{"id":1799,"date":"2018-10-21T17:44:55","date_gmt":"2018-10-21T15:44:55","guid":{"rendered":"http:\/\/www.pacienti.cz\/?p=1799"},"modified":"2018-10-21T18:03:09","modified_gmt":"2018-10-21T16:03:09","slug":"devaskularizace-tumoru-jako-potencialni-imunoterapeuticka-strategie","status":"publish","type":"post","link":"https:\/\/www.pacienti.cz\/?p=1799","title":{"rendered":"Devaskularizace tumoru jako potenci\u00e1ln\u00ed imunoterapeutick\u00e1 strategie"},"content":{"rendered":"
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Devaskularizace tumoru jako potenci\u00e1ln\u00ed imunoterapeutick\u00e1 strategie<\/span><\/a> (EN<\/span>)
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Devaskularizace tumoru jako potenci\u00e1ln\u00ed imunoterapeutick\u00e1 strategie<\/strong>
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Tom\u00e1\u0161 Buchler Ikona ORCID, Pavel Vasek, Radek \u0160picek, Pavel \u0160rob\u00e1nek a V\u00e1clav Horejsi Ikona ORCID
\n<\/span>P\u0159ijato 18 \u010derven 2018, Akceptov\u00e1no 15 z\u00e1\u0159\u00ed 2018, zve\u0159ejn\u011bno online: 11 \u0159\u00edjna 2018<\/span><\/span><\/h4>\n

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St\u00e1hnout citace https:\/\/doi.org\/10.1080\/2162402X.2018.1526614<\/span><\/span><\/h4>\n

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V tomto \u010dl\u00e1nku<\/span><\/span><\/h4>\n

\u00a0\u00a0<\/strong><\/p>\n

ABSTRAKTN\u00cd<\/span><\/strong><\/span><\/h4>\n


\n<\/span>\u00davod
\n<\/span>Indukce n\u00e1dorov\u00e9 isch\u00e9mie jako imunoterapeutick\u00e9 strategie
\n<\/span>Technika \u00fapln\u00e9 devaskularizace n\u00e1doru
\n<\/span>Kompletn\u00ed devaskularizace n\u00e1dor\u016f: p\u0159edklinick\u00e9 studie
\n<\/span>Kompletn\u00ed devaskularizace n\u00e1doru: klinick\u00e9 zku\u0161enosti
\n<\/span>Imunitn\u00ed odpov\u011b\u010f na \u00faplnou devaskularizaci n\u00e1doru
\n<\/span>Kompletn\u00ed devaskularizace n\u00e1doru v kontextu
\n<\/span>Z\u00e1v\u011br
\n<\/span>Reference<\/span><\/span><\/p>\n

ABSTRAKTN\u00cd<\/strong><\/span><\/p>\n

Kompletn\u00ed devaskularizace n\u00e1dor\u016f (CTD) je chirurgick\u00e1 technika, kter\u00e1 vede k \u00fapln\u00e9mu naru\u0161en\u00ed ligac\u00ed nebo \u0159ez\u00e1n\u00ed aferentn\u00ed a eferentn\u00ed n\u00e1dorov\u00e9 vaskulatury, kter\u00e1 z\u016fst\u00e1v\u00e1 in situ. <\/span>U n\u011bkter\u00fdch zv\u00ed\u0159ec\u00edch model\u016f indukuje CTD imunitn\u00ed odpov\u011bdi, kter\u00e9 vedou k regresi vzd\u00e1len\u00fdch metast\u00e1z a ochrann\u00e9 imunity.
\n<\/span>Kl\u00ed\u010dov\u00e1 slova: imunoterapie, isch\u00e9mie, devaskularizace, rakovina, ligace n\u00e1dor\u016f<\/span><\/p>\n


\n<\/span>\u00davod<\/span><\/p>\n

Imunitn\u00ed syst\u00e9m hraje d\u016fle\u017eitou roli p\u0159i karcinogenezi a progresi rakoviny. <\/span>Ned\u00e1vno nov\u00e9 imunoterapeutick\u00e9 strategie umo\u017enily onkolog\u016fm vyu\u017e\u00edvat potenci\u00e1ln\u00ed protin\u00e1dorov\u00e9 imunitn\u00ed odpov\u011bdi, co\u017e vedlo ke zlep\u0161en\u00ed p\u0159e\u017eit\u00ed n\u011bkter\u00fdch rakovin a dokonce k l\u00e9\u010db\u011b pokro\u010dil\u00fdch malign\u00edch onemocn\u011bn\u00ed u men\u0161iny pacient\u016f.<\/span><\/p>\n

Koncepce, \u017ee by devaskularizace n\u00e1doru mohla indukovat imunitn\u00ed reakce, kter\u00e9 vedou k ochran\u011b imunity, byla propagov\u00e1na Lewisem a Aptekmanem.1 Lewis MR, Aptekman PM. <\/span>Antigenita sarkom\u016f podstupuj\u00edc\u00edch atrofii u potkan\u016f. <\/span>J Immunol. <\/span>1951 Sep; 67 (3): 193-195. <\/span>PMID: 14888881. [PubMed], [Web of Science \u00ae], [Google Scholar] Dal\u0161\u00ed experimenty uk\u00e1zaly, \u017ee ochrann\u00e1 imunita je omezena na vysoce imunogenn\u00ed n\u00e1dory, jako jsou ty indukovan\u00e9 3-methylcholantrenem nebo n\u00e1dory, kter\u00e9 pro\u0161ly zna\u010dnou passage.2 Fardon <\/span>JC, princ JE. <\/span>Pokus vyvolat rezistenci u inbredn\u00edho kmene my\u0161\u00ed ligac\u00ed homologn\u00edho n\u00e1doru. <\/span>Cancer Res. <\/span>1953 Jan 13 (1): 9-13. <\/span>PMID: 13032942. [PubMed], [Web of Science \u00ae], [Google Scholar] -4 Prehn RT, Hlavn\u00ed JM. <\/span>Imunita v\u016f\u010di sarkom\u016fm vyvolan\u00fdm methylcholantrenem. <\/span>J Natl Cancer Inst. <\/span>1957 Jun; 18 (6): 769-778. <\/span>PMID: 13502695. [PubMed], [Google Scholar] Nicm\u00e9n\u011b u t\u011bchto typ\u016f n\u00e1dor\u016f byla tak\u00e9 vylou\u010dena jednoduch\u00e1 excize. 4 Prehn RT, Main JM. <\/span>Imunita v\u016f\u010di sarkom\u016fm vyvolan\u00fdm methylcholantrenem. <\/span>J Natl Cancer Inst. <\/span>1957 Jun; 18 (6): 769-778. <\/span>PMID: 13502695. [PubMed], [Google Scholar] V\u00fdvoj t\u011bchto pojm\u016f byl d\u0159\u00edve p\u0159ezkoum\u00e1n Gorelikem.5 Gorelik E. Soub\u011b\u017en\u00e1 imunita n\u00e1doru a rezistence na druhou n\u00e1dorovou v\u00fdzvu. <\/span>Adv Cancer Res. <\/span>1983; 39: 71-120. <\/span>PMID: 6194674. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar]<\/span><\/p>\n

V \u010cesk\u00e9 republice byl vyvinut koncept devaskularizace n\u00e1dor\u016f chirurgem Karel Fort\u00fdn.6 Fort\u00fdn K, Hradeck\u00fd J, Pazdera J, Klaudy J, Hruban V, Dvo\u0159\u00e1k P, Matousek J, Tich\u00fd J, Kol\u00edn V <\/span>Devitalizace a potenci\u00e1l devaskularizace mal\u00e9ho a hrub\u00e9ho st\u0159eva v terapeutick\u00e9m pou\u017eit\u00ed t\u00e9to opera\u010dn\u00ed metody. <\/span>Z Exp Chir Transplantace Kunstliche Organe. <\/span>1985; 18 (1): 42-50. <\/span>PMID: 2986369. [PubMed], [Google Scholar] -8 Hor\u00e1k V, Fortyn K, Hruban V, Klaudy J. D\u011bdi\u010dn\u00fd melanoblastom u miniaturn\u00edch prasat a jeho \u00fasp\u011b\u0161n\u00e1 terapie devitaliza\u010dn\u00ed technikou. <\/span>Cell Mol Biol (Noisy-Le-Grand). <\/span>1999, 45 (7): 1119-1129. <\/span>PMID: 10644016. [PubMed], [Web of Science\u00ae], [Google Scholar] Vyvinul experiment\u00e1ln\u00ed zv\u00ed\u0159ec\u00ed model pro n\u00e1dorovou devaskularizaci8 Hor\u00e1k V, Fortyn K, Hruban V, Klaudy J. D\u011bdi\u010dn\u00fd melanoblastom u miniaturn\u00edch prasat a jeho \u00fasp\u011b\u0161n\u00e1 l\u00e9\u010dba <\/span>devitaliza\u010dn\u00ed technikou. <\/span>Cell Mol Biol (Noisy-Le-Grand). <\/span>1999, 45 (7): 1119-1129. <\/span>PMID: 10644016. [PubMed], [Web of Science \u00ae], [Google Scholar] a v roce 2001 byla provedena studie f\u00e1ze I u pacient\u016f s metastatick\u00fdmi solidn\u00edmi tumory.9 Fi\u0161er B List zdravotn\u00edho tajemn\u00edka, ministerstvo zdravotnictv\u00ed \u010desk\u00e9ho <\/span>prezidenta \u010cesk\u00e9 asociace pacient\u016f Zpr\u00e1va o p\u0159edb\u011b\u017en\u00fdch v\u00fdsledc\u00edch klinick\u00fdch studi\u00ed; <\/span>2002, ref. <\/span>3924\/02. <\/span>doi: 10.1044 \/ 1059-0889 (2002 \/ er01) [Google Scholar]<\/span><\/p>\n

