Cancer, mainly in its advanced stage, is characterized by a complex of biological and clinical symptoms which are critical for the further course and therefore for prognosis. A very important role among them is played by cachexia and oxidative stress (OS). The cancer-related anorexia/cachexia syndrome (CACS) is a complex phenomen characterized by symptoms such as anorexia, weight loss, increased resting energy expenditure associated to several abnormalities of glucose, lipid and protein metabolism, nausea and/or vomiting, immunodepression, reduced efficacy and increased side effects of antineoplastic agents. Several factors contribute to the pathogenesis of CACS: abnormalities of the energy metabolism, proinflammatory cytokines produced by the immune system and by the tumor itself, circulating tumor-derived catabolic factors, and probably additional unknown factors. OS has recently received much attention for its potential cancerogenic role and above all for its involvement in the pathogenesis of CACS. Moreover, proinflammatory cytokines are able to induce OS and in turn reactive oxygen species (ROS) may induce CACS. Several mechanisms have been proposed that lead to OS in cancer patients: 1) the altered intermediate and energy metabolism as well as of single nutrients (the defective metabolism of nutrients, particularly glucose, may indue a lack of principal reducing agents, that are synthetised during glucose metabolism and indispensable for the neutralisation of ROS); 2) a nonspecific chronic activation of the immune system with an excessive production of proinflammatory cytokines, which in turn may increase ROS production; 3) the use of antineoplastic drugs, particularly alkylating agents and cisplatin. Our recently published studies have demonstrated that: ROS levels and antioxidant enzymes activity (mainly Glutathione Peroxidase, GPx), serum levels of proinflammatory cytokines, leptin and C Reactive Protein of cancer patients are correlated with the most important clinical indexes of disease such as Stage and ECOG PS. Moreover, antioxidant agents either administered alone or in combination are able to reduce ROS levels and increase GPx activity, counteracting OS involved in CACS. On the basis of these results we have activated in our Institution a pilot non randomised Phase II study with the aim to evaluate the anticachectic efficacy of an integrated treatment consisting of a diet with high polyphenols contents + pharmaco- nutritional support enriched with n-3 PUFA + oral progestagen (MPA) + antioxidant agents + COX-2 inhibitor.

Anorexia/Cachexia and oxidative stress in cancer patients = Anoressia/Cachessia e stress ossidativo nei pazienti con cancro

Mantovani G;Macciò A;MADEDDU, CLELIA
Data Curation
;
Massa E;
2003-01-01

Abstract

Cancer, mainly in its advanced stage, is characterized by a complex of biological and clinical symptoms which are critical for the further course and therefore for prognosis. A very important role among them is played by cachexia and oxidative stress (OS). The cancer-related anorexia/cachexia syndrome (CACS) is a complex phenomen characterized by symptoms such as anorexia, weight loss, increased resting energy expenditure associated to several abnormalities of glucose, lipid and protein metabolism, nausea and/or vomiting, immunodepression, reduced efficacy and increased side effects of antineoplastic agents. Several factors contribute to the pathogenesis of CACS: abnormalities of the energy metabolism, proinflammatory cytokines produced by the immune system and by the tumor itself, circulating tumor-derived catabolic factors, and probably additional unknown factors. OS has recently received much attention for its potential cancerogenic role and above all for its involvement in the pathogenesis of CACS. Moreover, proinflammatory cytokines are able to induce OS and in turn reactive oxygen species (ROS) may induce CACS. Several mechanisms have been proposed that lead to OS in cancer patients: 1) the altered intermediate and energy metabolism as well as of single nutrients (the defective metabolism of nutrients, particularly glucose, may indue a lack of principal reducing agents, that are synthetised during glucose metabolism and indispensable for the neutralisation of ROS); 2) a nonspecific chronic activation of the immune system with an excessive production of proinflammatory cytokines, which in turn may increase ROS production; 3) the use of antineoplastic drugs, particularly alkylating agents and cisplatin. Our recently published studies have demonstrated that: ROS levels and antioxidant enzymes activity (mainly Glutathione Peroxidase, GPx), serum levels of proinflammatory cytokines, leptin and C Reactive Protein of cancer patients are correlated with the most important clinical indexes of disease such as Stage and ECOG PS. Moreover, antioxidant agents either administered alone or in combination are able to reduce ROS levels and increase GPx activity, counteracting OS involved in CACS. On the basis of these results we have activated in our Institution a pilot non randomised Phase II study with the aim to evaluate the anticachectic efficacy of an integrated treatment consisting of a diet with high polyphenols contents + pharmaco- nutritional support enriched with n-3 PUFA + oral progestagen (MPA) + antioxidant agents + COX-2 inhibitor.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/46856
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