Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the dismal prognosis of advanced ductal pancreatic adenocarcinoma, recent investigational strategies have focused on improved detection and therapeutic intervention in early-stage pancreatic cancer. The obvious cost constraints of screening populations at risk but with a low tumor yield will restrict screening protocols to only the highest risk groups (hereditary pancreatitis = age 50, certain hereditary pancreatic cancer kindreds). The vast majority of patients, either lacking or exhibiting an inherited predisposition to pancreatic cancer, will continue to present with disease not resectable for cure. The authors believe that the best hope for these patients lies in the further delineation of the integrative pathophysiology driving tumor growth; this would facilitate the future development of a computer program or other modality that would predict the dominant pathways driving the growth and spread of each tumor based on its "molecular profile." This article reviews the authors' current knowledge regarding the growth factors, receptors, and molecular alterations driving uncontrolled proliferation, local invasion, and metastatic spread of these tumors. The current and potential contributions of studies in cohorts with an inherited predisposition to pancreatic cancer to this pathophysiologic model are also discussed. The future strategy for incorporating this information into a working pathophysiologic road map with clinical relevance is subsequently outlined.
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PMID:Growth factors, receptors, and molecular alterations in pancreatic cancer. Putting it all together. 1087 26

Immunosuppressive therapy after transplantation increases the risk of developing neoplasms, and neoplasms of the digestive organs are very common in Asia. We experienced a patient with an intracystic hemorrhage of pancreatic serous cystadenoma during the follow-up after renal transplantation. Pancreatic cystadenomas are not frequent. Only two cases, presenting with acute abdomen, have so far been reported in the literature. The intracystic hemorrhage in our case may have been related to a rapid tumor growth due to weakened antitumor immunity and azathioprine-induced pancreatitis.
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PMID:Intracystic hemorrhage of pancreatic serous cystadenoma after renal transplantation: report of a case. 1093 Feb 37

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

The understanding of the regulation of apoptosis and necrosis, the two principal cell death pathways, is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis and pancreatic cancer. For example, in acute pancreatitis significant amounts of pancreatic necrosis are associated with increased morbidity and mortality. Thus, determining the key steps regulating necrosis should provide insights into potential therapeutic strategies for improving outcome in these patients. On the other hand, in pancreatic cancer various survival mechanisms act to prevent cell death, resulting in promotion of tumor growth and metastasis. Resistance of pancreatic cancer to apoptosis is the key factor preventing responses to therapies. Investigations of the regulation of cell death mechanisms specific to pancreatic cancer should lead to improvements in our current therapies for this disease. The present review is designed to provide information about cell death pathways in pancreatitis and pancreatic cancer with reference to areas that need further investigation, as well as to provide measurement techniques adapted to pancreatic tissue and cells.
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PMID:Cell death pathways in pancreatitis and pancreatic cancer. 1555 Jul 66

Recently, we have reported that surgical stress promoted the metastasis of murine colon carcinoma cells to the lung by inducing the expression of proteases such as matrix metalloprotease-9 (MMP-9) in lung tissue. Urinary trypsin inhibitor (UTI) is a serine protease inhibitor frequently used to treat pancreatitis and to improve the microcirculatory environment. The purpose of this study was to investigate the anti-metastatic properties of UTI in an animal model of surgical stress-induced cancer metastasis. The intraperitoneal administration of UTI after the intravenous injection of colon 26-L5 carcinoma (colon 26-L5) cells into mice subjected to surgical stress suppressed the enhancement of lung metastasis (p<0.05). Furthermore, we investigated the effect of UTI on tumor growth, adhesion to fibronectin, migration, invasion and enzymatic degradation in colon 26-L5. UTI reduced the invasive ability and the degradation by MMP-9 of gelatin substrate in colon 26-L5 cells. UTI may improve therapeutic efficacy in cancer patients after major surgery.
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PMID:Urinary trypsin inhibitor suppresses surgical stress-facilitated lung metastasis of murine colon 26-L5 carcinoma cells. 1586 13

We screened an orthotopic nude mouse model of human pancreatic cancer for candidate serum biomarkers and examined their presence in the plasma of pancreatic cancer patients. Nude mice were injected in the pancreas with L3.9pl human pancreatic cancer cells. One week later, the mice were randomized into 4 treatment groups: i) control, saline; ii) oral STI 571; iii) intraperitoneal gemcitabine; and iv) STI 571 and gemcitabine. After 1, 2, and 3 weeks of treatment, sera and tumors were collected from mice in each group as well as uninjected mice. All sera were analyzed by surface enhanced laser desorption ionization mass spectrometry using ProteinChip technology. Protein profiles were analyzed with the Biomarker Wizard software package. The concentration of candidate proteins was evaluated in mouse sera and plasma from 135 pancreatic cancer patients, 7 pancreatitis patients, and 113 healthy volunteers. The combination therapy inhibited tumor growth. A 11.7-kDa protein peak correlating with tumor weight was purified by gel filtration, separated by SDS-PAGE, and identified as mouse serum amyloid A (SAA) by amino acid sequencing and public database searches. The expression of SAA in mouse sera was confirmed by Western blotting and correlated with tumor weight. The level of SAA in plasma of pancreatic cancer patients correlated with clinical stage and was significantly higher than in normal volunteers (mean value: 180.1 microg/ml vs 27.9 microg/ml: P<0.01) or pancreatitis patients. For SAA used as a single tumor marker with a cut-off of 75 microg/ml, the sensitivity for pancreatic cancer was 96.5% and specificity was 31.9%. Our search for specific marker proteins to identify pancreatic cancer was unsuccessful. Although SAA is not specific for pancreatic cancer and not sensitive enough to detect stage I patients, it may be a candidate biomarker for detecting and monitoring the progressive growth of pancreatic cancer.
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PMID:Serum amyloid A as a tumor marker in sera of nude mice with orthotopic human pancreatic cancer and in plasma of patients with pancreatic cancer. 1621 Dec 33

