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981.
Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.  相似文献   
982.
卵巢癌治疗新进展   总被引:3,自引:0,他引:3  
卵巢癌是继子宫内膜癌及宫颈癌发生率居第三的妇科恶性肿瘤,而其死亡率却居妇科恶性肿瘤之首。卵巢癌的治疗一直是临床工作面临的最艰巨的挑战。传统的根治性手术联合辅助性化疗仍是其基本的治疗方法,新辅助化疗、放疗、生物治疗、免疫治疗和分子靶向治疗给中晚期的卵巢癌治疗提供了新的选择。本文综述卵巢癌的治疗现状及最新的研究进展。  相似文献   
983.
目的:探讨miRNA-141在非小细胞肺癌中的表达及其与临床病理特征的关系。方法:采用real time-PCR法对54例非小细胞患者,肺癌组织及正常肺组织的miRNA-141表达水平进行定量分析,结果由2-△△CT处理,并分析与临床病理资料的关系。结果:在NSCLC患者肿瘤组织中miRNA-141表达水平明显升高,其表达与临床分期、病理类型显著相关(P<0.05)。而在不同年龄、性别、肿瘤大小、吸烟史患者间差异无统计学意义(P>0.05)。结论:MiRNA-141高表达与非小细胞肺癌的临床分期、病理分型密切相关,miRNA-141有可能作为非小细胞肺癌的重要肿瘤标志物之一。  相似文献   
984.
MicroRNA作为生物小分子参与调控机体内环境稳态和许多疾病发生与发展的过程。Let-7是目前研究最为广泛microRNA之一,在多种肿瘤中表达下调,提示let-7与肿瘤存在一些重要的联系。本文主要讨论let-7家族与肿瘤的研究进展,以进一步了解肿瘤发病机制,为肿瘤的预防和诊治提供新思路。  相似文献   
985.
目的 应用Meta分析的方法探讨脑转移瘤的合理治疗模式.方法 以中英文关键词检索中外数据库,检索时限为自各数据库建立起至2012年12月30日.以Jadad评分评价文献质量,采用RevMan5.0软件完成统计分析.共纳入25篇文献,2 750例患者,依据不同的治疗方法进行分组.结果 与单一治疗相比,综合治疗能提高患者的1年生存率(OR =0.58,95% CI为0.46 ~0.71,P<0.000 01);在综合治疗组中,与2种联合治疗方式相比,3种联合治疗方式能提高患者的1年生存率(OR=0.63,95% CI为0.50~0.80,P=0.000 1);与局部治疗相比,全身+局部治疗能提高患者的1年生存率(OR=0.68,95% CI为0.53 ~0.86,P=0.001);与全身治疗相比,全身+局部治疗能提高患者的1年生存率(OR =0.59,95% CI为0.41 ~0.86,P=0.006);在全身+局部治疗中,与2种联合治疗方式相比,3种联合治疗方式能提高患者的1年生存率(OR=0.52,95% CI为0.35 ~0.78,P=0.002);与非靶向治疗相比,分子靶向药物治疗能提高患者的1年生存率(OR=0.76,95% CI为0.67 ~0.87,P<0.000 1).结论 脑转移瘤的合理治疗模式为手术、放疗、化疗3种治疗方式结合,即全身+局部治疗,如果具有应用分子靶向药物的指征,在原方案基础上联合分子靶向药物效果更佳.  相似文献   
986.
Human mesenchymal stem/stromal cells (hMSCs) have been shown to support breast cancer cell proliferation and metastasis, partly through their secretome. hMSCs have a remarkable ability to survive for long periods under stress, and their secretome is tumor supportive. In this study, we have characterized the cargo of extracellular vesicular (EV) fraction (that is in the size range of 40-150nm) of serum deprived hMSCs (SD-MSCs). Next Generation Sequencing assays were used to identify small RNA secreted in the EVs, which indicated presence of tumor supportive miRNA. Further assays demonstrated the role of miRNA-21 and 34a as tumor supportive miRNAs. Next, proteomic assays revealed the presence of ≈150 different proteins, most of which are known tumor supportive factors such as PDGFR-β, TIMP-1, and TIMP-2. Lipidomic assays verified presence of bioactive lipids such as sphingomyelin. Furthermore, metabolite assays identified the presence of lactic acid and glutamic acid in EVs. The co-injection xenograft assays using MCF-7 breast cancer cells demonstrated the tumor supportive function of these EVs. To our knowledge this is the first comprehensive -omics based study that characterized the complex cargo of extracellular vesicles secreted by hMSCs and their role in supporting breast cancers.  相似文献   
987.
