Ran HLA-A 2.1限制性CTL表位的预测及初步鉴定

目的 寻找并鉴定肿瘤相关抗原Ran来源的HLA-A2．1限制性CTL表位，为临床开展基于Ran表位的特异性免疫治疗奠定基础。方法应用超基序和量化基序相结合的方法初步预测Ran的HLA-A2．1限制性CTL表位，利用其与他细胞亲和力实验以及与T2细胞结合稳定性试验初步验证预测结果。结果应用超基序和量化基序相结合的方法得到4个候选表位IMFDVTSRV（88-96），TLGVEVHPL（42-50），YVATLGVEV（39-47）和VLCGNKVDI（118-126），亲和力试验结果显示IMFDVTSRV，TLGVEVHPL和YVATLGVEV有较高的的亲和力而VLCGNKVDI无明显亲和力，结合稳定性试验显示在这4个候选肽中IMFDVTSRV的结合稳定性最好。结论IMFDVTSRV最有可能是肿瘤抗原Ran的HLA-A2．1限制性CTL表位。     

The proliferation marker pKi-67 organizes the nucleolus during the cell cycle depending on Ran and cyclin B

The proliferation marker pKi-67 ('Ki-67 antigen') is commonly used in clinical and research pathology to detect proliferating cells, as it is only expressed during cell-cycle progression. Despite the fact that this antigen has been known for nearly two decades, there is still no adequate understanding of its function. This study has therefore identified proteins that interact with pKi-67, using a yeast two-hybrid system. A mammalian two-hybrid system and immunoprecipitation studies were used to verify these interactions. Among other cell-cycle regulatory proteins, two binding partners associated with the small GTPase Ran were identified. In addition, DNA-structural and nucleolus-associated proteins binding to pKi-67 were found. Moreover, it was demonstrated that the N-terminal domain of pKi-67 is capable of self-binding to its own repeat region encoded by exon 13. Since RanBP, a protein involved in the transport of macromolecules over the nuclear lamina, was found to be a binding partner, a possible effect of pKi-67 on the localization of cell-cycle regulatory proteins was proposed. To test this hypothesis, a tetracycline-responsive gene expression system was used to induce the pKi-67 fragments previously used for the two-hybrid screens in HeLa cells. Subsequent immunostaining revealed the translocation of cyclin B1 from cytoplasm to nucleoli in response to this expression. It is suggested that pKi-67 is a Ran-associated protein with a role in the disintegration and reformation of the nucleolus and thereby in entry into and exit from the M-phase.     

浅探“南冉北张”的中医药文化研究价值

介绍了张锡纯与冉雪峰的学术成就,在上世纪30年代向民国政府争取中医社会地位所作的斗争,对中医教育作出的贡献及在中医界的影响。主张从南北地域气候与生活环境的差异对张、冉两位中医大家的中医药学术思想与临床特点进行研究。     

冉氏“益气通经”指针结合阿是穴苍龟探穴法治疗慢性非特异性下腰痛

目的：观察冉氏“益气通经”指针法结合阿是穴苍龟探穴针法治疗慢性非特异性下腰痛的临床疗效,为慢性非特异性下腰痛提供新的临床思路和治疗方法。方法：将符合入选标准的慢性非特异性腰痛患者60例,随机分为治疗组和对照组,每组30例,分别采用冉氏“益气通经”指针与阿是穴苍龟探穴针法、常规推拿针刺法,每组各治疗1个疗程,观察临床综合疗效。结果：从临床症状方面评价,冉氏“益气通经”指针结合阿是穴苍龟探穴法均优于常规推拿针刺法。结论：冉氏“益气通经”指针结合阿是穴苍龟探穴法治疗慢性非特异性下腰痛效显便廉,值得临床推广。     

Karyopherins家族与核孔转运的研究进展

大分子物质入核是靠其核内定位序列 (NLS) ,而核内输出是靠其核输出信号 (NES)。不同的NLS和NES直接或靠配体间接的被转运受体识别。目前确定的转运受体都属于同一家族 -Karyopherins家族 ,它们可以在核和胞质间穿梭 ,可以与小的RanGTPase以及核孔蛋白相结合。RanGTPase调节转运受体与转运物、配体、核孔蛋白间的结合 ,而这是决定核孔转运的关键。然而一部分受体转运物复合物通过核孔复合体 (NPC)并不需要Ran水解GTP。     

大鼠皮肤成纤维细胞中Ran蛋白的定位及可能作用

目的 探讨Ras相关核蛋白(Ran)在大鼠体细胞中的定位,及其与细胞周期相关蛋白间的相互作用.进一步揭示细胞周期调控和有丝分裂的分子机制. 方法 用组织块培养法成功地分离培养了大鼠皮肤成纤维细胞,并采用激光扫描共焦显微技术研究细胞有丝分裂过程中Ran的定位变化,至少重复3次. 结果 发现在有丝分裂间期,大鼠成纤维细胞中Ran主要分布于细胞核内,核仁内没有Ran分布,细胞质中Ran浓度极低.核膜破裂,细胞进入有丝分裂,Ran分布到整个细胞,但在染色体周围浓集,浓集区形态和纺锤体的形态一致;在后期和末期浓集区域随纺锤体的变化而变化,分布在被分开的染色体之间,其他地方浓度较低;核膜形成后又重新浓集于细胞核内;在整个有丝分裂中,Ran在细胞分裂区的细胞膜下未见特殊分布. 结论 Ran的分布随大鼠细胞周期的变化而改变,与其对间期细胞核的内输和外运,有丝分裂中正常纺锤体的组装和染色体的正确分配,以及细胞周期的正常的调控作用是一致的.     

Ran promotes the proliferation and migration ability of head and neck squamous cell carcinoma cells

HNSCC is an aggressive tumor that often recurrence and metastasis. Although the treatment of HNSCC has improved over the past few decades, it is easy to recurrence even after comprehensive treatment. Ran is a small Ras-related GTPase belonging to the Ras superfamily. Recently, Ran has been proven to be an important oncogene involved in the metastatic progression of many human cancers. But there is seldom research on HNSCC about Ran. This study revealed the relationship between Ran expression and HNSCC characteristics, investigated the expression and role of Ran in HNSCC tissues and cells by means of immunohistochemistry, qRT-PCR, CCK-8, FCM and transwell migration assays. The results indicated that HNSCC tissues had significantly higher Ran expression than adjacent non-tumor tissues. The overall survival rate was significantly lower in patients with Ran-positive tumors than in those with Ran-negative tumors. Moreover, Ran was positively correlated with tumor grade, lymph node metastasis and recurrence. Ran was also high expressed in the HNSCC cell lines (PCI-37B and SCC9) and down regulated of Ran could evidently inhibit their proliferation, migration and down-regulate of Met protein. In conclusion, our findings suggested Ran could promote the proliferation and migration ability of HNSCC cells. Ran may play an important role in the development of HNSCC and may serve as a novel prognostic indicator of HNSCC.