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| Project leader |
Rucevic Marijana |
| Project co-leader: |
Djuro Josic, Ph.D. Professor (Research) Medicine |
| Administering organization: |
Rudjer Boskovic Institute, Bijenicka 54, HR-10000 Zagreb, Croatia
www.irb.hr
Director: Danica Ramljak, Ph.D. |
| Partner Institution/Company: |
Brown University/COBRE Center for Cancer Research Development |
| Grant type: |
2A |
| Project title: |
Endemic Nephropathy: proteomics approach for biomarkers discovery and etiology study |
| Project summary: |
Endemic Nephropathy (EN) is a chronic renal disease that occurs in some rural areas in Southeastern Europe. Despite numerous studies conducted to date, the etiology of this disease still remains unknown. Aristolochic acids (AA) present in Aristolochia plants are the toxins responsible for Chinese Herbs Nephropathy (CHN). Recently, strong indications have been presented, that dietary poisoning by AA is also responsible for EN and its associated urothelial cancer (UC). In the present study, we are going to investigate proteomic changes in urinary and blood specimens of model animals prone to poisoning with AA and, of patients suffering from EN and/or UC by using SELDI-TOF MS. In addition, imaging mass spectrometry (IMS), a recently developed approach for direct spatial distribution determination of tissue specific proteins will be established. The IMS will be applied for discovery and determination of specific tissue markers within the kidneys of model animals, in degenerated kidneys and/or UC of affected patients. At final, the significant proteins will be identified with LC-ESI-MS/MS and MALDI-MS. Completion of this research should provide an insight into the etiology of EN and, will lead to discovery of renal EN and associated UC biomarkers thus, enabling early diagnosis and most effective follow-up treatments. |
| Hrvatski sažetak: |
Endemska nefropatija (EN) kronična je bubrežna bolest progresivnog tijeka i učestalijeg javljanja u ruralnim područjima sjeveroistočne Europe. Unatoč brojnim provedenim studijama, etiologija ove bolesti još uvijek je nepoznata. Aristolohična kiselina (AK), glavni sastojak biljke Aristolochia clematitis (vučja stopa), toksična je supstanca odgovorna za pojavu bolesti tzv. “Chinese Herbs Nephrophaty“. Nedavna istraživanja, provedena na nivou genoma, ukazuju da je prisustvo AK u hrani također glavni čimbenik nastanaka EN i njoj pripadnog karcinoma urotela. U ovoj studiji, provesti će se analiza proteoma u uzorcima urina i krvi pokusnih životinja izloženih trovanju sa AK, te u uzorcima urina i krvi bolesnika oboljelih od EN i/ili karcinoma urotela SELDI-TOF MS metodom. Pomoću “imaging mass spectrometry” (IMS), nedavno razvijeni sistem za direktno određivanje tkivnih supstanci i njihove raspodjele unutar tkiva, provesti će se analiza i otkrivanje specifičnih markera u uzorcima tkiva bubrega pokusnih životinja, bubrega EN bolesnika te unutar malignih tkiva. Konačno, identifikacija karakterističnih, potencijalno značajnih supstanci otkrivenih u uzorcima urina, krvi i tkiva provesti će se LC-ESI-MS/MS i MALDI-MS metodama. Rezultati ovog istraživanja razjasniti će prirodu nastanka bolesti, te omogućiti otkrivanje i identifikaciju potencijalnih biomarkera za ranu dijagnozu i daljnju terapiju bolesnika oboljelih od EN i/ili njoj pripadnog karcinoma urotela.
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| Amount requested from UKF: |
10.000 EUR |
| Amount of matching funding: |
32.000 EUR |
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