review of literature on clinical pancreatology - The Pancreapedia

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MatriptaseMatriptase, also known as MT-SP1, is a type II transmembrane serine protease stronglyimplicated in both the development and progression <strong>of</strong> a variety <strong>of</strong> epithelial cancers.Evidence comes from studies <strong>of</strong> its expression in human cancers and from mouse models <strong>of</strong>spontaneous cancer. Matriptase is considered to be a major activator <strong>of</strong> two key stimulators<strong>of</strong> invasive growth, namely hepatocyte growth factor/scatter factor and urokinase-typeplasminogen activator. The aim <strong>of</strong> one study was to examine the role <strong>of</strong> matriptase inpancreatic ductal adenocarcinoma by expression analysis and functional assays in vitro.Immunohistochemical analysis <strong>of</strong> matriptase performed on microtissue arrays and largesamples <strong>of</strong> 55 pancreatic ductal adenocarcinomas and on 31 samples <strong>of</strong> normal pancreaticducts revealed that although matriptase expression differed greatly in both malignant andnormal ductal pancreatic tissue, matriptase scores were significantly elevated in pancreaticductal adenocarcinoma compared to normal pancreatic ducts. To evaluate the role <strong>of</strong>matriptase during development <strong>of</strong> pancreatic cancer, we studied the effects <strong>of</strong> newlydesigned matriptase inhibitors on the processing <strong>of</strong> the zymogen <strong>of</strong> urokinase-typeplasminogen activator in the human adenocarcinoma cell lines AsPC-1 and BxPC-3. In bothcell lines, at 1 microM, all matriptase inhibitors completely prevented zymogen activation. Atlower inhibitor concentrations, the degree <strong>of</strong> inhibition <strong>of</strong> zymogen processing correlated withthe affinities <strong>of</strong> the inhibitors towards matriptase indicating that this is a specific result <strong>of</strong>matriptase inhibition. Furthermore, matriptase inhibitors reduced the phosphorylation <strong>of</strong> theHGF receptor/cMet and the overall cellular invasiveness <strong>of</strong> the human pancreaticadenocarcinoma cell line AsPC-1. The findings demonstrate for the first time that matriptasemay be involved in the progression <strong>of</strong> pancreatic ductal adenocarcinoma and that matriptaseinhibition may contribute to preventing the progression <strong>of</strong> this disease [387].Mitochondrial DNAThe majority <strong>of</strong> cancer cells harbor homoplasmic somatic mutations in the mitochondrialgenome. It was now shown that mutations in mitochondrial DNA (mtDNA) are responsible foranticancer drug tolerance. It was constructed several trans-mitochondrial hybrids (cybrids)with mtDNA derived from human pancreas cancer cell lines CFPAC-1 and CAPAN-2 as wellas from healthy individuals. These cybrids contained the different mitochondrial genomeswith the common nuclear background. It was compared the mutant and wild-type cybrids forresistance against an apoptosis-inducing reagent and anticancer drugs by exposing thecybrids to staurosporine, 5-fluorouracil, and cisplatin in vitro, and found that all mutantcybrids were more resistant to the apoptosis-inducing and anticancer drugs than wild-typecybrids. Next, it was transplanted mutant and wild-type cybrids into nude mice to generatetumors. Tumors derived from mutant cybrids were more resistant than those from wild-typecybrids in suppressing tumor growth and inducing massive apoptosis when 5-fluorouracil andcisplatin were administered. To confirm the tolerance <strong>of</strong> mutant cybrids to anticancer drugs, itwas transplanted a mixture <strong>of</strong> mutant and wild-type cybrids at a 1:1 ratio into nude mice andexamined the effect by the drugs on the drift <strong>of</strong> the ratio <strong>of</strong> mutant and wild-type mtDNA. Themutant mtDNA showed better survival, indicating that mutant cybrids were more resistant tothe anticancer drugs [388].NF-kappaBTranscription factor nuclear factor-kappaB (NF-kappaB) is constitutively activated in mostpancreatic cancer tissues and cell lines but not in normal pancreas nor in immortalized ornontumorigenic human pancreatic ductal epithelial cells. Inhibition <strong>of</strong> constitutive NF-kappaBactivation in pancreatic cancer cell lines suppresses tumorigenesis and tumor metastasis.Recently, we identified autocrine secretion <strong>of</strong> proinflammatory cytokine interleukin (IL)-1alphaas the mechanism <strong>of</strong> constitutive NF-kappaB activation in metastatic pancreatic cancer cell
