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Kanser Kök Hücresi ve Notch Yolağında Umut Veren Ortak Embriyonik Dönem inhibisyonu

The promising inhibition of the joint embriyonic period in the cancer stem cells and notch pathway

Journal Name:

  • Cerrahpaşa Tıp Dergisi

Publication Year:

  • 2009

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Objectives: The Notch signaling plays role to provide determining of cell fate and surviving of stem cell in the embryonic and postnatal development. The retardation effects of Notch in adult acts as oncogene or tumor suppressor gene. Notch 1 receptor and Notch ligands, Delta 1 and Jagged 1 interconnect with plasma membrane plays active role in duration of embryogenesis and malign diseases development. Cancer Stem Cells (CSC) are tumor cancer cells, their many characteristics are similar with stem cells. Verapamil is a calcium canal blocker which completely disappeared “Side Population” (SP) cells. If effective mechanism of Verapamil enlightened in the embryonic development, it could be guide in cancer researches for many new alternative therapies by the way of CSC. Methods: In our study, we aimed to examine possible changes in the Notch pathway of sublethal doses of Verapamil in the fetal kidney during embryogenesis. Verapamil was administrated 2x10mg/kg/day from embryonic 9th day (E9) and fetal kidneys were removed in 18th (E18) and 21th (E21). C-kit receptor tyrosine kinase (CD 117) for stem cells and Notch 1 receptor, Delta 1 and Jagged 1 ligands in the Notch pathway was determined by immunohistochemistry. Results: As a result, inhibitor effect (E21) of Verapamil in Notch pathway was significantly increased, immunoreactivity of c-kit decreased especially in glomerular and tubular areas in the metanephric kidney. Conclusion: In conclusion the effects of Verapamil in embryonic development and the correlative mechanism with CSC can be guide for the treatment of cancer and enable to new alternative therapies.
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Abstract (Original Language): 
Amaç: Notch sinyal iletisi, embriyonik ve postnatal gelişimde hücre kaderinin belirlenmesi ve kök hücre devamlılığının sağlanmasında rol oynar. Erişkinde bu etkilerin çeşitli nedenlerle aksamasıyla Notch, onkogen veya tümör baskılayıcı gen olarak etki eder. Notch 1 reseptörü, ligantları Delta 1 ve Jagged 1 hücre membranı ile bağlantılı olup embriyogenezis ve malign hastalıkların gelişim sürecinde etkilidir. Kanser Kök Hücreleri (KKH), pek çok özelliğiyle kök hücreye benzeyen tümör hücreleridir. Verapamil, KKH’de “Side Population” (SP) hücrelerini tamamen ortadan kaldırabilen bir Ca+2 kanal blokeridir. Verapamil uygulamalarının embriyonik gelişimde etki mekanizmalarının belirlenmesi, tedaviye dirençli KKH’nin yok edilmesi için yeni tedavi seçeneklerinin ortaya konmasında yol gösterici olabilir. Yöntem: Bu çalışmada, Verapamil’in sublethal dozlarının embriyogenezis sürecindeki etkileri fötal böbrekte inceleyerek Notch yolağındaki olası değişimlerin gösterilmesi amaçlandı. Gebeliğin 9. gününden (E9) itibaren 2x10mg/kg/gün Verapamil uygulandıktan sonra (E18) ve (E21) günlerde fötal böbrek dokuları incelendi. Kök hücreleri için c-kit reseptör tirozin kinaz (CD 117) ile Notch yolağında ise Notch 1 reseptörü, Delta 1 ve Jagged 1 immunohistokimyasal olarak değerlendirildi. Bulgular: Verapamilin böbrek embriyonik gelişim sürecinde Notch yolağındaki inhibitör etkisinin (E21)’de belirgin olarak arttığı, glomerüler ve tübüler alanlarda c-kit immunoreaktivitesinin azaldığı görüldü. Sonuç: Verapamilin embriyonik gelişim üzerindeki etkilerinin, KKH’nin yok edilmesi için yeni tedavi seçeneklerinin ortaya konmasında yol gösterici olabileceği düşünüldü.
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  • 1
23-27
  • Turkish

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