http___medlib.mef.hr_557__1.xml
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Pavelić, Jasminka and Radaković, Branko and Pavelić, Krešimir (2007) Insulin-like growth factor 2 and its receptors (IGF 1R and IGF 2R/mannose 6-phosphate) in endometrial adenocarcinoma. Gynecologic Oncology, 105 (3). English abstract OBJECTIVE: To investigate the consequences of IGF proteins dysfunction in development of endometrial adenocarcinomas. ----- METHODS: The expression of IGF 2 and IGF 1R was correlated with the expression of IGF 2R and apoptosis rate in 59 human endometrial adenocarcinomas, 10 endometrial hyperplasias and 7 normal tissues. The presence of mutations in the IGF 2R gene was followed in 46 adenocarcinomas. We also examined the effect of IGF 1 receptor blockage on cancer cell proliferation. In groups of either IGF 2-positive or IGF 2-negative tumors (stages III and IV) the expression of IGF 1 and IGF 1R was correlated with cell proliferation index and telomerase activity. ----- RESULTS: The expression of IGF 2 and IGF 1R was much higher in malignant tissue of stages III and IV than in tumors of stages I and II and normal or hyperplastic endometrium. This correlated with a decreased apoptosis rate and IGF 2R expression. Eight adenocarcinomas expressed biallelic mutation of the IGF 2R gene. The specific inhibition of IGF 1R and IGF 2 decreased tumor cell proliferation in IGF 2/IGF 1R-positive tumors. Furthermore, the positive correlation between increased expression of IGF 1 and IGF 1R proteins and increased telomerase activity and cell proliferation index was found in both IGF 2-negative and IGF 2-positive tumors. ----- CONCLUSION: Our data suggest that IGF 1, IGF 2 and their receptors are involved in the progression of endometrial adenocarcinomas. As cancer cell proliferation can be abrogated by blocking mRNA or protein products of these genes, tumors with extensive involvement of the IGF 2 pathway would be candidates for the therapeutics strategies aimed at interference with this pathway. Actions (login required)
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Jakopović, Marko (2007) Posljedice disfunkcije inzulinu sličnih čimbenika rasta i njihovih receptora u karcinomu pluća nemalih stanica [The consequences of Insulin–like growth factors/receptors dysfunction in non–small cell lung cancer]. PhD thesis, Sveučilište u Zagrebu. Croatian abstract U patogenezi karcinoma pluća, kao i u ostalim solidnim tumorima, brojne promjene u biološkim regulatornim putovima imaju značajnu ulogu. IGF - I koji luče ili tumorske stanice ili stanice zdravog tkiva ima značajnu ulogu u samoj tumorigenezi djelujući na proliferaciju, rast te metastaziranje tumorskih stanica u karcinomu pluća. Većina tumorskih stanica odgovara na stimulaciju inzulinu sličnih čimbenika rasta putem IGF – IR. U stanicama karcinoma pluća velikih stanica, stanicama adenokarcinoma i pločastim stanicama nađena je povećana razina IGF – I i IGF – IR uz istodobno smanjen broj apoptotičkih stanica. Dokazana je i pozitivna korelacija između povišene ekspresije mRNA za IGF – I i IGF – IR i smanjenog broja stanica u kojima je u tijeku apoptoza što upućuje da aktivacija IGF – IR smanjuje apoptozu stanica karcinoma pluća te tako potiče rast tumora. Nađena je i pozitivna korelacija ekspresije istih molekula s povećanjem proliferacije karcinomskih stanica. U četiri uzorka tkiva od 15 adenokarcinoma nađen je gubitak heterozigotnosti alela i mutacije gena za M6P/IGF – IIR. U planocelularnom karcinomu dokazana je povećana aktivnost telomeraze. Aktivacija telomeraza ima za posljedicu besmrtnost tumorskih stanica. Rezultati ovoga rada sugeriraju da IGF sustav, prije svega IGF – I, IGF – II i IGF – IR imaju jednu od ključnih uloga u razvoju karcinoma pluća. English abstract Numerous changes in biological pathways have significant role in pathogenesis of lung cancer. IGF – I, secreted by tumorous or normal tissue, has a significant role in tumorigenesis of cancer, influencing proliferation, growth and metastasing of cancer cells. Majority of tumorigenic effects of IGFs is mediated through IGF – IR. Increased expression of IGF – I, IGF - II and IGF – IR were found in lung cancer cell, with increased proliferation and decreased apoptosis of cancer cells. In four samples of adenocarcinoma loss of heterozigosity for M6P/IGF – IIR was found. In planocellular carcinoma increased activity of telomerase was found. Increased activity of telomerase has a role in cancer cell immortality. Results of this study suggests that disruption in IGF/IGF receptor axis is involved in tumorigenesis of non – small cell lung cancer. Actions (login required)