L\u00e9\u010dba \u00faplnou devaskularizac\u00ed n\u00e1dor\u016f (CTD) je prakticky nezn\u00e1m\u00e1 mimo \u00fazem\u00ed \u010cesk\u00e9 republiky a je velmi kontroverzn\u00ed iv r\u00e1mci \u010desk\u00e9 l\u00e9ka\u0159sk\u00e9 komunity. <\/span>P\u0159esto\u017ee l\u00e9\u010dba nen\u00ed schv\u00e1lena pro klinick\u00e9 pou\u017eit\u00ed u lid\u00ed, CTD se ob\u010das pou\u017e\u00edv\u00e1 ve veterin\u00e1rn\u00ed medic\u00edn\u011b.<\/span><\/p>\n

C\u00edlem tohoto p\u0159ehledu je poskytnout stru\u010dn\u00fd p\u0159ehled metody a kritickou anal\u00fdzu jej\u00edho potenci\u00e1lu v r\u00e1mci spektra sou\u010dasn\u00fdch antineoplastick\u00fdch imunoterapeutick\u00fdch strategi\u00ed.<\/span><\/p>\n


\n<\/span>Indukce n\u00e1dorov\u00e9 isch\u00e9mie jako imunoterapeutick\u00e9 strategie
\n<\/span>Ligace n\u00e1dor\u016f<\/span><\/strong><\/p>\n

Potenci\u00e1l ischemie n\u00e1dor\u016f k vyvol\u00e1n\u00ed imunitn\u00ed odpov\u011bdi byl zkoum\u00e1n od poloviny 20. stolet\u00ed. <\/span>V pr\u016fkopnick\u00fdch pokusech publikovan\u00fdch v letech 1951 a 1952 indukovaly Lewis a Aptekman regresi n\u00e1dor\u016f u r\u016fzn\u00fdch plemen potkan\u016f s u\u0161krcen\u00edm c\u00e9v u syngenn\u00edch karcinom\u016f, sarkom\u016f a fibrosarkom\u016f. <\/span>V\u00fdsledn\u00fd ischemicky poran\u011bn\u00fd n\u00e1dor byl ponech\u00e1n in situ po dobu 24 a\u017e 96 hodin podle studijn\u00edho protokolu. <\/span>Postup vyvolal ochrannou imunitu proti op\u011btovn\u00e9mu z\u00e1sahu se stejn\u00fdmi n\u00e1dory u 70-100% krys.1 Lewis MR, Aptekman PM. <\/span>Antigenita sarkom\u016f podstupuj\u00edc\u00edch atrofii u potkan\u016f. <\/span>J Immunol. <\/span>1951 Sep; 67 (3): 193-195. <\/span>PMID: 14888881. [PubMed], [Web of Science\u00ae], [Google Scholar], 10 Lewis MR, Maxwell DB, Aptekman PM, Demchur P. Atrofie sarkomu u potkan\u016f \u200b\u200bs n\u00e1slednou imunitn\u00ed odolnost\u00ed; <\/span>chirurgick\u00e1 metoda pro v\u00fdvoj n\u00e1dorov\u00e9 imunity u potkan\u016f. <\/span><\/span><\/p>\n

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Chirurgick\u00e1 operace. <\/span>1951 Oct; 30 (4): 689-694. <\/span>PMID: 14893047. [PubMed], [Web of Science \u00ae], [Google Scholar], 11 Lewis MR, Aptekman PM. <\/span>Atrofie n\u00e1dor\u016f zp\u016fsoben\u00e1 u\u0161krcen\u00edm a doprov\u00e1zen\u00e1 v\u00fdvojem n\u00e1dorov\u00e9 imunity u potkan\u016f. <\/span>Rakovina. <\/span>1952 Mar 5; (2): 411-413. <\/span>PMID: 14905430 doi: 10,1002 \/ 1097 – 0142 (195203). 5: 2 <411 :: AID-CNCR2820050233> 3.0.CO 2-R [crossRef], [PubMed], [Web of Science \u00ae], [Google Scholar <\/span>] Mezi mnoha dostupn\u00fdmi lok\u00e1ln\u00edmi l\u00e9\u010debn\u00fdmi postupy bylo prok\u00e1z\u00e1no, \u017ee ligace n\u00e1dor\u016f indukuje pom\u011brn\u011b silnou z\u00e1n\u011btlivou odpov\u011b\u010f a n\u00e1sledn\u011b imunitn\u00ed reakci specifickou pro n\u00e1dory.12 Baldwin RW. <\/span>Imunita n\u00e1dor\u016f indukovan\u00fdch methylcholantrenem u inbredn\u00edch potkan\u016f \u200b\u200bpo atrofii a regresi implantovan\u00fdch n\u00e1dor\u016f. <\/span>Br J Rakovina. <\/span>1955. december 9; (4): 652-657. <\/span>PMID: 13304228; <\/span>PubMed Central PMCID: PMC2073778 doi: 10.1038 \/ bjc.1955.70. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] -15 Mohr SJ, Whitesel JA. <\/span>Spont\u00e1nn\u00ed regrese metast\u00e1z ren\u00e1ln\u00edch karcinom\u016f po p\u0159edopera\u010dn\u00ed embolizaci prim\u00e1rn\u00edho n\u00e1doru a n\u00e1sledn\u00e9 nefrektomii. <\/span>Urologie. <\/span>1979 \u010derven; 14 (1): 5-8. <\/span>PMID: 452221. [crossRef], [PubMed], [Web of Science \u00ae], [v\u011bnovan\u00e9 Scholar] Neel a Ritts uv\u00e1d\u011bj\u00ed v\u00fdsledky srovn\u00e1vac\u00ed studie, kde my\u0161i nesouc\u00ed syngenn\u00ed n\u00e1dory, v\u010detn\u011b virov\u011b indukovan\u00e9 prsn\u00edho adenokarcinomu a 3- <\/span>methylcholantrenem byl podroben op\u011btovn\u00e9mu pou\u017eit\u00ed s \u200b\u200bn\u00e1dorov\u00fdmi bu\u0148kami po jednoduch\u00e9 excizi, kryochirurgii, elektrokoagulaci, excizi n\u00e1doru ligovan\u00e9ho po dobu 4 nebo 24 hodin a ligace bez excise. <\/span>\u017d\u00e1dn\u00e1 ochrann\u00e1 imunita nebyla vyvol\u00e1na jednoduchou excizi\u00ed nebo exciz\u00ed po 4 hodin\u00e1ch ligace. <\/span>Ligace bez vy\u0159\u00edznut\u00ed v\u0161ak vedla k m\u00e9n\u011b \u010dast\u00e9mu nebo zpo\u017ed\u011bn\u00e9mu vzhledu n\u00e1dor\u016f v m\u00edst\u011b obnoven\u00ed, zat\u00edmco v\u00fdsledky excize po 24hodinov\u00e9 ligaci spadly mezi ty, kter\u00e9 byly pro jednoduchou excizi a ligaci bez excise.14 Neel HB 3., Ritts RE Jr <\/span>Imunoterapeutick\u00fd \u00fa\u010dinek nekr\u00f3zy n\u00e1dor\u016f po kryochirurgii, elektrokoagulaci a ligaci. <\/span>J Surg Oncol. <\/span>1979, 11 (1): 45-52. <\/span>PMID: 431082. [crossRef], [PubMed], [Web of Science \u00ae], [v\u011bnovan\u00e9 Scholar] Krom\u011b toho bylo tak\u00e9 pops\u00e1no, \u017ee arteri\u00e1ln\u00ed embolizace potenci\u00e1ln\u011b vyvol\u00e1v\u00e1 protin\u00e1dorov\u00e9 imunity u lid\u00ed, i kdy\u017e ale \u017e\u00e1dn\u00e9 spolehliv\u00e9 \u00fadaje zobrazuj\u00edc\u00ed kvantifikaci <\/span>tento \u00fa\u010dinek je v sou\u010dasn\u00e9 dob\u011b k dispozici.15 Mohr SJ, Whitesel JA. <\/span>Spont\u00e1nn\u00ed regrese metast\u00e1z ren\u00e1ln\u00edch karcinom\u016f po p\u0159edopera\u010dn\u00ed embolizaci prim\u00e1rn\u00edho n\u00e1doru a n\u00e1sledn\u00e9 nefrektomii. <\/span><\/span><\/p>\n

