二氧化硅活化巨噬细胞中早期生长反应因子-1及其信号转导通路的研究

目的 探讨早期生长反应因子(Egr-1)及其信号转导在矽肺发生发展中的作用。方法用细胞免疫荧光、原位杂交方法检测二氧化硅(SiO2)刺激后Egr-1的表达定位,用报道质粒及EMSA检测其活性改变;用激酶活性分析法检测si0：刺激巨噬细胞后ERK1／2活性改变,进一步用激酶抑制剂初步探讨SiO2活化Egr-1的信号转导通路。结果SiO2刺激RAW264．7细胞短时间Egr-1核蛋白表达及转录因子明显增加;且在处理后30～60min,Egr-1核蛋白结合活性明显升高(为未处理组的20倍);在刺激后15min ERK1／2活性开始升高,30min达高峰(活性为对照组的29倍)而后渐降至基础水平;进一步用激酶阻断发现,Egr-1 mRNA及蛋白表达均减少。结论SiO2能激活巨噬细胞中Egr-1,且此过程可能由ERK1／2、p38介导,提示SiO2-ERK1／2、p38-Egr-1通路可能在矽肺发生发展过程中起重要作用。     

FARP2 triggers signals for Sema3A-mediated axonal repulsion

Sema3A, a prototypical semaphorin, acts as a chemorepellent or a chemoattractant for axons by activating a receptor complex comprising neuropilin-1 as the ligand-binding subunit and plexin-A1 as the signal-transducing subunit. How the signals downstream of plexin-A1 are triggered upon Sema3A stimulation, however, is unknown. Here we show that, in the presence of neuropilin-1, the FERM domain-containing guanine nucleotide exchange factor (GEF) FARP2 associates directly with plexin-A1. Sema3A binding to neuropilin-1 induces the dissociation of FARP2 from plexin-A1, resulting in activation of FARP2's Rac GEF activity, Rnd1 recruitment to plexin-A1, and downregulation of R-Ras. Simultaneously, the FERM domain of FARP2 sequesters phosphatidylinositol phosphate kinase type I isoform PIPKIgamma661 from talin, thereby inhibiting its kinase activity. These activities are required for Sema3A-mediated repulsion of outgrowing axons and suppression of neuronal adhesion. We therefore conclude that FARP2 is a key molecule involved in the response of neuronal growth cones to class-3 semaphorins.     

不同来源潜伏膜蛋白1基因转染对鼻咽癌CNE1细胞生长的影响

目的:探讨不同来源的EB病毒潜伏膜蛋白1(LMP1)基因转染对人高分化鼻咽癌(NPC)细胞系CNE1生长的影响。方法:采用脂质体介导法分别将含有来源于B95-8淋巴细胞标准株的LMP1基因(B95-8-LMP1)和来源于NPC组织的LMP1基因(CAO-LMP1)的质粒转染CNE1;RT-PCR和蛋白印迹法分别鉴定LMP1mRNA和蛋白表达;结晶紫法、流式细胞术和平板克隆形成法测定不同来源的LMP1对CNE1生长特性的影响。结果:成功建立稳定表达不同来源LMP1的CNE1细胞系。两种不同来源的LMP1均可促进CNE1细胞的生长(P<0.01);CAO-LMP1比B95-8-LMP1具有更强促进CNE1生长的作用(P<0.01)。结论:不同来源LMP1对CNE1的体外生长均有促进作用,CAO-LMP1比B95-8-LMP1具有更强的促增殖能力。     

Synergistic antiviral activity of human interferon combinations in the hepatitis C virus replicon system.

