Identificarea profilelor moleculare transcriptomice in cancerul de col ...
Identificarea profilelor moleculare transcriptomice in cancerul de col ...
Identificarea profilelor moleculare transcriptomice in cancerul de col ...
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Nr proiect: 42-160/ 2008Titlul Proiect:“<strong>I<strong>de</strong>ntificarea</strong> <strong>profilelor</strong> <strong>moleculare</strong><strong>transcriptomice</strong> <strong>in</strong> <strong>cancerul</strong> <strong>de</strong> <strong>col</strong> uter<strong>in</strong>avansat pr<strong>in</strong> studii <strong>de</strong> genomica functionala.CERVIX-array .”Coordonator:Institutul On<strong>col</strong>ogic „ Prof Dr. Ion Chiricuta” Cluj-Napoca (IOCN)Director proiect:Dr. Ovidiu Balacescu
Componenta Consortiului <strong>de</strong> cercetare :CO- Institutul On<strong>col</strong>ogic „ Prof Dr. Ion Chiricuta” Cluj-Napoca (IOCN)P1- Universitatea <strong>de</strong> Medic<strong>in</strong>a si Framacie „I. Hatieganu” Cluj Napoca (UMFCN)P2-Institutul <strong>de</strong> Sanatate Publica “Iuliu Moldovan„ Cluj-Napoca (ISPCN)F<strong>in</strong>anţare: buget <strong>de</strong> stat: 2.000.000 leiCof<strong>in</strong>antare 0 leiAdresa web: http://www.iocn.ro/CERCETARE/Pag<strong>in</strong>i-Web-proiecte/CERVIXarray.html
Obiectiv: Realizarea unui mo<strong>de</strong>l experimental, bazat pe studii <strong>de</strong> genomicafunctionala si genotipare HPV, ca factor <strong>de</strong> predictie <strong>in</strong> raspunsul la radiochimioterapie<strong>in</strong> <strong>cancerul</strong> <strong>de</strong> <strong>col</strong> uter<strong>in</strong> (IIB-IIIB).Rezultatul f<strong>in</strong>al al proiectului: O metoda moleculara <strong>de</strong> <strong>in</strong>vestigatie <strong>in</strong>medic<strong>in</strong>a pentru predictia la terapie <strong>in</strong> <strong>cancerul</strong> <strong>de</strong> <strong>col</strong> uter<strong>in</strong>.Elemente <strong>de</strong> noutate:Stabilirea unei semnaturi <strong>moleculare</strong> <strong>transcriptomice</strong> la nivelul <strong>in</strong>treguluigenom uman ca predictie a raspunsului la terapie functie <strong>de</strong> <strong>in</strong>carcaturavirala HPV.Orig<strong>in</strong>alitate:Comb<strong>in</strong>area analizei <strong>transcriptomice</strong> cu genotiparea HPV (37 subtipuri)Beneficiarii rezulatelor, potentialul <strong>de</strong> aplicare <strong>in</strong> economie• bolnavii on<strong>col</strong>ogi care pot beneficia <strong>de</strong> un tratament <strong>in</strong>dividualizat;• sistemul <strong>de</strong> sanatate pr<strong>in</strong> costurilor legate <strong>de</strong> eficientizarea tratamenteloron<strong>col</strong>ogice;• t<strong>in</strong>erii doctoranzi –specializare <strong>in</strong> domenii <strong>de</strong> varf – genomica• comunitatea sti<strong>in</strong>tifica <strong>in</strong>ternationala pr<strong>in</strong> prezentarea datelor obt<strong>in</strong>ute <strong>in</strong>urma studiului <strong>de</strong> cerectare.• companii farmaceutice <strong>in</strong>teresate sa utilizeze <strong>in</strong>formatiile genomice pentrustabilirea <strong>de</strong> teste <strong>de</strong> predictie si <strong>de</strong> medicamente mai eficiente.
