{"id":1800,"date":"2019-10-28T15:13:59","date_gmt":"2019-10-28T14:13:59","guid":{"rendered":"https:\/\/www.newslab.sk\/2019\/10\/28\/zmeny-sialyzacie-proteinov-v-karcinome-prostaty-vysledky-pilotnej-studie\/"},"modified":"2019-11-04T14:32:49","modified_gmt":"2019-11-04T13:32:49","slug":"zmeny-sialyzacie-proteinov-v-karcinome-prostaty-vysledky-pilotnej-studie","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/zmeny-sialyzacie-proteinov-v-karcinome-prostaty-vysledky-pilotnej-studie\/","title":{"rendered":"Changes in sialylation of proteins in prostatic carcinoma (results of the pilot study)"},"content":{"rendered":"

*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.<\/strong><\/span><\/p>\n

 <\/p>\n

\u00davod<\/strong><\/h2>\n

Karcin\u00f3m prostaty je jedna z naj\u010dastej\u0161\u00edch foriem rakoviny u mu\u017eov. \u0160tatistiky uv\u00e1dzaj\u00fa celosvetovo viac ako jeden mili\u00f3n nov\u00fdch pr\u00edpadov ro\u010dne. Na Slovensku je incidencia karcin\u00f3mu prostaty u mu\u017eov na druhom mieste po karcin\u00f3me hrub\u00e9ho \u010dreva a m\u00e1 st\u00fapaj\u00faci trend. V obdob\u00ed rokov 2000 \u2013 2010 sa jeho incidencia takmer zdvojn\u00e1sobila (obr\u00e1zok<\/em><\/strong> 1)<\/em><\/strong>. Napriek dostupnej diagnostike a lie\u010dbe predstavuje u mu\u017eov tretiu naj\u010dastej\u0161iu pr\u00ed\u010dinu \u00famrtia na n\u00e1dorov\u00fa chorobu(1).<\/p>\n

Hlavn\u00fdmi rizikov\u00fdmi faktormi karcin\u00f3mu s\u00fa vek, rodinn\u00e1 anamn\u00e9za a rasa. V skor\u00fdch \u0161t\u00e1di\u00e1ch s\u00fa pacienti \u010dasto asymptomatick\u00ed alebo maj\u00fa len ne\u0161pecifick\u00e9 pr\u00edznaky s\u00favisiace s probl\u00e9mami s mo\u010den\u00edm. Medzi pr\u00edznaky pokro\u010dilej choroby patr\u00ed napr\u00edklad boles\u0165 a patologick\u00e9 zlomeniny kost\u00ed v s\u00favislosti so vznikom metast\u00e1z, fyzick\u00e9 vy\u010derpanie a strata hmotnosti. V s\u00fa\u010dasnosti je snaha o v\u010dasn\u00fa diagnostiku karcin\u00f3mu prostaty prostredn\u00edctvom prevent\u00edvnych vy\u0161etren\u00ed. V diagnostike sa prim\u00e1rne vyu\u017e\u00edva najm\u00e4 laborat\u00f3rne hodnotenie s\u00e9rovej hladiny prostatick\u00e9ho \u0161pecifick\u00e9ho antig\u00e9nu (PSA). Viacer\u00e9 \u0161t\u00fadie sleduj\u00face \u00fa\u010dinok skr\u00edningov\u00fdch vy\u0161etren\u00ed na progn\u00f3zu pacientov (napr. PLCO) v\u0161ak nepreuk\u00e1zali jednozna\u010dn\u00fd benefit vy\u0161etrenia PSA. \u0160t\u00fadie poukazuj\u00fa na v\u00fdrazne n\u00edzku senzitivitu a\/alebo \u0161pecificitu vy\u0161etrenia hladiny PSA pre stanovenie diagn\u00f3zy n\u00e1dorov prostaty v z\u00e1vislosti od stanovenej cut-off hodnoty (1,1 ng\/ml PSA zodpoved\u00e1 senzitivite 83,4 % a \u0161pecificite 38,9 %, hodnota 4,1 ng\/ml senzitivite 20,5 % a \u0161pecificite 93,8 %)(2). Mo\u017en\u00e9 s\u00fa falo\u0161ne pozit\u00edvne a falo\u0161ne negat\u00edvne v\u00fdsledky. Aj u mu\u017eov s n\u00edzkou hladinou celkov\u00e9ho PSA sa m\u00f4\u017ee vyskytn\u00fa\u0165 rakovina vysok\u00e9ho stup\u0148a. Moment\u00e1lne neexistuje fixn\u00e1 a spo\u013eahliv\u00e1 hrani\u010dn\u00e1 hodnota hladiny PSA v s\u00e9re, ktor\u00e1 by odl\u00ed\u0161ila neagres\u00edvny karcin\u00f3m od agres\u00edvneho(3).<\/p>\n