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Urologie. <\/span>1979 \u010derven; 14 (1): 5-8. <\/span>PMID: 452221. [CrossRef], [PubMed], [Web of Science \u00ae], [Google Scholar] indukovan\u00e9 ischemicky reperfuzn\u00ed poran\u011bn\u00ed n\u00e1dor\u016fN\u011bkolik autor\u016f provedlo pokusy o ischemicko-reperfuzn\u00ed poran\u011bn\u00ed n\u00e1dorov\u00e9 tk\u00e1n\u011b s c\u00edlem indukovat ochrannou <\/span>imunitn\u00ed odpov\u011bdi.16 Khafagy M, Wanebo HJ, Alfieri A, Hahn EW. <\/span>\u00da\u010dinek r\u016fzn\u00fdch zp\u016fsob\u016f l\u00e9\u010dby rakoviny na imunitu v\u016f\u010di antigenn\u00edmu transplantovateln\u00e9mu my\u0161\u00edmu fibrosarkomu (Meth A). <\/span>AJR Am J Roentgenol. <\/span>1977 Jun; <\/span>128 (6): 1027-1029. <\/span>PMID: 414534 doi: 10,2214 \/ ajr.128.6.1027 [crossRef], [PubMed], [Web of Science \u00ae], [v\u011bnovan\u00e9 Scholar] -18 Kamijo A, Koshino T, M, Uesugi Nitto H, Saito T. inhibice. <\/span>plicn\u00ed metast\u00e1zy bun\u011b\u010dn\u00e9 linie osteosarkomu POS-1 transplantovan\u00e9 my\u0161\u00edm pomoc\u00ed ligace stehna. <\/span>Cancer Lett. <\/span>2002, 15, 188 (1-2): 213-219. <\/span>PMID: 12406567. [CrossRef], [PubMed], [Web of Science \u00ae], [Google Scholar] Specifick\u00e1 imunita v\u016f\u010di n\u00e1sleduj\u00edc\u00edmu o\u010dkov\u00e1n\u00ed n\u00e1dorov\u00fdm o\u010dkov\u00e1n\u00edm byla lep\u0161\u00ed po 24hodinov\u00e9m postupu ligace \/ uvol\u0148ov\u00e1n\u00ed ve srovn\u00e1n\u00ed s exciz\u00ed n\u00e1doru, n\u00e1sledovalo p\u0159edopera\u010dn\u00ed oza\u0159ov\u00e1n\u00ed <\/span>excize, kryochirurgie, oz\u00e1\u0159en\u00ed vysok\u00fdmi d\u00e1vkami a oz\u00e1\u0159en\u00ed n\u00edzk\u00fdmi d\u00e1vkami u my\u0161\u00ed nesouc\u00edch n\u00e1dory vyvolan\u00e9 3-methylcholantrenem.16 Khafagy M, Wanebo HJ, Alfieri A, Hahn EW. <\/span>\u00da\u010dinek r\u016fzn\u00fdch zp\u016fsob\u016f l\u00e9\u010dby rakoviny na imunitu v\u016f\u010di antigenn\u00edmu transplantovateln\u00e9mu my\u0161\u00edmu fibrosarkomu (Meth A). <\/span>AJR Am J Roentgenol. <\/span>1977 Jun; <\/span>128 (6): 1027-1029. <\/span>PMID: 414534 doi: 10.2214 \/ ajr.128.6.1027 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Bylo hl\u00e1\u0161eno osm hodinov\u00e1 ligace s n\u00e1sledn\u00fdm uvoln\u011bn\u00edm n\u00e1dorov\u00e9 vaskulatury, <\/span>chr\u00e1n\u00edc\u00ed imunitu jako je kryochirurgie p\u0159i p\u0159ekro\u010den\u00ed efektu jednoduch\u00e9 excize v my\u0161\u00edm modelu.17 Neel HB 3., Ketcham AS, Hammond WG. <\/span>Experiment\u00e1ln\u00ed hodnocen\u00ed oncocidu in situ pro prim\u00e1rn\u00ed l\u00e9\u010dbu n\u00e1dor\u016f: srovn\u00e1n\u00ed n\u00e1dorov\u011b specifick\u00e9 imunity po \u00fapln\u00e9m exci kryonekr\u00f3zy a ligace. <\/span>Laryngoskop. <\/span>1973 Mar; 83 (3): 376-387. <\/span>PMID: 4690029 doi: 10.1288 \/ 00005537-197303000-00009 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Podle Kamijo et. <\/span>al. <\/span>liga\u010dn\u00ed \/ uvol\u0148ovac\u00ed postup v\u00fdznamn\u011b sn\u00ed\u017eil metastatick\u00fd potenci\u00e1l n\u00e1dor\u016f v my\u0161\u00edm modelu, kter\u00fd byl inokulov\u00e1n bun\u011b\u010dnou lini\u00ed my\u0161\u00ed osteosarkomu POS-1. <\/span>Tento \u00fa\u010dinek byl p\u0159i\u010d\u00edt\u00e1n vy\u0161\u0161\u00ed citlivosti na reaktivn\u00ed kysl\u00edk, kter\u00e9 byly produkov\u00e1ny b\u011bhem reperf\u00faze bun\u011b\u010dn\u00e9 subpopulace s vysok\u00fdm metastatick\u00fdm potenci\u00e1lem.18 Kamijo A, Koshino T, Uesugi M, Nitto H, Saito T. Inhibice plicn\u00ed metast\u00e1zy bun\u011b\u010dn\u00e9 linie osteosarkomu <\/span>POS-1 transplantovan\u00fd do my\u0161\u00ed ligac\u00ed stehna. <\/span>Cancer Lett. <\/span>2002, 15, 188 (1-2): 213-219. <\/span>PMID: 12406567. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Technika \u00fapln\u00e9 devaskularizace n\u00e1doruCTD je chirurgick\u00e1 technika, kter\u00e1 sest\u00e1v\u00e1 z \u00fapln\u00e9ho p\u0159eru\u0161en\u00ed v\u0161ech aferentn\u00edch a eferen\u010dn\u00edch vaskulatur n\u00e1doru ligac\u00ed nebo <\/span>\u0159ez\u00e1n\u00ed, kter\u00e9 je pak ponech\u00e1no in situ (obr\u00e1zek 1). <\/span>V obou experimentech na zv\u00ed\u0159atech a p\u0159i hl\u00e1\u0161en\u00fdch lidsk\u00fdch postupech byly \u010d\u00e1sti norm\u00e1ln\u00edch org\u00e1n\u016f, kter\u00e9 obsahovaly n\u00e1dor, rovn\u011b\u017e devaskularizov\u00e1ny, nap\u0159. <\/span>(obr. 2) .6 Fort\u00fdn K, Hradeck\u00fd J, Pazdera J, Klaudy J, Hruban V, Dvo\u0159\u00e1k P, Matousek J, Tich\u00fd J, Kol\u00edn V. Mal\u00e9 a tlust\u00e9 st\u0159evo <\/span>deviskulariza\u010dn\u00ed devitalizace a potenci\u00e1l v terapeutick\u00e9m pou\u017eit\u00ed t\u00e9to opera\u010dn\u00ed metody. <\/span>Z Exp Chir Transplantace Kunstliche Organe. <\/span>1985; 18 (1): 42-50. <\/span>PMID: 2986369. [PubMed], [Google Scholar], 19 Kalina V, Kopsk\u00fd DJ. <\/span>Autologn\u00ed n\u00e1dor imunizuj\u00edc\u00ed devaskularizaci v l\u00e9\u010db\u011b rakoviny. <\/span>Med hypot\u00e9zy. <\/span>2016 duben; <\/span>89: 72-78. <\/span>PMID: 26968914 doi: 10.1016 \/ j.mehy.2016.02.004 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar], 20 Va\u0161ek P, Krajnik J, Kopsk\u00fd DJ, Kalina V, Frydrych M <\/span>Autologn\u00ed n\u00e1dor imunizuj\u00edc\u00ed devaskularizaci invazivn\u00edho kolorekt\u00e1ln\u00edho karcinomu: p\u0159\u00edpadov\u00e1 studie a p\u0159ehled literatury. <\/span>Mol Clin Oncol. <\/span>2016 5. listopadu, 5: 521-526. <\/span>PMID: 27882237 PMCID: PMC5103851. <\/span>2: 10.3892 \/ mco.2016.1033 [Crossref], [PubMed], [Google Scholar] <\/span><\/span><\/p>\n

Obr\u00e1zek 1.<\/span><\/span><\/p>\n

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Kompletn\u00ed devaskularizace n\u00e1dor\u016f vy\u017eaduje trval\u00e9 naru\u0161en\u00ed aferentn\u00ed a eferen\u010dn\u00ed vaskulatury.7 Fortyn K, Hruban V, Hor\u00e1k V. L\u00e9\u010dba malign\u00edho melanomu. <\/span>Br J Surg. <\/span>1994; 81 (1): 146-147. <\/span>PMID: 8155151. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar], 19 Kalina V, Kopsky DJ. <\/span>Autologn\u00ed n\u00e1dor imunizuj\u00edc\u00ed devaskularizaci v l\u00e9\u010db\u011b rakoviny. <\/span>Med hypot\u00e9zy. <\/span>2016 duben; <\/span>89: 72-78. <\/span>PMID: 26968914 doi: 10.1016 \/ j.mehy.2016.02.004 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Nejprve je izolov\u00e1n n\u00e1dor a jeho vaskul\u00e1rn\u00ed a lymfatick\u00e1 dod\u00e1vka je ligov\u00e1na <\/span>(b). <\/span>Ligovan\u00fd n\u00e1dor je ponech\u00e1n in situ (c) a r\u00e1na se uzav\u0159e (d). <\/span>Ligace skrz k\u016f\u017ei je mo\u017en\u00e1 tak\u00e9 v p\u0159\u00edpad\u011b povrchov\u00e9ho lokalizov\u00e1n\u00ed n\u00e1doru, jako u ko\u017en\u00edho melanomu (upraven\u00e9ho z kresby Karla Fort\u00fdna). <\/span><\/span><\/p>\n

