13. Immunogenetherapy combined with brain metastases irradiation in melanoma patients

AimsTo assess toxicity and results of melanoma brain metastases irradiation in patients treated with genetically modified tumour vaccine.Materials/methodsA group of 45 melanoma stage IV (AJCC) patients was treated with vaccine consisted of autologic melanoma cells admixed with allogeneic cells modified with IL-6 and slL-6R genes. During the treatment 14 patients developed symptoms of brain metastases. 5 patients had solitary metastases, 9 multiple lesions. 4 patients with single metastasis were treated surgically. All 14 patients were irradiated with the doses 30–39 Gy, using 3 Gy/fracion, 5 fractions/week. Toxicity of cranial irradiation (clinically, CT) and clinical results (CT, survival) were evaluated. Immunological cellular responses were assessed in vitro.ResultsAcute effects of irradiation were tolerable and manageable using standard dexamethasone treatment. There was no radiation encephalopathy or radiation necrosis. In 7/14 patients stabilization or partial remission of brain lesions was observed. Overall survival measured from brain metastases diagnosis ranged from 2 to 21 months (2 patients are still alive), median survival was 316 days. In 4 treated patients radiation enhanced immune responses to the vaccine.ConclusionsPalliative cranial irradiation is well tolerated by patients treated with novel systemic approaches such as immunogene therapy, relives symptoms and may extend survival. Radiation of metastases modulates immune responses to melanoma cells

Macrophage Inhibitory Cytokine 1 (MIC-1/GDF15) Decreases Food Intake, Body Weight and Improves Glucose Tolerance in Mice on Normal & Obesogenic Diets

Food intake and body weight are controlled by a variety of central and peripheral factors, but the exact mechanisms behind these processes are still not fully understood. Here we show that that macrophage inhibitory cytokine-1 (MIC-1/GDF15), known to have anorexigenic effects particularly in cancer, provides protection against the development of obesity. Both under a normal chow diet and an obesogenic diet, the transgenic overexpression of MIC-1/GDF15 in mice leads to decreased body weight and fat mass. This lean phenotype was associated with decreased spontaneous but not fasting-induced food intake, on a background of unaltered energy expenditure and reduced physical activity. Importantly, the overexpression of MIC-1/GDF15 improved glucose tolerance, both under normal and high fat-fed conditions. Altogether, this work shows that the molecule MIC-1/GDF15 might be beneficial for the treatment of obesity as well as perturbations in glucose homeostasis