Slab\u00e1 predikt\u00edvna hodnota vy\u0161etrenia PSA viedla k nadmernej diagnostike chorobn\u00fdch zmien prostaty(4). Na z\u00e1klade prebehnut\u00fdch \u0161t\u00fadi\u00ed vr\u00e1tane ERSPC (European Randomized Study of Screening for Prostate Cancer) kon\u0161tatovala p\u00f4vodne Eur\u00f3pska urologick\u00e1 spolo\u010dnos\u0165 (European Association of Urology), \u017ee nie s\u00fa jednozna\u010dne splnen\u00e9 predpoklady na \u0161irok\u00fd skr\u00edning n\u00e1dorov prostaty v celej popul\u00e1cii a odpor\u00fa\u010dala realizova\u0165\/pon\u00faknu\u0165 vy\u0161etrenie len pacientov po predch\u00e1dzaj\u00facom adekv\u00e1tnom pou\u010den\u00ed s oh\u013eadom na riziko(5,6). Vzh\u013eadom na rast incidencie choroby v s\u00fa\u010dasnosti prebiehaj\u00fa rozsiahle diskusie o potrebe celopopula\u010dn\u00e9ho skr\u00edning karcin\u00f3mu prostaty. Aj z toho d\u00f4vodu m\u00e1 v\u00fdznam h\u013eadanie nov\u00fdch diagnostick\u00fdch postupov a markerov vyu\u017eite\u013en\u00fdch v diagnostike. Eur\u00f3pska urologick\u00e1 spolo\u010dnos\u0165 vyzvala Eur\u00f3psku komisiu na intenz\u00edvnej\u0161iu podporu a financovanie tohto v\u00fdskumu.<\/p>\n

Nov\u00fd marker v diagnostike by mohla predstavova\u0165 kyselina sialov\u00e1. Kyselina sialov\u00e1 je monosacharid, ktor\u00fd je procesom sialyz\u00e1cie exprimovan\u00fd na termin\u00e1lnych \u010dastiach glykoprote\u00ednov na povrchu buniek. Sialov\u00e9 kyseliny sa nach\u00e1dzaj\u00fa na Naj O-viazan\u00fdch glyk\u00e1noch, \u010dasto pripojen\u00fdch k z\u00e1kladn\u00e9mu galakt\u00f3zov\u00e9mu zvy\u0161ku, naj\u010dastej\u0161ie prostredn\u00edctvom \u03b1-2,6 alebo \u03b1-2,3 glykozidovej v\u00e4zby(7). Tento monosacharid je d\u00f4le\u017eit\u00fd v interakci\u00e1ch medzi bunkami navz\u00e1jom aj medzi bunkami a okolit\u00fdm mikroprostred\u00edm. Hr\u00e1 z\u00e1sadn\u00fa \u00falohu v stabiliz\u00e1cii glykoprote\u00ednovej \u0161trukt\u00fary a pri ur\u010dovan\u00ed povrchov\u00fdch charakterist\u00edk buniek(8,9).<\/p>\n

Zmenen\u00e1 sialyz\u00e1cia \u010dasto sprev\u00e1dza mal\u00edgnu transform\u00e1ciu, podie\u013ea sa na zv\u00fd\u0161enej agresivite a raste n\u00e1dorov. N\u00e1dorov\u00e9 bunky z\u00edskavaj\u00fa nov\u00e9 vlastnosti, ktor\u00e9 im umo\u017e\u0148uj\u00fa unikn\u00fa\u0165 imunitn\u00e9mu syst\u00e9mu organizmu, ovplyv\u0148uj\u00fa schopnos\u0165 inv\u00e1zie do okolit\u00e9ho tkaniva a metast\u00e1zovania. V mnoh\u00fdch n\u00e1doroch bola preuk\u00e1zan\u00e1 zmena sialyz\u00e1cie prote\u00ednov v s\u00favislosti s biologick\u00fdm spr\u00e1van\u00edm n\u00e1doru a progn\u00f3zou pacienta. Sialyz\u00e1cia ovplyv\u0148uje apopt\u00f3zu(10), neovaskulariz\u00e1ciu(11) v n\u00e1dore, m\u00e1 vplyv na rezistenciu proti chemoterapii a r\u00e1dioterapii(12,13). Zmenu hlad\u00edn kyseliny sialovej mo\u017eno dok\u00e1za\u0165 aj v s\u00e9re pacientov. Bol zisten\u00fd rozdiel v s\u00e9rov\u00fdch hladin\u00e1ch kyseliny sialovej u pacientov s ben\u00edgnymi l\u00e9ziami a mal\u00edgnymi n\u00e1dormi(9).<\/p>\n

