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)

Very late activation (VLA) receptors mediate cell adhesion to extracellular matrix, mainly by acting as adhesion receptors to fibronectin, collagen, and laminin as well as to other cells. These interactions not only regulate normal cell-extracellular matrix contact, but also are thought to be involved in metastasis and invasive tumor growth. Using immunohistochemistry [the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique] we compared the expression and distribution of VLA receptors in normal pancreatic tissue, chronic pancreatitis, and ductal pancreatic adenocarcinoma. Immunohistochemically, VLA alpha 2 and VLA alpha 6 were moderately to strongly expressed on the basal surface of ductal and acinar cells in normal pancreatic tissue, whereas centroacinar cells predominantly expressed VLA alpha 3 and VLA alpha 5. Similarly, pancreatic carcinoma showed an intensive staining for VLA alpha 2 and VLA alpha 6 with a diffuse distribution on the cell surface. Expression of VLA alpha 3 and VLA alpha 5 in pancreatic carcinoma was heterogeneous, ranging from moderate to weak and lost in about 50% of the cells. As our results suggest, cell-basement membrane interaction in ductal and acinar pancreatic cells is primarily mediated through VLA alpha 2 and VLA alpha 6, whereas VLA alpha 3 and VLA alpha 5 are the major VLA receptors on centroacinar cells. In pancreatic carcinoma a loss (VLA alpha 5) or redistribution (VLA alpha 2, VLA alpha 6) of VLAs was observed. This redistribution of VLA alpha 2 and VLA alpha 6 may reflect a loss of spatial arrangement of tumor cells and their ability to randomly interact with extracellular matrix structures during invasion and metastasis.
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PMID:Expression and distribution of VLA receptors in the pancreas: an immunohistochemical study. 825 85

Chronic pancreatitis, K-ras oncogene mutations, and the subsequent generation of reactive oxygen species (ROS) appear to be linked to pancreatic cancer. ROS have also been suggested to be mitogenic and capable of stimulating cell proliferation. Cells contain antioxidant enzymes to regulate steady state levels of ROS produced by products of metabolism. The aims of our study were to determine antioxidant enzyme activity in pancreatic cancer cells and correlate enzyme activity with tumor growth, as well as determine whether tumor cell growth could be altered with antioxidant gene transfection. Western blots, enzyme activity, and enzyme activity gels were performed for manganese superoxide dismutase (MnSOD), copper/zinc, catalase, and glutathione peroxidase in normal human pancreas and in the human pancreatic cancer cell lines BxPC-3, Capan-1, MIA PaCa-2, and AsPC-1. Cell population doubling times were determined and correlated with antioxidant enzyme activity. MnSOD was overexpressed in MIA PaCa-2 using an adenoviral vector, and the effect on cell growth was determined. The cell pancreatic cancer lines BxPC-3, MIA PaCa-2, and AsPC-1 had decreased levels of MnSOD immunoreactive protein as well as activity and decreases in MnSOD levels correlated well with increased rates of tumor cell proliferation as determined by cell doubling time. No correlation could be found between cell growth and levels of copper/zinc superoxide dismutase, catalase, or glutathione peroxidase. Enforced expression of MnSOD by adenovirus transfection in the rapid growing cell line MIA PaCa-2 increased MnSOD immunoreactivity and MnSOD activity and decreased growth rate. Overexpression of MnSOD may be effective in growth suppression of pancreatic cancer.
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PMID:The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma. 1264 90