lines. However, the role <strong>of</strong> IL-1alpha in determining the metastatic potential <strong>of</strong> pancreatictumor remains to be further investigated. In one study, it was stably expressed IL-1alpha inthe nonmetastatic, IL-1alpha-negative MiaPaCa-2 cell lines. Our results showed that thesecretion <strong>of</strong> IL-1alpha in MiaPaCa-2 cells constitutively activated NF-kappaB and increasedthe expression <strong>of</strong> NF-kappaB downstream genes involved in the different steps <strong>of</strong> themetastatic cascade, such as urokinase-type plasminogen activator, vascular endothelialgrowth factor, and IL-8. MiaPaCa-2/IL-1alpha cells showed an enhanced cell invasion in vitrocompared with parental MiaPaCa-2 cells and induced liver metastasis in an orthotopicmouse model. The metastatic phenotype induced by IL-1alpha was inhibited by theexpression <strong>of</strong> phosphorylation-defective IkappaB (IkappaB S32, 36A), which blocked NFkappaBactivation. Consistently, silencing the expression <strong>of</strong> IL-1alpha by short hairpin RNAin the highly metastatic L3.6pl pancreatic cancer cells completely suppressed their metastaticspread. In summary, these findings showed that IL-1alpha plays key roles in pancreaticcancer metastatic behavior through the constitutive activation <strong>of</strong> NF-kappaB [389].OsteopontinPancreatic ductal adenocarcinoma is a lethal disease with etiological association withcigarette smoking. Nicotine, an important component <strong>of</strong> cigarettes, exists at highconcentrations in the bloodstream <strong>of</strong> smokers. Osteopontin is a secreted phosphoprotein thatconfers on cancer cells a migratory phenotype and activates signaling pathways that inducecell survival, proliferation, invasion, and metastasis. Here, it was investigated the potentialmolecular basis <strong>of</strong> nicotine's role in pancreatic cancer through studying its effect onosteopontin. Nicotine significantly increased osteopontin mRNA and protein secretion inpancreatic cancer cells through activation <strong>of</strong> the osteopontin gene promoter. The osteopontinmRNA induction was inhibited by the nicotinic acetylcholine receptor antagonist,mechamylamine. Further, the tyrosine kinase inhibitor genistein inhibited the nicotinemediatedinduction <strong>of</strong> osteopontin, suggesting that mitogen activated protein kinase signalingmechanism is involved. Nicotine activated the phosphorylation <strong>of</strong> ERK1/2, but not p38 or c-Jun NH2-terminal MAP kinases. Inhibition <strong>of</strong> ERK1/2 activation reduced the nicotine-inducedosteopontin synthesis. Rats exposed to cigarette smoke showed a dose-dependent increasein pancreatic OPN that paralleled the rise <strong>of</strong> pancreatic and plasma nicotine levels. Analysis<strong>of</strong> cancer tissue from invasive pancreatic cancer patients, the majority <strong>of</strong> whom weresmokers, showed the presence <strong>of</strong> significant amounts <strong>of</strong> osteopontin in the malignant ductsand the surrounding pancreatic acini. The data suggest that nicotine may contribute topancreatic cancer pathogenesis through upregulation <strong>of</strong> osteopontin. They provide the firstinsight into a nicotine-initiated signal transduction pathway that regulates osteopontin as apossible tumorigenic mechanism in pancreatic cancer [390].p21/p27p21 (WAF1/Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members <strong>of</strong> the Cip/Kip family <strong>of</strong>cyclin-dependent kinase inhibitors, which can induce cell cycle arrest and serve as tumorsuppressors. It was hypothesized that genetic variants in p21 and p27 may modify individualsusceptibility to pancreatic cancer. To test this hypothesis, it was evaluated the associations<strong>of</strong> the Ser31Arg polymorphism in p21 and the Gly109Val polymorphism in p27, and theircombinations, with pancreatic cancer risk in a case-control study <strong>of</strong> 509 pathologicallyconfirmed pancreatic adenocarcinoma patients and 462 age- and sex-matched cancer-freecontrols in non-Hispanic whites. It was found that the heterozygous and homozygous variantgenotypes combined in a dominant model <strong>of</strong> the p21 polymorphism were associated withincreased risk <strong>of</strong> pancreatic cancer compared with the homozygous wild type (adjusted oddsratio 1.70; 95 % confidence interval 1.13 to 2.55). This increased risk was more pronouncedin carriers with the p27 homozygous wild type (adjusted odds ratio 2.20; 95 % confidenceinterval 1.32 to 3.68) and in nonsmokers (adjusted odds ratio 2.16; 95 % confidence interval