Hodnotenie sialyl\u00e1cie by preto mohlo predstavova\u0165 zauj\u00ed- mav\u00fd prognostick\u00fd, pr\u00edpadne diagnostick\u00fd marker s oh\u013eadom na mo\u017en\u00e9 vyu\u017eitie aj v tekutej biopsii. Cie\u013eom predlo\u017eenej \u0161t\u00fadie bolo preto pos\u00fadi\u0165 zmeny sialyl\u00e1cie glykokonjug\u00e1tov vo vz\u0165ahu k n\u00e1dorovej transform\u00e1cii v tkanive prostaty.<\/p>\n

 <\/p>\n

Metodika<\/strong><\/p>\n

Z\u00e1kladom \u0161t\u00fadie sa stali arch\u00edvne mikroskopick\u00e9 prepar\u00e1ty tkaniva prostaty fixovan\u00e9 formal\u00ednom a zaliate v paraf\u00edne zo zdrojov \u00dastavu patologickej anat\u00f3mie Lek\u00e1rskej fakulty UK. Pod\u013ea stanoven\u00fdch patologick\u00fdch diagn\u00f3z sme vybrali celkovo 24 vzoriek. S\u00fastredili sme sa na pr\u00edpady nen\u00e1dorov\u00fdch zmien prostaty (6 pacientov), adenokarcin\u00f3mu prostaty s r\u00f4znym Gleasonov\u00fdm sk\u00f3re; 3 + 4 (6 pacientov), 4 + 4 (6 pacientov) a 4 + 5 (6 pacientov).<\/p>\n

Tie sme opakovane histopatologicky zhodnotili pod\u013ea publikovan\u00fdch WHO krit\u00e9ri\u00ed. Z vybrat\u00fdch prepar\u00e1tov sme zhotovili po dva paraleln\u00e9 rezy a histochemicky sme ich farbili pomocou dvoch typov lekt\u00ednov. Pou\u017eili sme aglutin\u00ednSambucus nigra <\/em>(SNA) \u0161pecifick\u00fd pre \u03b1-2,6 v\u00e4zbu a leukoaglutin\u00edn Maackia amurensis <\/em>(MAL) \u0161pecifick\u00fd pre \u03b1-2,3 v\u00e4zbu sialovej kyseliny. Odparaf\u00ednovan\u00e9 prepar\u00e1ty boli preplachovan\u00e9 5 min\u00fat v PBS (vo fyziologickom so\u013enom roztoku pufrovanom fosf\u00e1t- mi s 0,5 % BSA, 0,05 % NaN3 0,005 % Tween, pH 7,2). Prepar\u00e1ty sme inkubovali 90 min\u00fat v roztoku \/ml biotinylovan\u00e9ho SNA a MAL (Vector, Carpinteria, CA) pri izbovej teplote. Po trojn\u00e1sobnom prepl\u00e1chnut\u00ed v PBS sme prepar\u00e1ty inkubovali 30 min\u00fat s komplexom streptavidinperoxid\u00e1za a po opakova- nom prepl\u00e1chnut\u00ed min\u00fatu farbili roztokom diaminobenzid\u00ednu. Prepar\u00e1ty boli n\u00e1sledne dofarben\u00e9 hematoxyl\u00ednom.<\/p>\n

Prepar\u00e1ty sme hodnotili vo svetelnom mikroskope, s\u00fastredili sme sa na pos\u00fadenie cytoplazmovej a lumin\u00e1lnej membr\u00e1novej pozitivity hodnoten\u00e9ho markera. Hodnoten\u00e1 bola cel\u00e1 plocha prepar\u00e1tu, pre ka\u017ed\u00e9 hodnoten\u00e9 pole bolo stanoven\u00e9 Gleasonovo sk\u00f3re a ka\u017ed\u00e9 pole bolo n\u00e1sledne hodnoten\u00e9 samostatne. N\u00e1lezy sme vyjadrili semikvantitat\u00edvne s vyu\u017eit\u00edm semikvantitat\u00edvneho sk\u00f3re nasledovne:<\/p>\n

    \n
  • negativita 0,5 slab\u00e1, resp. nepravideln\u00e1 pozitivita<\/li>\n<\/ul>\n
      \n
    • dobre hodnotite\u013en\u00e1 pravideln\u00e1 pozitivita<\/li>\n
    • siln\u00e1 pravideln\u00e1 pozitivita<\/li>\n
    • ve\u013emi siln\u00e1 pravideln\u00e1 pozitivita<\/li>\n<\/ul>\n