Stadiul <strong>de</strong> realizare al proiectului <strong>in</strong> 2010Etapa a III-a (01.10.2008-15.02.2009 )Consolidarea Biobancii; Pregatirea studiului <strong>de</strong> GenomicaBuget <strong>de</strong> stat: 286.145 lei d<strong>in</strong> 1.000.200 lei contractat pt etapa a III-a.cof<strong>in</strong>antare:0 RONActivitati realizate• Consolidarea Biobancii. Re<strong>col</strong>tarea si prelucrea probelor biologice– Proce<strong>de</strong>e (Formulare <strong>de</strong> consimtamant <strong>in</strong>format); Chestionare <strong>de</strong> evaluare a factorilor <strong>de</strong>risc• Evaluare <strong>in</strong>caractura virala HPV risc crescut (43 <strong>de</strong> paciente)– Proce<strong>de</strong>e (Raport) evaluare 37 subtipuri HPV• S<strong>in</strong>teza <strong>de</strong> son<strong>de</strong> microarray (Cy-cRNA)si evaluarea calitativa sicantitativa a acestora– Medo<strong>de</strong> (Raport )<strong>de</strong> analiza evaluare son<strong>de</strong> microarray pr<strong>in</strong> nanotehnologie• Disem<strong>in</strong>are rezultate– Confer<strong>in</strong>te, publicatii• Achiziti realizatereactivi +consumabile reactivi procesare probe biologice, reactivi analiza genomica(microarray) kituri genotipare, consumabile birotica)
Participare t<strong>in</strong>eri cercetatoriDomeniile <strong>de</strong> implicare:Evaluari cl<strong>in</strong>ice: Puscas Emil, Achimas PatriciuTerapie: Ca<strong>in</strong>ap Cal<strong>in</strong>, Burz Claudia, Ioana BrieEvaluari <strong>de</strong> anatomie patologica: Fetica Bogdan, Buiga RaresEvaluari <strong>de</strong> biologie moleculara si genomica: Tudoran Oana,Gherman Claudia, Rus Meda, Dragla FlaviuEvaluari <strong>de</strong> bio<strong>in</strong>formatica: Balacescu LoredanaComun: redactari <strong>de</strong> lucrari sti<strong>in</strong>tifice si participari la confer<strong>in</strong>te2010- lipsa fondurilor pentru specializari/stagii <strong>de</strong> formare pentrudoctorate, post-doc
Indicatori <strong>de</strong> rezultat realizati <strong>in</strong> cadrulproiectuluiProce<strong>de</strong>e (Formulare <strong>de</strong> consimtamant <strong>in</strong>format); Chestionare <strong>de</strong> evaluare afactorilor <strong>de</strong> risc.Proce<strong>de</strong>e (Raport) evaluare 37 subtipuri HPVMedo<strong>de</strong> (Raport ) <strong>de</strong> analiza evaluare son<strong>de</strong> microarrayRaport studiu prelim<strong>in</strong>ar evaluare mecanism <strong>de</strong> angiogeneza (PCR array)
Indicatori <strong>de</strong> rezultat realizati <strong>in</strong> cadrulproiectuluiArti<strong>col</strong>e trimise spre publicare:• O. Tudoran, O. Balacescu, O. Soritau, L. Balacescu, C. Braicu, M. Rus, C. Gherman, C.Burz, F.D. Irimie, I. Ber<strong>in</strong>dan Neagoe. Transcriptional mechanism of apoptosis <strong>in</strong>duced byVEGFA <strong>in</strong>hibition <strong>in</strong> cervical cancer cells. Resp<strong>in</strong>sa la European Journal of Pharma<strong>col</strong>ogy,este <strong>in</strong> modificari si urmeaza sa fie trimisa spre publicare <strong>in</strong> Apoptosis.