Down-regulation of α-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface

α-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels were detected by real-time PCR, and there was a greater than 139-fold increase in FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue samples (*P = 0.005, n = 236). Higher FUCA1 mRNA expression was preferentially detected in early-stage tumors (stage 0 to 2) compared with advanced-stage tumors (stage 3 to 4) (stage 0-1 versus stage 3, *P = 0.015; stage 0-1 versus stage 4, *P = 0.024). FUCA1 protein levels were higher in advanced-stage tumors concomitant with decreased fucosylated Lewis-x antigen expression, as evidenced using the immunohistochemical staining H-score method (*P < 0.001). Statistical analysis revealed that lower FUCA1 levels significantly predicted an inferior overall survival rate among triple-negative breast cancer (TNBC) patients compared with non-TNBC patients (*P = 0.009). Two stable FUCA1 siRNA knock-down MDA-MB-231 cell lines were established, and the results suggest that transient FUCA inhibition creates a selective pressure that triggers the metastasis of primary tumor cells, as detected by wound healing and invasion assays (*P < 0.01). The results suggest that FUCA1 may be a potential prognostic molecular target for clinical use, especially in TNBC patients.     

人原发性直肠恶性淋巴瘤裸小鼠原位移植模型的建立及其生物学特性

目的:建立人原发性直肠恶性淋巴瘤裸小鼠原位移植模型,探讨其生物学特性.方法:采用人直肠原发性恶性淋巴瘤术中的新鲜瘤组织块植入裸鼠的直肠黏膜层内,观察原位移植的成瘤率,移植瘤的侵袭和转移率.进行形态学(光镜、电镜、免疫组织化学),染色体核型,流式细胞分析.结果:依据WHO新的分类标准,建成1株人直肠原发性(非霍奇金B细胞性)恶性淋巴瘤裸鼠原位移植模型HRBL-0305.移植瘤组织病理学为(非霍奇金B细胞性)高度恶性淋巴瘤;免疫组织化学示CD19,CD20,CD22,CD45阳性,CD3,CD7阴性.染色体众数56-69条,流式细胞DI值为1.57-1.61,均为异倍体.HRBL-0305已传至31代;共移植裸鼠187只.其肿瘤移植生长率和液氮冻存复苏成活率均为100.0%,肝转移率为45.4%,淋巴结和腹腔种植转移率均为38.0%,移植瘤在裸鼠的直肠内自主侵袭性生长,发生血液、淋巴转移和腹腔内种植性转移,移植瘤组织病理学,超微结构的观察,流式细胞DNA含量测定及染色体核型的分析,表明与人源直肠恶性淋巴瘤细胞相一致.结论:HRBL-0305是首次成功建立的人直肠原发性恶性淋巴瘤裸鼠原位移植模型,完整地重现了人直肠原发性恶性淋巴瘤的自然临床病理过程,且转移模式与临床患者相似,为研究直肠恶性淋巴瘤的生物学特性和治疗提供了理想动物模型平台.     

Relationship between Egr—1 gene expression and apoptosis in esophageal carcinoma and precancerous lesions

AIM: To study the expression of early growth response gene-1 (Egr-1 gene) and Bcl-X/(L) protein and its relationship with the cell apoptosis in human esophageal carcinoma (EC) and precancerous lesions. METHODS: In situ hybridization(ISH), immunohistochemistry (IHC) and TUNEL method were used respectively to detect Egr-1mRNA, Egr-1 protein, apoptosis related-protein Bcl-X/(L) and cell apoptosis in situ from 66 cases of esophageal squamous cell carcinoma and their upper cut edge and paracancerous mucosa. RESULTS: Egr-1 gene in situ hybridization, Bcl-X/(L) immunohistochemistry positive products were located in the cytoplasm, while Egr-1 immunohistochemistry and TUNEL positive signal were located in the nuclei. The apoptosis index(AI) and the frequency of apoptosis occurrence were increased gradually from precancerous lesion to cancer (P<0.01) and the expression of Egr-1mRNA and Egr-1 protein in dysplasia was the highest among all specimens (P<0.01). The AI of Egr-1 positive cancer tissues was much higher than that of Egr-1 negative cancer tissues (P<0.01), while the AI of Bcl-X/(L) positive cancer tissues was much lower than that of Bcl-X/(L) negative cancer tissues (P<0.01). The AI and Egr-1 expression were not correlated with invasiveness and lymphatic metastasis in EC. CONCLUSION: Cell apoptosis was present through esophageal carcinogenesis. The expression of Egr-1 mRNA and Egr-1 protein were high in precancerous lesion of esophagus. The AI was increased significantly in Egr-1 positive squamous cell carcinoma. Egr-1 might promote apoptotic effect. Egr-1 expression and cell apoptosis may have an important biological significance in esophageal carcinogenesis.     