       <\/p>\n

      V \u010fal\u0161om kroku sme intenzitu pozitivity kvantifikovali s pou\u017eit\u00edm histomorfometrick\u00e9ho softv\u00e9ru ImageJ, v. 1.52p(14,15) a vyjadrili ako sk\u00f3re DAB intenzity (SDI), kde 0 je minim\u00e1lna teoretick\u00e1 intenzita, 1 maxim\u00e1lna teoretick\u00e1 intenzita. Semikvantitat\u00edvne sk\u00f3re DAB pozitivity (SDP) je vyjadren\u00e9 ako priemer jednotliv\u00fdch hodnoten\u00ed \u00b1 SEM. V\u00fdsledky boli vyhodnoten\u00e9 \u0161tatisticky pou\u017eit\u00edm \u0161tatistick\u00e9ho softv\u00e9ru Graph Pad Prism s pou\u017eit\u00edm Kruskalovho-Wallisovho neparametrick\u00e9ho testu, hodnoty p < 0,05 boli pova\u017eovan\u00e9 za signifikantn\u00e9.<\/p>\n

       <\/p>\n

      V\u00fdsledky<\/h3>\n

      V tkanive prostaty sme pozorovali pr\u00edtomnos\u0165 glykokonjug\u00e1tov tak s \u03b1-2,3, ako aj s \u03b1-2,6 v\u00e4zbou kyseliny sialovej, pri\u010dom dominovala najm\u00e4 jej \u03b1-2,6 v\u00e4zba. Pozorovali sme rozdiely pozitivity glykokonjug\u00e1tov v s\u00favislosti s n\u00e1dorovou transform\u00e1ciou v tkanive a v z\u00e1vislosti od gradingu n\u00e1doru.<\/p>\n

      V tkanive norm\u00e1lnej prostaty dominovala najm\u00e4 ve\u013emi siln\u00e1 cytoplazmov\u00e1 (SDP 2,83 \u00b1 0,08) a lumin\u00e1lna membr\u00e1nov\u00e1 (SDP 2,62 \u00b1 0,1 1) pozitivita \u03b1-2,6 viazanej sialovej kyseliny (obr\u00e1zok 2) <\/em><\/strong>a preva\u017ene pravideln\u00e1 lumin\u00e1lna (SDP 1,92 \u00b1 0,19) pozitivita \u03b1-2,3 viazanej sialovej kyseliny (obr\u00e1zok 3)<\/em><\/strong>. Cytoplazmov\u00e1 pozitivita \u03b1-2,3 sialyzovan\u00fdch glykokonjug\u00e1tov bola slab\u00e1. Lo\u017eisk\u00e1 s prostatickou intraepitelovou neopl\u00e1ziou vykazovali mierny pokles pozitivity sialyzovan\u00fdch glykokonjug\u00e1tov, ktor\u00fd v\u0161ak nebol signifikantne odli\u0161n\u00fd v porovnan\u00ed s tkanivom norm\u00e1lnej prostaty.<\/p>\n

      V s\u00favislosti s n\u00e1dorovou transform\u00e1ciou doch\u00e1dza k signifikantn\u00e9mu poklesu cytoplazmovej (SDP 1,81 \u00b1 0,07 v pr\u00edpade Gleasonovho sk\u00f3re 3, 1,07 \u00b1 0,0,10 v pr\u00edpade Gleasonovho sk\u00f3re 4 a 0,9 \u00b1 0,10 v pr\u00edpade Gleasonovho sk\u00f3re 5) a lumin\u00e1lnej membr\u00e1novej (SDP 1,33 \u00b1 0,06 v pr\u00edpade Gleasonovho sk\u00f3re 3, 1,04 \u00b1 0,0,04 v pr\u00edpade Gleasonovho sk\u00f3re 4) pozitivity \u03b1-2,6 sialyzovan\u00fdch glykokonjug\u00e1tov. Pokles bol v\u00fdraznej\u0161\u00ed v pr\u00edpade n\u00e1dorov s vy\u0161\u0161\u00edm Gleasonov\u00fdm sk\u00f3re a bol potvrden\u00fd aj morfometrickou kvantifik\u00e1ciou (obr\u00e1zok 4)<\/em><\/strong>.<\/p>\n