• Challenge: The Gyne<strong>col</strong>ogic Cancers. September 30 – October 2, 2010. Cluj-Napoca. OanaTudoran, Olga Soritau, Ovidiu Balacescu, Loredana Balacescu, Cornelia Braicu, Meda Rus,Claudia Gherman, Flor<strong>in</strong> Irimie, Ioana Ber<strong>in</strong>dan Neagoe. Early transcriptional pattern ofangiogenesis <strong>in</strong>duced by EGCG treatment <strong>in</strong> cervical tumor cells - sub review la Journal ofCellular and Molecular Medic<strong>in</strong>e.• Sor<strong>in</strong>a IRIMIE, Mariana VLAD, Ileana Maria MIRESTEAN, Ovidiu BALACESCU, Rus Meda,#Loredana BALACESCU , Ioana BERINDAN-NEAGOE, Rares BUIGA, Oana TUDORAN,Viorica NAGY, Alexandru IRIMIE. Risk profile <strong>in</strong> a sample of patients with advancedcervical cancer. Trimisa <strong>in</strong> The Journal of Epi<strong>de</strong>miology and Community Health.Participare la confer<strong>in</strong>te si congrese:• Ovidiu Balacescu, Oana Tudoran, Meda Rus, Loredana Balacescu, Rares Buiga, VioricaNagy, Ioana Neagoe. Detection of HPV <strong>in</strong>fection and its cl<strong>in</strong>ical utility. The 20th Congressof the Romanian Society for Radiotherapy and Medical On<strong>col</strong>ogy. A Cont<strong>in</strong>uous
Activitati prevazute pt 2011:Perspective 2011Realizarea studiului <strong>de</strong> genomica (hibridarea son<strong>de</strong>lor microarray pelame WHG (4x44k); validarea rezultatelor microarray pr<strong>in</strong> qRT-PCR;corelarea datelor <strong>de</strong> genomica cu subtipul viral HPV si raspunsul laterapie;Obiectivele preconizate a fi at<strong>in</strong>se:Realizarea unui mo<strong>de</strong>l experimental, bazat pe studii <strong>de</strong> genomicafunctionala si genotipare HPV, ca factor <strong>de</strong> predictie <strong>in</strong> raspunsul laradio- chimioterapie <strong>in</strong> <strong>cancerul</strong> <strong>de</strong> <strong>col</strong> uter<strong>in</strong> (IIB-IIIB).Elemente <strong>de</strong> orig<strong>in</strong>alitate:Comb<strong>in</strong>area analizei <strong>transcriptomice</strong> cu genotiparea HPV (37 subtipuri)Necesar f<strong>in</strong>antare pt 2011:Ramas d<strong>in</strong> contractare: 1.533.355 leiAt<strong>in</strong>gerea obiectivelor propuse <strong>in</strong>itial: 650.000-700.000 lei
Perspective: HPV- genomica-genotipareName ofGeneCDH5FGFR3(VEGFR)KDRNOTCH4PLAUSTAB1THBS1Descriptioncadher<strong>in</strong> 5, type 2 (vascular endothelium)fibroblast growth factor receptor 3, mitogeneza sidiferentierek<strong>in</strong>ase <strong>in</strong>sert doma<strong>in</strong> receptor (a type III receptortyros<strong>in</strong>e k<strong>in</strong>ase); receptor for VEGFNotch homolog 4 (Drosophila), <strong>de</strong>velopementplasm<strong>in</strong>ogen activator, urok<strong>in</strong>ase; <strong>in</strong>volved <strong>in</strong><strong>de</strong>gradation of the extracellular matrix and possiblytumor cell migration and proliferationstabil<strong>in</strong> 1; function <strong>in</strong> angiogenesis, lymphocytehom<strong>in</strong>g, cell adhesion, or receptor scaveng<strong>in</strong>gthrombospond<strong>in</strong> 1; angiogenesis, and tumorigenesisFold Up- or Down- regulationHPV16/HPV45, 58 p value3.22210.00050210.73810.0041662.6970.0143913.70120.001723.35120.0187631.58520.0283173.65870.037926