RESUMO
The cannabinoid receptor-1 (CNR-1) and endogenous agonists of this receptor are present in the central and peripheral nervous systems including the gastrointestinal nervous system. The surgically rejected specimens of human colorectal cancers and paired normal tissues were studied to detect mutations in the CNR1 gene by sequencing method. The results were compared to clinicopathological parameters and correlated with overall survival time. Sixty-three colorectal cancer patients, who underwent surgical excision of colorectal carcinoma, were included in this study. The coding region of the CNR1 gene was studied: a nucleotide change (G-->A) at position 1359 was identified by direct sequencing of PCR. Thirty-eight patients had the G/G genotype (wild type) in tumor areas and 25 patients had G/A heterozygous or A/A homozygous genotype. Univariate analysis revealed 2 independent variables associated with CNR1 gene mutation. The results show that the patients with Dukes stage C and D had a 2.9 times (p = 0.04) and patients that were lymph node positive had 2.8 times (p = 0.05) greater probability of nucleotide change in CNR1 gene. Genotype G/A plus A/A had a shorter overall survival time than G/G wild-type patients (p < 0.05). Indeed nontumor paired colorectal tissues showed nucleotide change. A large number of patients with mutation in the CNR1 gene were observed. These preliminary findings highlight the importance of further studies in the use of cannabinoid analogs as receptor ligands to analyze potential therapeutic effects.
Assuntos
Carcinoma/genética , Carcinoma/mortalidade , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Mutação Puntual , Receptor CB1 de Canabinoide/genética , Idoso , Carcinoma/terapia , Neoplasias Colorretais/terapia , Feminino , Heterozigoto , Homozigoto , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Risco , Análise de Sequência de DNA , Resultado do TratamentoRESUMO
AIMS AND BACKGROUND: Cannabinoid receptors have an impact on gastrointestinal function, but it remains unknown whether mutations may affect tumor susceptibility in patients with esophageal carcinoma. The aim of this study was to determine mutation in the cannabinoid receptor-1 (CNR1) gene and its relation to vascular endothelial growth factor (VEGF) expression as an angiogenic and poor prognostic factor. METHODS: 179 esophageal tissue samples from 69 patients (29 with esophageal cancer and 40 controls) were studied. CNR1 gene mutation (1359 G --> A in codon 453) was detected with PCR, using the MspI restriction enzyme. VEGF was determined by immunoassay. RESULTS: Genotyping in control patients' samples revealed that 24/40 were G/G wild type and 16/40 were G/A; no samples were A/A. Of the 139 tissue samples from the 29 esophageal cancer patients, 15 were G/G homozygous, 85 G/A heterozygous, 11 had an A/A genotype and 28 were without amplification. In the normal tissue adjacent to tumor, some mutations were observed. The overall survival time was reduced in patients with the A/A type in all their 5 samples, in comparison to G/G type (P = 0.04, chi-square: 4.26). VEGF expression was higher in tumor than nontumor areas (P < 0.025). VEGF expression was not correlated with survival time. CONCLUSIONS: Our preliminary findings in esophageal tissue showed a high frequency of G --> A mutation in the CNR1 gene. No correlation between VEGF expression and gene receptor mutation was found. Patients with mutation in all their samples had a reduced survival time.
Assuntos
Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Receptor CB1 de Canabinoide/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/mortalidade , Genótipo , Humanos , Estimativa de Kaplan-Meier , Mutação , Neovascularização Patológica/genética , Reação em Cadeia da Polimerase , PrognósticoRESUMO
Tobacco and immunosuppression are risk factors for developing upper aerodigestive and lung tumors after transplantation. This study comprises 701 adult recipients who survived more than 2 months after transplant: 276 patients underwent orthotopic liver transplantation (OLT) for alcoholic cirrhosis (AC) and 425 for nonalcoholic disease. The aim is to analyze the incidence, clinical characteristics, risk factors, and outcome of patients who develop lung malignancies after OLT. Incidence of lung cancer was 2.1% (15 patients): 4.3% (12 patients) in the alcoholic group and 0.7% (three patients) in the nonalcoholic group (P < 0.001). Mean time from OLT to tumor diagnosis was 86 months. Thirteen patients were smokers; 12 patients were heavy drinkers; and 11 were drinkers and smokers. Squamous cell carcinoma was diagnosed in nine patients, large cell carcinoma in three, adenocarcinoma in two, and broncoalveolar in one. Tumor staging: 10 patients at stage IV; three at stage IIIB; and two at stage IIB. Tumor resection was performed in one patient, and three also received chemotherapy. Mean survival after tumor diagnosis was 5.4 months. There is a higher risk of lung cancer in smoker patients who have undergone OLT for AC, and have a very poor prognosis because tumors are diagnosed at advanced stages.
Assuntos
Transplante de Fígado/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Humanos , Terapia de Imunossupressão/efeitos adversos , Incidência , Transplante de Fígado/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Espanha/epidemiologia , Análise de Sobrevida , SobreviventesRESUMO
GOALS/BACKGROUND: The aim of this study was to decipher whether end-stage liver failure modifies peripheral blood lymphocytes (PBL) in a homogeneous manner, independently of the base pathology, or, if on the contrary, PBL subsets show a different profile in each hepatic disease. METHODS: We studied PBL subsets in 71 patients with end-stage liver disease, before liver transplant, and 74 healthy controls by flow cytometry. The results were statistically compared between patients and controls, and cohorts of patients classified according to their base pathology. RESULTS: We observed lower absolute numbers in all lymphocyte populations in patients compared with controls. We found an increment of CD3+ activated cells (P<10) and CD45RO+CD4+ (P<10) in chronic hepatitis C virus versus controls; hepatitis B virus showed high TCRgammadelta+ and CD8+ T cells with respect to controls (P=0.008 and P=0.029, respectively); alcoholic cirrhotic patients showed low CD8+, mainly CD45RA+CD8+ (P=0.007) and high CD45RO+CD4+ (P<10) compared with the normal population; autoimmune diseases showed lower CD3+ and TCRalphabeta+ (P=0.002 and P=0.0001) than controls. CONCLUSIONS: Regardless of the base pathology, patients with end-stage liver disease show a low absolute number of lymphocyte populations compared with controls. However, PBL profiles are different, characteristic, and specific of every disease causing chronic liver failure.