      Pozorovali sme taktie\u017e pokles cytoplazmovej pozitivity \u03b1-2,3 viazanej sialovej kyseliny, ktor\u00fd bol v\u00fdznamnej\u0161\u00ed iba v pr\u00edpadoch n\u00e1dorov s vy\u0161\u0161\u00edm Gleasonov\u00fdm sk\u00f3re. V pr\u00edpade cytoplazmovej pozitivity sme zistili signifikantn\u00fd rozdiel pri n\u00e1doroch s Gleasonov\u00fdm sk\u00f3re 4 a 5 (SDP 0,44 \u00b1 0,06 a 0,32 \u00b1 0,06) v porovnan\u00ed s norm\u00e1lnym tkanivom prostaty (SDP 0,75 \u00b1 0,15). Rozdiel sa uk\u00e1zal v\u00fdraznej\u0161\u00ed pri morfometrickom hodnoten\u00ed, kde signifikantn\u00fd pokles \u03b1-2,3 viazanej sialovej kyseliny bol pozorovan\u00fd v pr\u00edpadoch karcin\u00f3mov prostaty s r\u00f4znym Gleasonov\u00fdm sk\u00f3re, rovnako aj v pr\u00edpadoch prostatickej intraepitelovej neopl\u00e1zie (obr\u00e1zok<\/em><\/strong> 5)<\/em><\/strong>. N\u00e1dorov\u00e1 transform\u00e1cia sa nesp\u00e1jala so signifikantn\u00fdmi zmenami lumin\u00e1lnej membr\u00e1novej pozitivity \u03b1-2,3 sialyzovan\u00fdch glykokonjug\u00e1tov.<\/p>\n

       <\/p>\n

      Diskusia<\/h3>\n

      Preuk\u00e1zali sme zmeny sialyz\u00e1cie glykokonjug\u00e1tov v s\u00favislosti s n\u00e1dorovou transform\u00e1ciou v prostate. Zmeny jej koncentr\u00e1cie boli hodnoten\u00e9 vo vzork\u00e1ch z biopsie s vyu\u017eit\u00edm dvoch typov lekt\u00ednov. Lekt\u00edn Sambucus nigra (SNA), izolovan\u00fd z k\u00f4ry bazy, sa prednostne via\u017ee na kyselinu sialov\u00fa pripojen\u00fa ku koncovej galakt\u00f3ze na v\u00e4zbu \u03b1-2,6 a lekt\u00edn Maackia amurensis (MAL) sa via\u017ee na kyselinu sialov\u00fa viazan\u00fa \u03b1-2,3 v\u00e4zbou. Tak\u00e9to hodnotenie s diferencovan\u00edm typu jej termin\u00e1lnej v\u00e4zby doposia\u013e nebolo v dostupnej literat\u00fare dokumentovan\u00e9. Pri hodnoten\u00ed boli pozorovan\u00e9 rozdiely medzi ben\u00edgnymi procesmi a mal\u00edgnymi karcin\u00f3mami.<\/p>\n

      V tkanive prostaty sme preuk\u00e1zali pr\u00edtomnos\u0165 \u03b1-2,3 aj \u03b1-2,6 sialyzovan\u00fdch glykokonjug\u00e1tov s dominanciou \u03b1-2,6 v\u00e4zby. Pozorovali sme v\u00fdrazn\u00fd pokles sialyz\u00e1cie najm\u00e4 v \u03b1-2,6 v\u00e4zbe v s\u00favislosti s n\u00e1dorovou transform\u00e1ciou v prostate, a to cytoplazmovej aj lumin\u00e1lnej membr\u00e1novej pozitivity. Sialyz\u00e1cia v \u03b1-2,6 v\u00e4zbe sa nemen\u00ed pri dysplastick\u00fdch zmen\u00e1ch v prostatickej intraepitelovej neopl\u00e1zii. Tento n\u00e1lez bol potvrden\u00fd aj morfometricky. Sialyz\u00e1cia v \u03b1-2,3 v\u00e4zbe je v tkanive prostaty menej v\u00fdrazn\u00e1, pokles v s\u00favislosti s dysplastick\u00fdmi zmenami a n\u00e1dorovou transform\u00e1ciou je preto \u0165a\u017e\u0161ie pozorovate\u013en\u00fd a hodnotite\u013en\u00fd a bol preuk\u00e1zan\u00fd najm\u00e4 pomocou morfometrickej anal\u00fdzy obrazu.<\/p>\n

      V tejto s\u00favislosti s\u00fa zauj\u00edmav\u00e9 n\u00e1lezy Meany et al.(16), ktor\u00ed pozorovali zv\u00fd\u0161en\u00fa sialyz\u00e1ciu PSA v s\u00e9re u pacientov s karcin\u00f3mom prostaty. Zv\u00fd\u0161en\u00e1 hladina kyseliny sialovej v s\u00e9re m\u00f4\u017ee by\u0165 zauj\u00edmav\u00fd pomocn\u00fd marker v pr\u00edpade, ak nie je PSA dostato\u010dne v\u00fdpovedn\u00e9(17) a je nez\u00e1visl\u00fdm prognostick\u00fdm faktorom karcin\u00f3mu prostaty vr\u00e1tane vzniku vzdialen\u00fdch metast\u00e1z(18) a agresivity n\u00e1doru(19). Predpoklad\u00e1me preto, \u017ee nami pozorovan\u00fd pokles sialyz\u00e1cie prote\u00ednov v tkanive prostaty s\u00favis\u00ed s jej zv\u00fd\u0161en\u00fdm uvo\u013e\u0148ovan\u00edm do s\u00e9ra.<\/p>\n

