TSH抑制疗法对分化型甲状腺癌患者术后血清Tg、VEGF、TSGF、CD44V6、sIL-2R及T淋巴细胞亚群水平的影响

目的:探讨促甲状腺激素(thyroid stimulating hormone,TSH)抑制疗法对分化型甲状腺癌(differentiated thyroid carcinoma,DTC)患者术后血清甲状腺球蛋白(thyroglobulin,Tg)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、肿瘤特异性生长因子(tumors pecific growth factor,TSGF)、白细胞分化抗原44变异型6(CD44V6)、可溶性白细胞介素-2受体(soluble interleukin-2receptor,sIL-2R)及T淋巴细胞亚群水平的影响。方法:选择2014年1月~2017年1月我院收治的接受甲状腺全切手术治疗的100例DTC患者,随机分为对照组和实验组,各50例。对照组患者常规给予甲状腺素替代治疗,实验组患者给予TSH抑制疗法(口服左甲状腺素钠片,控制血清TSH水平低于0.1mU/L),两组患者均给予治疗1个月。比较两组患者治疗前后血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平及外周血CD3^+、CD4^+、CD8^+水平。结果:两组治疗前的血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平比较,均无显著性差异(P>0.05);两组治疗后的血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平相比治疗前均较低,且实验组治疗后血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平变化均显著优于对照组(P<0.05)。两组治疗前的外周血CD3^+、CD4^+、CD8^+水平比较,均无显著性差异(P>0.05);两组治疗后的外周血CD3^+、CD4^+水平相比治疗前均较高、CD8^+水平相比治疗前均较低,且实验组治疗后血外周血CD3^+、CD4^+、CD8^+水平变化均优于对照组,具有显著性差异(P<0.05)。结论:DTC行甲状腺全切手术治疗后接受TSH抑制疗法能够有效降低血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平,改善细胞免疫功能,值得在临床上推广应用。

胰岛素样生长因子结合蛋白-2与肺癌关系的研究进展

胰岛素样生长因子结合蛋白-2（Insulin like growth factor binding protein -2，IGFBP-2）作为肺癌高敏感的生物标记物，在肺癌的发生、发展及治疗中扮演重要的角色。研究显示其通过激活IGF1R及整合素介导的信号转导通路促进肿瘤的进展；且目前发现其在肺癌的靶向治疗中也起着重要的作用，有望成为肺癌治疗的新靶点，因此本文就IGFBP-2与肺癌的关系进行总结及综述。

靶向转化生长因子-βⅡ型受体核酸适配子结合位点预测及相关验证研究

目的预测转化生长因子-βⅡ型受体(TRβⅡ)胞外段蛋白与靶向适配子S58的结合位点,并在体外进行验证,证实S58的结构稳定性。方法通过适配子ssDNA序列建立其三维结构,在蛋白质数据库搜索受体蛋白TRβⅡ胞外段的晶体结构,运用计算机辅助技术对两个分子进行对接实验,根据结果指导剪切优化适配子结构,分别用生物传感器技术及蛋白免疫印迹法验证其亲和力。结果核酸适配子ssDNA S58与TRβⅡ胞外段蛋白结合的可信位点包括位点Ⅰ(T4、T5、G6、C7)、位点Ⅱ(G13、A14、T15、C16、G17、C18)、位点Ⅲ(T31、G32、T33、C34)及位点Ⅳ(G40、A41、T42、T43、T44、G45、G46)。S58与TRβⅡ胞外段蛋白的亲和力高,S58的α-平滑肌肌动蛋白(α-SMA)表达明显较DMEM对照降低(P<0.05),根据结果剪切适配子S58后得到优化后的ssDNA亲和力、α-SMA表达均不如S58。结论核酸适配子S58为受体蛋白TβRⅡ的高特异性分子,具有一定稳定性,任何结构的改变均会降低与TβRⅡ的亲和力。计算机辅助的分子对接技术成为一项探索分子间作用的重要手段,为医学基础研究提供了良好的理论依据。

Lymphangiogenesis:A new player in cancer progression

Lymph node metastasis is the hallmark of colon cancer progression,and is considered one of the most important prognostic factors.Recently,there has been growing evidence that tumor lymphangiogenesis(formation of new lymphatic vessels) plays an important role in this process.Here,we review the latest f indings of the role of lymphangiogenesis in colorectal cancer progression,and discuss its clinical application as a biomarker and target for new therapy.Understanding the molecular pathways that regulate lymphangiogenesis is mandatory to pave the way for the development of new therapies for cancer.In the future,tailored treatments consisting of combinations of chemotherapy,other targeted therapies,and anti-lymphangiogenesis agents will hopefully improve patient outcomes.This progression to the clinic must be guided by new avenues of research,such as the identif ication of biomarkers that predict response to treatment.

Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells

Background:Epithelial-mesenchymal transition(EMT) is believed to be the critical process in malignant tumor invasion and metastases,and has a great influence on improving the survival rate in non-small-cell lung cancer(NSCLC) patients.Recent studies suggested that eukaryotic initiation factor 5A-2(eIF5A-2) might serve as an adverse prognostic marker of survival.We detected eIF5A-2 in NSCLC A549 cells,and found that the invasive capability correlates with the eIF5A-2 expression.Methods:Transforming growth factor(TGF)-β1 was used to induce EMT in A549 cells.Western blotting,immunofluorescence,wound healing assay,and transwell-matrigel invasion chambers were used to identify phenotype changes.Western blotting was also used to observe changes of the expression of eIF5A-2.We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence.We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers.Results:After stimulating with TGF-β1,almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities.These cells also had higher eIF5A-2 protein expression.Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly.Conclusions:The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells,which correlated with enhanced tumor invasion and metastatic capabilities.Furthermore,in the A549 cell line,the process of EMT phenotype change could be reversed by eIF5A-2 siRNA,with a consequent weakening of both invasive and metastatic capabilities.

TGF-β1-regulated miR-3691-3p targets E2F3 and PRDM1 to inhibit prostate cancer progression

Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.

LRG1 promotes corneal angiogenesis and lymphangiogenesis in a corneal alkali burn mouse model

AIM:To investigate the potential effect and mechanism of leucine-richα-2-glycoprotein-1(LRG1)on corneal angiogenesis and lymphangiogenesis.METHODS:Corneal neovascularization and lymphatics were induced by establishing alkali burn mouse model.Immunofluorescence staining was performed to detect the location of LRG1 in cornea tissues and to verify the source of LRG1-positive cells.Corneal whole-mount staining for CD31(a panendothelial cell marker)and lymphatic endothelial hyluronan receptor-1(LYVE-1;lymphatic marker)was performed to detect the growth of blood and lymphatic vessels after local application of exogenous LRG1 protein or LRG1 si RNA.In addition,expressions of the proangiogenic vascular endothelial growth factor(VEGF)related proteins were detected using Western blot analysis.RESULTS:LRG1 was dramatically increased in alkali burned corneal stroma in both the limbal and central areas.LRG1-positive cells in the corneal stroma were mainly derived from Vimentin-positive cells.Local application ofexogenous LRG1 protein not only aggravated angiogenesis but also lymphangiogenesis significantly(P<0.01).LRG1 group upregulated the levels of VEGF and the vascular endothelial growth factor receptor(VEGFR)family when compared with the phosphate-buffered saline(PBS)control group.We also found that LRG1-specific si RNA could suppress corneal angiogenesis and lymphangiogenesis when compared with the scramble si RNA-treated group(P<0.01).CONCLUSION:LRG1 can facilitate corneal angiogenesis and lymphangiogenesis through heightening the stromal expression of VEGF-A,B,C,D and VEGFR-1,2,3;LRG1-specific si RNA can suppress corneal angiogenesis and lymphangiogenesis in corneal alkali burn mice.

Phototropism in land plants： Molecules and mechanism from light perception to response

BACKGROUND： Phototropism is the response a plant exhibits when it is faced with a directional blue light stimulus. Though a seemingly simple differential cell elongation response within a responding tissue that results in organ curvature, phototropism is regulated through a complex set of signal perception and transduction events that move from the plasma membrane to the nucleus. In nature phototropism is one of several plant responses that have evolved to optimize photosynthesis and growth. OBJECTIVE： In the present work we will review the state of the field with respect to the molecules and mechanisms associated with phototropism in land plants. METHODS： A systematic literature search was done to identify relevant advances in the field. Though we tried to focus on literature within the past decade （1998-present）, we have discussed and cited older literature where appropriate because of context or its significant impact to the present field. Several previous review articles are also cited where appropriate and readers should seek those out. RESULTS： A total of 199 articles are cited that fulfill the criteria listed above. CONCLUSIONS： Though important numerous and significant advances have been made in our understanding of the molecular, biochemical, cell biological and physiologic mechanisms underlying phototropism in land plants over the past decade, there are many remaining unanswered questions. The future is indeed bright for researchers in the field and we look forward to the next decade worth of discoveries.