Zobrazit plnou velikost Obr\u00e1zek 2. <\/span><\/span><\/p>\n

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V n\u011bkter\u00fdch p\u0159\u00edpadech m\u016f\u017ee \u00fapln\u00fd postup devaskularizace n\u00e1doru zahrnovat izolaci \u010d\u00e1sti <\/span>posti\u017een\u00fd org\u00e1n, jako je tlust\u00e9 st\u0159evo, s obnoven\u00edm pr\u016fchodu kolostomi\u00ed nebo anastom\u00f3zou. 6Display full size Aby se usnadnilo \u00fasp\u011b\u0161n\u00e9 indukce imunitn\u00ed odpov\u011bdi pomoc\u00ed CTD, byla navr\u017eena \u0159ada podm\u00ednek: a) devaskularizace prim\u00e1rn\u00edho n\u00e1doru je v\u00fdhodn\u011bj\u0161\u00ed ne\u017e devaskularizace prim\u00e1rn\u00edho n\u00e1doru <\/span>metast\u00e1za; <\/span>b) alespo\u0148 50% celkov\u00e9 hmotnosti n\u00e1doru v t\u011ble by m\u011blo b\u00fdt devaskularizov\u00e1no; <\/span>c) pacient by nem\u011bl b\u00fdt p\u0159ed l\u00e9\u010dbou standardn\u00edmi re\u017eimy chemoterapie nebo radioterapie.19 Kalina V, Kopsk\u00fd DJ. <\/span>Autologn\u00ed n\u00e1dor imunizuj\u00edc\u00ed devaskularizaci v l\u00e9\u010db\u011b rakoviny. <\/span>Med hypot\u00e9zy. <\/span>2016 duben; <\/span>89: 72-78. <\/span>PMID: 26968914 doi: 10.1016 \/ j.mehy.2016.02.004 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar], 20 Va\u0161ek P, Krajnik J, Kopsk\u00fd DJ, Kalina V, Frydrych M <\/span>Autologn\u00ed n\u00e1dor imunizuj\u00edc\u00ed devaskularizaci invazivn\u00edho kolorekt\u00e1ln\u00edho karcinomu: p\u0159\u00edpadov\u00e1 studie a p\u0159ehled literatury. <\/span>Mol Clin Oncol. <\/span>2016 5. listopadu, 5: 521-526. <\/span>PMID: 27882237 PMCID: PMC5103851. <\/span>dva: 10.3892 \/ mco.2016.1033 [Crossref], [PubMed], [Google Scholar] Kinetick\u00fd model byl vyvinut pro stanoven\u00ed optim\u00e1ln\u00edho pom\u011bru mezi devaskularizovan\u00fdm n\u00e1dorem a zbytkem n\u00e1dorov\u00e9 hmoty.19 Kalina V, Kopsky DJ. <\/span>Autologn\u00ed n\u00e1dor imunizuj\u00edc\u00ed devaskularizaci v l\u00e9\u010db\u011b rakoviny. <\/span>Med hypot\u00e9zy. <\/span>2016 duben; <\/span>89: 72-78. <\/span>PMID: 26968914 doi: 10.1016 \/ j.mehy.2016.02.004. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Byly tak\u00e9 zkoum\u00e1ny r\u016fzn\u00e9 chirurgick\u00e9 techniky ligace n\u00e1dor\u016f. <\/span>Kdy\u017e byla ligace provedena p\u0159es k\u016f\u017ei, krysy Lewis p\u0159e\u017eily o 20 dn\u016f d\u00e9le ne\u017e ty zv\u00ed\u0159ata, jejich\u017e k\u016f\u017ee byla vy\u0159\u00edznut\u00e1, n\u00e1dor izolov\u00e1n, ligov\u00e1n v z\u00e1kladu a znovu sev\u0159en.21 Pokorn\u00e1 E, Hradeck\u00fd J, Mor\u00e1vkov\u00e1 A, Burda P, Kotrnoch J <\/span>, Klaudy J, Faldyna M, Sinkora J, Halouzka R, Jel\u00ednek F, et al. <\/span>Ligace n\u00e1dor\u016f (devitalizace) n\u00e1dor\u016f prsn\u00ed \u017el\u00e1zy u ps\u016f a sarkom u potkan\u016f \u200b\u200bLewis. <\/span>Prezentov\u00e1no na 28. onkologick\u00e9 konferenci v Brn\u011b, 2004. Abstract 168. [Google Scholar] Kompletn\u00ed devaskularizace n\u00e1dor\u016f: p\u0159edklinick\u00e9 studieDestinent\u00e1ln\u00ed prase\u010d\u00ed melanom Speci\u00e1ln\u00ed kmen prasete zn\u00e1m\u00fd jako Libechov Minipig (MeLiM), kter\u00fd se vyzna\u010duje melanoblastomem, se stal nej\u010dast\u011bji pou\u017e\u00edvan\u00fdm modelem pro experimenty CTD \u010desk\u00fdch v\u011bdc\u016f. <\/span>Spont\u00e1nn\u00ed n\u00e1sobn\u00e9 melanomy se vyv\u00edjej\u00ed u p\u0159ibli\u017en\u011b 60% prasat MeLiM.8 Hor\u00e1k V, Fortyn K, Hruban V, Klaudy J. D\u011bdi\u010dn\u00fd melanoblastom u miniaturn\u00edch prasat a jeho \u00fasp\u011b\u0161n\u00e1 terapie devitaliza\u010dn\u00ed technikou. <\/span>Cell Mol Biol (Noisy-Le-Grand). <\/span>1999, 45 (7): 1119-1129. <\/span>PMID: 10644016. [PubMed], [Web of Science\u00ae], [Google Scholar] V\u011bt\u0161ina melanom\u016f (p\u0159ibli\u017en\u011b 65%) se spont\u00e1nn\u011b regresuje, co\u017e vede k ochran\u011b imunity a vitiligu, b\u011b\u017en\u011b pozorovan\u00e9ho v\u00fdskytu.8 Hor\u00e1k V, Fortyn K, Hruban <\/span>V, Klaudy J. D\u011bdi\u010dn\u00fd melanoblastom u miniaturn\u00edch prasat a jeho \u00fasp\u011b\u0161n\u00e1 terapie devitaliza\u010dn\u00ed technikou. <\/span>Cell Mol Biol (Noisy-Le-Grand). <\/span>1999, 45 (7): 1119-1129. <\/span>PMID: 10644016. [PubMed], [Web of Science \u00ae], [Google Scholar] Spont\u00e1nn\u00ed melanomy se vyskytuj\u00edc\u00ed v MeLiM prok\u00e1zaly n\u011bkolik vlastnost\u00ed, kter\u00e9 up\u0159ednost\u0148uj\u00ed protin\u00e1dorovou imunitn\u00ed odpov\u011b\u010f, v\u010detn\u011b exprese melanomov\u00fdch antigen\u016f TYR, MLANA a gp100 <\/span>a konstitutivn\u00ed exprese hlavn\u00edch histokompatibiln\u00edch antigen\u016f t\u0159\u00eddy I.22 Rambow F, Piton G, Bouet S, Leplat JJ, Baulande S, Marrau A, Stam M, Horak V, Vincent-Naulleau S. Podpis exprese genu pro spont\u00e1nn\u00ed regresi rakoviny melanomu <\/span>prasata. <\/span>Neoplazie. <\/span>2008 Jul; 10 (7): 714-722. <\/span>PMID: 18592010 PMCID: PMC2435007 [Crossref], [PubMed], [Web of Science\u00ae], [Google Scholar] Kv\u016fli d\u011bdi\u010dn\u00e9mu melanomu byla \u00famrtnost prasat z \u010desk\u00e9 kohorty hl\u00e1\u0161ena na 34% a\u017e dvou m\u011bs\u00edc\u016f <\/span>v\u011bku.8 Hor\u00e1k V, Fortyn K, Hruban V, Klaudy J. D\u011bdi\u010dn\u00fd melanoblastom u miniaturn\u00edch prasat a jeho \u00fasp\u011b\u0161n\u00e1 terapie devitaliza\u010dn\u00ed technikou. <\/span>Cell Mol Biol (Noisy-Le-Grand). <\/span>1999, 45 (7): 1119-1129. <\/span>PMID: 10644016. [PubMed], [Web of Science \u00ae], [Google Scholar] Existuje tak\u00e9 Francouzsk\u00e1 kohorta prasat MeLiM, u kter\u00fdch byla pozorov\u00e1na m\u00edra spont\u00e1nn\u00ed regrese spont\u00e1nn\u00edch melanom\u016f a\u017e 96% .23 <\/span>Vincent-Naulleau S, Le Chalony C, Leplat JJ, Bouet S, Bailly C, Spatz A, Vielh P, Avril MF, Tricaud Y, Gruand J, et al. <\/span>Klinick\u00e1 a histopatologick\u00e1 charakterizace ko\u017en\u00edch melanom\u016f v modelu Libechov minipig, kter\u00fd nese melanoblastom. <\/span>Pigment Cell Res. <\/span>2004 Feb; 17 (1): 24-35. <\/span>PMID: 14717842. [CrossRef], [PubMed], [Google Scholar] V experimentu proveden\u00e9m Hor\u00e1kem a kol. Bylo o\u0161et\u0159eno 40 prasat MeLiM ve v\u011bku 1-2 m\u011bs\u00edc\u016f s pokro\u010dil\u00fdm multifok\u00e1ln\u00edm onemocn\u011bn\u00edm vedouc\u00edm k kachexii a p\u0159edpokl\u00e1dan\u00e9mu \u0161patn\u00e9mu prognostick\u00e9mu v\u00fdhledu <\/span>CTD. <\/span>Kompletn\u00ed odezva byla dosa\u017eena u v\u0161ech l\u00e9\u010den\u00fdch zv\u00ed\u0159at.8 Hor\u00e1k V, Fortyn K, Hruban V, Klaudy J. D\u011bdi\u010dn\u00fd melanoblastom u miniaturn\u00edch prasat a jeho \u00fasp\u011b\u0161n\u00e1 terapie devitaliza\u010dn\u00ed technikou. <\/span>Cell Mol Biol (Noisy-Le-Grand). <\/span>1999, 45 (7): 1119-1129. <\/span>PMID: 10644016. [PubMed], [Web of Science \u00ae], [Google Scholar] Studie bohu\u017eel neobsahovala kontrolu, tedy neinterven\u010dn\u00ed kohortu zv\u00ed\u0159at, a proto v\u00fdsledky mohly b\u00fdt ovlivn\u011bny velmi vysokou m\u00edrou <\/span>spont\u00e1nn\u00ed regrese tumoru, kter\u00e1 se obvykle pozoruje u prasat MeLiM. Sekvence ud\u00e1lost\u00ed po devaskularizaci melanomu v modelu MeLiM popsala Hor\u00e1k et. <\/span>al. 24 Horak V, Moravkov\u00e1 A, Strnadel J, Hradeck\u00fd J, Usvald D, Vannucci L Devitalizace jako speci\u00e1ln\u00ed chirurgick\u00e1 l\u00e9\u010dba n\u00e1dor\u016f vyvol\u00e1vaj\u00edc\u00ed protin\u00e1dorovou odpov\u011b\u010f – experiment\u00e1ln\u00ed studie na dvou zv\u00ed\u0159ec\u00edch modelech. <\/span>Abstrakty – 6. ro\u010dn\u00edk setk\u00e1n\u00ed CIMT, 15.-16.5. <\/span>2008, Mainz, N\u011bmecko, P65 [Google Scholar] B\u011bhem 24 hodin po ligaci byly v o\u0161et\u0159ovan\u00e9m n\u00e1doru detekov\u00e1ny zv\u00fd\u0161en\u00e9 hladiny protein\u016f tepeln\u00e9ho \u0161oku HSP70 a HSP90. <\/span>Po\u010dty CD8 + cytotoxick\u00fdch T bun\u011bk a pomocn\u00fdch \/ pam\u011b\u0165ov\u00fdch T bun\u011bk se zv\u00fd\u0161ily v perifern\u00ed krvi, stejn\u011b jako u nel\u00e9\u010den\u00fdch ko\u017en\u00edch n\u00e1dor\u016f p\u0159ibli\u017en\u011b 1-3 t\u00fddny po ukon\u010den\u00ed l\u00e9\u010dby, zat\u00edmco koncentrace interleukinu-8 poklesly. <\/span>Smrt bun\u011bk melanomu a jejich n\u00e1hrada vl\u00e1knitou tk\u00e1n\u00ed byla ukon\u010dena po 4-6 m\u011bs\u00edc\u00edch.24 Horak V, Moravkov\u00e1 A, Strnadel J, Hradeck\u00fd J, Usvald D, Vannucci L Devitalizace jako speci\u00e1ln\u00ed chirurgick\u00e1 l\u00e9\u010dba n\u00e1dor\u016f vyvol\u00e1vaj\u00edc\u00ed protirakovinovou odpov\u011b\u010f – <\/span>experiment\u00e1ln\u00ed studie u dvou zv\u00ed\u0159ec\u00edch model\u016f. <\/span>Abstrakty – 6. ro\u010dn\u00edk setk\u00e1n\u00ed CIMT, 15.-16.5. <\/span>2008, Mainz, N\u011bmecko, P65 Jin\u00e9 zv\u00ed\u0159ec\u00ed modelyV\u00fdsledky CTD sarkom\u016f byly m\u00e9n\u011b p\u0159esv\u011bd\u010div\u00e9 ne\u017e v\u00fdsledky zaznamenan\u00e9 s melanomem u prasat MeLiM. <\/span>Devaskularizace 50% inokulovan\u00fdch n\u00e1dor\u016f u potkan\u016f \u200b\u200bvedla k regresi neligovan\u00e9ho tumoru u 20% t\u011bchto zv\u00ed\u0159at.24 Horak V, Moravkov\u00e1 A, Strnadel J, Hradeck\u00fd J, Usvald D, Vannucci L Devitalizace jako speci\u00e1ln\u00ed chirurgick\u00e1 l\u00e9\u010dba n\u00e1dor\u016f <\/span>vyvol\u00e1n\u00ed protin\u00e1dorov\u00e9 odpov\u011bdi – experiment\u00e1ln\u00ed studie na dvou zv\u00ed\u0159ec\u00edch modelech. <\/span>Abstrakty – 6. ro\u010dn\u00edk setk\u00e1n\u00ed CIMT, 15.-16.5. <\/span>2008, Mainz, N\u011bmecko, P65 [Google Scholar] Nav\u00edc bylo zji\u0161t\u011bno pouze p\u0159echodn\u00e9 zv\u00fd\u0161en\u00ed hladin HSP bez zm\u011bn po\u010dtu podtyp\u016f T bun\u011bk<\/span><\/span><\/p>\n