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REVIEW OF LITERATURE ONCLINICAL PAN
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ABBREVIATIONAAPacute alcoholicABPac
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FMF AIPfocal mass-forming autoimmun
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ODPopen distal pancreatectomyOForga
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USUTDTVESDVTEZESWHOXIAPUnited State
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Ectopic pancreasCircumportal annula
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SymptomsEndocopic ultrasography (EU
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HSP27HuRIGF-1 receptorIntegrinesInt
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HemodialysisSerous cystadenomasSero
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CRPC-reactive proteinCRTchemoradiot
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ITNPintrathecal narcotics pumpJCGAI
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QSRquantitative systematic
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PANCREATIC HISTORYEarly conceptsPan
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derived from broadly Harveian anato
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acute appendicitis, intestinal obst
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dogma and its implied presence <str
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In the late 19th century, explorato
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performed. In 1880, Carl Thiersch <
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cancer was reported by Nestor Dimit
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Modern pancreatic historyHoward Reb
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PANCREATIC DEVELOPMENT, EMBRYOLOGY
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preparations. They were also employ
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pancreas can be diagnosed without t
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PANCREATIC PHYSIOLOGYSphincter <str
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acid profile and d
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hormones. The roles of</str
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ACUTE PANCREATITISAcute pancreatiti
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necrosis or a severe course, and lo
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of 245 cases <stro
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plasty of the mino
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no significant difference. The stro
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Urinary trypsinogen-2There is not a
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groups. None of th
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evaluated the presence or absence <
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adical, etc, further studies are st
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Precut at sphincterotomyPrecut is p
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indications [204].Hypercalcemia-ind
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endoscopic retrograde cholangiopanc
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(before ERCP), serum TAP was detect
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concentration and clinical symptoms
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However, the recipients of<
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less safe for predominantly cephali
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increased mortality. Mortality in p
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Epidemiology and demographyChinaCHR
Page 89 and 90: for the first time the significance
Page 91 and 92: endoscopic ultrasound accurately de
Page 93 and 94: possible to at least reduce relapse
Page 95 and 96: etiologies have been proposed and a
Page 97 and 98: patients, can be performed with mod
Page 99 and 100: negative binomial model. One hundre
Page 101 and 102: Halofuginone did n
Page 103 and 104: years, the risk of
Page 105 and 106: patients with a proven exocrine pan
Page 107 and 108: high-risk patients [296].Cystic fib
Page 109 and 110: TNF-alpha promoter were performed.
Page 111 and 112: were validated in another series <s
Page 113 and 114: vascular invasion (14/15). Abnormal
Page 115 and 116: and other lymph nodes, salivary gla
Page 117 and 118: HEREDITARY PANCREATITISPatients wit
Page 119 and 120: Classification of
Page 121 and 122: historically, but recent life-style
Page 123 and 124: carcinogen exposure with cancer ris
Page 125 and 126: the risk of pancre
Page 127 and 128: conducted a cohort analysis <strong
Page 129 and 130: emain to be solved in screening for
Page 131 and 132: considered for women with Lynch syn
Page 133 and 134: Annexin A5Protein misfolding is a c
Page 135 and 136: CTNNB1To use fluorescence in situ h
Page 137 and 138: expression was not associated with
Page 139: (ECM) are not fully understood. In
Page 143 and 144: andomized to high-dose vitamin A, t
Page 145 and 146: Synuclein-gammaPerineural invasion
Page 147 and 148: interventions. Cancer nests were ma
Page 149 and 150: the optimal combination of<
Page 151 and 152: which is essential in tumor and nod
Page 153 and 154: provide conclusive evidence for the
Page 155 and 156: MD-CT is suitable for evaluating tu
Page 157 and 158: approved study and imaged during sh
Page 159 and 160: Quantum dotsIt was reported the suc
Page 161 and 162: clearly have a very high incidence
Page 163 and 164: patients for operation and when cou
Page 165 and 166: demonstrated using the confocal mic
Page 167 and 168: cancer [468].To evaluate pancreatic
Page 169 and 170: pancreaticoduodenectomy (PD). The s
Page 171 and 172: safe option as an interposition gra
Page 173 and 174: a curative surgery, while double-by
Page 175 and 176: %), pseudocyst (3 %), and trauma (3
Page 177 and 178: procedure is failing to progress la
Page 179 and 180: Glucos metabolism after pancreatect
Page 181 and 182: Quality of lifeOne
Page 183 and 184: was observed in the NACRT group. Th
Page 185 and 186: interval 0.80 to 0.96]. On subgroup
Page 187 and 188: ate in patients with pancreatic can
Page 189 and 190: median survival time was 7 versus 7
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and the endoscopic ultrasound-guide
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local recurrence of1.5 cm (odds ratio 2.4), and
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adenocarcinoma must be addressed at
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Molecular biologyCD44v6The purpose
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IPMN were studied. Two-dimensional
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the NT-IPMN-Br group. Eleven patien
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metastatic neoplasms showing cystic
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Solid pseudopapillary neoplasms <st
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The tumor cells were negative for p
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Duodenal tumorsColorectal polyposis
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Colorectal carcinomaPancreatic meta
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It was described a case of<
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evaluation. The purpose of<
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perforation of a p
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the 28 had pancreatic duct injury <
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ENDOCRINE PANCREATIC TUMORSHistoryA
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25-111 pg/mL). Mean Hemoglobin A1C
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clinical features, misdiagnosis occ
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achieved in selected cases by tissu
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Overall survivalPancreatic neuroend
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REFERENCES001. Metter CC. History <
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044. Fitz RH. The symptomatology an
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089. McClusky DA, Skandalakis LJ, C
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126. Toouli J. Sphincter of
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162. Deshpande AV, Thomas G, Shun A
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196. Park JH, Lee TH, Cheon SL, Sun
Page 247 and 248:
226. Botoi G, Andercou A. Early and
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260. Nakamura H, Morifuji M, Muraka
Page 251 and 252:
292. Borak GD, Romagnuolo J, Alsola
Page 253 and 254:
324. Oh HC, Kim MH, Choi KS, Moon S
Page 255 and 256:
358. Koornstra JJ, Mourits MJ, Sijm
Page 257 and 258:
391. Chen JY, Amos CI, Merriman KW,
Page 259 and 260:
421. Horwhat JD, Gerke H, Acosta RD
Page 261 and 262:
451. Zamboni G, Capelli P, Scarpa A
Page 263 and 264:
483. Rosa F, Pacelli F, Papa V, Tor
Page 265 and 266:
517. Isayama H, Nakai Y, Togawa O,
Page 267 and 268:
545. Pino MS, Milella M, Gelibter A
Page 269 and 270:
576. Tanno S, Sasajima J, Koizumi K
Page 271 and 272:
605. Ayadi L, Ellouze S, Khabir A,
Page 273 and 274:
637. Nagar AM, Raut AA, Morani AC,
Page 275 and 276:
670. Lejonklou M, Edfeldt K, Johans
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