Invasion and metastasis are currently recognized as early events in cancer progression. Trends in the management of advanced metastatic disease include the use of molecular techniques for the early diagnosis of disseminated disease and the clinical application of serum markers that may indicate a more precise indication of immunomodulation. The knowledge gained by means of sophisticated molecular techniques involving cell adhesion, proteolysis of the extracellular matrix, migration, and angiogenesis signaling has opened a wide field of novel therapies. The use of agents against growth factor receptors and integrin receptors, matrix metalloproteinase inhibitors, and products inhibiting the signaling pathways underlying metastasis, including oncoprotein signaling cascades and calcium mobilization, may lead to the interruption of the metastatic process in selected patients.

FIGURE 4.4. Orbital venous drainage and the periorbital lymphatic system.


1. Liotta LA, Stetler-Stevenson WG. Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res 1991;51:5054-5059.

2. Kohn EC, Liotta LA. Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res 1995;51: 1862-1865.

3. Yokota J. Tumor progression and metastasis. Carcinogenesis 2000;21:497-503.

4. Woodhouse EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer 1997;80:1529-1537.

5. Fidler IJ. Critical factors in the biology of human cancer metastasis: 28 th G H A Clowes Memorial Award Lecture. Cancer Res 1990;50:6130-6138.

6. Fidler IJ, Hart IR. Biologic diversity in metastastic neoplasms: origins and implications. Science 1982;217:998-1003.

7. Nicolson GL. Gene expression, cellular diversification and tumor progression to the metastatic phenotype. BioEssays 1991;13:337-342.

8. Yokota J, Sugimura T. Multiple steps in carcinogenesis involving alterations of multiple tumor suppressor genes. FASEB J 1993;7:920-925.

9. Pluda JM. Tumor-associated angiogenesis: mechanisms, clinical implications, and therapeutic strategies. Semin Oncol 1997; 15:61-75.

10. Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000;21:505-515.

11. Ohene-Abuakwa Y, Pignatelli M. Adhesion molecules in cancer biology. Adv Exp Med Biol 2000;465:115-126.

12. Liotta LA. Tumor invasion: role of extracellular matrix. Cancer Res 1986;46:1-7.

13. Seftor REB. Role of the integrin subunit in human primary melanoma progression. Am J Pathol 1998;153:1347-1351.

14. Coussens LM, Werb Z. Matrix metalloproteinases and the development of cancer. Chem Biol 1996;3:895-904.

15. Chambers AF, Matisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 1997; 89:1260-1270.

16. Kawamata H, Kawai K, Kameyama S, et al. Over-expression of tissue inhibitor of matrix metalloproteinases (TIMP1 and TIMP2) suppresses extravasation of pulmonary metastasis of a rat bladder carcinoma. Int J Cancer 1995;63:680-687.

17. Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature 1997;386:623-627.

18. Ishimaru G, Ookawa K, Yamaguchi N, et al. Allelic losses associated with the metastatic potential of colorectal carcinoma. Int J Oncol 1994;5:267-273.

19. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancer. Science 1991;53:49-53.

20. Ducasse A, Segal A, Delattre JF, Burette A, Flament JB. Participation of the external carotid artery in orbital vasculariza-tion. J Fr Ophtalmol 1985;8:333-339.

21. Ducasse A, Segal A, Delattre JF, Flament JB. Macroscopic aspects of arterial vascularization of the orbit. Bull Soc Ophtal-mol Fr 1989;89:989-993.

22. Bergen MP. Some histological aspects of the structure of the connective tissue system and its relationships with the blood vessels in the human orbit. Acta Morphol Neerl Scand 1982;20:293-308.

23. Goldberg RA, Rootman J, Cline RA: Tumors metastatic to the orbit: a changing picture. Surv Ophthalmol 1990;35:1-24.

24. Sherman DD, Gonnering RS, Wallow IH, et al. Identification of orbital lymphatics: enzyme histochemical light microscopic and electron microscopic studies. Ophthalmic Plast Reconstr Surg 1993;9:153-169.

25. Gausas RE, Gonnering RS, Lemke BN, et al. Identification of human orbital lymphatics. Ophthalmic Plast Reconstr Surg 1999;15:252-259.