s. <\/span>Vyskytl se v\u00fdrazn\u00fd n\u00e1r\u016fst myeloidn\u00edch bun\u011bk CD11b + CD45 +, kter\u00e9 mohou p\u0159edstavovat makrof\u00e1gy nebo myeloidn\u00ed supresorov\u00e9 bu\u0148ky (MDSC). 24 Horak V, Moravkov\u00e1 A, Strnadel J, Hradeck\u00fd J, Usvald D, Vannucci L Devitalizace jako zvl\u00e1\u0161tn\u00ed chirurgick\u00fd tumor <\/span>l\u00e9\u010dba vyvol\u00e1vaj\u00edc\u00ed protirakovinovou odpov\u011b\u010f – experiment\u00e1ln\u00ed studie u dvou zv\u00ed\u0159ec\u00edch model\u016f. <\/span>Abstrakty – 6. ro\u010dn\u00edk setk\u00e1n\u00ed CIMT, 15.-16.5. <\/span>2008, Mainz, N\u011bmecko, P65 U ps\u016f nesouc\u00edch rakovinu prsn\u00ed \u017el\u00e1zy divok\u00e9ho typu byl zji\u0161t\u011bn zv\u00fd\u0161en\u00fd po\u010det cirkuluj\u00edc\u00edch CD8 + T bun\u011bk a\u017e p\u0159ibli\u017en\u011b 40 dn\u016f po ligaci. <\/span>Zv\u00fd\u0161en\u00e9 hladiny proteinu tepeln\u00e9ho \u0161oku (HSP) 70 byly rovn\u011b\u017e detekov\u00e1ny p\u0159ibli\u017en\u011b jeden t\u00fdden po postupu. <\/span>P\u0159e\u017eit\u00ed t\u011bchto ps\u016f po CTD bylo podobn\u00e9 jako u zv\u00ed\u0159at l\u00e9\u010den\u00fdch exciz\u00ed n\u00e1doru.21 Pokorn\u00e1 E, Hradeck\u00fd J, Mor\u00e1vkov\u00e1 A, Burda P, Kotrnoch J, Klaudy J, Faldyna M, Sinkora J, Halouzka R, Jel\u00ednek <\/span>F, et al. <\/span>Ligace n\u00e1dor\u016f (devitalizace) n\u00e1dor\u016f prsn\u00ed \u017el\u00e1zy u ps\u016f a sarkom u potkan\u016f \u200b\u200bLewis. <\/span>Prezentov\u00e1no na 28. Onkologick\u00e9 konferenci v Brn\u011b, 2004. Abstrakt 168. Zv\u00fd\u0161en\u00ed p\u0159e\u017eit\u00ed spolu se zv\u00fd\u0161en\u00fdm po\u010dtem plicn\u00edch metast\u00e1z bylo pozorov\u00e1no u potkan\u016f \u200b\u200bLewis, kter\u00e9 byly nao\u010dkov\u00e1ny sarkomy s vysok\u00fdm nebo n\u00edzk\u00fdm stupn\u011bm.21 Pokorn\u00e1 E, Hradeck\u00fd <\/span>J, Mor\u00e1vkov\u00e1 A, Burda P, Kotrnoch J, Klaudy J, Faldyna M, Sinkora J, Halouzka R, Jel\u00ednek F, et al. <\/span>Ligace n\u00e1dor\u016f (devitalizace) n\u00e1dor\u016f prsn\u00ed \u017el\u00e1zy u ps\u016f a sarkom u potkan\u016f \u200b\u200bLewis. <\/span>Prezentov\u00e1no na 28. onkologick\u00e9 konferenci v Brn\u011b, 2004. Abstrakt 168. Je dob\u0159e zn\u00e1mo, \u017ee hypoxie vyvol\u00e1v\u00e1 epiderm\u00e1ln\u011b-mezenchym\u00e1ln\u00ed p\u0159echod vedouc\u00ed ke zv\u00fd\u0161en\u00e9 migraci a metast\u00e1zov\u00e1n\u00ed malign\u00edch bun\u011bk a tento jev by mohl vysv\u011btlit zv\u00fd\u0161en\u00fd po\u010det plicn\u00edch metast\u00e1z v t\u011bchto <\/span>kter\u00e9 pou\u017e\u00edvaly vysoce malign\u00ed A297Nb sarkomovou bun\u011b\u010dnou linii a m\u00e9n\u011b agresivn\u00ed bun\u011b\u010dnou linii K2.2 Pokorn\u00e1 E, Hradeck\u00fd J, Mor\u00e1vkov\u00e1 A, Burda P, Kotrnoch J, Klaudy J, Faldyna M, Sinkora J, Halouzka R, Jel\u00ednek F, et <\/span>al. <\/span>Ligace n\u00e1dor\u016f (devitalizace) n\u00e1dor\u016f prsn\u00ed \u017el\u00e1zy u ps\u016f a sarkom u potkan\u016f \u200b\u200bLewis. <\/span>Prezentov\u00e1no na 28. onkologick\u00e9 konferenci v Brn\u011b, 2004. Abstrakt 168. [Google Scholar] Dokon\u010den\u00ed devaskularizace n\u00e1dor\u016f: klinick\u00e9 zku\u0161enostiPrvn\u00ed \u010desk\u00fd pr\u016fkopn\u00edk CTD Karel Fort\u00fdn l\u00e9\u010dil p\u0159ibli\u017en\u011b 20 pacient\u016f s nefunk\u010dn\u00edmi pokro\u010dil\u00fdmi solidn\u00edmi tumory. <\/span>Uvedl, \u017ee v\u011bt\u0161ina t\u011bchto pacient\u016f se zcela zotavila, v\u010detn\u011b \u00fapln\u00e9 regrese vzd\u00e1len\u00fdch metast\u00e1z. 6 Fort\u00fdn K, Hradeck\u00fd J, Pazdera J, Klaudy J, Hruban V, Dvor\u00e1k P, Matousek J, Tich\u00fd J, Kol\u00edn V. <\/span>deviskulariza\u010dn\u00ed devitalizace a potenci\u00e1l v terapeutick\u00e9m pou\u017eit\u00ed t\u00e9to opera\u010dn\u00ed metody. <\/span>Z Exp Chir Transplantace Kunstliche Organe. <\/span>1985; 18 (1): 42-50. <\/span>PMID: 2986369. [PubMed], [Google Scholar], 7 Fortyn K, Hruban V, Hor\u00e1k V. L\u00e9\u010dba malign\u00edho melanomu. <\/span>Br J Surg. <\/span>1994; 81 (1): 146-147. <\/span>PMID: 8155151. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Bohu\u017eel je nyn\u00ed mo\u017en\u00e9 tyto studie nez\u00e1visle ov\u011b\u0159it, proto\u017ee operace byly roz\u0161\u00ed\u0159eny b\u011bhem n\u011bkolika desetilet\u00ed a p\u016fvodn\u00ed l\u00e9ka\u0159sk\u00e9 z\u00e1znamy jsou ztraceny. <\/span>V roce 2001 byla d\u00edla Dr. Fort\u00fdna „objevena“ m\u00e9dii, co\u017e vyvolalo v n\u00e1sleduj\u00edc\u00edch letech n\u00e1hl\u00fd a obnoven\u00fd z\u00e1jem o metodu u \u010desk\u00e9 ve\u0159ejnosti, v\u011bdc\u016f a klinik\u016f. V roce 2001 byla organizov\u00e1na klinick\u00e1 studie f\u00e1ze I <\/span>ve \u010dty\u0159ech hlavn\u00edch \u010desk\u00fdch rakovinov\u00fdch centrech, kde se \u00fa\u010dastn\u00ed pacienti s metastatick\u00fdm kolorekt\u00e1ln\u00edm karcinomem (mCRC) a melanomem. <\/span>Bohu\u017eel v\u00fdsledky klinick\u00e9ho hodnocen\u00ed nebyly nikdy publikov\u00e1ny v peer-reviewed \u010dasopise a jsou k dispozici pouze formou dopisu Ministerstva zdravotnictv\u00ed \u010cR. Fi\u0161er B List zdravotn\u00edho tajemn\u00edka, ministerstva zdravotnictv\u00ed \u010cR, <\/span>p\u0159edsedovi \u010cesk\u00e9 asociace pacient\u016f Zpr\u00e1va o p\u0159edb\u011b\u017en\u00fdch v\u00fdsledc\u00edch klinick\u00fdch studi\u00ed; <\/span>2002, ref. <\/span>3924\/02. <\/span>Pacienti s mCRC (16 mu\u017e\u016f a 9 \u017een) byli diagnostikov\u00e1ni s pokro\u010dilou malignitou a byli pova\u017eov\u00e1ni za nevhodn\u00fdch pro konven\u010dn\u00ed terapii, v\u010detn\u011b chemoterapie a radioterapie. <\/span>Jeden z pacient\u016f dos\u00e1hl stabilizace nemoci, zat\u00edmco dal\u0161\u00ed pacient z\u016fstal bez n\u00e1doru po jednoro\u010dn\u00edm sledov\u00e1n\u00ed po \u00fapln\u00e9 resekci prim\u00e1rn\u00edho n\u00e1doru a devaskularizaci jedn\u00e9 lymfatick\u00e9 metast\u00e1zy. <\/span>Nebyly pozorov\u00e1ny \u017e\u00e1dn\u00e9 odpov\u011bdi na vzd\u00e1len\u00e9 metast\u00e1zy ani v\u00fdznamn\u00e9 zlep\u0161en\u00ed kvality \u017eivota. <\/span>Neexistovala \u017e\u00e1dn\u00e1 \u00famrtnost spojen\u00e1 s devaskulariza\u010dn\u00edm z\u00e1krokem, i kdy\u017e bylo hl\u00e1\u0161eno p\u011bt p\u0159\u00edpad\u016f komplikac\u00ed ran a jednoho p\u0159\u00edpadu hnisav\u00e9 peritonitidy.9 Fi\u0161er B List zdravotn\u00edho tajemn\u00edka, ministerstvo zdravotnictv\u00ed \u010cesk\u00e9 republiky, prezidentu \u010cesk\u00e9 asociace pacient\u016f Zpr\u00e1va o p\u0159edb\u011b\u017en\u00e9 ot\u00e1zce <\/span>v\u00fdsledky klinick\u00fdch studi\u00ed; <\/span>2002, ref. <\/span>3924\/02. <\/span>Pacienti s melanomem zahrnovali 26 pacient\u016f (15 mu\u017e\u016f a 11 \u017een), z