarly decreased the binding of [N-methyl-3H]scopolamine to isolated rat pancreatic acini. While aclatonium napadisilate was 20–30 times less potent than carbamylcholine in stimulations of amylase release and45Ca2+efflux, the potency of aclatonium napadisilate in inhibiting [N-methyl-3H]scopolamine binding was nearly the same as that of carbamylcholine. These results indicate that aclatonium napadisilate stimulates pancreatic exocrine secretion via muscarinic receptors and Ca2+mobilization, and its intrinsic activity is less than carbamylcholine in the isolated rat pancreatic acini. Since aclatonium napadisilate is known to increase motility and peristalsis of the gastrointestinal tract, stimulatory effects of aclatonium napadisilate, shown in the present study, on digestive enzyme secretion from the pancreas may provide additional benefit of aclatonium napadisilate in the treatment of various gastrointestinal disorders.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We examined whether endogenous cholecystokinin (CCK) is involved in growth of the preweanling rat pancreas. Twice daily for 14 days, 7-day-old neonatal rats received an oral gavage of either 2.5 mg/kg or 5.0 mg/kg of the potent and specific CCK receptor antagonist L-364,718 (the 2.5 mg/kg dose of antagonist was shown in the present study to abolish totally the pancreas growth-promoting effects of exogenously administered caerulein (CR) in neonatal rats). Control pups received oral gavages of the L-364,718 vehicle alone. The final body weights, pancreas weights, total pancreatic DNA contents, and total pancreatic protein contents did not differ significantly between the 21-day-old control pups and the 21-day-old pups that were pretreated for 14 days with either the low or the high doses of L-364,718. These findings suggest that endogenous CCK is not required for growth of the neonatal rat pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID