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The effect of bevacizumab on serum soluble FAS/FASL and TRAIL and its receptors (DR4 and DR5) in metastatic colorectal cancer

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Abstract

Purpose

Bevacizumab-based chemotherapy has become the standard of care in metastatic colorectal cancer (MCRC). We aimed to measure the levels of serum soluble FAS, FASL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and its death receptors DR4 and DR5 in MCRC patients and to define prognostic significance of these parameters in response to bevacizumab in these patients.

Patients and methods

The levels of these parameters in serum samples were quantified by a commercially available ELISA kit in 31 MCRC patients before and after 2 cycles of therapy and 25 healthy controls.

Results

Pretreatment sFAS levels in MCRC patients was significantly lower than the levels of controls (p = 0.043). There was no significant difference in sFAS and sFASL levels in MCRC patients before and after bevacizumab-based treatment. There was no significant difference in sFAS/sFASL ratio in MCRC patients before and after treatment and controls. Soluble DR5 levels were significantly higher in pretreatment serum samples compared with controls (p = 0.008). However, pretreatment sTRAIL and sDR4 levels were similar to the levels of controls. There was no significant difference in sTRAIL, sDR4, and sDR5 levels in MCRC patients before and after treatment. When patients were grouped according to treatment response (responders vs. non-responders), post-treatment sFAS/sFASL ratio was significantly lower in responding patients compared with non-responders (p = 0.029). Significant correlations were observed between post-treatment sFASL and sDR4, sFAS and sTRAIL, sTRAIL and sFAS/sFASL ratio, and sFASL and sDR5.

Conclusion

Non-significant changes in apoptotic markers with bevacizumab-based chemotherapy showed that they have no prognostic significance in MCRC patients. Significant change in sFAS/sFASL ratio according to treatment response could be an indicator of chemosensitivity.

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Authors and Affiliations

  1. Department of Medical Oncology, Gazi University Faculty of Medicine, Besevler, Ankara, 06500, Turkey

    Ramazan Yildiz, Mustafa Benekli, Suleyman Buyukberber, Ali Osman Kaya, Banu Ozturk, Emel Yaman, Ugur Coskun, Deniz Yamac & Aytug Uner

  2. Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey

    Veli Berk

  3. Department of Biochemistry, Gazi University Faculty of Medicine, Ankara, Turkey

    Banu Sancak

Authors
  1. Ramazan Yildiz
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  2. Mustafa Benekli
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  3. Suleyman Buyukberber
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  4. Ali Osman Kaya
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  11. Aytug Uner
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Correspondence to Mustafa Benekli.

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Yildiz, R., Benekli, M., Buyukberber, S. et al. The effect of bevacizumab on serum soluble FAS/FASL and TRAIL and its receptors (DR4 and DR5) in metastatic colorectal cancer. J Cancer Res Clin Oncol 136, 1471–1476 (2010). https://doi.org/10.1007/s00432-010-0803-1

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  • DOI: https://doi.org/10.1007/s00432-010-0803-1

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