Loading...
2 results
Search Results
Now showing 1 - 2 of 2
- Clinical and metabolic implications of obesity in prostate cancer: is testosterone a missing link?Publication . Duarte, Fernanda; Luís, C.; Baylina, Pilar; Faria, Isabel; Fernandes, Rúben; La Fuente, J. M.Objectives: To assess sex hormones in men with obesity and prostate cancer (PCa) and to study association between androgens and the pathogenesis biology of PCa in vitro. Subjects and methods: One hundred and eighty-one men older than 45 years selected from of a population attending to Urology departments screening for PCa, (78 participants without PCa and 103 patients with PCa). All participants were assessed for body mass index (BMI), age, Gleason score, and PSA. Endocrine profile was determined for LH, total testosterone (TT), 17β-estradiol (E2), prolactin and leptin. Biochemical profile (HbA1c, triacylglycerols and lipoproteins) was also determined. In vitro experiments were also performed, involving the study of 5α-dihydrotestosterone (DHT) and E2 in the presence of adipocyte-conditioned medium (aCM). Results: All variables were continuous and described a Gaussian distribution unless mentioned. To determine the relation of aggressiveness, variable were transformed into categories. Thus, PCa aggressiveness is associated with the increase of age and BMI (p < .0001) but with is decreased with TT and E2 (p < .05). Moreover, adipocyte-secreted molecules increase aggressiveness of PCa cells in vitro. Lastly, DTH but not E2 enables invasiveness in vitro. Conclusions: It was observed a coexistence of hormone axis profile alteration with sex hormones and BMI in PCa patients, in accordance with the new perspective of PCa pathogenesis.
- Warburg Effect Inversion: Adiposity shifts central primary metabolism in MCF-7 breast cancer cellsPublication . Luís, Carla; Duarte, Fernanda; Faria, Isabel; Jarak, Ivana; Oliveira, Pedro F.; Alves, Marco G.; Soares, Raquel; Fernandes, RúbenObesity is a complex health disorder and a trigger to many diseases like Diabetes mellitus (DM) and breast cancer (BrCa), both leading causes of morbidity and mortality worldwide. Also evidence demonstrates that abnormal glucose metabolism termed ‘the Warburg effect’ in cancer cell is closely associated with malignant phenotypes and promote the aggressiveness of several types of cancer, including BrCa. In this study, we evaluated the breast cancer cell metabolism in normoglycemia, hyperglycemia and in an obesity condition in order to clarify the potential underlined mechanisms that link these disorders. Materials and methods MCF-7 cells were exposed to low and high glucose levels, the latter either in the presence of 3T3-L1 adipocyte conditioned medium (CM), thus mimicking the adiposity observed in obese patients. Cell viability, migration, proliferation, cytotoxicity and cell death assays were performed under the different culture conditions. Hormonal and lipid profile were also characterized by biochemical assays and primary metabolism was determined by Nuclear Magnetic Resonance (NMR)-based metabolomics. Results Our results show an increased aggressiveness in the condition mimicking diabetogenic obesity with an altered energy/lipid metabolism. Interestingly in the experimental obesity-mimicking status, lipids and amino acids were expended while glucose was produced by tumor cells from lactate. These findings reveal a shift on tumor cells metabolism that is opposite to ‘the Warburg effect’. Conclusions Overall, this experimentally obesity-mimicking condition not only revealed an increased tumor proliferation and aggressiveness but also disclosed a new mechanism of cancer metabolism, the ‘Warburg Effect Inversion’.