nich\u017e 24 bylo hodnoceno z hlediska bezpe\u010dnosti, odezvy a p\u0159e\u017eit\u00ed, zat\u00edmco dva byli ztraceni n\u00e1sledkem <\/span>surgery. <\/span>Jeden pacient s melanomem m\u011bl dva odvzdu\u0161\u0148ovac\u00ed postupy prov\u00e1d\u011bn\u00e9 dva m\u011bs\u00edce od sebe. <\/span>Regrese devaskularizovan\u00e9ho n\u00e1doru se objevila u t\u0159\u00ed z 24 pacient\u016f a u jednoho pacienta byla pozorov\u00e1na stabilizace onemocn\u011bn\u00ed, ale u v\u0161ech pacient\u016f do\u0161lo k pokro\u010dil\u00fdm metast\u00e1z\u00e1m. <\/span>Nebyly pozorov\u00e1ny \u017e\u00e1dn\u00e9 zlep\u0161en\u00ed v kvalit\u011b \u017eivota. <\/span>Byly \u010dty\u0159i komplikace infek\u010dn\u00edch ran. <\/span>Studie byla p\u0159ed\u010dasn\u011b ukon\u010dena kv\u016fli obav\u00e1m z l\u00e9ka\u0159sk\u00e9 m\u00e1rnosti citovan\u00e9mu monitorovac\u00edm v\u00fdborem.9 Fi\u0161er B List zdravotn\u00edho tajemn\u00edka, ministerstvo zdravotnictv\u00ed \u010cesk\u00e9 republiky, prezidentu \u010cesk\u00e9 asociace pacient\u016f Zpr\u00e1va o p\u0159edb\u011b\u017en\u00fdch v\u00fdsledc\u00edch klinick\u00fdch studi\u00ed; <\/span>2002, ref. <\/span>3924\/02. <\/span>doi: 10.1044 \/ 1059-0889 (2002 \/ er01) [Google Scholar] Studijn\u00ed protokol byl n\u00e1sledn\u011b siln\u011b kritizov\u00e1n zast\u00e1nci CTD, proto\u017ee navrhovan\u00e9 p\u0159edpoklady pro \u00fasp\u011b\u0161n\u00e9 CTD popsan\u00e9 v\u00fd\u0161e nebyly spln\u011bny. <\/span>N\u011bkolik chirurg\u016f v\u0161ak provedlo tento typ chirurgie za posledn\u00edch 20 let, ale tyto postupy byly provedeny mimo r\u00e1mce klinick\u00e9ho hodnocen\u00ed, a proto byly publikov\u00e1ny pouze p\u0159\u00edpadov\u00e9 zpr\u00e1vy.19 Kalina V, Kopsk\u00fd DJ. <\/span>Autologn\u00ed n\u00e1dor imunizuj\u00edc\u00ed devaskularizaci v l\u00e9\u010db\u011b rakoviny. <\/span>Med hypot\u00e9zy. <\/span>2016 duben; <\/span>89: 72-78. <\/span>PMID: 26968914 doi: 10.1016 \/ j.mehy.2016.02.004 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Imunitn\u00ed odpov\u011b\u010f na \u00faplnou devaskularizaci n\u00e1dor\u016f Studie nazna\u010duj\u00ed, \u017ee ischemick\u00e1 destrukce n\u00e1dor\u016f aktivuje vrozen\u00e9 a n\u00e1sledn\u011b <\/span>adaptivn\u00ed imunita. <\/span>Jak je uvedeno v\u00fd\u0161e, CTD vede k akutn\u00ed isch\u00e9mii spojen\u00e9 s ven\u00f3zn\u00ed kongesc\u00ed a p\u0159eru\u0161en\u00edm lymfatick\u00e9 dren\u00e1\u017ee. <\/span>Rychl\u00e1 dezintegrace bun\u011b\u010dn\u00e9 membr\u00e1ny, ke kter\u00e9 doch\u00e1z\u00ed v t\u011bchto \u0161patn\u00fdch metabolick\u00fdch podm\u00ednk\u00e1ch, vede k uvoln\u011bn\u00ed n\u011bkolika typ\u016f molekul molekul\u00e1rn\u00edch struktur spojen\u00fdch s po\u0161kozen\u00edm (DAMP). <\/span>Molekuly, kter\u00e9 se uvol\u0148uj\u00ed, zahrnuj\u00ed HSPs, kalretikulin, adenosintrifosf\u00e1t (ATP), protein pro skupinu 1 s vysokou pohyblivost\u00ed (HMGB1) a dal\u0161\u00ed aktiv\u00e1tory vrozen\u00e9 imunity, co\u017e vede k z\u00e1n\u011btu, kter\u00fd se odr\u00e1\u017e\u00ed zv\u00fd\u0161enou produkc\u00ed interleukin\u016f-1\u00df a -18. <\/span>Tyto molekuly pak aktivuj\u00ed mRNA 2 a 4 a CD91 na dendritick\u00fdch bu\u0148k\u00e1ch, kter\u00e9 podporuj\u00ed endocyt\u00f3zu bun\u011b\u010dn\u00fdch \u00falomk\u016f, stejn\u011b jako zpracov\u00e1n\u00ed a prezentaci n\u00e1dorov\u00e9ho antigenu.25 Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak <\/span>H, Vandenabeele P. Regulovan\u00e1 nekr\u00f3za: roz\u0161i\u0159uj\u00edc\u00ed se s\u00ed\u0165 neapoptotick\u00fdch bun\u011b\u010dn\u00fdch cest smrti. <\/span>Nat Rev Mol Cell Biol. <\/span>2014 Feb; 15 (2): 135-147. <\/span>PMID: 24452471 doi: 10.1038 \/ nrm3737. 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[Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Krom\u011b toho bylo prok\u00e1z\u00e1no, \u017ee isch\u00e9mie vede k expozici <\/span>autoantigeny, kter\u00e9 jsou rozpozn\u00e1v\u00e1ny ji\u017e existuj\u00edc\u00edmi autoprotil\u00e1tkami, kter\u00e9 naopak aktivuj\u00ed kask\u00e1du komplementu, co\u017e vede k po\u0161kozen\u00ed membr\u00e1ny, zv\u00fd\u0161en\u00e9 infiltraci a aktivaci neutrofil\u016f.29 Weiser MR, Williams JP, Moore FD Jr, Kobzik L, Ma M, Hechtman HB, <\/span>Carroll MC. <\/span>Reperfusn\u00ed po\u0161kozen\u00ed ischemick\u00e9ho kostern\u00edho svalu je zprost\u0159edkov\u00e1no p\u0159irozen\u00fdmi protil\u00e1tkami a komplementy. <\/span>J Exp Med. <\/span>1996, 1. kv\u011btna, 183 (5): 2343-2348. <\/span>PubMed PMID: 8642343; <\/span>PubMed Central PMCID: PMC2192547. [CrossRef], [PubMed], [Web of Science \u00ae], [Google Scholar] V roce 2011 Sheu et al. <\/span>p\u0159edlo\u017eila studii, kter\u00e1 prok\u00e1zala, \u017ee ischemick\u00e1 ur\u00e1\u017eka prim\u00e1rn\u00edho n\u00e1doru vyvolala z\u00e1n\u011btlivou kask\u00e1du a sn\u00ed\u017eila po\u010det metast\u00e1z u divok\u00e9ho typu, ale ne u Rag1 – \/ – my\u0161\u00ed, co\u017e siln\u011b nazna\u010dovalo, \u017ee adaptivn\u00ed imunita hr\u00e1la kl\u00ed\u010dovou roli v procesu. Sheu <\/span>EG, Wakatsuki K, Younan G, Oakes SM, Moore FD. <\/span>Ischemick\u00e9 po\u0161kozen\u00ed inhibuje rakovinn\u00e9 metast\u00e1zy modulac\u00ed hostitelsk\u00e9 adaptivn\u00ed imunity. <\/span>J Am Coll surgeons. <\/span>2011, 213 (3) S137. <\/span>[A\u010dkoli specifick\u00e9 bu\u0148ky CD8 + jsou pova\u017eov\u00e1ny za kl\u00ed\u010dov\u00e9 pro protin\u00e1dorovou imunitu, adaptivn\u00ed odezva zprost\u0159edkovan\u00e1 protil\u00e1tkou hraje roli v absopc\u00e1ln\u00edm \u00fa\u010dinku radioterapie (viz n\u00ed\u017ee) a p\u0159isp\u00edv\u00e1 k \u00fa\u010dinku protin\u00e1dorov\u00e9 vakcinace.31 Postow <\/span>MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E a kol. <\/span>Imunologick\u00e1 korelace abskopu u pacient\u016f s melanomem. <\/span>N Engl J Med. <\/span>2012 Mar 8; 366 (10): 925-931. <\/span>PubMed PMID: 22397654; <\/span>PubMed Central PMCID: PMC3345206. <\/span>dva: 10.1056 \/ NEJMoa1112824. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar], 32 Reed CM, Cresce ND, Mauldin IS, Slingluff CL Jr, Olson WC. <\/span>O\u010dkov\u00e1n\u00ed pomoc\u00ed melanomov\u00fdch pomocn\u00fdch peptid\u016f indukuje protil\u00e1tkov\u00e9 odpov\u011bdi spojen\u00e9 se zlep\u0161en\u00edm celkov\u00e9ho p\u0159e\u017eit\u00ed. <\/span>Clin Cancer Res. <\/span>2015 Sep 1; 21 (17): 3879-3887. <\/span>Epub 2015 12. kv\u011btna PubMed PMID: 25967144; <\/span>PubMed Centr\u00e1ln\u00ed PMCID: PMC4558239 doi: 10.1158 \/ 1078-0432.CCR-15-0233 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] Procesy, kter\u00e9 se pravd\u011bpodobn\u011b vyskytuj\u00ed u devaskularizovan\u00fdch n\u00e1dor\u016f, <\/span>Obr\u00e1zek 3). <\/span><\/span><\/p>\n

