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- Adipocyte secretome increases radioresistance of malignant melanocytes by improving cell survival and decreasing oxidative statusPublication . Coelho, Pedro; Silva, Liliana; Faria, Isabel; Vieira, Mónica; Monteiro, Armanda; Pinto, Gabriela; Prudêncio, Cristina; Fernandes, Rúben; Soares, RaquelRadiotherapy is a treatment option for the majority of malignancies. However, because melanoma is known to be radioresistant, the use of ionizing radiation as an adjuvant therapy in cutaneous melanoma patients is ineffective. Obesity has now been recognized as a risk factor for melanoma. High adiposity is generally associated with a more pro-oxidative status. Oxidative stress is a major player in radiation therapy and also a common link between obesity and cancer. Several adipocyte-released proteins are known to have a role in controlling cellular growth and pro-survival signaling. For that reason, we investigated the influence of 3T3-L1 mature adipocyte secretome in B16-F10 malignant melanocyte radiosensitivity. We evaluated B16-F10 cell survival and redox homeostasis when exposed to four daily doses of ionizing radiation (2 Gy per day) up to a total of 8 Gy in a medical linear accelerator. B16-F10 melanocytes exhibited slight alterations in survival, catalase activity, nitrative stress and total oxidant concentration after the first 2 Gy irradiation. The motility of the melanocytes was also delayed by ionizing radiation. Subsequent irradiations of the malignant melanocytes led to more prominent reductions in overall survival. Remarkably, 3T3-L1 adipocyte-secreted molecules were able to increase the viability and migration of melanocytes, as well as lessen the pro-oxidant burden induced by both the single and cumulative X-ray doses. In vitro adipocyte-released factors protected B16-F10 malignant melanocytes from both oxidative stress and loss of viability triggered by radiation, enhancing the radioresistant phenoyype of these cells with a concomitant activation of the AKT signaling pathway These results both help to elucidate how obesity influences melanoma radioresistance and support the usage of conventional medical linear accelerators as a valid model for the in vitro radiobiological study of tumor cell lines.
- Differential imune response to vitamin A in B16-F10 malignant melanocytesPublication . Oliveira, S.; Coelho, Pedro; Costa, J.; Prudêncio, Cristina; Soares, R.; Guerreiro, S. G.; Fernandes, RúbenMelanoma is an aggressive form of skin cancer with a poor prognosis, due to its refractory behavior to radiation and chemotherapy. Although the diagnosis is straightforward, there are many disagreements regarding its treatment and surveillance. In order to surpass some of the limitations addressed to the treatment, preventive methods like antioxidant vitamins are nowadays a relevant field of research, as well as immunostimulation by external agents. Despite the knowledge about melanoma biology, pathogenesis and developed therapies, is important to understand the effect of vitamin A in order to suggest alternatives to conventional therapies, which are known to be ineffective against melanoma.
- Metabolic syndrome and inflammation: is there a microvascular and an incretin system impairment in the gastrointestinal tract?Publication . Costa, J.; Almeida, J.; Coelho, Pedro; Oliveira, S.; Prudêncio, Cristina; Soares, R.; Gomes-Guerreiro, S.; Fernandes, RúbenMetabolic syndrome is a multifactorial disorder characterized by increased plasma levels of glucose, cholesterol and triglycerides, but also overweight and obesity promoted by increase of body fat mass, alterations in oxidative stress, chronic low grade inflammation and resistance to insulin leading to risk of cardiovascular diseases. The stomach and the intestine have an essential role in metabolism with functions of digesting food and absorption of nutrients. Also, the intestine produces incretin hormones, such as GLP-1 which regulates glucose metabolism and processes of the gastrointestinal tract.
- Is the MTHFR C677T polymorphism associated with obesity risk? – a meta-analysis.Publication . Costa, J.; Oliveira, R.; Prudêncio, Cristina; Fernandes, RúbenOverweight and obesity are a major worldwide health problem and its incidence is increasing every year. Methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and as a regulator of DNA methylation, synthesis, and repair. MTHFR gene is polymorphic at nucleotides 677 (C→T) and 1298 (A→C). MTHFR C677T polymorphism results in alloenzymes with decreased activity and several studies have pointed to association between the MTHFR C677T polymorphism and overweight/obesity risk.