In this paper the possible roles of cholecystokinin (CCK), gastrin, or gastrin-related peptides and their receptors in human gastrointestinal diseases are reviewed. For CCK/CCK(A) receptors (CCK(A)-R), the evidence for their proposed involvement in diseases caused by impaired CCK release or CCK(A)-R mutations, pancreatic disorders (acute/chronic pancreatitis), gastrointestinal motility disorders (gallbladder disease, irritable bowel syndrome), pancreatic tumor growth and satiety disorders, is briefly reviewed. The evidence that has established the involvement of gastrin/CCK(B)-R in mediating the action of hypergastrinaemic disorders, mediating hypergastrinaemic effects on the gastric mucosa (ECL hyperplasia, carcinoids, parietal cell mass), and acid-peptic diseases, is reviewed. The evidence for their possible involvement in mediating growth of gastric and pancreatic tumours and possible involvement of gastrin-related peptides in colon cancers, is reviewed briefly.
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PMID:Involvement of cholecystokinin/gastrin-related peptides and their receptors in clinical gastrointestinal disorders. 1268 77

To elucidate the distribution and role of myofibroblasts and CD34-positive stromal cells in various pancreatic lesions, we performed an immunohistochemical study using a streptoavidin-biotin immunoperoxidase technique. We selected 43 pancreatic lesions from 1 biopsied, 22 surgically resected and 12 autopsied specimens: acute pancreatitis (n=3), chronic non-obstructive pancreatitis (n=4), obstructive pancreatitis (n=7), islet cell tumor (n=4), serous cystadenoma (n=7), mucinous cystadenoma (n=6), and invasive ductal carcinoma (n=12). In normal pancreas, myofibroblasts and CD34-positive stromal cells were predominantly present in the peridcutal and periacinar areas, respectively. Both myofibroblasts and CD34-positive cells were observed in the stroma of chronic pancreatitis. In four islet cell tumors, myofibroblasts were present in the stroma of the tumor center, but no CD34-positive stromal cells were identified. Additionally, myofibroblasts and CD34-positive stromal cells were located in the inner layer and the outer layer of the capsule of three islet cell tumors, respectively. In nine of the thirteen cystadenomas, only myofibroblasts were recognized in the cyst wall. In the remaining four cystadenomas, a small number of CD34-positive cells were observed in the cyst wall. In 12 invasive ductal carcinomas, the stroma possessed a lot of myofibroblasts, but there were no or few CD34-positive stromal cells. In conclusion, it seems that the abundant amount of CD34-stromal cells in the main lesions is characteristic of chronic inflammatory lesions. Myofibroblasts and CD34-positive stromal cells may play a role in regulating the tumor growth in the capsule of islet cell tumors of the pancreas.
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PMID:The distribution and role of myofibroblasts and CD34-positive stromal cells in normal pancreas and various pancreatic lesions. 1470 72

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with an overall 5-year survival rate of less than 5%. Invasive tumor growth and early metastasis are two important reasons for this dismal prognosis. Osteopontin (OPN) is a secretory protein with a variety of functions, for example in cell adhesion and migration, inflammatory reaction and apoptosis. In this study the functional role of OPN in human pancreatic cancer and its potential use as a disease marker were analyzed. By real time quantitative PCR, there was a 2.2-fold and 1.6-fold increase of OPN mRNA in pancreatic cancers (n = 23) and chronic pancreatitis samples (n = 22), respectively, compared to normal pancreatic tissues (n = 20). Immunohistochemical analysis demonstrated OPN staining in 60% of the primary pancreatic tumors and in 72% of the lymph node and liver metastases. ELISA analysis of serum samples obtained from pancreatic cancer patients (n = 70), chronic pancreatitis patients (n = 12), and healthy donors (n = 20) showed a 1.6-fold increase in OPN serum levels in patients with tumors and a 1.9-fold increase in patients with chronic pancreatitis. Recombinant human OPN significantly increased the invasiveness of pancreatic cancer cells, without having any impact on cell proliferation. In addition, down regulation of OPN by specific siRNA molecules decreased pancreatic cancer cell invasion. In conclusion, OPN serum levels in pancreatic cancer and chronic pancreatitis patients are not significantly different, thereby restricting its role as a prognostic or follow-up marker. Our results do suggest, however, that blockade of OPN might be useful as a therapeutic approach to inhibit invasion and metastasis of pancreatic cancer cells.
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PMID:Osteopontin influences the invasiveness of pancreatic cancer cells and is increased in neoplastic and inflammatory conditions. 1597 Jun 85

