{"id":2371,"date":"2022-02-09T11:13:54","date_gmt":"2022-02-09T10:13:54","guid":{"rendered":"https:\/\/www.newslab.sk\/molekularny-mechanizmus-karcinogenezy-indukovanej-prostrednictvom-bakterii\/"},"modified":"2022-02-10T02:22:18","modified_gmt":"2022-02-10T01:22:18","slug":"molecular-mechanism-of-bacterial-induced-carcinogenesis","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/molecular-mechanism-of-bacterial-induced-carcinogenesis\/","title":{"rendered":"Molecular mechanism of bacterial-induced carcinogenesis"},"content":{"rendered":"

*A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens<\/strong><\/span><\/p>\n

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\u00davod<\/strong><\/h3>\n

Medzi prv\u00e9 asoci\u00e1cie bakt\u00e9ri\u00ed s rakovinou patr\u00ed te\u00f3ria z roku 1772, ktor\u00e1 predpokladala \u00fa\u010das\u0165 Mycobacterium tuberculosis na vzniku malign\u00edt. Te\u00f3ria zalo\u017een\u00e1 na pozorovan\u00ed bronchog\u00e9nnych karcin\u00f3mov v miestach zjazven\u00fdch v d\u00f4sledku tuberkul\u00f3zy bola takisto podporen\u00e1 pozorovan\u00edm vy\u0161\u0161ieho v\u00fdskytu akt\u00edvnej tuberkul\u00f3zy pr\u00e1ve u pacientov s rakovinou p\u013e\u00fac oproti be\u017enej popul\u00e1cii. Nesk\u00f4r v\u0161ak bola t\u00e1to te\u00f3ria vyvr\u00e1ten\u00e1, preto\u017ee sa uk\u00e1zalo, \u017ee p\u013e\u00facne n\u00e1dory boli lokalizovan\u00e9 inde, nie v mieste zjazvenia po tuberkul\u00f3ze(1). V roku 1890, William Russell pozoroval vo vzork\u00e1ch n\u00e1dorov objekty, ktor\u00e9 nazval fuchsine bodies. I ke\u010f tieto objekty s\u00e1m \u010falej nesk\u00famal, nazna\u010dil, \u017ee mohlo \u00eds\u0165 o bakt\u00e9rie(2). N\u00e1sledne za\u010dali prib\u00fada\u0165 spojitosti \u010fal\u0161\u00edch bakt\u00e9ri\u00ed s r\u00f4znymi typmi n\u00e1dorov, ale v roku 1963 skupina vedcov z N\u00e1rodn\u00e9ho in\u0161tit\u00fatu rakoviny v Spojen\u00fdch \u0161t\u00e1toch americk\u00fdch odmietla ak\u00e9ko\u013evek hypot\u00e9zy tohto typu, preto\u017ee us\u00fadili, \u017ee dan\u00e9 bakt\u00e9rie boli pozorovan\u00e9 v n\u00e1dorovom tkanive len ako d\u00f4sledok kontamin\u00e1cie alebo sekund\u00e1rnej infekcie. O \u0161es\u0165 rokov nesk\u00f4r bola t\u00e1to hypot\u00e9za zamietnut\u00e1 a vedci sa op\u00e4\u0165 vr\u00e1tili ku sk\u00famaniu tohto spojenia. Najlep\u0161ie op\u00edsan\u00fd vz\u0165ah je medzi bakt\u00e9riou Helicobacter pylori a rakovinou \u017eal\u00fadka. \u010ealej boli pomerne podrobne op\u00edsan\u00e9 spojenia medzi Streptococcus bovis a rakovinou hrub\u00e9ho \u010dreva, Chlamydia pneumoniae a rakovinou p\u013e\u00fac a tie\u017e spojenie Bartonella species s tvorbou cievnych n\u00e1dorov(3).<\/p>\n

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Molekul\u00e1rne mechanizmy karcinogen\u00e9zy<\/h3>\n

Spojitos\u0165 medzi bakt\u00e9riami a rakovinou nie je ani v s\u00fa\u010dasnosti \u00faplne presk\u00faman\u00e1, ale podstatne promovanou je hypot\u00e9za, ktor\u00e1 sa sklad\u00e1 z dvoch \u010dast\u00ed: 1. Chronick\u00fd z\u00e1pal sp\u00f4soben\u00fd perzistentnou bakteri\u00e1lnou infekciou m\u00f4\u017ee vies\u0165 ku vzniku rakoviny; 2. Bakteri\u00e1lne tox\u00edny a sekund\u00e1rne metabolity produkovan\u00e9 pri chronickej bakteri\u00e1lnej infekcii m\u00f4\u017eu indukova\u0165 karcinogen\u00e9zu(4). Okrem toho v\u0161ak boli objaven\u00e9 aj \u010fal\u0161ie sp\u00f4soby, konkr\u00e9tne dysbi\u00f3za a bakteri\u00e1lne RNA, ktor\u00e9 takisto m\u00f4\u017eu by\u0165 \u00fa\u010dastn\u00e9 na karcinogen\u00e9ze (obr\u00e1zok 1).<\/p>\n

Chronick\u00fd z\u00e1pal<\/h3>\n

Imunitn\u00fd syst\u00e9m cicavcov deteguje pr\u00edtomnos\u0165 mikrobi\u00e1lnej infekcie pomocou viacer\u00fdch receptorov, z\u00a0 ktor\u00fdch najv\u00fdraznej\u0161\u00edmi s\u00fa tolllike receptory (TLR) rozozn\u00e1vaj\u00face molekul\u00e1rne vzory asociovan\u00e9 s patog\u00e9nmi (angl. pathogen-associated molecular patterns). Po ich aktiv\u00e1cii doch\u00e1dza k produkcii proz\u00e1palov\u00fdch cytok\u00ednov a \u010fal\u0161\u00edch z\u00e1palov\u00fdch medi\u00e1torov, pri\u010dom kr\u00e1tkodob\u00fd ak\u00fatny z\u00e1pal je pre organizmus prospe\u0161n\u00e1 reakcia, ktorej cie\u013eom je obnovenie po\u0161koden\u00e9ho tkaniva a odstr\u00e1nenie patog\u00e9nnych agensov z tela. Ak sa nepodar\u00ed odstr\u00e1ni\u0165 pr\u00ed\u010dinu vyvol\u00e1vaj\u00facu z\u00e1pal, ak\u00fatny z\u00e1pal prerastie do chronick\u00e9ho z\u00e1palu, ktor\u00fd je pre organizmus \u0161kodliv\u00fd, vyvol\u00e1va oxida\u010dn\u00e9 po\u0161kodenie DNA a nar\u00fa\u0161a k\u013e\u00fa\u010dov\u00e9 kask\u00e1dy reguluj\u00face rast a\u00a0rozmno\u017eovanie buniek, \u010d\u00edm m\u00f4\u017ee d\u00f4js\u0165 k\u00a0mal\u00edgnej transform\u00e1cii buniek v\u00a0organizme(5).<\/p>\n

