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1.
Clin Invest Med ; 42(1): E31-E38, 2019 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-30904034

RESUMO

BACKGROUND: Colorectal cancer is one of the primary causes of cancer-related deaths and 5-fluorouracil (5-FU) therapy remains the cornerstone of treatment in these patients. Resistance to 5-FU represents a major obstacle; therefore, finding new predictive and prognostic markers is crucial for improvement of patient outcomes. Recently a new type of programmed cell death was discovered-necroptosis, which depends on receptor interacting protein 3 (RIPK3). Preclinical data showed that necroptotic cell death is an important effector mechanism of 5-FU-mediated anticancer activity. PURPOSE: To investigate the predictive and prognostic performance of RIPK3 expression in primary tumors. METHODS: Colon cancer patients (n=74) with metastatic stage were included in this retrospective study and all were treated with first-line 5-FU based chemotherapy. Immunohistochemical staining was performed. RESULTS: The progression free survival for the low expression group of RIPK3 was 5.6 months (95% CI, 4.4-6.8) vs 8.4 months (95% CI, 6.4-10.3) of the group with high expression (p=0.02). Moreover, patients with high expression of RIPK3 were associated with lower risk of disease progression HR 0.61 (95% CI, 0.38-0.97; p=0.044). Patients with high expression levels of RIPK3 also had significantly longer mean overall survival (OS) of 29.3 months (95% CI, 20.8-37.8) as compared with those with low expression: 18.5 months (95% CI, 15.06-21.9) (p= 0.036). In addition, univariate analysis showed that high level of RIPK3 expression was associated with a longer OS HR 0.59 (95% CI, 0.35-0.98; p=0.044). CONCLUSIONS: This study suggests that expression of RIPK3 in primary tumors of metastatic colon cancer patients should be further investigated for its potential as a promising predictive and prognostic marker.


Assuntos
Neoplasias do Colo/metabolismo , Neoplasias Colorretais/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias Colorretais/genética , Feminino , Fluoruracila/farmacologia , Humanos , Masculino , Prognóstico , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Estudos Retrospectivos
2.
Biosci Trends ; 11(2): 221-228, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28250335

RESUMO

The current study sought to evaluate the predictive and prognostic performance of the maximum standardized uptake value (SUVmax) prior to treatment in 43 patients with colon cancer and unresectable liver metastases. Patients with colon cancer who underwent 18F-FDG-PET/computed tomography (CT) scans for staging before the start of first-line 5-fluorouracil-based chemotherapy were retrospectively analyzed. Expression of Beclin-1 in cancer cells was evaluated in primary tumors using immunohistochemical staining. The pretreatment SUVmax for liver metastases was not able to predict progression-free survival but was significantly associated with poorer overall survival, with a hazard ratio of 2.05 (95 % CI, 1.016-4.155). Moreover, a negative correlation was noted between SUVmax and expression of a marker of autophagy - Beclin-1 (rho = -0.42, p = 0.006). This suggests that the pretreatment SUVmax in 18F-FDG PET/CT is a useful tool to help predict survival outcome in patients with colon cancer and unresectable liver metastases and may significantly distinguish between patients with low and high levels of Beclin-1 expression (AUC = 0.809, 95% CI: 0.670-0.948, p = 0.001).


Assuntos
Proteína Beclina-1/metabolismo , Neoplasias do Colo/diagnóstico por imagem , Fluordesoxiglucose F18/análise , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Neoplasias do Colo/complicações , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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