التفاصيل البيبلوغرافية
| العنوان: |
Haem oxygenase 1 expression is associated with prognosis in cholangiocarcinoma patients and with drug sensitivity in xenografted mice. |
| المؤلفون: |
Kongpetch, S., Puapairoj, A., Ong, C. K., Senggunprai, L., Prawan, A., Kukongviriyapan, U., Chan‐On, W., Siew, E. Y., Khuntikeo, N., Teh, B. T., Kukongviriyapan, V. |
| المصدر: |
Cell Proliferation; Feb2016, Vol. 49 Issue 1, p90-101, 12p |
| مصطلحات موضوعية: |
CHOLANGIOCARCINOMA, HEME oxygenase, IMMUNOHISTOCHEMISTRY techniques, DRUG allergy, TUMOR growth, XENOGRAFTS, CYTOPROTECTION, PATIENTS |
| مستخلص: |
Objective Haem oxygenase-1 ( HO-1) plays important roles in cytoprotection and tumour growth. Cholangiocarcinoma ( CCA) is a deadly malignancy with very poor prognosis. The role of HO-1 in tumour progression in CCA up to now has been relatively unexplored, thus, its possible therapeutic implications in CCA have been investigated here. Materials and methods HO-1 expression in tumour tissues from 50 CCA patients was determined by immunohistochemical analysis and its association with survival time was evaluated using the Kaplan-Meier method. Its role in CCA cells in vitro was evaluated by transwell and wound healing assays and suppression of HO-1 expression by si RNA. Effects of HO-1 inhibition on gemicitabine ( GEM)-mediated tumour suppression was evaluated in nude mice xenografted with CCA cells. Results HO-1 expression was inversely associated with median overall survival time. Hazard ratio of patients with high HO-1 expression was 2.42 (95% CI: 1.16-5.08) with reference to low expression and HO-1 knock-down expression inhibited transwell cell migration. Suppression of HO-1 by Zn-protoporphyrin (Zn PP) enhanced cytotoxicity to GEM in CCA cells, validated in CCA xenografts. Treatment with GEM and Zn PP almost completely arrested tumour growth, whereas treatment with only a single reagent, retarded it. Tumour inhibition was associated with reduction in expression of Ki-67 and microvascular density, and enhanced p53 and p21 immunohistochemical staining. Conclusion High HO-1 expression was associated with poor prognosis of CCA. Synergistic role of HO-1 inhibition in chemotherapy of CCA is a promising insight for treatment of this tumour and warrants further investigation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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