26. McGetrick JJ, Wilson DG, Dortzbach RK, et al. A search for lymphatic drainage of the monkey orbit. Arch Ophthalmol 1989;107:255-260.

27. Sanding M, Negrou E, Rogers KA. Changes in the distribution of LFA-1, catenins, and F-actin during transendothelial migration of monocytes in cultures. J Cell Sci 1997;110:2807-2818.

28. Naot D, Sionov RV, Ish-Shalom D. CD44: structure, function, and association with the malignant process. Adv Cancer Res 1997;71:241-319.

29. Hoffmann M, Rudy W, Zoller M, et al. CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines. Cancer Res 1991;51: 5292-5297.

30. Heufelder AE, Bahn RS, Boergen KP, Scriba PC. Detection, localization and modulation of hyaluronic acid/CD44 receptor expression in patients with endocrine orbitopathy. Med Klin 1993;88:181-184.

31. Kohn EC, Francis A. Liotta LA, Schiffmann E. Heterogeneity of the motility responses in malignant tumor cells: a biological basis for the diversity and homing of metastatic cells. Int J Cancer 1990;46:287-292.

32. Moore MA. The role of chemoattraction in cancer metastases. BioEssays 2001;23:674-676.

33. Hartstein ME, Grove AS Jr, Woog JJ. The role of the integrin family of adhesion molecules in the development of tumors metastatic to the orbit. Ophthalmic Plast Reconstr Surg 1997;13:227-238.

34. Shields JA, Shields CL, Brotman HK, et al. Cancer metastatic to the orbit: The 2000 Robert M Curts Lecture. Ophthalmic Plast Reconstr Surg 2001;17:346-354.

35. Demirci H, Shields CL, Shields JA, et al. Orbital tumors in the older adult population. Ophthalmology 2002;109:243-248.

36. Font RL, Ferry AP. Carcinoma metastatic to the eye and orbit III. A clinicopathologic study of 28 cases metastatic to the orbit. Cancer 1976;38:1326-1335.

37. Godtfredsen E. On the frequency of secondary carcinomas in the choroid. Acta Ophthalmol 1944;22:394-400.

38. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to the eye. I. Incidence in 213 adult patients with generalized malignancy. Am J Ophthalmol 1967;63:723-726.

39. Bloch MS, Gartner S. The incidence of ocular metastatic carcinoma. Arch Ophthalmol 1971;85:673-675.

40. Amemiya T, Hayashida H, Dake Y. Metastatic orbital tumors in Japan: a review of the literature. Ophthalmic Epidemiol 2002;9:35-47.

41. Albert DM, Rubenstein RA, Scheie HG: Tumor metastases to the eye. II. Clinical study in infants and children. Am J Oph-thalmol 1967;63:727-732.

42. Musarella MA, Chen HS, DeBoer G, Gallie BL. Ocular involvement in neuroblastoma: prognostic implications. Ophthalmology 1984;91:936-940.

43. Fatkin JD, Purcell JJ, Krachmer JH, Taylor JC. Wilms' tumor metastatic to the orbit. JAMA 1977;238:1841-1842.

44. Capone A, Slamovits TL. Discrete metastasis of solid tumors to extraocular muscles. Arch Ophthalmol 1990;108:237-243.

45. Bullock JD, Yanes B. Ophthalmic manifestations of metastat-ic breast cancer. Ophthalmology 1980;87:961-973.

46. Char DH, Miller T, Kroll S. Orbital metastases: diagnosis and course. Br J Ophthalmol 1997;81:386-390.

47. Dresner SK, Kennerdell JS, Dekker A. Fine needle aspiration biopsy of metastatic orbital tumors. Surv Ophthalmol 1983;27: 397-398.

48. Orcutt JC, Char DH. Melanoma metastatic to the orbit. Ophthalmology 1988;95:1033-1037.

49. Avril MF, Charpentier P, Margulis A, Guillaume JC. Regression of primary melanoma with metastases. Cancer 1992;69: 1377-1381.

50. Vijuk G, Coates AS. Survival of patients with visceral meta-static melanoma from an occult primary lesion: a retrospective matched cohort study. Ann Oncol 1998;9:419-422.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment