RESUMO
BACKGROUND: Heat-shock proteins (HSPs) are members of a chaperone protein family reported to modify stress responses. The aim of this study was to clarify the hypothesis of whether pre-treatment with heat shock reduces liver damage and influences liver regeneration after partial hepatectomy. MATERIALS AND METHODS: Mice (N=6) were divided into two groups: the control group underwent partial hepatectomy without heat shock pre-treatment, the heat shock (HS) group underwent partial hepatectomy 12 hours after pre-treatment with heat shock. Mice were sacrificed at different time points after hepatectomy, remnant liver and blood were collected for further analyses in blood samples and liver tissues. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-6 (IL6), and tumor necrosis factor-alpha (TNFα) were measured using enzyme-linked immunosorbent assay (ELISA). We used tissue samples for several experiments: staining by 5-bromo-2-deoxyuridine (BrdU), evaluation of cytokines, transcription factors and signal-transduction associated proteins. RESULTS: HSP70 levels in the liver were clearly increased from 6 h to 72 h after heat shock treatment. Serum ALT and AST levels were significantly reduced in the HS group compared to the control group after partial hepatectomy. Liver regeneration rate and BrdU labeling index were significantly higher in the HS group than in the control group after partial hepatectomy. IL6 and TNFα in serum and liver tissues were significantly reduced in the HS group compared to the control group after hepatectomy. We did not detect phosphorylation of signal transducer and activator of transcription-3 (STAT3) protein by western blotting. Binding activities of transcription factors: nuclear factor-interleukin-6 (NF-IL6) and nuclear factor-kappa B (NF-kB) were significantly lower in the HS group than in the control group after hepatectomy. CONCLUSION: Pre-treatment with heat shock appears to reduce liver injury and promote liver regeneration, as HSP70 can reduce the inflammatory response and up-regulate liver regeneration without IL6 STAT signaling pathway in the liver after partial hepatectomy.
Assuntos
Hepatectomia , Hipertermia Induzida , Regeneração Hepática , Fígado/crescimento & desenvolvimento , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Western Blotting , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Proteínas de Choque Térmico HSP70/metabolismo , Mediadores da Inflamação , Interleucina-6/metabolismo , Fígado/lesões , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: To investigate the potential involvement of claudin-1 (CL-1) in the tumorigenesis of rectal cancer by analyzing the correlation between CL-1 expression, clinicopathological factors and prognosis. PATIENTS AND METHODS: Rectal cancer tissue specimens from 306 patients that had undergone surgical treatment were evaluated using immunohistochemical analysis for expression of CL-1 and correlated with clinicopathological factors. RESULTS: A reduced expression of CL-1 (less than 30% of tumor cells strongly, positively stained) correlated significantly with poor prognosis in stage II and III rectal cancer. Moreover, the expression levels of CL-1 correlated significantly with tumor differentiation and perineural invasion (p=0.037 and 0.009, respectively). However, no significant differences were detected between the expression levels of CL-1 and other clinicopathological factors. CONCLUSION: Loss of claudin-1 expression is a strong predictor of disease recurrence and poor patient survival in stage II and III rectal cancer.
Assuntos
Adenocarcinoma/metabolismo , Proteínas de Membrana/fisiologia , Proteínas de Neoplasias/fisiologia , Neoplasias Retais/metabolismo , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Antígeno Carcinoembrionário/análise , Diferenciação Celular , Membrana Celular/química , Claudina-1 , Citoplasma/química , Regulação para Baixo , Feminino , Humanos , Metástase Linfática , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/biossíntese , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/química , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , RecidivaRESUMO
BACKGROUND: Expression of insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) has been shown to increase in colorectal cancer. We examined the correlation between expression of IGF-1 and IGF-1R and clinicopathological factors in colorectal cancer. PATIENTS AND METHODS: A prospective study was conducted of 210 colorectal cancer patients that underwent resection from January 2002 to December 2004. The clinicopathological data was correlated to expression of IGF-1 and IGF-1R obtained from immunohistochemical analysis. Statistical analysis was carried using univariate and multivariate analysis. RESULTS: IGF1 and IGF-1R staining was positive in 169 (80%) and 139 (66%) cases, respectively. Univariate and multivariate analyses showed significant correlation between expression of IGF-1 and tumor size (p=0.0024), and depth of invasion (p=0.0147). While IGF-1R was significantly correlated to tumor size and depth of invasion in univariate analysis, only tumor size (p=0.0658) had a strong association in multivariate analysis. CONCLUSION: Expression of IGF-1 and IGF-1R seems to increase with tumor size in colorectal cancer.