阿尔茨海默病差异表达基因的生物信息学分析

目的：应用生物信息学方法分析阿尔茨海默病(Alzheimer,s disease,AD)不同病情程度的差异表达基因（differentially expressed genes,DEGs）,在分子水平上探讨AD的发病制,为研究AD提供新思路。方法：从基因表达综合数据库(gene expression omnibus,GEO)下载基因芯片数据集GSE28146,使用在线分析工具GEO2R分别筛选AD轻度组、中度组和重度组与正常对照组比较的DEGs。运用DAVID 数据库对筛选出的DEGs进行基因本体（gene ontology,GO）富集分析和京都基因与基因百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路分析,通过STRING数据库构建蛋白相互作用网络,并采用Cytoscape软件筛选关键基因。结果：AD轻度组、中度组和重度组分别筛选出881、896和1142个DEGs。GO功能富集显示：轻度组与凋亡相关过程的激活、调节免疫反应、蛋白质磷酸化等生物过程密切相关,中度组与炎症反应、凋亡调节、钙离子的释放等生物过程密切相关,重度组与NF-κB的激活、蛋白质磷酸化和去磷酸化、细胞外基质的降解等生物过程密切相关。KEGG分析显示：轻度组主要富集到p53和TGF-β等信号通路,中度组主要富集到癌症途径、自然杀伤细胞介导的细胞毒性、细胞黏附分子等信号通路,重度组主要富集到细胞周期、Hippo信号通路、神经活性配体-受体相互作用等信号通路。蛋白互作网路分析各组富集程度最高的前5个关键基因：轻度组为GART、EHMT2、KRAS、ESR1、CD44;中度组为CBLB、HERC1、UBE2G1、UBE2M、HECW2;重度组为UBE2C、SOCS3、FBXW7、UBE3B、UBA6。结论：采用生物信息学方法分析不同病情程度的AD,所富集的信号通路和筛选出的关键基因可能在AD发生发展过程中起重要作用,为进一步深入研究AD提供了依据和思路。     

Predictive value of MMP-7 expression for response to chemotherapy and survival in patients with non-small cell lung cancer

Fundamental studies have suggested that matrix metalloproteinases-7 (MMP-7) expression is associated with chemoresistance and constitutes a prognostic factor in several solid tumors. The present study assessed the prognostic and predictive value of MMP-7 in tumors of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. Immunohistochemistry was performed to evaluate the expression of MMP-7, apoptosis-related proteins Bcl-2, Bax, Fas and FasL and the Ki-67 proliferation marker. The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) method was performed to investigate tumor apoptosis. Ninety carcinomas (56.6%) were identified as high expression of MMP-7. Overexpression of MMP-7 was more frequent in adenocarcinomas than in squamous cell carcinomas (P = 0.032). The expression of MMP-7 was positively related with Ki-67 index and Bcl-2, but not apoptosis index. MMP-7 status was correlated inversely with response to chemotherapy in overall patients (response rates, 20.0% and 35.8%, for patients with high-MMP-7 and low-MMP-7 tumors, respectively, P = 0.036), especially in adenocarcinoma (P = 0.021), but not in patients with squamous cell carcinomas (P = 0.373). The overall survival was significantly lower in NSCLC patients with high MMP-7 than in those with low MMP-7 (P < 0.001). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 5.49 P = 0.001). These findings suggest that the expression level of MMP-7 in tumor cells is predictive of response to chemotherapy and outcome in patients with advanced NSCLC receiving platinum-based chemotherapy.     

食管、贲门癌围手术期细胞免疫功能动态变化的临床研究

目的：探讨食管、贲门癌全身、局部细胞免疫功能状态及生物治疗的可行性。方法：采用免疫组化观察分析５０例食管、贲门癌局部肿瘤浸润淋巴细胞（ＴＩＬ）、肿瘤相关性巨噬细胞（ＴＡＭ）的分布特征,采用ＥＬＩＳＡ法和硝酸还原酶法分别地体内可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）表达和一氧化氮（ＮＯ）生成水平进行动态检测。结果：１）癌周物浸润密度大于癌果间质;２）２术前血清ｓＩＬ－２Ｒ水平高于正常对照组,根治术后ｓ     

Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis

It has been shown that acetylcholinesterase (AChE) expression was induced during apoptosis and the anti-sense oligonucleotides and siRNA of AChE may prevent apoptosis in various cell types. However, the mechanisms underlying AChE upregulation remain elusive. We demonstrated here that c-Jun NH2-terminal kinase (JNK) could mediate AChE expression. In this study, both etoposide and excisanin A, two anticancer agents, induced apoptosis in colon cancer cell line SW620 as determined by Annexin V staining, the cleavage of caspase-3 and the proteolytic degradation of poly (ADP-ribose) polymerase (PARP). The results showed that both the agents upregulated AChE in SW620 cells. In the meantime, JNK was also activated and the expression and phosphorylation of c-Jun increased in SW620 cells exposed to the two agents. The induced AChE mRNA and protein expression could be blocked by SP600125, a specific inhibitor of SAPK/JNK, and small interfering RNA directed against JNK1/2. Transfection with adenovirus-mediated dominant negative c-Jun also blocked the upregulation of AChE expression. Together, these results suggest that AChE expression may be mediated by the activation of JNK pathway during apoptosis through a c-Jun-dependent mechanism.     

