RESUMO
Guanylyl cyclase C (GCC) is expressed exclusively in normal intestinal mucosal cells, primary and metastatic colorectal cancers (CRC). The aim of this study was to determine the possible association between the GCC expressions in peripheral blood, prognostic parameters and response to chemotherapy in CRC patients. Fourty-nine metastatic CRC patients and 41 healthy controls with similar age and sex were included to this study. Peripheral blood GCC expressions are measured by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Interstingly, no GCC expression was measured in healthy controls but GCC expressions of the patients were detectable. Although there was a significant reduction in GCC expressions in 30 patients with regression (from 5.46 ± 4.12 to 0.06 ± 0.03, p < 0.0001), marked increase in GCC expressions was observed in 19 patients with progression following chemotherapy (from 0.43 ± 0.19 to 1.38 ± 0.52, p = 0.0174). Significant correlation was found between the GCC expressions and carbohydrate antigen 19-9 (CA19-9) levels (p = 0.0041) in 30 patients with regression before chemotherapy. Marked correlation was also detected between the GCC expressions and carcinoembryonic antigen (CEA) levels (p = 0.0072) in 19 patients with progression before chemotherapy. The results of the present study suggest that peripheral blood GCC expressions along with CEA and CA19-9 can be used to determine the early respose to chemotherapy in patients with metastatic CRC. These findings imply that higher expression of GCC in peripheral blood seems to be an indicator of good therapeutic response to chemotherapy and remission. Monitoring the peripheral blood GCC expressions may allow employing different treatment options to metastatic CRC patients.
Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Receptores Acoplados a Guanilato Ciclase/genética , Receptores de Peptídeos/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Receptores de Enterotoxina , Receptores Acoplados a Guanilato Ciclase/sangue , Receptores de Peptídeos/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do TratamentoRESUMO
The aim of this study is to evaluate the effects of losartan on blood pressure (BP), creatinine clearance (Ccr) and urinary albumin excretion (UAE), and to assess metabolic parameters in comparison with ACEI. Thirty-three type 2 diabetic hypertensive patients were enrolled in the study. Twenty patients were randomized to receive 50 mg/day losartan and 13 patients to 10 mg/day fosinopril. Patients were studied at baseline and after 1 and 6 months. BP was significantly decreased in both groups at the end of the 1st and 6th month to a similar extent. Ccr had fallen in both groups at the end of 1st and 6th months. The effect of each drug on Ccr was similar (64.2+/-70.6 and 42.8+/-53.8 ml/min, respectively, NS). In the subgroup with microalbuminuria at baseline, UAE rate was lower in both groups at the end of the 1st and 6th months. However, when compared with the end of 1st month, the antiproteinuric effect of losartan was slightly decreased at the end of 6th month. Metabolic parameters did not change with either drug. Both drugs were well tolerated. Thus the antihypertensive effects of the two drugs were comparable. In conclusion, this study confirms the efficacy and safety of losartan as an antihypertensive drug in diabetic patients.
