451 REVIEW42522701004486135155197270 ARTICLES71022701004591132151192226269309 Is42533701001645 autoimmune4863370100347198137152212272310347383 pancreatitis88533701003772110141165200234261277304320349 a1250337010034 risk13003370100233968102 factor14183370100205586114152177 for16113370100205882 pancreatic170933701003873110141165200235261277307 adenocarcinoma?203333701003372107145184215250274305320357396456491521 E1220422701004170106 |325227010043 VNITŘNÍ4268043010746106127172220280301 LÉKAŘSTVÍ748804301074185130188236280325378400 /11688043010757 Vnitř12458043010771118137165191 Lék1456804301074083122 2021;1597804301074487129168178 67(1):1794804301074486106145163178 e9–e131991804301074488135181219256 /22678043010757 www.casopisvnitrnilekarstvi.cz442680430107651332012142542953293774274464795215705896176436927117307748128548809159449871007102310631101 nucleus,425552301074791129145186230260274 which7155523010759104120157202 in934552301071358 turn100955230107226690135 activates1161552301073572100116154192216256286 transcriptionof146455230107224685130160197221237283308324369414473494 pro‑inflammatory1975552301074367111138155199220240277347417454479522546586 cytokines,2578552301073473101145180198242283314327 adhesionmolecules,425566301074086131172203218263308392437454495533577594634665678 chemokines,1120566301073479120190235271288333374404418 growth1555566301074266109171199244 factors,181656630107175694121164188220233 anti‑apoptotic2066566301073579103120144182228274321346389413429467 genes,2549566301074384129170201214 and2780566301073579125 cyclinD1425580301074079116132148193262299 (26,27).74158030107185898111153192214224 It983580301071338 shouldbe1038580301072873118164180226287329 noted1384580301074288113152199 that1600580301072368106130 NF‑kappaB1747580301075290114151190237284322365 induces2129580301071358105149187226257 the2403580301072368109 production2529580301074468112159204242269286331376 of425594301074870 other512594301074369115157181 proteins,711594301074570115140180197243274288 such1017594301072873112157 as1192594301073667 COX-212775943010746102146168205 and1500594301073682129 nitric164759430107435985110127166 oxide183059430107437996143185 synthetase.2033594301072968115140186228254293324366379 Thus,2430594301073784130161175 it2622594301071440 can2680594301073575121 be2818594301074588 deduced425608301074991139184222263311 that753608301072369108133 NK‑kappaB904608301075294117154194242290329372 forms129460830107196489161192 themolecular1504608301072369111197243261303342387404443467 link198960830107143076112 between2119608301074487113178219262308 the2445608301072369111 activation2573608301073675103120159198223240286332 of425622301074870 inflammation51362230107186486106145217288327353370416463 and994622301074086134 the1145622301072774116 simultaneous1279622301073349121167184210249296338385432463 loss176062230107186496127 of1905622301074770 the1992622301072774116 physiological2126622301074996133165181227245292340357395435452 cell259662230107398097114 cycle2728622301073980118135177 in425636301071965 carcinomas,508636301073878102140156202249321360392406 which9326363010763110127165211 is1161636301071748 referred122763630107256688130154180221269 to1514636301072671 as1603636301073970 a16916363010739 dualistic1748636301074793132149166197224241279 effect.204563630107426490131171199214 The565650301074190133 three71765030107247196138182 findings91865030107193985133151198246278 that1215650301072471111137 indicate1371650301071562110128167207234275 that1665650301072471111137 NF‑kappaB1821650301075394119157198247296336380 is2220650301071647 an2286650301073784 essential2389650301073972105148195221239278296 factor2704650301072061100130175201 in425664301071967 pancreatic511664301075092140180207250290317336376 cancer907664301074081129170212239 are:1166664301074067110125 „4256786010067 1)565678301074360 NF‑kappaB643678301075393119157197245294334378 is1040678301071546 activated1105678301073676105123162202228269318 in1442678301071561 70%1522678301073979145 of1686678301074366 pancreatic1771678301074585132171196238276302320359 cancers2149678301073676122161202228261 and2428678301073784131 in2578678301071561 human2658678301074490161201247 pancreatic565692301075091139180206249289317335376 cell960692301074183102121 lines110169230107193785129163 such1283692301073481122170 as1472692301074174 PANC-11566692301074592150201218256 and1842692301074189138 BxPC-32000692301074585130181198238 (28,29).2258692301072467109125171214236249 „4257066010067 2)565706301074363 Supporting646706301073680127175221246274291336383 arguments1046706301073660105150221262308332365 fromexperimental142870630107184488159215252299342366383453495541565604620 studies2066706301072855100147163204235 –23197063010739 e.g.237670630107385097110 