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Avemar Uvjeti poslovanja

Isključimo „gorivo“ karcinomu

Maureen Palletier, MD, CCN, FACOG

Anti-aging medical news, 2008 

Dr. Palletier je predavač, autor i ravnatelj katedre za funkcionalnu medicinu

na LaValle Metabolic Institute u Cincinnatiju, Ohio, SAD.


Isključimo „gorivo“ karcinomu


Dr. OttoWarburg dobio je Nobelovu nagradu prije više od 70 godina za otkriće da stanice raka koriste glukozu 10-50 puta više od zdravih stanica, kroz direktnu glukolizu, neoksidativnim putovima.

Nazvana «Warburg efekt» , ova karakteristična hipermetabolička aktivnost je gorivo za eksplozivni rast raka, ona krade glukozu iz zdravog tkiva i stvara metabolički nusprodukt koji doprinosi sustavnom oboljenju. Warburg je smatrao da bi, ako se spriječi dotok glukoze u stanice raka, njihova opskrba energijom bila blokirana, zagušena, što bi usporilo ili zaustavilo rast raka i prisililo stanice raka na smrt.

Nekoliko godina kasnije, mađarski biokemičar dr. Albert Szent-Gyorgyi, također Nobelovac, počeo je istraživati razlog niskoj stopi oboljelih od raka kod populacije koja konzumira značajne količine proizvoda od cjelovitog zrnja.

Do 1980. godine, Szent-Gyorgyi je izolirao prirodne spojeve u pšeničnoj klici za koje je vjerovao da imaju antikancerogeno djelovanje ako se uzimaju u određenim količinama.

Nedavna istraživanja povezala su otkrića ovih dvaju Nobelovih laureata :

Jedinstveni fermentirani ekstrakt pšenične klice (FWGE), blokira unos glukoze u stanice raka, isključujući im dovod energije, smanjujući im sposobnost rasta i proliferacije i na kraju uzrokujući njihovu smrt APOPTOZOM bez štetnog učinka na zdrave stanice.

Ciljane terapije


Ograničenja konvencionalnog liječenja karcinoma kemoterapijom i radijacijom su posve jasna. Ono je letalno i za kancerozne i za zdrave stanice, te stvara neželjene nuspojave uključujući i povećanje rizika od novog karcinoma. Ova saznanja dovela su do razvoja ciljanih terapija (tzv. pametnih lijekova), koji inhibiraju molekule ili preobilje molekula prisutnih samo u stanicama raka. Međutim, početno oduševljenje ranim uspjesima ciljanih terapija splasnulo je nedavnim otkrićem da mutirani geni koji i proizvode takve molekule s vremenom nastavljaju mutacijama. To znači da ciljane molekule poprimaju nove oblike i na njih više ne djeluju lijekovi formulirani da se vezuju na raniju, originalnu verziju.

Ciljevi koje nudi Warburg efekt su sasvim različiti. Oni nisu rezultat mutiranih gena. Oni su jednostavno enzimi o kojima stanice raka ovise više nego normalne stanice. Ovakve enzimske mete su stabilne, esencijalne su za rast, preživljavanje i proliferaciju tumorski stanica, a prisutne su kod svih vrsta raka.

Mogućnost učinkovitog fokusiranja na ove ciljeve u teoriji je postojala već dulje vrijeme ali je tek nedavno realizirana kad su oruđa moderne znanosti uhvatila korak s mudrošću i vizionarstvom od prije tričetvrt stoljeća.

Nova oruđa rasvjetljavaju metaboličke ciljeve


Dr Warburg je istaknuo u svom govoru pri dodjeli Nobelove nagrade da je puno razumijevanje staničnog metabolizma izrazito teško zbog brzih, kratkoročnih i mnogobrojnih kemijskih reakcija koje stvaraju metaboličke putove. On je znao što se događa – stanice raka koriste ogromne količine glukoze ali nije znao biokemijske pojedinosti o načinu na koji to čine.

Sredinom i koncem devedesetih godina prošlog stoljeća istraživači su razvili sofisticirana nova oruđa za proučavanje metaboličkih reakcija, sve do preciznih detalja. Jedna takva tehnika, nazvana dinamičko metaboličko profiliranje na bazi izotopa (SiDMAP), koristi glukozu označenu specijalnim, teškim izotopima ugljika (C-13) radi praćenja korištenja glukoze u sintezi RNA, DNA i masnih kiselina.

Ova tehnika identificira ključne metaboličke kemikalije koje mogu biti korištene kao ciljevi, koji, ako se blokiraju, mogu inhibirati stanice raka u dobivanju energije ili stvaranju DNA potrebne za njihovu replikaciju.

SiDMAP tehnika bila je primijenjena da bi se razumjelo kako fermentirani ekstrakt pšeničnih klica utječe na metabolizam MIA stanica raka gušterače.

Rezultat je bio radikalna inhibicija enzima transketolaze (TK), koja je, ovisno o doziranju, usporila unos glukoze u tumorske stanice gušterače i na taj način spriječila njihovu sintezu riboze i RNA. Istovremeno, ekstrakt je povećao izravnu oksidaciju glukoze i uspostavio normalni stanični metabolizam.

Tumorske stanice bile su prisiljene okrenuti se metaboličkim putovima koje koriste normalne stanice, a to je dovelo bilo do promjene fenotipa tumorskih stanica u normalne, bilo do njihove smrti APOPTOZOM.

Slične rezultate je ekstrakt pšeničnih klica pokazao kod mnogih drugih vrsta raka.


Reference:

  1. Xu RH, Pelicano H, Zhou Y. et  - Inhibicija glukolize tumorskih stanica i nove strategije u prevladavanju rezistencije na lijekove povezane s mitohondrijskim  respiratornim defektom i hipoksijom. Cancer Res, siječanj 2005., 15;65 (2) : 61.
  2. Fabarius A., Haferlach C., Muller MC et al. – Dinamika citogenetske aberacije kod filadelfijske kromosom pozitivne i negativne hematopoeze za vrijeme terapije kronične mijeloidne leukemije. (Haematologica, 2007.lipanj; 92(6): 834-7
  3. Haber DA, Bell DW, Sordella R,et al. : Ciljana molekularna terapija raka pluća : EGFR mutacije i reakcija na EGFR inhibitore. Cold Spring Harb Symp., Quant Biol. 2005; 70:419-26.
  4. Comin-Anduix B. Boros LG,Marin S. et al. : Fermentirani ekstrakt pšeničnih klica inhibira enzime glukolizno-pentoznog kruga i inducira apoptozu kroz poli (ADP ribozu) polimeraznu aktivaciju u tumorskim stanicama Jurkat leukemije. J.Biol Chem, 2002. studeni, 29;277 (48):46408-14.
  5. Jakob F.Shoenfeld Y., Balogh A. et al.: Medicinska hrana koja ima suportivnu vrijednost u liječenju kolorektalnog karcinoma. Br.J.Cancer, kolovoz 2003., 4;89(3).465-9.
  6. Demidov LV.,et al. : Antimetastatski učinal Avemara kod visokorizičnih melanoma. 18. UICC međunarodni kongres o karcinomu, Oslo,Norveška, 30.lipnja- 5.srpnja,2002.Int.J.Cancer, 2002; 100(S13);408.

 

 

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