کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1995405 1064967 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tumour overexpression of inducible nitric oxide synthase (iNOS) increases angiogenesis and may modulate the anti-tumour effects of the vascular disrupting agent ZD6126
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Tumour overexpression of inducible nitric oxide synthase (iNOS) increases angiogenesis and may modulate the anti-tumour effects of the vascular disrupting agent ZD6126
چکیده انگلیسی

Tumours derived from DLD-1 colon adenocarcinoma cells, transfected to either overexpress inducible nitric oxide synthase (clone iNOS-19) or with empty vector (pBAN2R), were utilised to test the hypothesis that tumour expression of iNOS (a) increases tumour angiogenesis and (b) modulates the anti-tumour activity of the vascular disrupting agent ZD6126. Overexpression of iNOS by clone iNOS-19 cells and murine xenografts was confirmed by the Griess assay and western blot analysis respectively. Clone iNOS-19 tumours grew more rapidly than pBAN2R tumours. Tumour perfusion, assessed by Hoechst 33342 uptake, was significantly greater in the clone iNOS-19 tumours (P < 0.001). A significant reduction in the perfusion of only the pBAN2R tumours, compared with control, was obtained 24 h after treatment with an intermediate dose of 100 mg/kg ZD6126 (P < 0.001), whereas 200 mg/kg significantly reduced the perfusion of both tumour types (P < 0.001). Whilst pBAN2R tumour necrosis increased in a dose-dependent manner, significant at 100 and 200 mg/kg ZD6126 (P < 0.05), intermediate doses did not induce a similar degree of necrosis in clone iNOS-19 tumours. A significant reduction in splenic perfusion was found 24 h after treatment with 100 mg/kg ZD6126, primarily associated with the red pulp. Overexpression of iNOS increases tumour growth, the degree of functionally perfused vasculature and angiogenesis, and also confers resistance to the vascular disrupting agent ZD6126.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microvascular Research - Volume 71, Issue 2, March 2006, Pages 76–84
نویسندگان
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