射波刀治疗35例肝脏肿瘤的临床分析

目的：观察射波刀（cyberknife）治疗肝脏恶性肿瘤的疗效和安全性。方法：回顾性分析35例经射波刀治疗的肝脏恶性肿瘤患者,其中原发性肝癌12例,消化系统肿瘤肝转移16例,其他肿瘤肝转移7例。共57个病灶。所有患者行金标植入术,1周后行射波刀照射。平均肿瘤体积98.64ml,处方剂量18-51Gy,分割3-7次,等剂量线56%-85%。治疗后1-6个月复查,观察近期疗效,之后每3个月随访1次。结果：7例患者达到完全缓解,20例部分缓解,6例稳定,2例进展,有效率（CR＋PR）77.1%,局部控制率94.29%,中位TTP为12个月,中位生存期为23个月。所有患者耐受性良好,主要的不良反应为白细胞降低、食欲减退和疲劳。无Ⅳ级和Ⅳ级以上不良反应发生。结论：射波刀治疗肝脏恶性肿瘤有较高的有效率,安全性好,不良反应轻,患者易耐受。     

Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences

Background

We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients.

Patients and methods

Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m² docetaxel and 75 mg/m² thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m² docetaxel to mobilize peripheral CD34⁺ progenitor cells, a sequence of HDC (120 mg/m² docetaxel, plus 175 mg/m² thiotepa) + DC/CIK, with or without 400 mg/m² carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS).

Results

Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports.

Conclusion

Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.     

组织激肽释放酶7在不同前列腺组织中的表达

目的通过测定组织激肽释放酶7 mRNA（KLK7）在正常前列腺、良性增生前列腺及前列腺癌组织中的表达量,探讨KLK7与前列腺良、恶性病变之间的关系,并阐明其在肿瘤发生发展中的表达状态。方法利用荧光实时定量PCR（quantitative real-time PCR）的方法,检测15例正常前列腺、25例良性增生前列腺和53例前列腺癌组织中KLK7的表达量。比较其在上述前列腺组织中表达量的差异;比较KLK在不同临床分期以及是否存在骨转移的前列腺癌组织间的表达差异。结果KLK7在前列腺癌组织中的平均表达量低于正常或良性病变的前列腺组织,差异有统计学意义（P＜0.05）;在晚期前列腺癌组织中的表达低于局限性前列腺癌,差异有统计学意义（P＜0.05）,在有或无骨转移的前列腺癌组织中的表达差异无统计学意义（P＞0.05）。结论KLK7在前列腺癌组织中呈低表达,在晚期前列腺癌组织中的表达低于局限性前列腺癌,提示该基因可能是潜在的诊断前列腺癌及判断预后的分子标志。     

乳腺癌新辅助化疗后改良根治术后放疗开始时间对预后的影响

目的 本研究旨在分析接受新辅助化疗的局部晚期乳腺癌患者改良根治手术时间到放疗开始时间(SRI)对患者预后的影响。方法 回顾性分析全国11家肿瘤中心的1087例接受新辅助化疗和改良根治术后放疗的乳腺癌患者。用Maxstat方法寻找手术到放疗间隔时间对预后影响的最佳界值。采用Cox多因素回归和倾向配比评分(PSM)分析手术距放疗间隔时间对预后的影响。结果 全组中位随访72.9个月,5年无瘤生存(DFS)率和总生存(OS)率分别为68.1%和81.8%。全组患者分为SRI≤18周(917例)和 SRI>18周(170例)两组。多因素分析显示激素受体状态、病理T分期、病理N分期和SRI是DFS影响因素(P<0.001、<0.001、<0.001、0.023)。激素受体状态、病理T分期、病理N分期、内分泌治疗和SRI是OS影响因素(P=0.013、0.006、<0.001、0.013、0.001)。采用PSM均衡两组患者临床病理因素后SRI≤18周患者DFS和OS仍然优于SRI>18周者。结论 新辅助化疗后乳腺癌患者改良根治手术到放疗间隔时间影响预后,患者应尽量在手术后18周内开始放疗。     

电针"合谷""三阴交"穴促分娩作用机理的实验研究

目的：通过动物实验探讨电针“合谷”“三阴交”穴促分娩的作用机理。方法：选健康成年Wistar大鼠55只,分正常对照组、模型对照组、“合谷”组、“三阴交”组、“合谷”加“三阴交”组。以子宫颈及子宫体组织前列腺素E2(PGEa)、血清及羊水雌二醇(E2)和孕酮(P)为指标。结果：电针“合谷”穴使晚孕大鼠宫体及宫颈组织PGEa、血清E2、羊水中P含量显著升高;电针“三阴交”穴仅使晚孕大鼠羊水中P含量显著升高;同时电针“合谷”“三阴交”穴对本实验所测各项内分泌指标影响不显著。     

心血瘀阻证大鼠血浆代谢网络模型分析

目的：探讨心血瘀阻证大鼠血浆代谢网络模型。方法：代谢通路分析采用KEGG 数据库,代谢产物分子注释、相关的酶或转运蛋白及其相关性质分析采用HMDB 数据库,代谢网络模型可视化采用metPA 网络软件。结果：9 个代谢产物参与了15 条代谢通路,其中泛酸盐和CoA 生物合成、丙酸代谢、不饱和脂肪酸生物合成通路影响值P＜0.05。结论：泛酸盐和CoA 生物合成、丙酸代谢、不饱和脂肪酸生物合成通路参与大鼠心血瘀阻证的病理过程。