The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases.

Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate l-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of l-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that l-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.

Does physical exercise improve quality of life of advanced cancer patients?

PURPOSE OF REVIEW: We discuss the principal issues about physical activity in advanced cancer patients through the analyses of the last articles and our experience in this field. RECENT FINDINGS: The efficacy of exercise training intervention could improve quality of life (QOL), fatigue and well being in advanced cancer patients. Several published studies have included, nevertheless, patients with early stage of disease and more recently, populations of patients with local advanced tumors of the breast, rectum and lung, who are undergoing neoadjuvant therapy. Despite the insufficient sample of patients in these studies, physical exercise is considered to improve both cardiopulmonary function and physical muscle fitness. Cancer-related fatigue is a devastating symptom in advanced cancer patients that implies loss of mobility and independence. SUMMARY: Physical exercise could be a treatment to increase skeletal muscle endurance and improve well being. In palliative medicine, physical activity could be applied to medical assistance or to design prospective and controlled trials so as to evaluate possible usefulness.