Bakteri\u00e1lne tox\u00edny<\/h3>\n

Tox\u00edny tvoria \u0161irok\u00fa skupinu biologicky akt\u00edvnych l\u00e1tok, ktor\u00e9 produkuj\u00fa organizmy s cie\u013eom po\u0161kodi\u0165 in\u00e9 organizmy, a t\u00fdm prispie\u0165 k vlastn\u00e9mu pre\u017eitiu v danom prostred\u00ed. Pri p\u00f4soben\u00ed v\u00e4\u010d\u0161iny sk\u00faman\u00fdch bakteri\u00e1lnych tox\u00ednov doch\u00e1dza naj\u010dastej\u0161ie k naru\u0161eniu sign\u00e1lnych dr\u00e1h MAPK\/ERK (mitog\u00e9nom aktivovanej prote\u00ednkin\u00e1zy\/extracelul\u00e1rnymi sign\u00e1lmi regulovanej kin\u00e1zy) a tie\u017e dr\u00e1hy Wnt\/\u03b2-katen\u00edn (angl. winglessrelated integration site). Obe tieto dr\u00e1hy s\u00fa zapojen\u00e9 v regul\u00e1cii bunkovej adh\u00e9zie, elong\u00e1cie, prolifer\u00e1cie a tie\u017e v regul\u00e1cii expresie tumorov\u00fdch supresorov\u00fdch g\u00e9nov. Pri ich naru\u0161en\u00ed s\u00fa deregulovan\u00e9 v\u0161etky tieto deje, doch\u00e1dza najm\u00e4 k inhib\u00edcii tumorov\u00fdch supresorov a zv\u00fd\u0161enej expresii regula\u010dn\u00fdch g\u00e9nov c-MYC a cykl\u00ednu D. Expresia c-MYC a cykl\u00ednu D sa zvy\u0161uje t\u00fdm, \u017ee sa rozru\u0161uje komplex transmembr\u00e1nov\u00e9ho prote\u00ednu s funkciou tumorov\u00e9ho supresora E-kadher\u00ednu a prote\u00ednu riadiaceho bunkov\u00e9 adh\u00e9zie a transkripciu g\u00e9nov \u03b2-katen\u00ednu, kde \u03b2-katen\u00edn n\u00e1sledne prech\u00e1dza do jadra a sp\u00f4sobuje zv\u00fd\u0161enie bunkov\u00e9ho delenia(6,7,11,13). V\u00e4\u010d\u0161ina tox\u00ednov takisto iniciuje vo svojich hostite\u013esk\u00fdch bunk\u00e1ch z\u00e1palov\u00e9 reakcie ved\u00face k produkcii reakt\u00edvnych foriem kysl\u00edka a\u00a0 dus\u00edka, ktor\u00e9 po\u0161kodzuj\u00fa DNA, ovplyv\u0148uj\u00fa imunitn\u00e9 reakcie hostite\u013ea vo svoj prospech a\u00a0 vyh\u00fdbaj\u00fa sa tak de\u0161trukcii. Mnoh\u00e9 tox\u00edny s\u00fa zn\u00e1me t\u00fdm, \u017ee zvy\u0161uj\u00fa epiteli\u00e1lnu permeabilitu, \u010d\u00edm u\u013eah\u010duj\u00fa koloniz\u00e1ciu nielen sebe, ale aj in\u00fdm patog\u00e9nom a s\u00fa schopn\u00e9 inhibova\u0165 proces apopt\u00f3zy a mechanizmy opr\u00e1v po\u0161kodenej DNA(6,7,9,11-13). K t\u00fdmto tox\u00ednom patr\u00ed tox\u00edn Bacteroides fragilis, g\u00e9n A asociovan\u00fd s cytotox\u00ednmi a vakuolizuj\u00faci cytotox\u00edn A, oba produkovan\u00e9 Helicobacterom pylori, \u010falej sem patr\u00ed tox\u00edn Pasteurella mutocida, cytolet\u00e1lne tox\u00edny a dentiliz\u00edn produkovan\u00fd bakt\u00e9riami Treponema species, Fusobacterium adhez\u00edn A, Fusobacterium prote\u00edn apopt\u00f3zy 2, tox\u00edny Escherichia coli, konkr\u00e9tne kolibakt\u00edn, cytotoxick\u00e9 nekrotizuj\u00face faktory a \u03b1-hemolyz\u00edn a tox\u00edn produkovan\u00fd bakt\u00e9riou Salmoenlla enterica, prote\u00edn avirulencie A. Pasteurella mutocida tox\u00edn sa vyzna\u010duje navy\u0161e schopnos\u0165ou ovplyv\u0148ova\u0165 regula\u010dn\u00e9 G-prote\u00edny, o ktor\u00fdch je zn\u00e1me, \u017ee s\u00fa pri rakovinovom bujnen\u00ed zapojen\u00e9 do procesu angiogen\u00e9zy, migr\u00e1cie buniek a apopt\u00f3zy(10). G\u00e9n A asociovan\u00fd s cytotox\u00ednmi podporuje proces epitelovo-mezench\u00fdmov\u00e9ho prechodu, ke\u010f bunky nadob\u00fadaj\u00fa zv\u00fd\u0161en\u00fa invaz\u00edvnos\u0165 a schopnos\u0165 migr\u00e1cie, \u010d\u00edm doch\u00e1dza k podpore metast\u00e1z a bunky tie\u017e nadob\u00fadaj\u00fa vlastnosti rakovinov\u00fdch kme\u0148ov\u00fdch buniek, ktor\u00fdmi s\u00fa schopnos\u0165 obnovova\u0165 sa a diferencova\u0165 na ve\u013ek\u00e9 mno\u017estvo buniek(8). Bacteroides fragilis tox\u00edn tie\u017e nar\u00fa\u0161a regul\u00e1ciu metyl\u00f3mov, otv\u00e1ra chromat\u00edn a zvy\u0161uje je-ho pr\u00edstupnos\u0165 pre transkrip\u010dn\u00e9 faktory a zvy\u0161uje metyl\u00e1ciu prom\u00f3torov n\u00edzkoexprimovan\u00fdch g\u00e9nov(6). Na zvy\u0161ovan\u00ed nestability gen\u00f3mu hostite\u013eov s\u00fa takisto \u00fa\u010dastn\u00e9 tox\u00edny Escherichia coli a cytolet\u00e1lne tox\u00edny, preto\u017ee podporuj\u00fa akumul\u00e1ciu mut\u00e1ci\u00ed a vznik chromoz\u00f3mov\u00fdch aber\u00e1ci\u00ed(13).<\/p>\n

