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Objective:Previous studies have shown an association between programmed death-ligand 1 expression(PD-L1)in non-small cell lung cancer(NSCLC)and clinical factors and that PD-L1 is positively correlated with TNM staging.This study aimed to explore the prognostic significance of PD-L1 and its correlation with the maximum standardized uptake value(SUVmax).Methods:Clinicopath-ological data and the follow-up information of the 122 de novo primary NSCLC patients were analyzed.PD-L1 expression was detected by immunohistochemistry in this 122 surgically resected non-small cell lung carcinoma tissues.Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model.Correlation between SUVmax and PD-L1 expression was analyzed using Spearman's rank correlation analysis.Results:Multivariate analysis revealed that PD-L1 expression(HR=4.518,95% CI:1.176-17.352,P=0.028)and tumor size(HR=1.404,95%CI:1.020-1.933,P=0.037)were independent risk factors for overall survival(OS) in early NSCLC patients.Sex,age,pathological type,CEA level,and SUVmax group had no obvious effect on OS(P 0.05)in early NSCLC patients.In univariate analyses,sex,pathological type,tumor size,and SUVmax group affected OS in stageⅢ-ⅣNSCLC patients.How-ever,age,CEA level,and PD-L1 expression had no effect on OS.PD-L1 expression was not an independent risk factor for OS in stageⅢ-ⅣNSCLC patients.The SUVmax group had no association with PD-L1 in all patients.Conclusions:PD-L1 expression is an independent risk factor for OS in early NSCLC patients but not in stageⅢ-Ⅳpatients.
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Background and purpose:Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is one of the ASPP family. It binds to p53 to inhibit the transcriptional activity of p53-target genes and cell apoptosis, which is asso-ciated with tumor formation. Previously, we found a new subtype of iASPP, iASPP splice variant (iASPP-SV), which is a nuclear protein containing 407 amino acid residues and can bind to p53, inhibiting p53 transcriptional activity. However, the relationship of iASPP-SV and breast cancer is still obscure. Therefore, the purpose of this research was to study the role of iASPP-SV on breast cancer tumorigenesis and progression.Methods:5’-rapid ampliifcation of cDNA ends (RACE) was used to identify the 5’-end of iASPP-SV mRNA in MCF-7 cells. HEK 293 cells were transfected with pFLAG-iASPP-SV and pFLAG-iASPP (828). Then Western blot was used to identify whether endogenous iASPP-SV was expressed in HEK 293 cells and 8 types of human tumor cell lines. This study established the stable clones of NIH 3T3 expressing FLAG-iASPP-SV and FLAG-iASPP (828). Cell proliferation assay, colony formation and soft agar colony formation assay were used to identify whether iASPP-SV and iASPP (828) can promote cell proliferation and iASPP-SV is an oncogene. Real-time lfuorescent quantitative polymerase chain reactive (RTFQ-PCR) was used to de-tect the levels of iASPP-SV and iASPP (828) mRNA in primary breast cancers. Luciferase assays were used to identify the relationships between iASPP-SV, iASPP (828), p53 and NF-κB p65.Results:The study identiifed that iASPP-SV was encoded by previously reported NF-κB p65 subunit (RelA)-associated inhibitor (RAI), and endogenously expressed in many human cancer cell lines. Analysis of cell proliferation, colony formation assay and soft agar assay for colony formation identiifed that similarly to iASPP (828), iASPP-SV promoted tumor cell proliferation and acted as an onco-gene. RTFQ-PCR result showed that the median values of iASPP-SV and iASPP (828) in breast cancers with wild-type p53 were more signiifcantly over-expressed than those of mutant p53. Luciferase assays showed that iASPP-SV and iASPP (828) could suppress NF-κB p65 transcriptional activity. Thus iASPP family may participate in the regulation of p53 and NF-κB activity, which imply that iASPP perhaps shows pro- or anti-survival activities when it interacts with different proteins.Conclusion:These ifndings indicate that iASPP-SV may be a potential target for breast cancer thera-py.
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Cell-cycle deregulation leading to excessive cellproliferation is an important mechanism of human tumorigenesis. CDK6 and CDK4 have been found to be significant regulators of cellcycle, particularly in promoting cell -cycle progress. Moreover, these proteins are usually overly active in most tumors and closely related to tumor development. Recently, research has confirmed CDK4/6 as prospective targets for cancer therapy. However, the mechanism of excessive CDK6 activation leading to tumorigenesis is not completely understood. Therefore, further understanding of the role of CDK4/6 in cell -cycle regulatory pathways and celldifferenti-ation is essential, as well as their overexpression in different types of tumors. This information will elucidate the mechanisms of tumor development and treatment. Therefore, this review intends to discuss the structure and biological function of CDK6, the role and mecha-nism of CDK6 in carcinogenesis, and the clinical application of CDK6 inhibitors.