Obr\u00e1zek 3. <\/span><\/span><\/p>\n

Mo\u017en\u00e9 imunitn\u00ed mechanismy, kter\u00e9 vedou k regresi dist\u00e1ln\u00edch l\u00e9z\u00ed a ochrann\u00e9 imunity po \u00fapln\u00e9 devaskularizaci n\u00e1doru (ATP, adenosin trifosf\u00e1t, TLR4, m\u00fdtn\u00fd receptor 4, DAMP, <\/span>protein HMGB1, skupina s vysokou pohyblivost\u00ed 1). <\/span><\/span><\/p>\n

\"\"<\/p>\n

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Zobrazit \u00faplnou velikost Kompletn\u00ed devaskularizace n\u00e1doru v kontextu.<\/strong> <\/span><\/span><\/p>\n

Pokud v\u00fdhody CTD u pacient\u016f s rakovinou z\u016fst\u00e1vaj\u00ed nedok\u00e1zaly, je dob\u0159e zn\u00e1mo, \u017ee jin\u00e9 lok\u00e1ln\u011b destruktivn\u00ed terapie mohou v\u00e9st k regresi vzd\u00e1len\u00fdch metast\u00e1z. <\/span>Dva prim\u00e1rn\u00ed p\u0159\u00edklady z klinice jsou radioterapie a intratumor\u00e1ln\u00ed onkolytick\u00e1 virov\u00e9 terapie. <\/span>Abskop\u00e1ln\u00ed \u00fa\u010dinek radioterapie m\u00e1 za n\u00e1sledek imunitn\u00ed zprost\u0159edkov\u00e1n\u00ed regrese vzd\u00e1len\u00fdch n\u00e1dor\u016f po lokalizovan\u00e9 radioterapii. <\/span>A\u010dkoli mechanismy nejsou pln\u011b pochopeny, zd\u00e1 se, \u017ee uvol\u0148ov\u00e1n\u00ed DAMP vedouc\u00edch ke zv\u00fd\u0161en\u00e9 antigenn\u00ed prezentaci a aktivaci T bun\u011bk hraje kl\u00ed\u010dovou roli.31 Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, <\/span>Rasalan T, Adamow M, Ritter E a kol. <\/span>Imunologick\u00e1 korelace abskop\u00e1ln\u00edho \u00fa\u010dinku u pacienta s melanomem. <\/span>N Engl J Med. <\/span>2012 Mar 8; 366 (10): 925-931. <\/span>PubMed PMID: 22397654; <\/span>PubMed Central PMCID: PMC3345206. <\/span>dva: 10.1056 \/ NEJMoa1112824. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar], 33 Hu ZI, McArthur HL, Ho AY. <\/span>Abskop\u00e1ln\u00ed \u00fa\u010dinek radia\u010dn\u00ed terapie: co je to a jak jej m\u016f\u017eeme pou\u017e\u00edt p\u0159i rakovin\u011b prsu? <\/span>Curr Breast Cancer Rep. 2017; 9 (1): 45-51. <\/span>PMID: 28344743 doi: 10.1007 \/ s12609-017-0234-y [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] V\u00fdznamn\u00fd pokles po\u010dtu MDSC a zv\u00fd\u0161en\u00fdch protil\u00e1tek proti NY-ESO1 <\/span>n\u00e1dorov\u00fd antigen, byly pozorov\u00e1ny v detailn\u00ed p\u0159\u00edpadov\u00e9 studii abskop\u00e1ln\u00edho \u00fa\u010dinku.31 Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E a kol. <\/span>Imunologick\u00e1 korelace abskop\u00e1ln\u00edho \u00fa\u010dinku u pacienta s melanomem. <\/span>N Engl J Med. <\/span>2012 Mar 8; 366 (10): 925-931. <\/span>PubMed PMID: 22397654; <\/span>PubMed Central PMCID: PMC3345206. <\/span>D\u016fle\u017eit\u00e9 je, \u017ee inhibitory cytotoxick\u00e9ho proteinu 4 asociovan\u00e9ho s T-lymfocyty (CTLA-4) a programovan\u00e9 bun\u011b\u010dn\u00e9 smrti-1 (PD-2) <\/span>1) zvy\u0161uj\u00ed pravd\u011bpodobnost abskop\u00e1ln\u00edho \u00fa\u010dinku, 33 Hu ZI, McArthur HL, Ho AY. <\/span>Abskop\u00e1ln\u00ed \u00fa\u010dinek radia\u010dn\u00ed terapie: co je to a jak jej m\u016f\u017eeme pou\u017e\u00edt p\u0159i rakovin\u011b prsu? <\/span>Curr Breast Cancer Rep. 2017; 9 (1): 45-51. <\/span>PMID: 28344743 doi: 10.1007 \/ s12609-017-0234-y. [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] a podporuj\u00ed tak pou\u017eit\u00ed inhibitor\u016f kontroln\u00edch bod\u016f v budouc\u00edch experimentech zahrnuj\u00edc\u00edch CTD. Intratumor\u00e1ln\u00ed onkolytick\u00e1 terapie <\/span>je ji\u017e zaregistrov\u00e1n a je k dispozici pro metastatick\u00fd melanom. <\/span>Injekce thalimogene laherparepvec (T-Vec), geneticky modifikovan\u00fd herpes virus, vedla k regresi l\u00e9\u010den\u00fdch i nel\u00e9\u010den\u00fdch n\u00e1dorov\u00fdch l\u00e9z\u00ed doprov\u00e1zen\u00fdch zv\u00fd\u0161enou intratumor\u00e1ln\u00ed infiltrac\u00ed bun\u011bk CD8 + specifick\u00fdch pro melanom a sn\u00ed\u017een\u00ed po\u010dtu regula\u010dn\u00edch CD4 + Foxp3 + T <\/span>bun\u011bk.34 Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS a kol. <\/span>Talimogene laherparepvec zlep\u0161uje trvanlivou odpov\u011b\u010f u pacient\u016f s pokro\u010dil\u00fdm melanomem. <\/span>J Clin Oncol. <\/span>2015 Sep 1; 33 (25): 2780-2788. <\/span>PMID: 26014293 doi: 10.1200 \/ JCO.2014.58.3377 [Crossref], [PubMed], [Web of Science \u00ae], [Google Scholar] <\/span><\/span><\/p>\n

Z\u00e1v\u011br<\/span><\/span><\/strong><\/p>\n

V sou\u010dasn\u00e9 dob\u011b nejsou publikovan\u00e9 \u00fadaje jednozna\u010dn\u011b prok\u00e1z\u00e1ny \u00fa\u010dinnost CTD pro malign\u00ed lidskou nebo zv\u00ed\u0159ec\u00ed tuhou <\/span>n\u00e1dor\u016f, zejm\u00e9na v kontextu standardn\u00ed protin\u00e1dorov\u00e9 l\u00e9\u010dby. <\/span><\/span><\/p>\n

CTD je potenci\u00e1ln\u00ed metoda pro indukci imunitn\u00edch odpov\u011bd\u00ed proti solidn\u00edm n\u00e1dor\u016fm. <\/span>Na z\u00e1klad\u011b zku\u0161enost\u00ed ze zv\u00ed\u0159ec\u00edch model\u016f je CTD pravd\u011bpodobn\u011b \u00fa\u010dinn\u00e1 u siln\u011b imunogenn\u00edch n\u00e1dor\u016f. <\/span>Navzdory rychl\u00e9mu pokroku v imunologii n\u00e1dor\u016f v uplynul\u00e9m desetilet\u00ed z\u016fst\u00e1vaj\u00ed procesy, kter\u00e9 jsou indukov\u00e1ny akutn\u00ed ischemi\u00ed n\u00e1dor\u016f a CTD, \u0161patn\u011b pochopiteln\u00e9. <\/span>Budouc\u00ed v\u00fdzkum by m\u011bl b\u00fdt zam\u011b\u0159en na posouzen\u00ed \u00fa\u010dinnosti postupu v r\u016fzn\u00fdch prost\u0159ed\u00edch, v\u010detn\u011b p\u0159edb\u011b\u017en\u00e9 l\u00e9\u010dby nebo kombinace s konven\u010dn\u00edmi antineoplastick\u00fdmi terapiemi a \/ nebo imunomodula\u010dn\u00edmi \u010dinidly, jako jsou inhibitory kontroln\u00edch bod\u016f, stejn\u011b jako identifikace optim\u00e1ln\u00ed chirurgick\u00e9 techniky pro specifick\u00e9 n\u00e1dory a specifick\u00e9 <\/span>um\u00edst\u011bn\u00ed tumor\u016f autor\u016f by r\u00e1d pod\u011bkoval Dr. Jasperovi Manningovi za jazykovou revizi rukopisu. <\/span><\/span><\/p>\n

Zve\u0159ejn\u011bn\u00ed potenci\u00e1ln\u00edch st\u0159et\u016f z\u00e1jm\u016f<\/span><\/span><\/strong><\/p>\n

Tomas Buchler z\u00edskal finan\u010dn\u00ed prost\u0159edky na v\u00fdzkum, mluven\u00ed a poradenstv\u00ed t\u00fdkaj\u00edc\u00ed se rakovinov\u00e9 imunoterapie od spole\u010dnost\u00ed Roche, Merck a Bristol Myers Squibb, nesouvisej\u00edc\u00edch s p\u0159\u00edtomnost\u00ed <\/span>\u010dl\u00e1nek. <\/span>Radek Spisek je zam\u011bstn\u00e1n spole\u010dnost\u00ed Sotio, kter\u00e1 vyv\u00edj\u00ed rakovinov\u00e9 imunoterapie. <\/span><\/span><\/p>\n

 <\/p>\n

P\u0159\u00edsp\u011bvek autora<\/span><\/span><\/strong><\/p>\n

Podpora a n\u00e1vrh p\u0159ehledu: T Buchler, P Vasek, R Spisek, V Horejsi<\/span><\/span><\/p>\n

Z\u00edsk\u00e1n\u00ed \u00fadaj\u016f: P Vasek, T Buchler<\/span><\/span><\/p>\n

Prvn\u00ed n\u00e1vrh: T Buchler<\/span><\/span><\/p>\n

P\u0159\u00edpravn\u00e9 \u00fadaje: P Skrobanek <\/span><\/span><\/p>\n

Zdravov\u00e1n\u00ed a <\/span>kone\u010dn\u00e9 schv\u00e1len\u00ed rukopisu: T Buchler, P Vasek, R Sp\u00ed\u0161ek, P Skrob\u00e1nek, V Horejsi <\/span><\/span><\/p>\n

 <\/p>\n

Reference<\/strong> <\/span><\/span><\/p>\n

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    Dal\u0161\u00ed informace<\/span><\/span><\/strong><\/p>\n

    Financov\u00e1n\u00ed<\/span>
    \nPoplatky za zve\u0159ejn\u011bn\u00ed byly pokryty neomezenou velikost\u00ed od Roche na 1. l\u00e9ka\u0159sk\u00e9 fakult\u011b Univerzity Karlovy v Praze, \u010cesk\u00e1 republika.<\/span><\/span><\/strong><\/p>\n

     <\/p>\n

    Zdroj:<\/p>\n

    https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/2162402x.2018.1526614<\/a><\/strong><\/span><\/p>\n

     <\/p>\n

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

    \u00a0 Devaskularizace tumoru jako potenci\u00e1ln\u00ed imunoterapeutick\u00e1 strategie (EN)         Devaskularizace tumoru jako potenci\u00e1ln\u00ed imunoterapeutick\u00e1 strategie Tom\u00e1\u0161 Buchler Ikona ORCID, Pavel Vasek, Radek \u0160picek, Pavel \u0160rob\u00e1nek a V\u00e1clav Horejsi Ikona ORCID P\u0159ijato 18 \u010derven 2018, Akceptov\u00e1no 15 z\u00e1\u0159\u00ed 2018, zve\u0159ejn\u011bno online: 11 \u0159\u00edjna 2018   St\u00e1hnout citace https:\/\/doi.org\/10.1080\/2162402X.2018.1526614   V tomto \u010dl\u00e1nku \u00a0\u00a0 […]<\/p>\n","protected":false},"author":1,"featured_media":498,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[14],"tags":[],"_links":{"self":[{"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=\/wp\/v2\/posts\/1799"}],"collection":[{"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1799"}],"version-history":[{"count":16,"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=\/wp\/v2\/posts\/1799\/revisions"}],"predecessor-version":[{"id":1818,"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=\/wp\/v2\/posts\/1799\/revisions\/1818"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=\/wp\/v2\/media\/498"}],"wp:attachment":[{"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1799"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1799"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.pacienti.cz\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1799"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}