suppression2504706301072872119167191232263294310355401 of565720301074870 NF‑kappaB6537203010762102126164204252300340384 leads1055720301072365104151182 to1255720301073277 re‑initiation1350720301073172100118164180207224262288305351398 of1765720301075375 apoptosis1858720301074593140189214259291307338 in2214720301072369 pancreatic2301720301075494140179204245283309326364 tumor2683720301073279150197222 cells56573430107408198115146 (30).729734301072262104125137 „4257486010067 3)565748301074465 NF‑kappaB650748301075496122161203253303345390 appears1060748301073787137182222248282 to1362748301072571 be1453748301074792 involved1564748301071664103151170211254304 in1888748301071664 the1971748301072573118 early2108748301074181107127167 stages2295748301073059100150194227 of2542748301074569 pancreatic263174830107468813617620324656576230107416887127 carcinogenesis,712762301074082108147166214262312356404448482500533549 which12817623010765114132172220 is1521762301071952 related159376230107266989129156199249 to1862762301072874 its195676230107194782 relationship205876230107277089129157175223272305353371421 to2498762301072975 the2593762301072876120 K‑ras273376230107457097139172 oncogene565776301074897137184234278326370 and955776301074189138 apoptotic1113776301074190139189217264291310350 resistance1483776301072669103121154183224272313355 (31).1858776301072466105123136 K‑ras318755230107467199141176 mutations33835523010782130159201229249298347381 play3785552301075777119158 a39645523010748 prominent4032552301075885133209228277322371399 role4451552301073482103147 in4619552301072675 the4714552301073584129 induction4864552301072675125174215246266315364 of5249552301075580 pancreatic534955230107571001493047566301074169113154183202244 carcinogenesis.3312566301074890118158178227277329374424470504524557575 In3908566301072675 2009,4004566301075296144189203 Kamisawa4227566301075397173192226269335378 et4626566301075180 al.472756630107496885 published48335663010757107158179198232281327379 a52325663010749 paper53025663010757100151198225 demonstrating3047580301075096172223273307338366409437457507558 high3626580301075776127177 positive38245803010758109144163192212255300 rates4145580301073477105150185 of4351580301075681 K‑ras4453580301075378107151185 mutation46595803010783132162205233253303353 in5033580301072676 pancreatic51305803010758101151193221266307336356397 tissue304759430107284779113160204 of3270594301074973 individuals3362594301071967117135176196245292333352385 with3766594301076585113161 AIP3947594301075371116 (32).4083594301072467108130143 He42465943010757101 found4367594301072371119167217 positive4603594301075099133151179198239282 rates490559430107276895138172 in5096594301071967 the5183594301072876120 tissue532359430107284780113160204 of3047608301074973 all314160830107486787 persons32486083010757103130165215264298 examined3567608301075191133208228277322373 with3960608301077393122171 an4151608301074898 autoimmune4269608301074897126173193268343391440485 form4775608301073079107183 of4978608301075580 pancreatitis.50786083010757100149191218262303331350379398432449 However,30476223010757105170213254297324336 K‑ras340262230107457097139172 mutation35946223010774121150191218237285334 can3947622301074182130 be4097622301075095 detected4211622301074993121164205235278328 in4559622301071967 90%4645622301074490157 of4822622301074872 cases4913622301074182116160193 of5126622301074872 sporadic5218622301073483132159201250269309 pancreatic3047636301075091139180206249289317335376 cancer3442636301074182130171213240 (33).3701636301072466108129142 Conclusion30476614013856118182232266330382415477541 AIP,3187678301075371116121 like332867830107193875118 sporadic3466678301073483132159201250269309 chronic3795678301074088115162210229269 pancreatitis,4084678301075091140180207250290317336364382415431 is4535678301071952 a46066783010741 risk466767830107274679117 factor4803678301072466107137184211 for503367830107247299 pancreatic5151678301075092140181207250290317336376 cancer.3047692301074081129170212238250 Chronic3317692301074896122169217236276 inflammation361269230107166487109150223296337364382430479 is4110692301071649 a41786923010738 precursor4235692301074774116158205231265314340 of4595692301074569 tumor4683692301072573146194221 growth.4924692301074572118183214262278 Whereas52216923010771120164190233273306 in3047706301071967 the3133706301072876120 case3273706301074081115159 of3451706301074872 chronic3543706301073987114161209228268 pancreatitis,3831706301074991139180206249289316335363382415431 the4281706301072876120 inflammation‑tumor442170630107186690112153226300341368386434483512539587661710736 sequence5177706301073378127175219267308350 is3047720301071952 only31197203010754103123163 connected3302720301074794143191235277307350401 