Bakteri\u00e1lne metabolity<\/h3>\n

Hlavnou dr\u00e1hou signaliz\u00e1cie medzi hostite\u013eom a mikrobi\u00f3mom je bakteri\u00e1lna produkcia metabolitov, ktor\u00e9 vstupuj\u00fa do obehu a pomocou cirkul\u00e1cie putuj\u00fa do org\u00e1nov, kde ovplyv\u0148uj\u00fa r\u00f4zne biologick\u00e9 funkcie. V\u00fdsledn\u00fd \u00fa\u010dinok metabolitov (tabu\u013eka 1) na organizmus m\u00f4\u017ee by\u0165 ochrann\u00fd, ale dok\u00e1\u017eu vytvori\u0165 aj predispoz\u00edciu na vznik rakoviny. Zmeny koncentr\u00e1cie alebo typu metabolitov m\u00f4\u017eu by\u0165 sp\u00f4soben\u00e9 r\u00f4znymi faktormi, ako je napr\u00edklad strava, \u017eivotn\u00fd \u0161t\u00fdl alebo bakteri\u00e1lna dysbi\u00f3za(14).<\/p>\n

Bakteri\u00e1lne RNA<\/h3>\n

Jedn\u00fdm z najnov\u0161ie objaven\u00fdch sp\u00f4sobov komunik\u00e1cie medzi bakt\u00e9riami a ich hostite\u013emi je v\u00fdmena inform\u00e1ci\u00ed prostredn\u00edctvom regula\u010dn\u00fdch RNA. Bakteri\u00e1lne RNA sa pova\u017euj\u00fa za molekul\u00e1rny vzor asociovan\u00fd s patog\u00e9nom, ktor\u00fd je \u00fa\u010dastn\u00fd v reakci\u00e1ch \u013eudsk\u00e9ho hostite\u013esk\u00e9ho organizmu na infekciu. RNA je v bakteri\u00e1lnych bunk\u00e1ch v nadbytku a m\u00f4\u017ee sa z nich uvo\u013eni\u0165 po l\u00fdze buniek, ale m\u00f4\u017eu ju vylu\u010dova\u0165 aj \u017eiv\u00e9 bakt\u00e9rie prostredn\u00edctvom membr\u00e1nov\u00fdch vezik\u00fal (MV), ktor\u00fdch hlavnou \u00falohou je prenos a ochrana RNA pred degrad\u00e1ciou(27). Experimenty s uropatog\u00e9nnou E. coli uk\u00e1zali, \u017ee t\u00e1to bakt\u00e9ria je schopn\u00e1 produkova\u0165 MV, ktor\u00e9 obsahuj\u00fa bakteri-\u00e1lne mRNA, rRNA, tRNA a mal\u00e9 nek\u00f3duj\u00face RNA. Autorom tejto pr\u00e1ce sa podarilo demon\u0161trova\u0165, \u017ee uveden\u00e9 molekuly dok\u00e1\u017eu vst\u00fapi\u0165 do hostite\u013esk\u00fdch buniek, kde by mohli ovplyv\u0148ova\u0165 d\u00f4le\u017eit\u00e9 biologick\u00e9 funkcie(28). Alternat\u00edvnym sp\u00f4sobom na doru\u010denie bakteri\u00e1lnych RNA do buniek hostite\u013ea je ich produkcia intracelul\u00e1rnymi bakt\u00e9riami, ku ktor\u00fdm patr\u00ed napr\u00edklad Listeria monocytogenes. Pri kultiv\u00e1cii buniek s tou-to bakt\u00e9riou boli detegovan\u00e9 jej RNA v cytosole hostite\u013esk\u00fdch buniek(29). \u010eal\u0161\u00edm sp\u00f4sobom, ako sa m\u00f4\u017eu bakteri\u00e1lne RNA dosta\u0165 do hostite\u013eskej bunky, je ich uvo\u013enenie z bakt\u00e9ri\u00ed, ktor\u00e9 zost\u00e1vaj\u00fa zachyten\u00e9 vo fagoz\u00f3me(30).
