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Objective The objective of this study was to explore the differences of serum metabolomics between small cell lung cancer(SCLC)patients and healthy volunteers,and to discover serum potential biomarkers for identification and small cell lung cancer staging. Methods Ultra-performance liquid chromatography time of flight mass spectrometry(UPLS-TOF/MS)was used to establish the serum metabolic profile of SCLC. Principal Component Analysis(PCA)and orthogonal hidden variables were analyzed by the EZinfo2. 0 software. Orthogonal Partial Least Squares Discriminant Analysis(OPLS-DA)was used to analyze the metabolic differ-ences between the case and normal control groups. Through cluster analysis using HMDB and METLIN database to search for the exact mass-to-charge ratio of the difference,preliminary identification of some substances with significant differences was carried out. Results Ten differential metabolites such as lysophosphatidylcholine between patients and control groups were screened and identi-fied by mass spectrometry and database search. There were 10 different metabolites such as glycocholic acid in the contour analysis of SCLC patients with different stages. Conclusion There is a significant difference in serum metabolism between SCLC patients and healthy controls. The discovery of differential metabolites provides experimental evidence for the identification of small cell lung cancer and potential markers of staging.
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Heat shock protein 90(Hsp90)is a highly conserved protein which have been proved to play an important role in the development and progression of malignant transformation .As one of small molecule inhibi-tors that has been detected to have potent antitumor activity in a wide range of malignancies ,NVP-AUY922 is a pyrazole scaffold drug with many advantages such as low toxicity and stable structure .As a result of this,NVP-AUY922 is extensively considered as a new promising kind of anti -tumor drug .This review intends to update the reader on advances made over the past four years in the clinical development of NVP -AUY922 in advanced cancers.
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Lung cancer is the leading cause of cancer mortality worldwide, and the cause of death is metastasis. The epithelial-to-mesenchymal transition (EMT) plays a key role in the process of metastasis. Macrophages within the lung cancer microenvironment release cytokines, such as interleukin-6 (IL-6), and promote lung cancer cell invasion and metastasis. However, the interaction between macrophages and lung cancer cells and the effect of this interaction on the expression of IL-6, EMT, and the invasiveness of lung cancer cells remain unclear. Therefore, we established an in vitro co-culture model of human lung adenocarcinoma A549 or H1299 cells with THP-1-derived macrophages to illuminate the important role of macrophages in the invasion of lung cancer. In this study, we demonstrated that the concentrations of IL-6 in the co-culture supernatants were significantly increased compared with controls. Thus, a complex chemical cross-talk is induced by the indirect cell-to-cell contact between lung cancer cells and THP-1-derived macrophages. THP-1-derived macrophages appeared to play an important initiator role in the process. The analysis of the mRNA expression profiles of the sorted cells from the co-culture system revealed that the co-cultured lung cancer cells are the main source of the observed increase in IL-6 secretion. In addition, the interactions between lung cancer cells and THP-1-derived macrophages are bidirectional. The THP-1-derived macrophages underwent differentiation towards the M2-macrophage phenotype during the co-culture process. The expression of IL-6 was correlated with the induction of EMT, which contributed to a significant increase in the invasiveness of the A549 and H1299 cells in vitro. In addition, the addition of an anti-IL-6 antibody reversed these changes. In summary, we demonstrated that the in vitro co-culture of A549 or H1299 cells with THP-1-derived macrophages upregulates IL-6 expression, which increases the invasion ability of the A549 and H1299 cells through the EMT pathway. The THP-1-derived macrophages that interacted with the lung cancer cells differentiated towards the M2-macrophage phenotype. Thus, the inhibition of IL-6 or of the interactions between lung cancer cells and macrophages may be an effective target for anti-cancer therapy in patients with non-small cell lung cancer.
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Adenocarcinoma/inmunología , Adenocarcinoma/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Interleucina-6/farmacología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Macrófagos/inmunología , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Biomarcadores/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Humanos , Interleucina-6/biosíntesis , Neoplasias Pulmonares/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Invasividad Neoplásica , FenotipoRESUMEN
Mel-18 gene is one of the core members of the PcG (polycomb group) family,which plays an important role in embryogenesis,cell growth and proliferation and self-renewal of stem cells.Mel-18 gene expressing abnormally has been related to human tumorigenesis,development process.Mel-18 serves as a tumor suppressor gene and inhibits tumor growth through transcriptional repression of Bmi-1 and c-myc.Mel-18 expression is decreased at transcriptional and translational levels in most human cancers including breast cancer,prostate cancer,and gastric cancer and other tumors.Mel-18 is expected to become a prognostic marker for human cancers.
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Objective:To investigate whether interferon-gamma inducible protein-10(IP-10) and interferon-gamma(IFN-?) participated in the human cerebral ischemia injury.Methods:Twenty-one cerebral ischemia specimens, collected from patients died of cerebral infarction, were divided into three groups: less than 7 days, 7-14 days and 15-21 days according to the lasting time of cerebral infarction. The infiltrating of inflammatory cells were observed using HE stain as non-ischemic hemisphere was for controls. Expression of IP-10 and IFN-? in sections both postmortem ischemic hemisphere and non-ischemic hemisphere were detected using immunohistochemistry.Results:In the groups of less than 7 days and 7-14 days large quantity of inflammatory cells were infiltrated in ischemia tissue. Expression of IP-10 in three groups was elevated in the ischemic hemisphere compared with non-ischemic hemisphere(1.74-folds, 1.41-folds and 1.52-folds increases respectively, P0.05).Conclusion:These results showed IP-10 and IFN-? are expressed in human cerebral ischemia. It was suggested that IP-10 and IFN-? involve in cerebral ischemia injury. Moreover, it was also suggested that IP-10 participate in the repair for the later stage of cerebral ischemia injury.