RESUMOVários estudos sugerem que existe uma hiperatividade do eixo hipotálamo-hipofisário-adrenal (HHA) na obesidade, com maior acúmulo de gordura na região abdominal. Estes trabalhos demonstram que, após injeções de hormônio liberador de corticotropina (CRF) ou hormônio adrenocorticotrófico (ACTH) e ainda através de testes de stress, os níveis de cortisol estão aumentados em comparação com pacientes com deposição periférica de gordura. Além do mais, alguns estudos mostram que em pacientes deprimidos, onde a hiperatividade do HHA é uma alteração endócrina importante e conhecida, o volume das adrenais está aumentado quando comparado com normais. Para investigar se o teor de gordura visceral de alguma maneira se relaciona com o volume das adrenais, 52 mulheres com idade entre 19 e 54 anos, com diferentes índices de corpulência, foram estudadas através de medidas antropométricas como peso, índice de massa corporal (IMC), cintura e relação cintura-quadril (RCQ). As áreas de gordura visceral (GV) e subcutânea (GSC), além do volume das adrenais, foram medidas através da tomografia computadorizada. Houve uma correlação extremamente significativa entre as medidas de distribuição de gordura (RCQ e cintura) e a GV, sendo que a RCQ não se correlacionou com a GSC. O somatório do volume das adrenais mostrou uma correlação positiva e significativa com a RCQ (r = 0,272, p = 0,02) e uma correlação positiva, mas no limite da significância com a GV (r = 0,228, p = 0,05), não mostrando qualquer correlação com a GSC. Além disso, o somatório do volume das adrenais foi maior naquelas com GV ³ 120 cm 2 quando comparado com pacientes com área de GV < 120 cm 2 (p = 0,05). Portanto, o estudo sugere que o depósito de GV parece inter-relacionar-se com a hiperatividade do HHA, aqui estimada anatomicamente através do volume das adrenais, glându-la alvo deste eixo. ABSTRACTMany studies suggest that there is a hyperactivity of the hypothalamicpituitary-adrenal (HPA) axis related to obesity with accumulation of fat in the abdominal region. Some studies demonstrate that after the injection of corticotrophin-releasing hormone (CRH) or corticotrophin (ACTH) and according to the results of stress tests, the levels of cortisol are increased when compared to patients with peripheral fat deposition. Moreover, some studies show that in depressed patients, where the hyperactivity of HPA is known and represents an important endocrinological change, the adrenal volume is increased. To investigate if the amount of visceral fat is related in some way to adrenal gland volume, a group of 52 women with different corpulence indexes was studied. Anthropometries measures, such as weight, body mass index (BMI), waist circumference and waist-to-hip ratio (WHR) were checked. The areas of visceral and subcutaneous fat, as well as adrenal gland volumes, were checked by abdominal computed tomography. There was an extremely relevant correlation between the measurements of central fat deposition (WHR
13081 Background: Pre-clinical data indicates that inhibition of epidermal growth factor receptor (EGFR) potentiates the effect of RT. This phase I trial aims to determine the maximal tolerated dose (MTD) of erlotinib, an oral EGFR tyrosine kinase inhibitor, when administered concurrently with standard chemoradiation (CRT) for cervical cancer. Methods: In a modified Fibonacci design, two cohorts of three patients received escalating doses of E (50 mg/100 mg) one week before and combined with C (40 mg/m2, weekly, 5 cycles) and RT (external beam RT - 5040 cGy in 28 fractions, followed by 4 fractions/700 cGy/weekly of brachytherapy). Eligibility criteria included histologically proven squamous cell cervical carcinoma, stage III; no prior therapy; ECOG PS <3 and adequate end-organ functions. Patients were allowed four additional weeks of toxicity observation after CRT + E before proceeding to the next cohort. Frozen tissue for molecular studies was collected before treatment. Results: Considering the first two cohorts, patients presented median age 48 (36–59), stage IIIB (all patients). Median duration of treatment was 71 (70–104) days. Most common non-hematological toxicity were mild to moderate rash, fatigue, diarrhea (grade 3 in one patient), nausea and dysuria. Grade 3 leukopenia was observed in only one patient. Dose limiting toxicities have not been reported so far. Five patients had complete response and one patient had partial response (MRI). Of note, 5/6 patients reported clinical benefit (bleeding cessation) after one week on E alone. The third study cohort (E = 150 mg) is ongoing. Conclusions: This is the first report of a combination of erlotinib, cisplatin and pelvic RT. The addition of E to standard CRT does not appear to increase in-field or systemic toxicities. MTD has not been defined so far. Final results of the phase I will be presented at the meeting. [Table: see text]
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