\nDosia\u013e bola op\u00edsan\u00e1 pr\u00edtomnos\u0165 bakteri\u00e1lnych RNA v cytosole, endozom\u00e1lnych a fagozom\u00e1lnych \u010dastiach a dokonca aj v jadre hostite\u013esk\u00fdch buniek. Bakteri\u00e1lna RNA v \u013eudsk\u00fdch bunk\u00e1ch aktivuje TLR vrodenej imunity, ktor\u00e9 aktivuj\u00fa kask\u00e1dy imunitn\u00e9ho syst\u00e9mu. Z\u00e1rove\u0148 sa predpoklad\u00e1, \u017ee by mohli ma\u0165 schopnos\u0165 ovplyvni\u0165 metabolick\u00e9 a apoptotick\u00e9 funkcie aj imunitn\u00fa odpove\u010f hostite\u013ea vo svoj prospech(27). V s\u00fa\u010dasnosti sa \u010doraz viac v\u00fdskumov zaober\u00e1 ot\u00e1zkou, \u010di bakteri\u00e1lne RNA dok\u00e1\u017eu regulova\u0165 expresiu g\u00e9nov hostite\u013ea, ke\u010f\u017ee je zn\u00e1me, \u017ee pribli\u017ene 60 % \u013eudsk\u00fdch g\u00e9nov m\u00e1 expresiu re-gulovan\u00fa pomocou svojich mikroRNA (miRNA)(31). Jedn\u00fdm z potenci\u00e1lnych sp\u00f4sobov, ako by bolo toto mo\u017en\u00e9, je v\u00e4zba bakteri\u00e1lnych sRNA (mal\u00e9 RNA), ktor\u00e9 s\u00fa obdobou \u013eudsk\u00fdch miRNA, na hostite\u013esk\u00e9 miRNA na z\u00e1klade komplementarity, \u010d\u00edm by p\u00f4sobili ako antisense RNA. Ke\u010f\u017ee maj\u00fa ove\u013ea v\u00e4\u010d-\u0161iu d\u013a\u017eku ne\u017e eukaryotick\u00e9 RNA, je potrebn\u00e9 eliminova\u0165 tento rozdiel, \u010do by sa teoreticky dalo ich fragment\u00e1ciou v hostite\u013eovi(32). Jeden z experimentov potvrdzuj\u00facich t\u00fato hypot\u00e9zu vyu\u017eil dve endog\u00e9nne sRNA z Escherichia coli (E. coli), ktor\u00e9 s\u00fa produkovan\u00e9, ak je bakt\u00e9ria vystavan\u00e1 stresu. Konkr\u00e9tne \u0161lo o OxyS a DsrA sRNA, pri\u010dom bol ich \u00fa\u010dinok sk\u00faman\u00fd na modelovom organizme Caenorhabditis elegans (C. elegans). Zistilo sa, \u017ee OxyS naru\u0161ila chemosenzorick\u00e9 vlastnosti C. elegans inhib\u00edciou expresie chemosenzorick\u00e9ho g\u00e9nu che-2 a DsrA zas obmedzila \u017eivotnos\u0165 C. elegans potla\u010den\u00edm expresie g\u00e9nu diacylglycerol lip\u00e1zy F42G9.6, \u010d\u00edm sa vo v\u00fdslednom efekte E. coli chr\u00e1nila pred po\u017eiaren\u00edm C. elegans(33).<\/p>\n