      Sialyl\u00e1cia glykokonjug\u00e1tov je v\u00fdsledkom rovnov\u00e1hy medzi enz\u00fdmami via\u017eucimi kyselinu sialov\u00fa na glykokonjug\u00e1ty a enz\u00fdmami, ktor\u00e9 ju uvo\u013e\u0148uj\u00fa z jej v\u00e4zby. Je preto mo\u017en\u00e9, \u017ee zmeny akumuluj\u00face sa v bunk\u00e1ch po\u010das n\u00e1dorovej transform\u00e1cie m\u00f4\u017eu vies\u0165 k zmen\u00e1m rovnov\u00e1hy medzi sialyltransfer\u00e1zami a neuraminid\u00e1zami v tkanive. Za fyziologick\u00fdch okolnost\u00ed je v tkanive prostaty exprimovan\u00e1 najm\u00e4 lyzozom\u00e1lna sialid\u00e1za NEU1(20). Cytozolick\u00e1 sialid\u00e1za NEU2 a membr\u00e1novo viazan\u00e1 NEU3 nie s\u00fa v tkanive prostaty opisovan\u00e9 v detegovate\u013enom mno\u017estve(20). Bolo v\u0161ak dok\u00e1zan\u00e9 zna\u010dn\u00e9 zv\u00fd\u0161enie expresie neuraminid\u00e1zy NEU3 v prostatickom karcin\u00f3me, ktor\u00e9 viedlo k zr\u00fdchleniu progresie n\u00e1doru, preva\u017ene pre naru\u0161en\u00fa bunkov\u00fa signaliz\u00e1ciu na bunkovom povrchu(21). Experiment\u00e1lna inhib\u00edcia neuraminid\u00e1z prostredn\u00edctvom siRNA sa d\u00e1va do s\u00favisu s poklesom pre\u017e\u00edvania n\u00e1dorov\u00fdch buniek prostaty a so zn\u00ed\u017een\u00edm ich metastatick\u00e9ho potenci\u00e1lu(22).<\/p>\n

      Hodnotenie expresie kyseliny sialovej priamo v tkanive prostaty tak m\u00f4\u017ee ma\u0165 hodnotn\u00fd pr\u00ednos v diagnostike mal\u00edgnych n\u00e1dorov v prostate. M\u00f4\u017ee ma\u0165 v\u00fdznam pre lep\u0161ie pochopenie ich mal\u00edgneho potenci\u00e1lu. O\u010dak\u00e1vame, \u017ee pr\u00e1ve komplexn\u00fd poh\u013ead na expresiu sialyzovan\u00fdch prote\u00ednov, sialyltransfer\u00e1z a neuraminid\u00e1z v n\u00e1dore prostaty m\u00f4\u017ee odkry\u0165 nov\u00e9 zauj\u00edmav\u00e9 potenci\u00e1lne terapeutick\u00e9 ciele v prostate.<\/p>\n

       <\/p>\n

      Po\u010fakovanie: <\/em><\/strong>\u0160t\u00fadia bola realizovan\u00e1 s podporou projektu VEGA 1\/0191\/17 \u201eDiagnostick\u00fd a predikt\u00edvny v\u00fdznam zmien zlo\u017eenia glykokonjug\u00e1tov asociovan\u00fdch s n\u00e1dorovou transform\u00e1ciou prostaty\u201c. \u0160t\u00fadia bola parci\u00e1lne realizovan\u00e1 ako s\u00fa\u010das\u0165 pr\u00e1ce v\u00fdskumn\u00e9ho centra vybudovan\u00e9ho v\u010faka podpore v r\u00e1mci OP V\u00fdskuma v\u00fdvoj pre projekt: \u201eCentrum v\u00fdskumu z\u00e1va\u017en\u00fdch ochoren\u00ed a ich komplik\u00e1ci\u00ed\u201c, ITMS 26240120038, spolufinancovan\u00fd zo zdrojov Eur\u00f3pskeho fondu region\u00e1lneho rozvoja.<\/em><\/p>\n

