RESUMO
Cripto-1 is a plasma membrane protein which is not expressed in adult tissue, but some tumors are accompanied by re-activation. We studied the clinical and biological significance of Cripto-1 in colorectal cancer. Cripto-1 was positive in 68 out of 192 cases (35%) by immunohistochemistry. Cripto-1 expression was correlated with worse prognosis and was an independent prognostic factor. Cripto-1-silenced colorectal cancer cell lines had reduced cell proliferation, migration, and activation of Akt and MAPK signaling pathways in vitro, and decreased tumor growth and lymph node metastasis in vivo. Cripto-1 could be a useful prognostic biomarker and therapeutic target in colorectal cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Proteínas Ligadas por GPI/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Proteínas Ligadas por GPI/genética , Técnicas de Silenciamento de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prognóstico , RNA Interferente Pequeno/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A 69 -year-old female with advanced gallbladder cancer underwent cholecystectomy, S4a/S5 segmentectomy of the liver, and resection of the extra-hepatic bile duct in October 2005. Adjuvant chemotherapy consisted of gemcitabine (GEM) and tegafururacil (UFT) administered consecutively. Four years after surgery, computed tomography revealed a single enlarged lymph node in the mediastinum, along with ¹8F-fluorodeoxyglucose accumulation and increased carcinoembryonic antigen (CEA) levels. Therefore, the mediastinal lymph node was considered to be a metastasis and GEM was readministered. Although the patient was treated with GEM for 1 year, the accumulation of 18F-fluorodeoxyglucose in the lymph node remained elevated. No other distant metastases were detected. Abronchoscopic biopsy histologically confirmed mucinous adenocarcinoma in the lymph node. Thus, the mediastinal lymph node was resected. Post-surgery, there was no evidence of recurrence during the 30-month follow up period without chemotherapy. Herein, we report a successful case of surgical treatment for solitary mediastinal lymph node metastasis of gallbladder cancer and review the relevant literature.
Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Adenocarcinoma Mucinoso/cirurgia , Idoso , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Metástase Linfática , Neoplasias do Mediastino/secundário , Neoplasias do Mediastino/cirurgia , Tegafur/administração & dosagem , Uracila/administração & dosagem , GencitabinaRESUMO
BACKGROUND: It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma. PATIENTS AND METHODS: We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies. RESULTS: HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property. CONCLUSION: These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients.