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1.
Br J Cancer ; 101(4): 666-72, 2009 Aug 18.
Article in English | MEDLINE | ID: mdl-19623180

ABSTRACT

BACKGROUND: The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS: Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial growth factor-A (VEGF) and tissue factor (TF) were quantified in 140 surgical specimens comprising normal human breast, benign and pre-malignant hyperplastic tissue, in situ and invasive breast cancer specimens. RESULTS: Significant increases in angiogenesis (microvessel density) were observed between normal and benign hyperplastic breast tissue (P<0.005), and between in situ and invasive carcinomas (P<0.0005). In addition, significant increases in proliferating ECs were observed in benign hyperplastic breast compared with normal breast (P<0.05) cancers and in invasive compared with in situ cancers (P<0.005). Hypoxia-inducible factor-1alpha, VEGF and TF expression were significantly associated with increases in both angiogenesis and proliferating ECs (P<0.05). Moreover, HIF-1alpha was expressed by 60-75% of the hyperplastic lesions, and a significant association was observed between VEGF and TF in ECs (P<0.005) and invasive tumour cells (P<0.01). CONCLUSIONS: These findings are the first to suggest that the angiogenic switch, associated with increases in HIF-1alpha, VEGF and TF expression, occurs at the onset of hyperplasia in the mammary duct, although the greatest increase in angiogenesis occurs with the development of invasion.


Subject(s)
Breast Neoplasms/pathology , Neovascularization, Pathologic/pathology , Precancerous Conditions/pathology , Biomarkers, Tumor/analysis , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Intraductal, Noninfiltrating/pathology , Cell Proliferation , Endothelial Cells/metabolism , Female , Humans , Hyperplasia/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Immunohistochemistry , Neovascularization, Pathologic/metabolism , Precancerous Conditions/metabolism , Prognosis , Thromboplastin/biosynthesis , Vascular Endothelial Growth Factor A/biosynthesis
2.
Br J Cancer ; 99(12): 1961-6, 2008 Dec 16.
Article in English | MEDLINE | ID: mdl-18941463

ABSTRACT

Evidence from human studies suggests that angiogenesis commences during the pre-malignant stages of cancer. Inhibiting angiogenesis may, therefore, be of potential value in preventing progression to invasive cancer. Understanding the mechanisms inducing angiogenesis in these lesions and identification of those important in human tumourigenesis are necessary to develop translational strategies that will help realise the goal of angioprevention.


Subject(s)
Neovascularization, Pathologic/pathology , Precancerous Conditions/blood supply , Precancerous Conditions/pathology , Animals , Humans , Hypoxia/metabolism , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/therapy , Precancerous Conditions/metabolism , Precancerous Conditions/therapy , Risk Factors
3.
Surgeon ; 4(6): 343-5, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17152198

ABSTRACT

INTRODUCTION: Audit of inguinal hernia repair is important in view of the magnitude of the problem and the fact that it is a common operation often performed by surgical trainees. Due to the disparity of the results of various workers with regard to the rate of complications, individual surgeons have been advised to audit their patients' outcomes. METHOD: Retrospective audit was performed, of all the inguinal hernias repaired between 1997 and 2003 inclusive, at two rural hospitals in northern Scotland, under a single consultant. Data were gathered from a hospital database and by means of postal questionnaire specifically aimed at wound complications, recurrence and chronic groin pain. RESULTS: One hundred and sixty-three inguinal hernias were repaired during this period. One hundred and fifty-eight questionnaires were sent to patients ascertained to be living at the time of audit initiation with a response from 129 (86%). At a mean follow-up of 4.34 years, no recurrences were noted and eight patients complained of chronic groin pain of whom only three (1.5%) were experiencing moderate to severe pain. The results achieved by senior house officers were comparable to those obtained by the senior surgeon. CONCLUSION: The incidence of recurrence of hernia after open mesh repair of inguinal hernias is very low. Excellent outcomes can be obtained for inguinal hernia even at remote and rural hospitals in the hands of both experienced and trainee surgeons


Subject(s)
Hernia, Inguinal/surgery , Hospitals, Rural , Adult , Chronic Disease , Emergency Medical Services , Female , Follow-Up Studies , Groin/pathology , Groin/surgery , Hospitals, Community , Humans , Male , Middle Aged , Pain Measurement , Pain, Postoperative/epidemiology , Pain, Postoperative/etiology , Patient Satisfaction , Recurrence , Retrospective Studies , Scotland , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Surveys and Questionnaires , Treatment Outcome
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