Glioblastomas respond differently to all-trans retinoic acid (RA) for unknown reasons. Because CRABP-II and FABP5 mediate RA intracellular signaling respectively and lead to distinct biological consequences, their expression patterns in different grades of astrocytomas and the glioblastoma cells lines LN18, LN428 and U251 were examined to identify potential correlations with RA sensitivities. The response of glioblastoma cells to RA, decitabine or the FABP5 competitive inhibitor, BMS309403, was analyzed. CRABP-II and FABP5 were expressed to varying degrees by the 84-astrocytoma cases examined. Treatment of LN428, U251 and LN18 cells with RA failed to suppress their growth; however, U251 proliferation was inhibited by decitabine. The combination of decitabine and RA suppressed the growth of all three cell lines and induced significant apoptosis of LN428 and U251 cells. Both CRABP-II and FABP5 were transcribed in the three cell lines but FABP5 proteins were undetectable in U251 cells. The ratio of CRABP-II to FABP5 was not altered after RA, decitabine or RA and decitabine treatment and the resistance of cells to RA was not reversed by BMS309403 treatment. In conclusion, CRABP-II and FABP5 expression patterns are neither related to the tumor grades nor correlated with RA sensitivity. Additional molecular factors may be present that determines the sensitivity of glioblastoma cells to RA. Dicitabine may improve the sensitivity of glioblastoma cells to RA, however, its underlying mechanism and its in vivo feasibility need to be investigated.  相似文献   
988.
The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UCA1 was aberrantly upregulated in HCC tissues and associated with TNM stage, metastasis and postoperative survival. UCA1 depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Furthermore, UCA1 could act as an endogenous sponge by directly binding to miR-216b and downregulation miR-216b expression. In addition, UCA1 could reverse the inhibitory effect of miR-216b on the growth and metastasis of HCC cells, which might be involved in the derepression of fibroblast growth factor receptor 1 (FGFR1) expression, a target gene of miR-216b, and the activation of ERK signaling pathway. Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC. Moreover, the present study elucidates a novel lncRNA- miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.  相似文献   
989.
LIM-only protein 3 (LMO3), a member of the LIM-only protein group, is a new DNA methylation gene that was identified in gliomas via the MeDIP-Chip in our previous study. In this study, we found that LIM-only protein 3 (LMO3) is hypomethylated and overexpressed in glioma cells and tissues. The overexpression of LMO3 was correlated with a poor prognosis in glioma patients, and LMO3 was indirectly inhibited by the tumor suppressor miR-101, which is a potential prognosis marker of gliomas. MiR-101 decreased the expression of LMO3 by reversing the methylation status of the LMO3 promoter and by inhibiting the presence of the methylation-related histones H3K4me2 and H3K27me3 and increasing the presence of H3K9me3 and H4K20me3 on the promoter. It was determined that miR-101 decreases the occupancy of H3K27me3 by inhibiting EZH2, DNMT3A and EED and decreases the H3K9me3 occupancy on the LMO3 promoter via SUV39H1, SUV39H2, G9a and PHF8. Furthermore, miR-101 suppresses the expression of LMO3 by decreasing USF and MZF1.  相似文献   
990.
We had previously reported that trivalent arsenic (As3+), a well-known environmental carcinogen, induces phosphorylation of several putative Akt substrates. In the present report, we characterized one of these substrates by immunoprecipitation and proteomics analysis. The results indicate that a cytoskeleton remodeling protein, filamin A, with a molecular weight around 280 kDa, is phosphorylated by Akt in HEK-293 cells treated with As3+, which was also confirmed in human bronchial epithelial cell line, BEAS-2B cells. Additional biochemical and biological studies revealed that serine 2152 (S2152) of filamin A is phosphorylated by activated Akt in the cells treated with As3+. To further confirm the importance of Akt-dependent filamin A S2152 phosphorylation in As3+-induced cell migration, we over-expressed either wild type filamin A or the mutated filamin A in which the S2152 was substituted with alanine (S2152A). The capability of cell migration was reduced significantly in the cells expressing the mutated filamin A (S2152A). Clinically, we found that increased expression of filamin A predicts poorer overall survival of the lung cancer patients with adenocarcinoma. Thus, these data suggest that Akt dependent filamin A phosphorylation is one of the key events in mediating As3+-induced carcinogenesis. Antagonizing Akt signaling can ameliorate As3+-induced filamin A phosphorylation and cell migration, which may serve as a molecular targeting strategy for malignancies associated with environmental As3+ exposure.  相似文献   
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