with3722720301077292120169 pancreatic3910720301075799147188215258298326345385 tissue,431572030107355487120168212227 in4561720301072674 the4655720301073583128 form4803720301073078105180 of5003720301075478 chronic5101720301074796122170218237278 AIP,5399720301075978123128 which30477343010765114132172220 is3287734301071952 one3358734301074897141 of3519734301074872 the3610734301072876121 clinical375073430107415978126144184226245 manifestations40157343010773114162181205248282311352379398446495528 of4562734301074872 a46547343010741 group4715734301074975122170220 of4954734301074872 diseases5046734301074968100145185218262296 referred536273430107266993136304774830107275497147 to3213748301072976 as3308748301074275 IgG4-RD,3403748301071969126171200247306319 malignancy37417483010775116135153202250291339379422 may41827483010775115154 occur4356748301074890129176203 in4578748301072068 an4665748301074290 organ4775748301074875123164212 other5007748301074876124168194 than5221748301072977118166 the5406748301072977121 pancreas.3047762301075091139180206249289323339 It3406762301072452 seems3478762301073882127201234 that3731762301073381122149 the3900762301073281125 appearance4045762301074595145190230256298346387429 of4494762301075276 such4590762301073986126174 cancers4784762301074586134175217244278 occurs5082762301075394133180207241 soon5343762301073887136184 after304777630107416496138165 the3232776301072776120 diagnosis3372776301074967107157205253287305338 of3730776301074771 AIP.3821776301075372117122 Fig.42561401134873125152 1.60461401135377 The70862301074087125 role8496230107246887125 of99062301074366 NF-kappaB107262301075393120157202247293339382 in147062301071763 the154962301072470108 inflammatory16746230107166285105150222293338364407433473 process216362301074470113152188219249 and242962301074389135 in258062301071662 the265962301072470108 case278362301073680110148 of294762301074366 inflammation30296230107176385105151222293338364382427474 associated351962301074374104148186204249275312357 with389362301076078104150 carcinoma405962301073580105141159205250322367 (modified444262301072291136182200223242280325 according478462301074380116159185229247293338 to513862301072568 Zhang522362301074389134180225 et546462301073663 al.4257330107456480 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inflammation.21858430107236991112157228299344370388433480496 B2698843010747 –2761843010750 Proinflammatory282784301074872116135181203223269340411456482526552591 factors343484301072872109137181207238 in368884301072369 the377384301073177115 microenvironment390484301077694132157201240286323342367411457529567613638 of455884301075073 latent46478430107236894131177202 pre-malignant486584301075076113140213258276295340386431477502 cells53838430107427997116145 lead42595301071957102147 to58995301072973 the67895301073076114 accumulation80895301074986122167238284302347373391436483 of130795301074871 DNA1394953010760115163 damage,157395301074994165211256294310 which,1899953010766112130167213229 in214495301072268 turn,222895301073075101147163 causes240795301074185131160198229 these265295301073076114145183 cells28519530107417795114143 to301095301073074 become310095301074987125168240278 malignant.3394953010775120139157202248293340365380 C3790953010752 –3858953010749 Activation392395301075289117135173217242260306352 of429195301074972 NF-kappaB437995301075898124162207252298344387 in478295301072268 pre-malignant486695301074975112139211257275293338385430476501 cells53839530107417796114144 induces425106301071964110155192229260 anti-apoptotic701106301074389114132158205251297342368411437455492 signals,121010630107284590136181200229245 which14711063010760106124161207 prevents1694106301074369106144181227252283 apoptosis1993106301074388134180206249279296325 and2334106301074389135 enhances2485106301073581127172218256292323 their2824106301072470108126151 proliferation.2992106301074268112131149171209234277303321366412428 D34371063010753 and3507106301074288134 E36571063010737 –37101063010742 Leukocytes3769106301073471117153197236274302339370 and4155106301074389134 stromal430510630107295580124196241259 cells458010630107357190108137 secret4733106301072966104129166192 proinflammatory4941106301074369113131177200220265336407452478522547587 proteins425117301074571115141178196242272 in713117301071864 their794117301072672110128154 chronically964117301073783109153199217255299317335372 inflamed135211730107196587108153224262308 microenvironment,1676117301077290127152196235282319337362406453524562608634649 which23421173010762108126163209 stimulates256811730107315775146191210255281317348 tumor2932117301072772144189215 progression3163117301074571115161187223255285302347394 and3573117301074591137 metastasis37261173010771110136179209236279309326355