The roles of lumican, a member of the small-leucine-rich-proteoglycan (SLRP) family, in pathological fibrosis, cancer tissues and tumor cell growth were reviewed. Lumican is predominantly localized in the areas of pathological fibrosis including the thickened intima of human coronary arteries, ischemic and reperfused hearts, and acute pancreatitis and chronic pancreatitis (CP)-like lesions adjacent to pancreatic cancer nests. In these lesions, lumican mRNA and protein were transiently and ectopically overexpressed in most of the vascular smooth muscle cells (VSMCs) that migrated into the thickened intima, myocardial cells adjacent to an ischemic lesion, acinar cells, islet cells and fibroblasts of pathological pancreatic tissues. The low expression level of lumican in breast cancer is associated with rapid progression and poor survival. Lumican mRNA in breast cancer is overexpressed in fibroblasts adjacent to cancer cells but not in cancer cells. Furthermore, the high expression level of lumican is associated with a high pathological tumor grade, a low estrogen receptor level in the cancer tissues, and young age of patients. The suppression of lumican expression in culture cells induces their cell growth. Lumican-transfected tumor cells are characterized by a strong suppression of their anchorage-independent growth and capacity of invasion. Lumican significantly suppressed subcutaneous tumor formation in syngenic mice, with a concomitant decrease in cyclin D1 expression level, and induced and/or enhanced the apoptosis of these cells. The autocrine mechanism in cancer cells and the paracrine mechanism in cancer cells and fibroblasts via transforming growth factor (TGF)-beta and Smad signals may play important roles in the regulation of tumor growth by SLRPs.
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PMID:Role of the small leucine-rich proteoglycan (SLRP) family in pathological lesions and cancer cell growth. 1604 29

SPARC-like protein 1 (SPARCL1), a member of the SPARC family, is downregulated in various tumors. In the present study, the expression and localization of SPARCL1 were analyzed in a wide range of nontumorous and neoplastic pancreatic tissues by quantitative reverse transcription-polymerase chain reaction, laser capture microdissection, microarray analysis, and immunohistochemistry. For functional analysis, proliferation and invasion assays were used in cultured pancreatic cancer cells. Pancreatic ductal adenocarcinoma (PDAC) and other pancreatic neoplasms exhibited increased SPARCL1 mRNA levels compared to those of the normal pancreas. SPARCL1 mRNA levels were low to absent in microdissected and cultured pancreatic cancer cells, and promoter demethylation increased SPARCL1 levels only slightly in three of eight cell lines. SPARCL1 was observed in small capillaries in areas of inflammation/tumor growth and in some islet cells. In PDAC, 15.4% of vessels were SPARCL1-positive. In contrast, the percentage of SPARCL1-positive vessels was higher in chronic pancreatitis and benign and borderline pancreatic tumors. Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and exerted moderate growth-inhibitory effects. In conclusion, SPARCL1 expression in pancreatic tissues is highly correlated with level of vascularity. Its anti-invasive effects and reduced expression in metastasis indicate tumor-suppressor function.
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PMID:Tumor-suppressor function of SPARC-like protein 1/Hevin in pancreatic cancer. 1732 39