V\u00fdskumn\u00e1 skupina Tanooka a\u00a0 kol. uskuto\u010dnila experiment, v ktorom sa zaoberali ot\u00e1zkou, \u010di cudzie bakteri\u00e1lne g\u00e9ny m\u00f4\u017eu vyv\u00edja\u0165 onkog\u00e9nnu aktivitu prostredn\u00edctvom interferencie s hostite\u013esk\u00fdmi RNA, ak s\u00fa endog\u00e9nne exprimovan\u00e9. Vych\u00e1dzali z toho, \u017ee miRNA dok\u00e1\u017eu regulova\u0165 expresiu onkog\u00e9nov prostredn\u00edctvom interakcie s ich mRNA v oblasti UTR (neprekladan\u00fd \u00fasek RNA). Spomedzi r\u00f4znych druhov interferuj\u00facich RNA m\u00e1 endog\u00e9nne exprimovan\u00e1 kompetit\u00edvna RNA \u201e\u0161pongiov\u00fd efekt\u201c na nahradenie funkcie miRNA. Na z\u00e1klade tohto je teda mo\u017en\u00e9 predpoklada\u0165, \u017ee aj endog\u00e9nne exprimovan\u00e1 cudzia RNA bakteri\u00e1lneho p\u00f4vodu m\u00f4\u017ee sp\u00f4sobi\u0165 rakovinu, ak sa uplatn\u00ed efekt \u0161pongie a\u00a0 bakteri\u00e1lna RNA ovplyvn\u00ed expresiu onkog\u00e9nov. Pri tomto experimente bol pou\u017eit\u00fd enterobakteri\u00e1lny plazmidov\u00fd g\u00e9n mucAB a jeho genomick\u00fd homol\u00f3g umuDC z E. coli. V bunk\u00e1ch, do ktor\u00fdch boli vnesen\u00e9 g\u00e9ny mucAB a umuDC, bola pozorovan\u00e1 deregul\u00e1cia viacer\u00fdch g\u00e9nov, pri\u010dom najviac bola pozorovan\u00e1 deregul\u00e1cia onkog\u00e9nu Nedd9. Na z\u00e1klade t\u00fdchto pozorovan\u00ed autori vyslovili hypot\u00e9zu, \u017ee mRNA g\u00e9nov mucAB\/umuDC kompetit\u00edvne interferuje s miRNA-145, ktor\u00e1 p\u00f4sob\u00ed regula\u010dne na dan\u00fa oblas\u0165, \u010d\u00edm zvy\u0161uj\u00fa expresiu Nedd9, \u010do vedie k mal\u00edgnej transform\u00e1cii buniek. Tieto zistenia indikuj\u00fa, \u017ee ak m\u00e1 RNA sekvenciu komplement\u00e1rnu k ur\u010ditej miRNA, dok\u00e1\u017ee s \u0148ou interagova\u0165 a ovplyvni\u0165 expresiu g\u00e9nov, ktor\u00e9 s\u00fa pod kontrolou danej miRNA, pri\u010dom interaguj\u00faca RNA m\u00f4\u017ee by\u0165 cudzieho p\u00f4vodu(34).<\/p>\n

