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ARTICLES: Carolyn C. Compton and Frederick L. Greene The Staging of Colorectal Cancer: 2004 and Beyond CA Cancer J Clin 2004; 54: 295-308 [Abstract] [Full text] [PDF]

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"Regarding The Need for a Metabolic Staging of Cancer"

Jaime Arias, Jose-Ignacio Arias and Maria-Angeles Aller.   (6 June 2005)

"Regarding The Need for a Metabolic Staging of Cancer" 6 June 2005
Jaime Arias, Facultad de Medicina Universidad Complutense de Madrid, Jose-Ignacio Arias and Maria-Angeles Aller. Send letter to journal: Re: "Regarding The Need for a Metabolic Staging of Cancer" jariasp{at}med.ucm.es Jaime Arias, et al.	Dear Sir: According to Compton et al. (1), a staging system for colorectal cancer should fulfill two important characteristics: the first of these would be to ensure a common terminology for cancer that can be understood by clinicians in all specialties and the second is that this system, ie the tumor, node, and metastasis one (TNM) should be continually submitted to critical evaluation and change when clinically indicated. One requirement for both conditions to be fulfilled would be that the staging system would also have a tumoral biological significance. Therefore, it should be born in mind that while a malign tumor develops it can express phenotypes that also share the inflammatory response such as: an ischemic phenotype (hypoxic)(3), the pro-inflammatory gene expression wit adoption of a leukocytic phenotype (4) and migration to the regional lymph nodes (5) and, finally, an angiogenic phenotype (6). It has already been proposed that these phenotypes represent the expression of trophic functional systems of increasing metabolic complexity in the inflammatory response (2). Their expression by cancer cells could have a similar significance. Owing to the plasticity of malignant tumor cells, these could adopt an inflammatory-like phenotype that evolves in three hypothetical functioal phases with trophic significance. In the first phase, characterized by the ischemia-reperfusion phenomenon, the tumoral cell undergoes oxidative stress, becomes independent and is nourished by diffusion. In the second or immune phase, the tumor cell could express a leukocytic phenotype with anaerobic glycolysis as the mains source of ATP, which permists lymphatic migration and invasiton of the host (by lymph nodes) and hematic migration (micrometastases or preangiogenic metastasis). Finally, in a third or endocrine phase, the tumor cell acquires the capacity for oxidative metabolism, inducing antiogenesis and also the capacity to proliferate and to cause cachexia in the host. This hypothetical approach to the mechanism that governs tumoral evolution could be based onteh incrasing metabolic capacity of the tumor cell to use oxygen over the succssive phases of release, migration, and proliferation. Since the phases of tumoral evolution, like the phases described of post-traumatic inflammation (2,7), go from ischemia to the development of a perfected oxidateive metabolism, it is also tempting to speculate on whether the tumor cell reprodeuces the successive stages by which life passes from its origin without oxygen until it develops an effective, althoug costly, system for the use of exygen (8). If so, in the successive metabolic switches or metamorphoses that cancer undergoes, ti acqyires an incrasing ability both to invade te host and to use its sources of substrates ntil its metabolic reserves are all used up. References 1. Compton CC, Greene FL. The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin 2004;54:295-308. 2. Aller MA, Arias JL, Nava MP, Arias J. Posttraumatiac inflammation is a complex response based on the pathological expression of the nervous, immune, and endocrine functional system. Exp Biol Med 2004;229:170-181. 3. Denko NC, Fontana LA, Hudson KM, et al. Investigating hypoxic tumor physiology through gene expression patterns. Oncogene 2003;22:5907- 5914. 4. Coussens LM, Werb A. Inflammation and cancer. Nature 2002;420:860- 867 5. Nathanason SD. Insights into the mechanisms of lymph node metastasis. Cancer 2003;98:413-423. 6. Naresh NK, Nerurkar AY, Borges AM. Angiogenesis is a redundant for tumor growth in lymph node metastases. Histopathology 2001;38:466-470. 7. Aller MA, Arias JL, Arias J. Post-traumatic inflammatory response: Perhaps a succession of phases with a nutritional purpose. Med Hypotheses 2004;63:42-46. 8. Nakamura H, Hase A. Cellular differentiation in the process of generation of the eukaryotic cell. Orig Life Evol Biosph 1990-91;20:499- 514.