Pancreatic cancer is a major oncological challenge due to its aggressive growth and metastasis. In the current study, we investigated the role of anterior gradient 2 (AGR2) in these processes. AGR2 mRNA, as assessed by quantitative real-time reverse transcription-PCR (Q-RT-PCR), was 14-fold higher in pancreatic cancer compared with normal and pancreatitis tissues. Immunohistochemistry revealed high expression of AGR2 in neoplastic cells with 98% (56 of 57) positivity on pancreatic cancer and minimal staining in normal and pancreatitis tissues. AGR2 was also expressed in early pancreatic intraepithelial neoplastic lesions. RT-PCR and Western blotting showed elevated AGR2 expression in seven of nine pancreatic cancer cell lines. AGR2, as detected in conditioned media from cancer cells, indicated that it was secreted. The influence of AGR2 on pancreatic cancer cells was evaluated by silencing with small interfering RNA and short hairpin RNA. Silencing of AGR2 significantly reduced cell proliferation (MTS assay) and invasion (Boyden chamber assay) and improved gemcitabine sensitivity (fluorescence-activated cell sorting analysis). Conditioned media from cells in which AGR2 was silenced had a reduced ability to stimulate proliferation of pancreatic cancer cells, suggesting that secreted AGR2 was active. In vivo, silencing of AGR2 in MPanc-96 cells led to a significant reduction of tumor growth and increased the effectiveness of gemcitabine treatments in orthotopic tumor models evaluated by noninvasive bioluminescence imaging. In summary, AGR2 is expressed and secreted during pancreatic cancer development and plays an important role in cancer cell growth and survival. These observations suggest that AGR2 may be a useful molecular target in pancreatic cancer.
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PMID:Anterior gradient 2 is expressed and secreted during the development of pancreatic cancer and promotes cancer cell survival. 1882 36

Apoptosis, or programmed cell death, is a physiological process of cellular autodestruction, or cell suicide. This process is strictly controlled in response to integrity of pro-death signaling and plays critical roles in development, maintenance of homeostasis and host defense in multicellular organisms. As pancreatologists, apoptosis plays a central role in the pancreas and its disease states, from diabetes to pancreatitis to pancreatic cancer. In pancreatic beta-cells, apoptotic cell death is involved in the pathogenesis of diabetes, as signals from death receptors and DNA damage have been widely accepted as being triggers of apoptosis in beta-cells. During acute pancreatitis, this common clinical condition is of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. However, recent research in this area has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In pancreatic cancer, various survival mechanisms have been shown to act in the prevention of cell death to result in promotion of tumor growth and metastasis. Thus, resistance of pancreatic cancer to apoptosis is the key factor preventing responses to therapies. Thus, it is for these reasons that in the current 'Primers on Molecular Pathways,' we take a closer look at the pathway cascade that is triggered during apoptosis.
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PMID:Primers on molecular pathways--caspase pathway. 1907 49

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

Risk of pancreatic cancer, the fourth deadliest cancer in the United States, is increased by obesity. Calorie restriction (CR) prevents obesity, suppresses carcinogenesis in many models, and reduces serum levels of IGF-1. In the present study, we examined the impact of CR on a model of inflammation-associated pancreatitis and pancreatic dysplasia, with a focus on the mechanistic contribution of systemic IGF-1. Administration of a 30% CR diet for 14 weeks decreased serum IGF-1 levels and hindered pancreatic ductal lesion formation and dysplastic severity, relative to a higher calorie control diet, in transgenic mice overexpressing COX-2 [bovine keratin-5 promoter (BK5.COX-2)]. These findings in CR mice correlated with reductions in Ki-67-positive cells, vascular luminal size, VEGF expression, and phosphorylation and total expression of downstream mediators of the IGF-1 pathway. Cell lines derived from BK5.COX-2 ductal lesions (JC101 cells) formed pancreatic tumors in wild-type FVB mice that were significantly reduced in size by a 14-week CR regimen, relative to the control diet. To further understand the impact of circulating levels of IGF-1 on tumor growth in this model, we orthotopically injected JC101 cells into liver-specific IGF-1-deficient (LID) mice. The approximate 65% reduction of serum IGF-1 levels in LID mice resulted in significantly decreased burden of JC101 tumors, despite modestly elevated levels of circulating insulin and leptin. These data show that CR prevents development of dysplasia and growth of pancreatic cancer through alterations in IGF-1, suggesting that modulation of this pathway with dietary and/or pharmacologic interventions is a promising pancreatic cancer prevention strategy.
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PMID:Genetic reduction of insulin-like growth factor-1 mimics the anticancer effects of calorie restriction on cyclooxygenase-2-driven pancreatic neoplasia. 2159 96


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