Factor X-activating activity in breast and colorectal cancer
Factor X-activating activity in breast and colorectal cancer
Cancer is often associated with abnormal haemostasis and tumours may express procoagulants which facilitate fibrin deposition and aid tumour growth. However, studies in human breast and colorectal cancer are limited, and the present study was therefore undertaken to measure and characterise the procoagulant activities of these common tumours. Malignant and adjacent normal tissues were obtained from patients undergoing surgery for breast (n= 131) or colorectal (n= 117) cancer. Samples were homogenized by cryofragmentation or tissue slicing and factor X-activating activity (FXAA) determined by chromogenic or clotting assays. Using cryofragmentation and the chromogenic assay, FXAA was detected in 86% of normal breast tissues and in all malignant tumours (n= 35), and the median tumour level was higher (p< 0.001) than in normal breast. However, after removal of fat from normal breast, FXAA was found in all tissue (n= 48) irrespective of malignancy and the difference between normal and tumour samples was abolished. FXAA was found in all colorectal tissues tested (n= 64) but was higher in tumours than in normal mucosa (p< 0.001). After tissue slicing, FXAA was detected in both normal and malignant breast (n= 48) and colon tissue (n= 71) but was higher (p< 0.001) in tumours. In colorectal tissues (n= 18), FXAA was higher (p< 0.001) when the tissue was extracted by slicing. Using the clotting assay, FXAA was higher (p< 0.05) in tumour tissue in both normal and FVII-deficient plasmas (n= 27). No significant correlation was found between FXAA and TNM (breast) or Dukes' (colorectal) staging. FXAA was adsorbed by Al(OH)3 and barium citrate, enhanced by FVII, virtually abolished by antibodies to FVII and tissue factor (TF), inhibited by DFP and PMSF (but not by mercuric chloride and iodoacetamide) and reduced by phospholipase C and concanavalin A. The presence of TF and FVII in normal and malignant tissue was confirmed by Western blotting. It is concluded that FXAA is a property of both normal and malignant breast and colorectal tissue, is a serine protease and is probably a TF-FVIIa complex.
University of Southampton
El-Baruni, Khaled Soliman
d229aaae-4df4-4b04-ba87-61e0ae546bd7
1990
El-Baruni, Khaled Soliman
d229aaae-4df4-4b04-ba87-61e0ae546bd7
El-Baruni, Khaled Soliman
(1990)
Factor X-activating activity in breast and colorectal cancer.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Cancer is often associated with abnormal haemostasis and tumours may express procoagulants which facilitate fibrin deposition and aid tumour growth. However, studies in human breast and colorectal cancer are limited, and the present study was therefore undertaken to measure and characterise the procoagulant activities of these common tumours. Malignant and adjacent normal tissues were obtained from patients undergoing surgery for breast (n= 131) or colorectal (n= 117) cancer. Samples were homogenized by cryofragmentation or tissue slicing and factor X-activating activity (FXAA) determined by chromogenic or clotting assays. Using cryofragmentation and the chromogenic assay, FXAA was detected in 86% of normal breast tissues and in all malignant tumours (n= 35), and the median tumour level was higher (p< 0.001) than in normal breast. However, after removal of fat from normal breast, FXAA was found in all tissue (n= 48) irrespective of malignancy and the difference between normal and tumour samples was abolished. FXAA was found in all colorectal tissues tested (n= 64) but was higher in tumours than in normal mucosa (p< 0.001). After tissue slicing, FXAA was detected in both normal and malignant breast (n= 48) and colon tissue (n= 71) but was higher (p< 0.001) in tumours. In colorectal tissues (n= 18), FXAA was higher (p< 0.001) when the tissue was extracted by slicing. Using the clotting assay, FXAA was higher (p< 0.05) in tumour tissue in both normal and FVII-deficient plasmas (n= 27). No significant correlation was found between FXAA and TNM (breast) or Dukes' (colorectal) staging. FXAA was adsorbed by Al(OH)3 and barium citrate, enhanced by FVII, virtually abolished by antibodies to FVII and tissue factor (TF), inhibited by DFP and PMSF (but not by mercuric chloride and iodoacetamide) and reduced by phospholipase C and concanavalin A. The presence of TF and FVII in normal and malignant tissue was confirmed by Western blotting. It is concluded that FXAA is a property of both normal and malignant breast and colorectal tissue, is a serine protease and is probably a TF-FVIIa complex.
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Published date: 1990
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Local EPrints ID: 460578
URI: http://eprints.soton.ac.uk/id/eprint/460578
PURE UUID: 26b7e91a-813f-4e78-a000-3e2bf67d420d
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Date deposited: 04 Jul 2022 18:24
Last modified: 23 Jul 2022 00:58
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Author:
Khaled Soliman El-Baruni
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