\u010eal\u0161ou skupinou zauj\u00edmav\u00fdch RNA s\u00fa dlh\u00e9 nek\u00f3duj\u00face RNA (lncRNA), ktor\u00fdm sa za\u010dala venova\u0165 pozornos\u0165 len ned\u00e1vno a od sRNA sa odli\u0161uj\u00fa svojou d\u013a\u017ekou. Je o nich zn\u00e1me, \u017ee pokr\u00fdvaj\u00fa relat\u00edvne ve\u013ek\u00fa \u010das\u0165 gen\u00f3mu a zistilo sa, \u017ee rovnako ako miRNA alebo sRNA dok\u00e1\u017eu ovplyvni\u0165 expresiu svojich cie\u013eov\u00fdch g\u00e9nov. Experimenty uk\u00e1zali, \u017ee bakt\u00e9rie po\u010das infekcie dok\u00e1\u017eu meni\u0165 expresiu hostite\u013esk\u00fdch lncRNA s cie\u013eom deregul\u00e1cie imunitn\u00fdch reakci\u00ed hostite\u013ea vo\u010di patog\u00e9nu. Rovnako aj bakt\u00e9rie produkuj\u00fa lncRNA, ktor\u00e9 im pom\u00e1haj\u00fa odol\u00e1va\u0165 bunkov\u00fdm antibakteri\u00e1lnym aktivit\u00e1m, no zatia\u013e neboli identifikovan\u00e9 \u017eiadne bakteri\u00e1lne lncRNA, ktor\u00e9 by sa podie\u013eali na epigenetick\u00fdch zmen\u00e1ch alebo na zmen\u00e1ch stability a regul\u00e1cie hostite\u013esk\u00fdch mRNA(35).<\/p>\n

Dysbi\u00f3za<\/h3>\n

\u010crevn\u00fd mikrobi\u00f3m zlo\u017eito interaguje s\u00a0 hostite\u013esk\u00fdm organizmom nielen na lok\u00e1lnej, ale aj vzdialenej \u00farovni. Zdrav\u00e9 a vyv\u00e1\u017een\u00e9 zlo\u017eenie \u010drevnej mikrofl\u00f3ry je esenci\u00e1lne pre zachovanie \u010drevnej bari\u00e9ry, imunity a metabolizmu. V\u00e4\u010d\u0161inu zdravej intestin\u00e1lnej mikrobioty tvoria bakt\u00e9rie z dvoch kme\u0148ov: Bacteroidetes a Firmicutes. Vo fek\u00e1lnej mikrofl\u00f3re zdrav\u00fdch jedincov boli najviac detegovan\u00e9 \u0161tyri bakteri\u00e1lne kmene, ktor\u00fdmi s\u00fa Bacteroidetes, Firmicutes, Proteobacteria a Actinobacteria(36). Bakteri\u00e1lna dysbi\u00f3za, zmeny v zlo\u017een\u00ed a\u00a0 podiele mikrobi\u00f3mu, sa sp\u00e1ja s\u00a0 mnoh\u00fdmi chorobami, ktor\u00fdmi s\u00fa metabolick\u00e9 ochorenia, psychiatrick\u00e9 poruchy, ale aj neoplastick\u00e9 choroby. Pri n\u00e1dorov\u00fdch ochoreniach je dysbi\u00f3za sp\u00e1jan\u00e1 s\u00a0 rakovinou mo\u010dov\u00fdch ciest, kr\u010dka maternice, prostaty, ko\u017ee, prsn\u00edkov, d\u00fdchac\u00edch ciest, lymfatick\u00fdch uzl\u00edn a hrub\u00e9ho \u010dreva(14). Na z\u00e1klade rast\u00facich d\u00f4kazov o tom, \u017ee dysbi\u00f3za m\u00f4\u017ee s\u00favisie\u0165 s karcinogen\u00e9zou, bolo vysloven\u00fdch p\u00e4\u0165 hypot\u00e9z, ako by k tomu mohlo d\u00f4js\u0165: 1. alfa-bug(37); 2. vodi\u010d spolujazdec; 3. efekt biofilmu(38); 4. dynamick\u00e1 rovnov\u00e1ha \u010drevnej mikrofl\u00f3ry; 5. n\u00e1hodn\u00fd ved\u013eaj\u0161\u00ed efekt(39). Tabu\u013eka 2 zn\u00e1zor\u0148uje detegovan\u00e9 altern\u00e1cie v mikrobi\u00f3me jedincov pri r\u00f4znych typoch rakoviny. Hoci existuje ve\u013ea d\u00f4kazov o spojen\u00ed bakteri\u00e1lnej dysbi\u00f3zy a karcinogen\u00e9zy, st\u00e1le zost\u00e1va ot\u00e1zne, \u010di rakovina vznik\u00e1 ako d\u00f4sledok zmien mikrobioty alebo zmeny v \u201enorm\u00e1lnej\u201c mikrofl\u00f3re s\u00fa sp\u00f4soben\u00e9 vznikom a progresiou karcinogen\u00e9zy(14).<\/p>\n

