1. Raportul Stiintific si Tehnic (RST) in extenso al proiectului cu titlul ...
1. Raportul Stiintific si Tehnic (RST) in extenso al proiectului cu titlul ...
1. Raportul Stiintific si Tehnic (RST) in extenso al proiectului cu titlul ...
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ar putea fi utilizat <strong>in</strong> comb<strong>in</strong>atie <strong>cu</strong> PSA seric, pentru reducerea numarului de biop<strong>si</strong>i<br />
<strong>in</strong>utile. (3) Un studiu mic a <strong>in</strong>dicat ca an<strong>al</strong>iza bazata pe re<strong>al</strong> time PCR a AMACR <strong>in</strong><br />
ur<strong>in</strong>a, dupa masajul prostate are po<strong>si</strong>bilitatea sa excluda pacientii <strong>cu</strong> bo<strong>al</strong>a cl<strong>in</strong>ica<br />
nesemnificativa, de vreme ce expre<strong>si</strong>a AMACR se norm<strong>al</strong>izeaza pentru PSA. (4)<br />
An<strong>al</strong>iza Western blot pe esantioane de ur<strong>in</strong>a obt<strong>in</strong>ute dupa masajul prostatei are<br />
sen<strong>si</strong>bilitate 100%, specificitate 58%, v<strong>al</strong>oare pozitiva predictiva (VPP) de 72% <strong>si</strong><br />
v<strong>al</strong>oare negativa predictiva (VNP).<br />
Numeroase studii au <strong>in</strong>dicat ca hep<strong>si</strong>na este una d<strong>in</strong> cele mai con<strong>si</strong>stent<br />
supraexprimate gene <strong>in</strong> CaP. Este o prote<strong>in</strong>a codificata tip ser<strong>in</strong> proteaza<br />
transmembranara tip II identificata pe suprafata hepatocitelor. Nivelul hep<strong>si</strong>nei se<br />
coreleaza <strong>cu</strong> gradul tumor<strong>al</strong> <strong>in</strong> primele stadii, expre<strong>si</strong>a sa scazuta s-a identificat <strong>in</strong><br />
stadiile tardive, hormon<strong>al</strong> refractare. Nu se stie functia fiziologica. Rapoartele priv<strong>in</strong>d<br />
rolul sau <strong>in</strong> controlul cresterii celulare sunt contradictorii; hep<strong>si</strong>na este necesara<br />
pentru proliferarea celulelor <strong>in</strong> hepatom dar supraexpre<strong>si</strong>a sa <strong>in</strong>hiba cresterea <strong>si</strong><br />
<strong>in</strong>vazia celuleoor <strong>in</strong> CaP.<br />
Sunt numeroase studii priv<strong>in</strong>d expre<strong>si</strong>a factorilor proangiogenici pre<strong>cu</strong>m factorul de<br />
crestere vas<strong>cu</strong>lar <strong>al</strong> endoteliilor (VEGF), factorul de crestere <strong>al</strong> celulelor endoteli<strong>al</strong>e<br />
derivat d<strong>in</strong> plachete (PD-ECGF), factorul de crestere asemanator <strong>in</strong>sul<strong>in</strong>ei (IGF),<br />
factorul de crestere transformator (TGF) <strong>in</strong> CaP. Un reglator <strong>cu</strong> functie cheie <strong>al</strong><br />
fenotipului angiogenic <strong>in</strong> multe cancere este VEGF, care este un potenti<strong>al</strong> mitogen<br />
pentru celulele endoteli<strong>al</strong>e. Cresterea expre<strong>si</strong>ei VEGF s-a raportat <strong>in</strong> Cap, <strong>si</strong> pe l<strong>in</strong>ii<br />
celulare derivate <strong>si</strong> pe fragmente de tumora. De asemenea nivele cres<strong>cu</strong>te <strong>al</strong>e<br />
receptorilor VEGF (VEGFR) k<strong>in</strong>aza 1 d<strong>in</strong> ficat fet<strong>al</strong> (Flk-1) <strong>si</strong> fms-asemanator tiroz<strong>in</strong>k<strong>in</strong>aza<br />
1 (Flt-1) s-au detectat <strong>in</strong> tumori de prostata la om. Adm<strong>in</strong>istrarea anticorpilor<br />
anti VEGF ce t<strong>in</strong>teste neovas<strong>cu</strong>larizatia, suprima efectiv cresterea xenogrefelor CaP<br />
la soricei imunodeprimati <strong>in</strong>a<strong>in</strong>te de faza <strong>in</strong>iti<strong>al</strong>a de crestere prevas<strong>cu</strong>lara pre<strong>cu</strong>m <strong>si</strong><br />
<strong>in</strong>a<strong>in</strong>te de metastazarea CaP stabilizat.<br />
FIGURE <strong>1.</strong> Modelul de progre<strong>si</strong>e <strong>in</strong> CaP. Pa<strong>si</strong>i histopatologici <strong>in</strong> tumorigeneza<br />
prostatica.<br />
In faza <strong>in</strong>iti<strong>al</strong>a, apar leziunile de neoplazie <strong>in</strong>traepiteli<strong>al</strong>a prostatica de grad scazut <strong>si</strong><br />
<strong>in</strong><strong>al</strong>t (LGPIN <strong>si</strong> HGPIN) , leziuni ce se pot identifica histopatologic. Este dificil de fa<strong>cu</strong>t<br />
deosebirea <strong>in</strong>tre leziunea dormanda (verde) <strong>si</strong> cea progre<strong>si</strong>va (rosu/ HGPIN)<br />
Progre<strong>si</strong>a catre <strong>in</strong>vazie loc<strong>al</strong>a <strong>si</strong> apoi metastazare (verde <strong>cu</strong> stelute) este probabil o<br />
consec<strong>in</strong>ta a a<strong>cu</strong>mularii cont<strong>in</strong>ue de <strong>al</strong>terari genetice.<br />
Grupuri de lucru au elaborat <strong>in</strong>dreptare pentru o ev<strong>al</strong>uare <strong>si</strong>stematica <strong>si</strong> critica a<br />
celor mai importanti markeri d<strong>in</strong> CaP , ev<strong>al</strong>uare care are 6 faze:
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