A shift of the angiogenic balance to the proangiogenic state, termed the "angiogenic switch," is a hallmark of cancer progression. Here we devise a strategy for identifying genetic participants of the angiogenic switch based on inverse regulation of genes in human endothelial cells in response to key endogenous pro- and antiangiogenic proteins. This approach reveals a global network pattern for vascular homeostasis connecting known angiogenesis-related genes with previously unknown signaling components. We also demonstrate that the angiogenic switch is governed by simultaneous regulations of multiple genes organized as transcriptional circuitries. In pancreatic cancer patients, we validate the transcriptome-derived switch of the identified "angiogenic network:" The angiogenic state in chronic pancreatitis specimens is intermediate between the normal (angiogenesis off) and neoplastic (angiogenesis on) condition, suggesting that aberrant proangiogenic environment contributes to the increased cancer risk in patients with chronic pancreatitis. In knockout experiments in mice, we show that the targeted removal of a hub node (peroxisome proliferative-activated receptor delta) of the angiogenic network markedly impairs angiogenesis and tumor growth. Further, in tumor patients, we show that peroxisome proliferative-activated receptor delta expression levels are correlated with advanced pathological tumor stage, increased risk for tumor recurrence, and distant metastasis. Our results therefore also may contribute to the rational design of antiangiogenic cancer agents; whereas "narrow" targeted cancer drugs may fail to shift the robust angiogenic regulatory network toward antiangiogenesis, the network may be more vulnerable to multiple or broad-spectrum inhibitors or to the targeted removal of the identified angiogenic "hub" nodes.
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PMID:Transcriptional network governing the angiogenic switch in human pancreatic cancer. 1765 68

Pancreatitis and pancreatic cancer represent two major diseases of the exocrine pancreas. Pancreatitis exhibits both acute and chronic manifestations. The commonest causes of acute pancreatitis are gallstones and alcohol abuse; the latter is also the predominant cause of chronic pancreatitis. Recent evidence indicates that endotoxinemia, which occurs in alcoholics due to increased gut permeability, may trigger overt necroinflammation of the pancreas in alcoholics and one that may also play a critical role in progression to chronic pancreatitis (acinar atrophy and fibrosis) via activation of pancreatic stellate cells (PSCs). Chronic pancreatitis is a major risk factor for the development of pancreatic cancer, which is the fourth leading cause of cancer-related deaths in humans. Increasing attention has been paid in recent years to the role of the stroma in pancreatic cancer progression. It is now well established that PSCs play a key role in the production of cancer stroma and that they interact closely with cancer cells to create a tumor facilitatory environment that stimulates local tumor growth and distant metastasis. This review summarizes recent advances in our understanding of the pathogenesis of alcoholic pancreatitis and pancreatic cancer, with particular reference to the central role played by PSCs in both diseases. An improved knowledge of PSC biology has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in chronic pancreatitis and interrupting stellate cell-cancer cell interactions so as to retard cancer progression.
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PMID:New insights into alcoholic pancreatitis and pancreatic cancer. 1979 99

Analyses of pancreatic juice by proteomics have identified many proteins that are overabundant in pancreatic cancer (PC) juice. The mechanism by which secretion of these proteins occur remains unclear. Pancreatic juice was collected from patients with three pancreatic diseases: PC, chronic pancreatitis (CP), and simple choledocholithiasis (CDS), and analyzed by 2-DE, MALDI-TOF/MS, and Western blot. Five PC cell lines, 30 PC tissues and their corresponding adjacent pancreatic tissues were used to validate the expression of genes which code for overabundant proteins in PC juice. The mRNA and protein levels were measured by RT-PCR and immunohistochemistry, respectively. Using proteomics, it was demonstrated that the protein transthyretin (TTR) was upregulated more than 2-fold in PC juice compared with CP and CDS, while apolipoprotein A-I, lithostathine, and regenerating islet-derived 1 beta precursor were downregulated more than 2-fold. Western blots confirmed that TTR was overabundant in the PC juice. However, TTR mRNA was not detected in any of the five PC cell lines, and was only detected in islet cells. By microscopy, it was shown that islet architecture was almost completely destroyed, and the islet's maximum diameter appeared larger in PC tissues than in normal. Some overabundant proteins in PC juice, such as TTR expressed only in islets, leak into the pancreatic ductal system due to hyperplasia and architectural damage in PC tissues. The destruction of organ and tissue architecture by tumor growth may result in novel tumor markers even if the markers are not secreted directly by tumor cells.
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PMID:Transthyretin, identified by proteomics, is overabundant in pancreatic juice from pancreatic carcinoma and originates from pancreatic islets. 2094 80


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