The use of type I interferon (IFN), in combination with ribvirin, to treat chronic hepatitis C virus (HCV) infection has many drawbacks that prevent widespread application, ultimately leading to a significant unmet clinical need. Potential improvements in IFN therapy through targeted delivery, molecular alteration, and combination with other agents are ongoing in an attempt to decrease adverse effects and increase efficacy. In this report, the HCV replicon cell culture system was used to assess potential synergistic antiviral effects of multiple IFN species when administered in combination. Quantitative analysis of HCV replicon RNA by TaqMan (PE Applied Biosystems, Foster City, CA) and qualitative analysis of HCV protein expression were used to measure the antiviral efficacy of individual and combination IFN treatments, and synergistic responses of IFN combinations were determined through statistical analysis of the TaqMan results. We found that when administered simultaneously, type I/II IFN combinations (IFN-alpha2b + IFN-gamma or IFN-beta + IFN-gamma) resulted in dramatic antiviral synergy, whereas a type I/I combination (IFN-alpha2b + IFN-beta) demonstrated a slightly antagonistic profile. The synergistic effect is likely due to differential cell surface receptors and signaling pathways employed by types I and II IFNs. Conversely, all type I IFN species bind the same receptor and signal through similar pathways, possibly accounting for the nearly additive response observed. In support of this hypothesis, IFN treatment resulted in differential induction of Stat1 phosphorylation at Tyr 701. In conclusion, simultaneous type I/II IFN combination treatment may allow an overall decreased effective IFN dose, which may reduce the side effect profiles that hinder current therapy.     

明胶-聚乳酸载药纳米微球的制备及其体外释药研究

采用复合乳液—溶剂挥发法制得明胶—聚乳酸载五氟脲嘧啶(5—Fu)微球，以混合型乳化剂Tween—80：Span—80＝5：1—作为初乳乳化剂，O—羧甲基壳聚糖作为复乳乳化剂，考察了明胶—聚乳酸载药微球的制备条件对微球的成球性、药物包封率及体外释药的影响。结果表明乳化剂的选择、内部水相药物浓度和PLA分子量等均对载药微球的结构与性能产生影响，经优化条件得到了成球性和体外释放都比较好的载药微球。     

Preoperative chemoradiation and pancreaticoduodenectomy with portal vein resection for localized advanced pancreatic cancer

Pancreatic adenocarcinoma is a common disease that is rarely cured. Surgical resection remains the only treatment modality that has a curative potential, although the majority of patients are unsuitable for resection at the time of diagnosis. Chemoradiation therapy prior to a pancreaticoduodenectomy ensures that a patient who undergoes a complete resection multimodality therapy, avoids a resection in patients who have a rapidly progressive disease, and allows radiation therapy to be given to well oxygenated cells before, surgical devasculation. This permits the chance of resection of an unresectable pancreatic cancer by downstaging. A patient with cytologic proof of localized adenocarcinoma of the pancreatic head received an intravenously chemoradiation (Taxol, 50 mg/m2 intravenously for 3 hours week on 5 cycles, of Gemcytabine 1000 mg/m2/day intravenously for 3 days week on 2 cycles, of 4500 cGy) with the intention of proceeding to a resection operation, restaging was performed by computed tomography, magnetic resonance imaging from 5 weeks every months due to ongoing decreasing of tumor size after the chemoradiation. At laparotomy, the patient didn't have suspected metastatic disease, the tumor size was 2 X 3 cm on the pancreas head and was infiltrating into the portal vein for about 3 cm length on right side. A pancreaticoduodenectomy along with a portal vein and superior mesenteric vein resection was done and then reconstruction of a vascular anastomosis by using the right side of the internal jugular vein. Perioperative complications didn't occur. In conclusion, preoperative chemoradiation of a localized advanced pancreatic tumor has no added risk to the operative complications and the prospects for resectability are enhanced.     

Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer

Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea.     

Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.     

银杏叶对小鼠海马神经元超微结构的影响及抗衰老作用

目的 研究银杏叶提取物对小鼠海马神经元超微结构的影响及抗衰老作用。方法 取小鼠海马作实验材料，用定量体视学方法观察两组小鼠在不同时期海马神经元胞体，胞核，核仁等形态参数的变化，然后对结果用逐步回归的方法进行分析。结果 随着鼠龄的增加，细胞核体积逐渐减少。神经元损失较多，而银杏叶组上述变化较不明显。结论 银杏叶提取物可以影响小鼠海马神经元的超微结构，具有抗衰老作用。     

红细胞衰老过程中渗透脆性的变化

作者在用抗体诱发红细胞溶血清建立的红细胞在体衰老模型的基础上，研究了红细胞衰老过程中渗透脆性的变化。结果显示，随着红细胞年龄的增加，其渗透脆性增加，推论其渗透脆性的变化可能与红细胞膜结构及红细胞几何形状（即红细胞表面积与体积之比）的变化有关。