Abstract - Effects of Imatinib, Nilotinib and Dasatinib on Serum VEGF and VEGFR-1 Levels in Patients with Chronic Phase Chronic Myelogenous Leukemia
< Back
[PDF]
Rahşan Yıldırım, Gülden Sincan, Çiğdem Pala, Musa Düdükcü, Leylagül Kaynar, Selin Merih Urlu, İlhami Kiki, Fuat Erdem, Mustafa Çetin, Mehmet Gündoğdu, Ömer Topdağı
ABSTRACT
Objective: Vascular endothelial growth factor (VEGF) is a protein that binding to VEGF receptors 1 (VEGFR-1) and accelerates angiogenesis. The relationship between angiogenesis and progression of tumors were observed in both solid and hematologic cancers. Monoclonal antibodies capable of inhibiting angiogenesis, tyrosine kinase inhibitors use for haematological cancer treatment. In this study; we investigated the effects of Imatinib mesylate (STI-571; Gleevec), Nilotinib (AMN107; Tasigna) and Dasatinib (BMS-354825;  Sprycell) on serum levels of VEGF and VEGFR-1, in patients with chronic phase of chronic myeloid leukemia (CML). Method: Serum levels of VEGF and VEGFR-1 were measured in 65 patients with chronic phase of CML. Serum VEGF and VEGFR-1 levels were determined using quantitative sandwich enzyme immunoassay technique according to the manufacturers’ instructions. Results: There were 33 (51%) male and 32 (49%) female patients in this study. 38 of 65 patients were using Imatinib, 15 Nilotinib, 12 Dasatinib. Mean serum VEGF and VEGFR-1 levels for the 65 patients with CML were 172.21±127.46 pg/mL and 199.62±122.22 pg/mL, respectively. In Dasatinib and Imatinib group, serum VEGF  and VEGFR-1 levels were significantly higher than in control group ( p= 0.008, p< 0.0001, and p< 0.0001, p< 0.0001). In Nilotinib group, serum VEGF levels were higher than control group, but; it was not statistically significant (p= 0.06) while . VEGFR-1 levels were significantly higher than those of controls (p< 0.0001). Conclusion: Imatinib, Nilotinib and Dasatinib were not superior to each other regarding to serum VEGF and VEGFR-1, but it may be said that Nilotinib may has slightly more effect on inhibition of anjiogenesis.
Key words: Angiogenesis, Tyrosin kinase inhibitors, VEGF, VEGFR-1
 
Kronik Myeloid Lösemili Hastalarda İmatinib, Nilotinib, Dasatinib’in VEGF ve VEGFR-1 Düzeyleri Üzerine Etkileri 
ÖZET
Amaç: Vasküler endotelyal büyüme faktörü (VEGF), VEGF reseptörlerine bağlanarak angiogenezi hızlandıran bir proteindir. Anjiogenez ile tümörlerin progresyonu arasındaki ilişki hem solid hemde hematolojik kanserlerde saptanmıştır. Anjiogenez inhibisyonu yapan monoklonal antikorlardan tirozin kinaz inhibitörleri tedavide kullanılabilir. Bu çalışmada amaç kronik faz Kronik Myeloid lösemi (KML) hastalarında İmatinib mesylate (STI-571; Gleevec), Nilotinib (AMN107; Tasigna) and dasatinib’in (BMS-354825;  Sprycell)  serum VEGF ve VEGF reseptör 1 (VEGFR-1)  düzeyine etkilerini araştırmaktır. Yöntem: 65 kronik faz KML hastasında serum VEGF ve VEGFR-1 düzeyi ölçüldü.  Serum VEGF and VEGFR-1 düzeyleri üretici firmanın önerisi doğrultusunda kantitatif sandviç enzim immunoassay yöntemi kullanılarak ölçüldü. Bulgular: Çalışmaya alınan hastaların 33’ü (% 51) erkek ve 32’si (% 49) kadındı. 65 hastadan 38’i İmatinib, 15’i Nilotinib ve 12’si Dasatinib kullanıyordu. Hastaların ortalama VEGF düzeyi 172.21±127.46 pg/mL iken VEGFR-1 düzeyi 199.62±122.22 pg/mL idi. Serum VEGF  and VEGFR-1 düzeyleri imatinib ve dasatinib kullanan gruplarda kontrol grubundan anlamlı yüksekti (p< 0.0001, p<0.0001 ve p= 0.008, p< 0.0001). Nilotinib grubunda ise serum VEGF düzeyi kontrol grubundan yüksek ancak istatiksel olarak anlamlı değildi (p= 0.06). VEGFR-1 düzeyi ise kontrol grubundan istatiksel olarak anlamlı yüksekti (p< 0.0001). Sonuç: Serum VEGF ve VEGFR-1 düzeyi açısından İmatinib, Nilotinib ve Dasatinib birbirine üstün değildir. Ancak Nilotinibin anjiogenez inhibisyonuna biraz daha fazla etkili olduğunu söyleyebiliriz.
Anahtar kelimeler: Anjiogenez, tirozin kinaz inhibitörleri, VEGF, VEGFR-1

 

Volume 13, Number 2 (2016)

The journal is currently indexed/included in Emerging Sources Citation IndexCrossRefBioline International, Chemical Abstracts Service, CINAHL Information System, EBSCO, Swets Information Services, Index Copernicus, SCOPUS, EMBASE, Turkiye Citation Index and TUBITAK ULAKBIM Turkish Medical Database.

  • Journal Search - IP & Science - Thomson Reuters
  • SCImago Journal & Country Rank
  • Turk Medline
  • Crossref
  • Scopus
  • Ulakbim
  • Türkiye Atıf Dizini
  • EBSCO
Other Journals