Z\u00e1ver<\/h3>\n

Hoci v\u00e4\u010d\u0161ine mechanizmov st\u00e1le ch\u00fdba \u00fapln\u00e9 objasnenie, teraj\u0161ie poznatky jasne potvrdzuj\u00fa \u00fa\u010das\u0165 bakteri\u00e1lnej infekcie na indukcii a progresii rakoviny. \u010eal\u0161ie v\u00fdskumy zaoberaj\u00face sa t\u00fdmto spojen\u00edm by mohli vies\u0165 k jeho \u00fapln\u00e9mu pochopeniu, \u010do by predstavovalo d\u00f4le\u017eit\u00fd pokrok ved\u00faci k zefekt\u00edvneniu rie\u0161enia jedn\u00e9ho z najv\u00e4\u010d\u0161\u00edch zdravotn\u00fdch probl\u00e9mov dne\u0161nej doby.<\/p>\n

Po\u010fakovanie<\/h3>\n

T\u00e1to pr\u00e1ca vznikla za podpory Opera\u010dn\u00e9ho programu Integrovan\u00e1 infra\u0161trukt\u00fara na z\u00e1klade projektu ITMS: 313011V446 spolufinancovan\u00e9ho Eur\u00f3pskym fondom region\u00e1lneho rozvoja.<\/p>\n

 <\/p>\n

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 <\/p>\n","protected":false},"excerpt":{"rendered":"

*A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens   \u00davod Medzi prv\u00e9 asoci\u00e1cie bakt\u00e9ri\u00ed s rakovinou patr\u00ed te\u00f3ria z roku 1772, ktor\u00e1 predpokladala \u00fa\u010das\u0165 Mycobacterium tuberculosis na vzniku malign\u00edt. Te\u00f3ria zalo\u017een\u00e1 na pozorovan\u00ed bronchog\u00e9nnych karcin\u00f3mov v miestach zjazven\u00fdch v d\u00f4sledku tuberkul\u00f3zy bola takisto<\/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":[290],"tags":[899,1821,1817,1820,1818,775,1328,1325,408,1819],"class_list":["post-2371","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-cancer","tag-dysbiosis","tag-dysbioza-en","tag-infection","tag-infekcia-en","tag-inflammation","tag-microbiome","tag-mikrobiom-en","tag-rakovina-en","tag-zapal-en","typ_clanku-review-article"],"acf":{"abstrakt":"

Microorganisms affect many physiological but also pathophysiological processes in their host organisms. Although the hypothesis of the involvement of bacteria in the induction and progression of cancer was initially rejected, scientific evidence is increasingly confirming the exact opposite. Although the number of directly carcinogenic bacteria is minimal and the relationship between these prokaryotic organisms and cancer is still not fully understood, it is known that bacteria can stimulate the onset or facilitate the development of tumorigenesis in several ways. This article describes the mechanisms by which bacteria can induce carcinogenesis or its progression and summarises the results of experiments dealing with this issue.<\/p>\n

Keywords:<\/strong> cancer, microbiome, infection, inflammation, dysbiosis<\/p>\n","casopis":[{"ID":2417,"post_author":"7","post_date":"2022-02-08 13:25:20","post_date_gmt":"2022-02-08 12:25:20","post_content":"Druh\u00e9 vydanie \u010dasopisu laborat\u00f3rnej medic\u00edny 2021\/2<\/strong>\r\n

    \r\n \t
  • Molekul\u00e1rny mechanizmus karcinogen\u00e9zy indukovanej prostredn\u00edctvom bakt\u00e9ri\u00ed<\/li>\r\n \t
  • Extracelul\u00e1rne vezikuly a ich potenci\u00e1lne vyu\u017eitie v klinickej praxi<\/li>\r\n \t
  • Detection of copy number variation from low-coverage whole-genome sequencing data<\/li>\r\n \t
  • Lengths of circulating DNA fragments as a promising predictor of cancer stage<\/li>\r\n \t
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