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Promene u apoptozi limfocita, parametrima oksidativnog stresa i profilu citokina kod bolesnika sa diferentovanim karcinomom štitaste žlezde

The changes in apoptosis of lymphocytes, parameters of oxidative stress and cytokine profile in patients with differentiated thyroid carcinoma

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Author
Mihaljević, Olgica
Mentor
Živančević-Simonović, Snežana
Committee members
Đukić, Aleksandar
Pejnović, Nada
Radosavljević, Tatjana
Milošević-Đorđević, Olivera
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Abstract
Osnovna terapija kod pacijenata sa diferentovanim karcinomom štitaste žlezde (DTC) je totalna ili skoro totalna tireoidektomija i primena radioaktivnog joda (131-I). Cilj terapije radioaktivnim 131-I je eliminacija postoperativno zaostalog tireoidnog tkiva i jodavidnih metastaza. Primena 131-I indukuje jonizaciju materije praćenu oksidativnim stresom i oslobađanjem pojedinih citokina, kao i oštećenje ćelija uz povećanje frekvence mikronukleusa i moguću indukciju apoptoze limfocita periferne krvi. Osnovni cilj ovog istraživanja je da se ispitaju celularne i biohemijske promene u perifernoj krvi pacijenata sa DTC pre i sedam dana nakon aplikacije radioaktivnog 131-I. Istraživanje je dizajnirano kao komparativna kliničko-eksperimentalna studija tokom koje su upoređivani testirani parametri u eksperimentalnoj i kontrolnoj grupi ispitanika. U kliničkom ispitivanju ukupno je učestvovalo 24 pacijenta (16 žena i 8 muškaraca), prosečne starosti 50.83±13.22 godina. Četiri do šest ne...delja posle totalne tireoidektomije, i 10 dana nakon dijete siromašne jodom, pacijentima je aplikovana ablaciona doza radioktivnog natrijum jodida (131-I), i to 3.7 GBq (100 mCi) (13 pacijenata) ili 5.5 GBq (150 mCi) (11 pacijenata). Kriterijumi za uključivanje u studiju bili su: histopatološki postavljena dijagnoza papilarnog ili folikularnog karcinoma štitaste žlezde nakon totalne tireoidektomije, konzilijarno doneta odluka o aplikaciji radioaktivnog 131-I, hipotireoidno stanje pacijenta (TSH>30 mIU/L) i potpisan formular informisanog pristanka saglasno Helsinškoj deklaraciji. Kliničkim ispitivanjem nisu obuhvaćeni pacijenti mlađi od 18 godina, pacijenti sa akutnim infekcijama (do mesec dana pre aplikacije 131-I), sa ranije dijagnostifikovanim i/ili lečenim autoimunskim bolestima, ranije dijagnostifikovanim i/ili lečenim hroničnim inflamatornim bolestima i ranije dijagnostifikovanim i/ili lečenim drugim tumorima, odnosno osobe kod kojih je primenjena zračna ili hemioterapija. Sve posmatrane varijable analizirane su u odnosu na kontrolnu grupu ispitanika, sastavljenu od 24 zdrava dobrovoljca, 19 žena i 5 muškaraca prosečne starosti 46.37±12.79 godina, kod kojih ranije nisu dijagnostifikovani tumori ili hronične inflamatorne bolesti, i koji mesec dana pre uzimanje uzorka krvi nisu imali akutnu infekciju sa povišenom temperaturom, a najmanje tri meseca nisu bili izloženi dejstvu jonizujućeg zračenja ili poznatih genotoksina.

The initial treatment in patients with differentiated thyroid carcinoma (DTC) includes total or near total thyroidectomy and radioactive iodine (131-I) therapy. The propose of 131-I therapy is to ablate remnant thyroid tissue and treat iodine-avid metastases. 131-I induces whole body irradiation followed by oxidative stress and the release of some cytokines, as well as the cellular damage with an increase of micronucleus frequency and potential apoptosis of peripheral blood lymphocytes. The aim of this study was to investigate the cellular and biochemical changes in the peripheral blood of DTC patients before and seven days after administration of radioactive 131-I. The investigation was designed as a comparative clinical-experimental study in which we compared tested parameters in the experimental and control group of subjects. The study population included 24 well-differentiated thyroid cancer patients (16 females and 8 males), with a mean age of 50.83±13.22 years. Four t...o six weeks after total thyreoidectomy and 10 days after a low iodine diet, the patients were treated with fixed nominal activities of 3.7 GBq (100 mCi)(13 patients) or 5.5 GBq (150 mCi)(11 patients) of orally administrated sodium iodide (131-I). Inclusion criteria were: histopathological confirmed diagnosis of papillary or follicular thyroid carcinoma after total thyroidectomy, consultative decision about the application of radioactive 131-I, hypothyroid condition (TSH>30 mIU/L), and written informed consent according to the Declaration of Helsinki. Patients younger than 18 years, those with acute infections (one month before the application of 131-I), and previously established and/or treated autoimmune diseases, chronic inflammatory diseases and other type of tumors, as persons who underwent the radio- or chemotherapy were not included in the study. The control group consisted of 24 healthy subjects, 19 females and 5 males, with a mean age of 46.37±12.79 who had never diagnosed tumors or chronic inflammatory diseases, had no an acute infection with а fever one month before taking the blood sample, and had not been exposed to radioactive sources or other known genotoxic agents within at least 3 months.

Faculty:
Универзитет у Крагујевцу, Факултет медицинских наука
Date:
09-09-2014
Projects:
  • Preclinical investigation of bioactive substances (RS-41010)
Keywords:
diferentovani karcinomi štitaste žlezde / radioaktivni jod 1431 / mikronukleusi / apoptoza limfocita
[ Google Scholar ]
Handle
https://hdl.handle.net/21.15107/rcub_nardus_3723
URI
http://eteze.kg.ac.rs/application/showtheses?thesesId=1043
https://nardus.mpn.gov.rs/handle/123456789/3723
https://fedorakg.kg.ac.rs/fedora/get/o:382/bdef:Content/download

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