RESUMEN
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and relevant side effect of antineoplastic agents such as cisplatin, paclitaxel, vincristine and bortezomib. Over the last years, significant progress has been achieved in elucidating the underlying pathomechanisms of CIPN using both in vivo and in vitro models. These studies suggest that mitochondrial toxicity, disturbed axonal transport, toxic effects on Schwann cells and activation of the immune system contribute to the pathogenesis of CIPN. This review provides an overview of the current pathogenetic concepts of CIPN. In addition, experimental approaches that aim at preventing or ameliorating neurotoxic effects of antineoplastic agents are discussed.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Animales , Antineoplásicos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/terapiaRESUMEN
Exercise has been proven to reduce the risk and progression of various diseases, such as cancer, diabetes and neurodegenerative disorders. Increasing evidence suggests that exercise affects the cytokine profile and changes distribution and function of tumor-competitive immune cells. Initial studies have shown that different exercise interventions are associated with epigenetic modifications in different tissues and cell types, such as muscle, fat, brain and blood. The present investigation examines the effect of an intense endurance run (half marathon) on global epigenetic modifications in natural killer (NK) cells in 14 cancer patients compared to 14 healthy controls. We were able to show that histone acetylation and NKG2D expression, a functional NK cell marker, were elevated for at least 24 h after the run. Thus, this is the first study to present a potential mechanism of how exercise may impact NK cell activity on the subcellular level. Further studies should focus on epigenetic mechanisms and dose-dependent effects of exercise.
Asunto(s)
Epigénesis Genética , Ejercicio Físico/fisiología , Células Asesinas Naturales/metabolismo , Neoplasias/inmunología , Acetilación , Biomarcadores/sangre , Citocinas/metabolismo , Femenino , Histonas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Subfamilia K de Receptores Similares a Lectina de Células NK/sangre , Resistencia Física/fisiología , Factores de Riesgo , Carrera/fisiologíaRESUMEN
BACKGROUND: Lymphoma patients undergoing therapy must cope with the side-effects of the disease itself, therapy and associated immobility. Peripheral neuropathy (PNP), loss of balance control and weakness not only diminishes patients' quality of life (QOL), it can also affect planning and the dosage of therapy. Exercise may enable patients to reverse these declines, improving their performance level and QOL. PATIENTS AND METHODS: We carried out a randomized, controlled trial, assigning 61 lymphoma patients either to a control group (CG; N=31) or to a 36-week intervention (IG; N=30), consisting of sensorimotor-, endurance- and strength training twice a week. Primary end point was QOL; secondary end points included movement coordination, endurance, strength and therapy-induced side-effects. RESULTS: Intergroup comparison revealed improved QOL- (ΔT1-T0; P=0.03) and PNP-related deep sensitivity in the IG: 87.5% were able to reduce the symptom, compared with 0% in the CG (P<0.001). Significant differences in the change of balance control could be found between the groups, with the IG improving while the CG steadily declined (monopedal static ΔT3-T0; P=0.03; dynamic ΔT3-T0; P=0.007; perturbed mono-ΔT3-T0; P=0.009 and bipedal ΔT3-T0; P=0.006), failed attempts (monopedal static ΔT3-T0; P=0.02, dynamic ΔT3-T0; P<0.001and perturbed ΔT3-T0; P=0.006) and improved time to regain balance (ΔT3-T0; P=0.04). Moreover, the change in the aerobic performance level (ΔT3-T0; P=0.05) and additional amount of exercise carried out per week [metabolic equivalent (MET); P=0.02] differed significantly across groups. CONCLUSIONS: Exercise, especially sensorimotor training, is a feasible and promising method to support cancer patients during therapy. It improves patients QOL, reduces restrictions from side-effects such as PNP and improves patients' balance control, physical performance level and mobility. GERMAN CLINICAL TRIALS REGISTER NUMBER: DRKS00003894.