       <\/p>\n

       <\/p>\n

      \u00a0<\/em><\/p>\n

      LITERAT\u00daRA<\/strong><\/p>\n

        \n
      1. European Cancer Information System. Estimates of cancer incidence and mortality in 2018, for all countries. 2016 1. 9. 2019]; https:\/\/ ecis.jrc.ec.europa.eu.<\/li>\n
      2. Andriole GL, Crawford \u00a0ED, \u00a0Grubb \u00a0RL, \u00a03rd, et Mortality \u00a0results from a randomized prostate-cancer screening trial. N Engl J Med 2009; 360(13): 1310-9.<\/li>\n
      3. Llop E, Ferrer-Batalle M, Barrabes S, et Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes. Theranostics 2016; 6(8): 1190-204.<\/li>\n
      4. Ferrer-Batalle M, Llop E, Ramirez M, et Comparative Study of BloodBased Biomarkers, alpha2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection. Int J Mol Sci 2017; 18(4).<\/li>\n
      5. Kilpelainen TP, Tammela TL, Malila N, et The Finnish prostate cancer screening trial: analyses on the screening failures. Int J Cancer 2015; 136(10): 2437-43.<\/li>\n
      6. Roobol MJ, Kerkhof M, Schroder FH, et Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC). Eur Urol 2009; 56(4): 584-591.<\/li>\n
      7. Pihikova D, Pakanova Z, Nemcovic M, et Sweet characterisation of prostate specific antigen using electrochemical lectin-based immunosensor assay and MALDI TOF\/TOF analysis: Focus on sialic acid. Proteomics 2016; 16(24): 3085-3095.<\/li>\n
      8. Samraj AN, Laubli H, Varki N, et Involvement of a non-human sialic Acid in human cancer. Front Oncol 2014; 4: 33.<\/li>\n
      9. Goswami K, Nandeesha H, Koner BC, et A comparative study of serum protein-bound sialic acid in benign and malignant prostatic growth: possible role of oxidative stress in sialic acid homeostasis. Prostate Cancer Prostatic Dis 2007; 10(4): 356-9.<\/li>\n
      10. Huang S, Day TW, Choi MR, et al. Human beta-galactoside alpha-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 Mol Cell Biochem 2009; 331(1-2): 81-8.<\/li>\n
      11. Chen JY, Tang YA, Huang SM, et A novel sialyltransferase inhibitor suppresses FAK\/paxillin signaling and cancer angiogenesis and metastasis pathways. Cancer Res 2011; 71(2): 473-83.<\/li>\n
      12. Dawson G, Moskal JR, Dawson Transfection of 2,6 and 2,3-sialyltransferase genes and GlcNAc-transferase genes into human glioma cell line U-373 MG affects glycoconjugate expression and enhances cell death. J Neurochem. 2004; 89(6): 1436-1444.<\/li>\n
      13. Schultz MJ, Swindall AF, Wright JW, et ST6Gal-I sialyltransferase confers cisplatin resistance in ovarian tumor cells. J Ovarian Res 2013; 6(1): 25.<\/li>\n
      14. Abramoff MD, Magelhaes PJ, Ram Image Processing with Image J. Biophotonics International 2004; 11(7): 36-42.<\/li>\n
      15. Schindelin J, Arganda-Carreras I, Frise E, et Fiji: an open-source platform for biological-image analysis. Nat Methods 2012; 9(7): 676-82.<\/li>\n
      16. Meany DL, Zhang Z, Sokoll LJ, et Glycoproteomics for prostate cancer detection: changes in serum PSA glycosylation patterns. J Proteome Res 2009; 8(2): 613-9.<\/li>\n
      17. Michalakis K, Ilias I, Triantafyllou A, et Detection of prostate cancer by sialic acid level in patients with non-diagnostic levels of prostate-specific antigen. Maturitas 2012; 73(4): 325-30.<\/li>\n
      18. Zhang C, Yan L, Song H, et Elevated Serum Sialic Acid Levels Predict Prostate Cancer As Well As Bone Metastases. J Cancer 2019; 10(2): 449-457.<\/li>\n
      19. Tkac J, Gajdosova V, Hroncekova S, et Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer. Interface Focus 2019; 9(2): 20180077.<\/li>\n
      20. Uhlen M, Fagerberg L, Hallstrom BM, et Proteomics. Tissue-based map of the human proteome. Science 2015; 347(6220): 1260419.<\/li>\n
      21. Hata K, Tochigi T, Sato I, et Increased sialidase activity in serum of cancer patients: Identification of sialidase and inhibitor activities in human serum. Cancer Sci 2015; 106(4): 383-9.<\/li>\n
      22. Li X, Zhang L, Shao Y, et Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion. Biochem Biophys Res Commun 2011; 416(3-4): 270-6.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

        *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.   \u00davod Karcin\u00f3m prostaty je jedna z naj\u010dastej\u0161\u00edch foriem rakoviny u mu\u017eov. \u0160tatistiky uv\u00e1dzaj\u00fa celosvetovo viac ako jeden mili\u00f3n nov\u00fdch pr\u00edpadov ro\u010dne. Na Slovensku je incidencia karcin\u00f3mu prostaty u mu\u017eov<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[297],"tags":[650,1278,1279,635,1276,1277,1280],"class_list":["post-1800","post","type-post","status-publish","format-standard","hentry","category-pathology","tag-glycoconjugates","tag-lectins","tag-neuraminidase","tag-prognostic-markers","tag-prostatic-adenocarcinoma","tag-sialic-acid","tag-sialyltransferase","typ_clanku-original-work"],"acf":{"abstrakt":"

        Introduction: <\/strong>Prostatic carcinoma is one of the most common forms of malignancy in men with an increasing incidence even in well-developed countries. Despite available diagnostic and treatment methods, it is the third leading cause of cancer death in males. Prostatic specific antigen levels in serum play a key role in diagnosis, but the examination has low both sensitivity and specificity. There are currently no reliable non-invasive diagnostic methods, and the diagnosis of prostate cancer needs to be confirmed by biopsy. Abnormal glycosylation of cell structures is important part of the neoplastic transformation process. The presented study aims to evaluate the changes of glycosylation pattern in neoplastic transformation of prostatic tissue.<\/p>\n

        Methods: <\/strong>24 cases of prostate tissue were analyzed, including cases of benign prostatic hyperplasia as well as prostatic adenocarcinoma with varying Gleason score; 3 + 4, 4 + 4 and 4 + 5. Lectin histochemistry using sialic acid-specific lectins specific for \u03b1-2,3 linkage (Maackia amurensis leukoagglutinin – MAL) and \u03b1-2,6 linkage (Sambucus nigra leukoagglutinin – SNA) was used. Changes were evaluated semi-quantitatively and subsequently by morphometric analysis.<\/p>\n

        Results: <\/strong>Changes of tissue glycosylation pattern accompany neoplastic transformation in prostatic tissue. In connection with tumour transformation in the prostate, we observed a significant decrease in sialylation of cellular glycoconjugates in both \u03b1-2,6 and \u03b1-2,3 linkage. This decrease was more pronounced in cases of adenocarcinomas with a higher Gleason score.<\/p>\n

        Conclusion: <\/strong>The changes of glycosylation pattern may affect the functional properties of neoplastic cells, including the survival, invasiveness and metastatic potential of cells. Evaluation of sialic acid expression in prostatic tissue may be of importance in the diagnosis of prostate tumours as well as in improving the comprehension of their malignant potential.<\/p>\n

        Keywords: <\/strong>prostatic adenocarcinoma, sialic acid, glycoconjugates, lectins, neuraminidase, sialyltransferase, prognostic markers<\/p>\n

         <\/p>\n","casopis":[{"ID":1883,"post_author":"7","post_date":"2019-10-28 13:35:57","post_date_gmt":"2019-10-28 12:35:57","post_content":"

          \r\n \t
        • Detection and validation of subchromosomal aberrations detected as additional findings in routine noninvasive prenatal testing for common trisomies<\/li>\r\n \t
        • Finding of a marker chromosome in a child with Cat-eye syndrome (case study)<\/li>\r\n \t
        • Experimental therapy with stem cells is promissing in the treatment of chronic diabetic ulcer \u2013 a case study<\/li>\r\n \t
        • Colonic mucosal Schwann cell hamartoma with tactile corpuscle-like bodies: a case report<\/li>\r\n \t
        • Accidental capture of the toxic strain Corynebacterium diphteriae<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-004","to_ping":"","pinged":"","post_modified":"2019-11-04 13:53:35","post_modified_gmt":"2019-11-04 12:53:35","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.newslab.sk\/casopis\/newslab-4\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"80-84","upload_clanok":{"ID":1798,"id":1798,"title":"NEWSLAB_2-2019_Kelleyov\u00e1","filename":"NEWSLAB_2-2019_Kelleyov\u00e1.pdf","filesize":801497,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2019\/10\/NEWSLAB_2-2019_Kelleyov\u00e1.pdf","link":"https:\/\/www.newslab.sk\/en\/zmeny-sialyzacie-proteinov-v-karcinome-prostaty-vysledky-pilotnej-studie\/newslab_2-2019_kelleyova-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab_2-2019_kelleyova-2","status":"inherit","uploaded_to":1800,"date":"2019-10-28 13:51:24","modified":"2019-10-28 13:51:24","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1800","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1800"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1800\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1800"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1800"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1800"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}