RESUMO
Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa.
Assuntos
Mitocôndrias/genética , Neoplasias Penianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Variações do Número de Cópias de DNA/genética , DNA Mitocondrial/genética , Variação Genética/genética , Genoma/genética , Genoma Mitocondrial/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Análise de Sequência de DNA/métodosAssuntos
Apêndice/transplante , Laparoscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Neoplasias do Colo Sigmoide/cirurgia , Estruturas Criadas Cirurgicamente , Ureter/cirurgia , Idoso , Humanos , Masculino , Invasividade Neoplásica , Reto/cirurgia , Neoplasias do Colo Sigmoide/patologiaRESUMO
BACKGROUND: Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. OBJECTIVES: Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. METHODS: This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. RESULTS: Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p=0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p=0.054). CONCLUSION: This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.
Assuntos
Adenocarcinoma/terapia , Androgênios , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/etiologia , Hormônio Liberador de Gonadotropina/agonistas , Síndrome Metabólica/complicações , Neoplasias Hormônio-Dependentes/terapia , Obesidade Mórbida/complicações , Orquiectomia/efeitos adversos , Neoplasias da Próstata/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores , Doenças Cardiovasculares/epidemiologia , Terapia Combinada , Humanos , Incidência , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/cirurgia , Obesidade Mórbida/fisiopatologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , RiscoRESUMO
Thirty-six patients on chronic anticoagulant therapy were submitted to dental surgery. The ages ranged between 20 and 68 (mean 43.5) years; twenty (55.6%) patients were female and 16 (44.4%) were female. Phenindione was administered to 33 (91.7%) patients, warfarin to one (2.7%) and hydroxycoumarin to two (5.6%). Mechanical heart valve prosthesis occurred in 23 (64%) patients, bioprosthesis in two (5.5%), mitral stenosis submitted to commissurotomy in two (5.5%) and other valvular heart disease occurred in nine patients (25%). Eighty-three elective procedures were performed. Anticoagulant drugs were stopped from two to seven days before, in order to prothrombin time reach 60%. Abnormal bleeding that was easily controlled with local measures occurred in two patients. Sixteen emergency procedures were performed without stopping anticoagulant treatment. Abnormal bleeding was observed in one patient and it subsided after local care. Thus, safe odontologic procedures may be carried on in patients during treatment with oral anticoagulants.