The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease

O'Byrne, Kenneth J., Dalgleish, A. G., Browning, M. J., Steward, W. P., & Harris, A. L. (2000) The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease. European Journal of Cancer, 36(2), pp. 151-169.

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Recent studies have demonstrated that angiogenesis and suppressed cell- mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein- Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-α, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-α have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease. (C) 2000 Elsevier Science Ltd.

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ID Code: 65256
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Angiogenesis, Carcinogenesis, Immune response, Malignant disease, acetylsalicylic acid, alpha interferon, antiestrogen, cyclooxygenase 1, cyclooxygenase 2, cytokine, indometacin, prostaglandin E2, protein p53, raloxifene, somatomedin C, tamoxifen, cancer, cancer prevention, cellular immunity, gene inactivation, helper cell, human, hygiene, immunization, immunomodulation, priority journal, review, Disease Progression, Gene Silencing, Genes, p53, Humans, Neoplasms, Neovascularization, Pathologic, Prostaglandin-Endoperoxide Synthases, Receptors, Interferon
DOI: 10.1016/S0959-8049(99)00241-5
ISSN: 0959-8049
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2000 Pergamon
Deposited On: 10 Dec 2013 02:47
Last Modified: 10 Dec 2013 02:47

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