Bone is one of the most frequent targets of small cell lung cancer (SCLC) metastasis and is closely associated with a poor prognosis, but the specific cellular gene alterations responsible for SCLC with bone metastasis are unclear. Zinc finger E-box binding homeobox 1 (ZEB1) as an E-box transcriptional repressor has been suggested that an important inducer of the epithelial-mesenchymal transition (EMT) and a promoter of tumor metastasis in colon, breast and lung cancers. However, the relationship between ZEB1 and SCLC with bone metastasis is unclear. In this study, ZEB1 was found to be highly expressed in bone-metastatic SCLC tissues and cell lines as compared with those that were non-metastatic (P < 0.05). Using a lentivirus RNA interference technique to knockdown ZEB1 expression in bone-metastatic SCLC cells (SBC-5 cell line), we found that ZEB1 siRNA could inhibit the invasive and migratory ability and decrease parathyroid hormone-related protein expression, as determined by invasion assays and enzyme-linked immunosorbent assays. Besides, ZEB1 siRNA significantly inhibited the bone metastasis of SBC-5 cells in vivo. Furthermore, overexpression of ZEB1 in SBC-3 cells, which demonstrate promoted bone-metastatic potential, dramatically promoted their invasive and migratory ability and parathyroid hormone-related proteinexpression as well as increased the number and sites of bone metastases in vivo compare to the control group. We also found that SBC-3 cells underwent EMT, as indicated by decreased epithelial markers and increased mesenchymal marker expression. Taken together, these results indicate that ZEB1 promoted the invasive ability and bone metastasis of SCLC cells, and that this was partially mediated via the EMT pathway. (Cancer Sci 2012; 103: 1420-1428 S mall cell lung cancer (SCLC) is the lung neoplasia with the poorest prognosis, due to its high ability of metastasis. SCLC in the advanced stage frequently metastasizes to multiple organs, including the liver, lungs, lymph nodes and bone.( 1) Bone is one of the most frequent targets of SCLC metastasis (as well as the brain and liver) and the bone metastasis is associated with high morbidity and poor prognosis (2,3) due to the consequences of skeletal-related events, including bone pain, pathologic and radiologic fractures and hypercalcemia. (4)(5)(6) However, the mechanisms underlying this rapid metastatic capacity of SCLC are unknown.Previous study shows that SBC-3 and SBC-5 are derived a similar genetic background from human SCLC, which have the same metastatic ablility of visceral organs except for bone. SBC-5 has a higher capability of bone metastasis than SBC-3.(7) We previously explored the preliminary mechanism of bone metastasis using SBC-5 and SBC-3. (8)(9)(10) Zinc finger E-box binding homeobox 1 (ZEB1) is an E-box transcriptional inducer that has emerged as a key player in cancer progression. The epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and is closely related with development and progression of tumors....
Brain metastasis is a frequent occurrence in lung cancer, especially non-small cell lung cancer (NSCLC), the prognosis for NSCLC with brain metastasis is very poor. Our previous study found high S100B expression in the brain-specific metastatic NSCLC line PC14/B, suggested S100B is closely correlated with brain metastasis in NSCLC. However, the details have not yet been revealed. The aim of this study was to investigate the correlation between S100B and brain metastasis in NSCLC and to study the effects of S100B on non-brain metastatic NSCLC line PC14. We investigated serum S100B levels in 30 newly diagnosed NSCLC patients (15 with brain metastasis and 15 without brain metastasis) using enzyme-linked immunosorbent assay. Results showed that serum S100B levels were significant higher in NSCLC patients with brain metastasis compared to those without brain metastasis (P<0.01). We constructed the full-length S100B expression vector and transfected into PC14 cells. MTT and flow cytometric analysis showed that S100B transfection promoted cell proliferation and inhibited cell apoptosis (P<0.05). Transwell migration and invasion assays indicated that S100B transfection promoted cell invasion and cell migration compared to control cells transfected with empty vector alone (P<0.01). These results suggested that S100B could be involved in the development of brain metastasis in NSCLC.
BackgroundControversy remains as to whether antiviral agents contribute to renal dysfunction in patients with chronic hepatitis B virus (HBV) infection. Thus, the aim of study was to analyze the changes in renal function of chronic hepatitis B (CHB) patients in response to anti-HBV therapy and the association with treatments.MethodWe performed a retrospective observational cohort study to investigate factors associated with renal function in 249 Chinese CHB patients who were treated with pegylated interferon α-2a (PEG-IFN-α-2a) or nucleos(t)ide analogues for 48 weeks. Changes of estimated glomerular filtration rate (eGFR), which was computed with both the Chronic Kidney Disease Epidemiology Collaboration and the Modification of Diet in Renal Disease formulas, were tested by repeated measures One-way analysis of variance within groups. A linear mixed effects model for repeated measures was also used to evaluate the association between baseline information and eGFR changes over time in all enrolled patients. The model considered the baseline age, sex, HBV DNA, aminotransferase, blood urea nitrogen, treatment group, time, and group-by-time interaction as fixed effects and incorporated random effects for individual subjects.ResultsThe eGFR increased in patients given PEG-IFN-α-2a, decreased in patients given adefovir, but remained stable in patients given entecavir. Age and blood urea nitrogen were significant negative predictive factors for eGFR changes.ConclusionIn real-life study, PEG-IFN-α-2a therapy in CHB patients increased eGFR, thus may associate with renoprotective effects when compared with adefovir or entecavir therapies.
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