Akciğer kanserlerinde dokudaki VEGFR-1 ve TRAILR-1 ekspresyonları ile serum solubl VEGFR-1 düzeylerinin tedaviye yanıtla ilişkilerinin incelenmesi
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Date
2004
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Uludağ Üniversitesi
Abstract
Artmış Vasküler Endotelyal Growth Faktör (VEGF) ekspresyonu akciğer kanseri dahil çeşitli kanserlerde gözlenmiştir. Vasküler Endotelyal Growth Faktör-Reseptör 1 (VEGF-R1) de bu etkilerine aracılık eden reseptörlerden biridir. Solubl Vasküler Endotelyal Growth Faktör-Reseptör 1 (sVEGF-R1) tümör anjiyogenezinde önemli endotelyal regülatörlerden biridir. VEGF'nin başlattığı sinyal iletimi yolunda tamamen zıt etki gösterir. Yani VEGF'nin etkisini inhibe eder. Tümör nekrozis Faktör (TNF) aracılı apoptozis indükleyici ligand (TRAIL), reseptörleri olan TRAIL-R1 ve TRAIL-R2 aracılığıyla selektif olarak kanser hücrelerini apoptozise götürerek metastazların önlenmesi ile ilişkili olabilir. Biz çalışmamızda malign akciğer kanserli hastaların serum sVEGF-R1 düzeyleri ile benign akciğer hastalıklı ve sağlıklı bireylerin sVEGF-R1 düzeylerini karşılaştırdık. sVEGF-RVin tedavi ve survi ile olası ilişkisini saptamaya çalıştık. Ayrıca çalışmamızda akciğer kanser dokusunda VEGF-R1 ve TRAIL-R1 ekspresyon düzeylerini inceleyerek tedavi ve survi ile ilişkisini saptamaya çalıştık. Malign olgular 42 kişiden oluşurken benign ve sağlıklı kontrol grubumuz toplam 55 kişiden oluşmaktaydı. Serum sVEGF-RI düzeyleri ELISA metodu ile ölçüldü. Doku VEGF-R1 ve TRAIL-R1 ekspresyon düzeyleri ise immunohistokimyasal olarak değerlendirildi.Serum sVEGF-RI düzeyleri bakımından malign ve nonmalign olgular arasında anlamlı bir fark gözlenmedi (p>0.05). Tedavi öncesi ve sonrası sVEGF-RI düzeyleri karşılaştırıldığında anlamlı bir fark saptanmadı (p>0.05). Fakat sVEGF-R1 düzeylerinin progresyon gösteren grupta anlamlı olarak daha az olduğu saptandı. Ayrıca tedavi yanıtı ile sVEGF-R1 düzeyleri karşılaştırıldığında, sVEGF-R1 düzeylerinin hastalığın progresif veya stabil olması durumu ile anlamlı bir korelasyon gösterdiği bulundu (p<0.05). Doku VEGF-R1 ekspresyon seviyeleri açısından progresif hastalar ile stabil hastalar arasında anlamlı bir fark saptandı. Doku sVEGF-R1 düzeyleri progresif grupta artmış olarak bulundu. Sonuç olarak serum sVEGF-RI düzeylerinin, tedaviye yanıtı tahmin etmede klinisyenlere yardımcı bir parametre olabileceği kanısına varıldı.
Vascular endothelial.growth factor (VEGF) overexpression has been observed in several malignant tumors including lung canceL VEGF- related actions are mediated through its receptors. Soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) is a negative counterpart of the VEGF signaling pathway that is characterized as one of the most important endothelial regulators in human tumor angiogenesis. Tumor 'necrosis factor- related apoptosls-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells through its receptors TRAIL-R1 and TRAIL-R2 and it may be involved in protection from metastases. In our study, we investigated the sVEGF-R1 levels in serum of 42 lung cancer patients and compared them with those in patients with benign lung disease and healthy subjects in total of 55 subjects. We also determined the possible relation of it with the treatment. In addition we examined the expression levels of VEGF-R1 and TRAIL-R1 in lung cancer tissues and their relation with the treatment and survival. Malign and nonmalign group (benign and control group all together) were consisted of 42 and 55 subjects, respectively. Levels of sVEGF-R1 in serum were measured by ELISA method. Tissue VEGF-R1 and TRAIL-R1 expressions were determined immunohistochemically.We observed no significant difference in terms of serum sVEGFR-1levels between malign and nonmalign groups (p>0.05). There was no significant difference in the levels of sVEGFR-1 before and after treatment, either. However there was a significant correlation between sVEGF-R1 levels and the response of therapy in the progresive or stable disease patients (p<0.05). We also observed statistical significance in terms of the expression levels of tissue VEGFR-1 between the progresive and the stabil disease groups. However, no significant correlation was determined between its expression and survival time. We conclude that sVEGFR-1 levels may help clinicians to predict the response to treatment.
Vascular endothelial.growth factor (VEGF) overexpression has been observed in several malignant tumors including lung canceL VEGF- related actions are mediated through its receptors. Soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) is a negative counterpart of the VEGF signaling pathway that is characterized as one of the most important endothelial regulators in human tumor angiogenesis. Tumor 'necrosis factor- related apoptosls-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells through its receptors TRAIL-R1 and TRAIL-R2 and it may be involved in protection from metastases. In our study, we investigated the sVEGF-R1 levels in serum of 42 lung cancer patients and compared them with those in patients with benign lung disease and healthy subjects in total of 55 subjects. We also determined the possible relation of it with the treatment. In addition we examined the expression levels of VEGF-R1 and TRAIL-R1 in lung cancer tissues and their relation with the treatment and survival. Malign and nonmalign group (benign and control group all together) were consisted of 42 and 55 subjects, respectively. Levels of sVEGF-R1 in serum were measured by ELISA method. Tissue VEGF-R1 and TRAIL-R1 expressions were determined immunohistochemically.We observed no significant difference in terms of serum sVEGFR-1levels between malign and nonmalign groups (p>0.05). There was no significant difference in the levels of sVEGFR-1 before and after treatment, either. However there was a significant correlation between sVEGF-R1 levels and the response of therapy in the progresive or stable disease patients (p<0.05). We also observed statistical significance in terms of the expression levels of tissue VEGFR-1 between the progresive and the stabil disease groups. However, no significant correlation was determined between its expression and survival time. We conclude that sVEGFR-1 levels may help clinicians to predict the response to treatment.
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Keywords
Akciğer kanseri, Apoptozis, TRAIL-R1, VEGF-R1, sVEGF-R1, Lung cancer, Apoptosis, TRAILR-1, VEGFR-1, sVEGFR-1
Citation
Yılmaztepe, A. (2004). Akciğer kanserlerinde dokudaki VEGFR-1 ve TRAILR-1 ekspresyonları ile serum solubl VEGFR-1 düzeylerinin tedaviye yanıtla ilişkilerinin incelenmesi. Yayınlanmamış tıpta uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.