Survivin i VEGF-C u papilarnom i anaplastičnom karcinomu štitaste žlezde: ekspresioni profili, uloga u biologiji tumora i kliničko-patološki značaj
Survivin and VEGF-C in papillary and anaplastic thyroid carcinoma: expression profiles, biological role and their clinico-patological significance
Докторанд
Šelemetjev, Sonja A.Ментор
Cvejić, DubravkaЧланови комисије
Matić, GordanaTatić, Svetislav
Метаподаци
Приказ свих података о дисертацијиСажетак
Progresija malignih tumora štitaste žlezde od dobro diferenciranih (papilarni karcinom)
u nediferencirane, agresivne forme (anaplastični karcinom) praćena je različitim
promenama na molekularnom nivou, koje omogućavaju malignoj ćeliji kontinuiranu
aberantnu stimulaciju rasta i izbegavanje apoptotske smrti, što uz neoangiogenezu
(formiranje novih krvnih i limfnih sudova) predstavlja preduslove tumorskog rasta i
širenja.
Predmet ovog rada je izučavanje molekularnih promena koje prate dediferencijaciju
papilarnog u anaplastični karcinom štitaste žlezde, tj. ispitivanje promena ekspresionih
profila apoptotskih molekula (Bcl-2, Bax, survivin) i limfangiogenog faktora (VEGF-C)
u korelaciji sa kliničkim parametrima tokom progresije maligniteta tumora štitaste
žlezde.
Imunohistohemijskom analizom ekspresionih profila članova Bcl-2 familije
konstatovano je da tokom progresije dolazi do smanjenja ekspresije Bcl-2
(antiapoptotski molekul), ali da je in situ apoptotska smrt detektovana TUNEL
metod...om na niskom nivou, uprkos visokih ekspresionih nivoa Bax (pro-apoptotskog)
molekula. U isto vreme sa smanjenjem ekspresije Bcl-2 tokom progresije maligniteta
dolazi do postepenog povećanja drugog antiapoptotskog molekula, survivina, koji je
operativan nizvodno od Bax-a. Visoka ekspresija survivina je bila u korelaciji sa
sniženim stepenom in situ detektovane apoptotske smrti, što sugeriše da survivin, a ne
odnos Bcl-2/Bax ima ulogu u inhibiciji finalizacije programirane ćelijske smrti.
Poređenjem imunohistohemijske ekspresije survivina sa kliničko-patološkim
parametrima pacijenata utvrđena je značajna korelacija između visoke ekspresije
survivina i prisustva metastaza u limfnim čvorovima. Ekspresioni profili VEGF-C
proteina (angiogeni faktor koji promoviše formiranje tumorske vaskulature, a time i rast
i širenje tumora) pokazali su porast tokom tumorske progresije i značajnu korelaciju sa
prisustvom limfnih metastaza, ekstratiroidnom invazijom i uznapredovalim stadijumom
tumorske bolesti...
Progression of malignancy of thyroid gland tumors from well differentiated (papillary
carcinoma) to undifferentiated, aggressive form (anaplastic carcinoma) is accompanied
by molecular changes. These enable continuous stimulation of aberrant growth and
escape from apoptotic death, together with neoangenesis (formation of new blood and
lymphatic vessels) which are prerequisites for tumor growth and spread.
The objective of this work was examination of some molecular changes accompaning
dedifferentiation of papillary to anaplastic carcinoma of the thyroid gland, i.e. an
investigation of alterations in expression profiles associated with apoptosis (Bcl-2, Bax,
survivin) and lympfhangiogenic factor, VEGF-C, in correlation with clinicopathological
parameters during the progression of malignancy of thyroid gland tumors.
Immunohistochemical analysis of expression profiles of Bcl-2 family members revealed
decrease of Bcl-2 expression (anti-apoptotic molecule) during this progression, but a
low... level of in situ apoptotic cell death detected by the TUNEL method, despite high
levels of Bax (pro-apoptotic molecule). The decrease of Bcl-2 expression was followed
by increase of another anti-apoptotic molecule, survivin, which acts downstream from
Bax. High survivin expression was found to correlate with the lower rate of in situ
apoptotic cell death, suggesting that survivin, but not the Bcl-2/Bax ratio, has a role in
finalization of programmed cell death. By comparing survivin immunohistochemical
expression with clinico-pathological parameters of patients we found a significant
positive correlation between high survivin expression and the presence of lymph node
metastases. Expression profiles of VEGF-C protein (an angiogenic factor which
promotes the formation of tumor vasculature, and thereby tumor growth and spread)
revealed increased levels during tumor progression and a significant correlation with the
presence of lymph node metastases, extrathyroid invasion and advanced stages of
disease. Significant correlation between the expressions of two molecules, survivin and
VEGF-C, in tumors with the presence of lymph metastases and in their metastatic
tissues, suggests their coordinated roles in the metastatic process...
Факултет:
Универзитет у Београду, Биолошки факултетДатум одбране:
27-05-2014Пројекти:
- Молекуларна карактеризација бактерија из родова Bacillus и Pseudomonas као потенцијалних агенаса за биолошку контролу (RS-MESTD-Basic Research (BR or ON)-173026)