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Remodeling and spacing factor-1 (Rsf-1), firstly discovered in 1998 and located in the nucleus, is one of the most commonly amplified gene and its protein molecular weight is about 240 ×103. The interaction between Rsf-1 and human sucrose non-fermenting protein 2 homologue (hSNF2H) changes the cell growth signals and environment, which is inclined to cause the cells loss of the normal regulation, leading to the abnormal proliferation and occurrence of tumors. Recent study has shown that Rsf-1 is closely related to the prognosis of a lot of human malignancies, such as genitourinary system tumors, gastrointestinal tumors, head and neck cancer, non-small cell lung cancer and glioma.
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Objective To investigate the influence of β-catenin gene deletion on Stat-5α phosphorylation in bcr-abl induced leukemia cells. Methods The established conditonal hematopoitic β-catenin knockout mice were used to isolate bone marrow cells. Exogenous bcr-abl fusion gene was transduced to these bone marrow cells by retroviral infection with intent to transfom them to leukemia cells.Immunofluorescence was performed to detect the phosphorylation status of Stat-5α in both β-catenin deletion cells and control cells. bcr-abl transcription and protein levels were evaluated with real-time PCR and western blotting. Results Phosphorylation of Stat-5α was reduced significantly in β-catenin deletion leukemia cells on comparison with control cells despite that total Stat-5α protein showed no obvious changes. Total tyrosine phosphorylation and bcr-abl protein expression were reduced in bcr-abl induced β-catenin deletion CML cells,on the contrary, both of the reduction were not seen in bcr-abl induced β-catenin deletion ALL cells.Conclusion Loss of β-catenin inhibits both Stat-5α phosphorylationin and bcr-abl expression in bcr-abl induced leukemia cells.
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<p><b>BACKGROUND</b>Drug-resistance of tumor is the main reason of the failure of che-motherapy. Much attention has been paid to the expression of multidrug resistance-associated protein (MRP) and its mechanism of drug-resistance in non-small cell lung cancer (NSCLC). Results of this research will contribute to reversing drug-resistance and improving curative effect. The aim of this study is to investigate the relationships between the expression of MRP and clinicopathological parameters and prognosis in patients with NSCLC.</p><p><b>METHODS</b>Expression of MRP was detected in 62 cases of paraffin-embedded NSCLC samples by streptavidin-biotin-peroxidase complex immunohistochemistry method, as well as in 30 fresh cases of NSCLC samples and corresponding normal lung tissues by immunohistochemistry and Western blot.</p><p><b>RESULTS</b>MRP expression of NSCLC tissues was significantly higher than that of normal lung tissues. The survival time of patients with negative MRP expression was (69.81±17.41) months, and that of patients with positive MPR expression was (25.38±4.46) months (P=0.0156). This statistically significant relationship between the survival time and prognosis was also showed in squamous cell carcinoma patients (P=0.015), but not in adenocarcinoma. Multivariate COX model analysis suggested that the survival time was significantly related to lymphatic metastasis (P=0.038) and expression of MRP (P=0.035).</p><p><b>CONCLUSIONS</b>MRP expression in NSCLC is significantly higher than that in the normal lung tissues. The mean survival time of patients with negative MRP expression is remarkably longer than that of patients with positive MRP expression. MRP expression may be an independent prognostic factor.</p>
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<p><b>BACKGROUND</b>To study the expression of MMP-2, MMP-9, TIMP-1 proteins and mRNA in NSCLC and to analyse their relations with prognosis.</p><p><b>METHODS</b>Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to detect the expression of MMP-2, MMP-9, TIMP-1 proteins and mRNA in pa-raffin-embedded NSCLC specimens.</p><p><b>RESULTS</b>There were no significant differences among the MMP-2, MMP-9, TIMP-1 expression and age, sex, histological type and differentiation. There was statistical relationship between expression of MMP-2, MMP-9, TIMP-1 and lymph node metastasis. Multivariate Cox model analysis suggested that the survival time was significantly related to lymph node metastasis, expression of MMP-2 and MMP-9. The results of IHC and ISH suggested that the concordant rates of MMP-2, MMP-9, TIMP-1 proteins and mRNA were of statistical significance (P < 0.01,P < 0.005,P < 0.025).</p><p><b>CONCLUSIONS</b>MMP-2 and MMP-9 are independent factors that affect prognosis, TIMP-1 is an useful parameter to the prognosis of NSCLC.</p>
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<p><b>OBJECTIVE</b>To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Seventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.</p><p><b>RESULTS</b>Of the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P < 0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P < 0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P < 0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P < 0.05). There was a significant correlation between LVD and MVD (R = 0.732, P < 0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P < 0.01).</p><p><b>CONCLUSIONS</b>In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.</p>
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Metabolism , Endothelial Growth Factors , Immunohistochemistry , Lung Neoplasms , Metabolism , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth Factor Receptor-3ABSTRACT
<p><b>BACKGROUND</b>To study the expression of MGMT and its relationship with efficacy of chemotherapy and prognosis in patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>MGMT was detected in 128 NSCLC tissues and 10 normal pulmonary tissues by immunohistochemistry. According to the level of MGMT , 128 patients with NSCLC were divided into the group Mer- with negative MGMT expression and the group Mer+ with positive MGMT expression.</p><p><b>RESULTS</b>MGMT positively expressed in 61 of 128 patients with NSCLC (47.66%), but none of normal group. No significant relationship was found among MGMT expression and TNM stages, lymph node metastasis and histological classification of the cancer. However, the mean survival periods and survival rates in group Mer- were significantly higher than those of group Mer+ (P < 0.01 , P < 0.05). In 45 evaluable patients, total response rates were 42.86% and 4.17% in Mer- and Mer+ patients respectively (P < 0.001); and there were remarkably longer mean survival periods and higher survival rates in Mer- patients than those in Mer+ patients (P < 0.01, P < 0.05).</p><p><b>CONCLUSIONS</b>Expression of MGMT may be helpful to predict efficacy of chemotherapy and prognosis in patients with NSCLC.</p>
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<p><b>OBJECTIVE</b>To investigate the protein and mRNA expression of E-cadherin and beta-catenin in nonsmall cell lung carcinoma (NSCLC) and to find their correlation with histological type, differentiation, metastasis and prognosis.</p><p><b>METHODS</b>High sensitive S-P immunohistochemical method and in situ hibridization were used to detect the protein and mRNA expression of E-cadherin and beta-catenin.</p><p><b>RESULTS</b>Immunohistochemistry revealed that among the 101 cases, the positive rates of E-cadherin and beta-catenin were 68.3% and 81.2% respectively. The abnormal expression rates of these two proteins were 61.4% and 64.4% respectively. There was no significant relationship between E-cadherin and beta-catenin staining and histological type of the tumor (P > 0.05). However, there was a statistically significant difference between well and moderately differentiated cells and poorly differentiated cells (P < 0.05). In cases with lymphatic metastasis, the abnormal expression rates of E-cadherin and beta-catenin were significantly higher than those in nonmetastatic cases (P < 0.05). The mean survival time in cases with abnormal E-cadherin and beta-catenin expression were significantly shorter than that in cases with the expression grading (+ +) approximately (+ + +). In situ hybridization showed that in NSCLC, the positive rate of E-cadherin and beta-catenin mRNA was 38.9% and 47.2% respectively. Their concordant rates with (+ +) approximately (+ + +) protein expression were 78.6% and 82.4%, respectively.</p><p><b>CONCLUSIONS</b>The concordant rate of E-cadherin and beta-catenin mRNA and protein expression was relatively high. They can be used as markers of prognosis of NSCLC in clinical practice.</p>