胆总管结石对血清CA19-9的影响

目的:探讨胆总管结石对血清CEA、CA19-9的影响.方法:回顾经ERCP或手术证实、治疗的胆总管结石患者68例,分析血清CEA,特别是血清CA19-9与胆总管结石患者总胆红素、直接胆红素的相关性:并对20例血清CA19-9值超过正常上限两倍以上的患者统一时间进行随访,分析治疗前后血清CA19-9变化值与总胆红素、直接胆红素变化值的相关性.结果:血清CA19-9与总胆红素、直接胆红素存在明显相关性(r=0.813,0.786,均P=0.000);血清CEA与总胆红素、直接胆红素不存在相关性;治疗前后血清CA19-9变化值与总胆红素、直接胆红素变化值存在明显相关性(r=0.787,0.806,均P=0.000).结论:胆总管结石合并阻塞性黄疸时,可导致血清CA19-9升高,此时血清CA19-9作为肿瘤标志物的特异性差.     

原代脐静脉内皮细胞与脐静脉内皮细胞株的生物学特性比较

目的:建立高效脐静脉内皮细胞(human umbilicalvein endothelial cell,HUVEC)体外培养方法,与HUVEC株生物学特性进行对比研究,为组织工程及相关医学基础研究提供更好的细胞来源.方法:在新鲜脐静脉内灌注2.5 g/L胰蛋白酶消化获得内皮细胞,内皮细胞培养基(endothelial cellmedium,ECM)进行培养;RPMI1640培养HUVEC株.比较两组细胞形态;免疫组化、RT-PCR检测vWF,CD144的表达;Western Blot检测两组冻存复苏后细胞vWF,CD144蛋白水平的表达.结果:原代HUVEC体外生长2～3 d可铺满单层,细胞呈梭形、饱满,漩涡状排列生长,传代后可见管腔样结构;HU-VEC株胞质多颗粒,细胞单薄.免疫组化原代HUVEC的vWF和CD144表达明显高于HUVEC株[vWF分别为(142.7±3.3),(113.6±0.7);CD144分别为(118.6±0.5),(74.2±0.4);P<0.01].在mRNA水平,原代HUVEC基因CD144(577 bp)的表达量为HUVEC株的(3.15±0.12)倍(P<0.05);vWF(434 bp)表达量为HUVEC株的(6.15±0.37)倍(P<0.05).蛋白水平冻存复苏的原代HUVEC的CD144(135ku)表达量为HUVEC株的(2.07±0.31)倍(P<0.05);vWF(210 ku)表达量为HUVEC株的(5.38±0.23)倍(P<0.05).结论:脐静脉灌注胰蛋白酶消化法配合ECM培养可迅速获取大量内皮细胞,其生物学特性明显优于HUVEC株,是组织工程及相关医学基础研究更好的细胞来源.     

Predictive factors for lymph node metastasis in early gastric cancer

AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. RESULTS: Of the 2936 patients who underwent gas-trectomy and lymph node dissection, 556 were diag-nosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors ...     

聚乳酸载阿奇霉素微球包裹和体外释放行为

以溶剂-挥发法制备的聚乳酸微球为载体材料,阿奇霉素为被包裹药物.通过紫外光谱(UV)和扫描电镜(SEM)研究微球的包裹行为;建立药物的UV回归方程,以高效液相色谱(HPLC)研究载药微球的体外释放行为,并建立药物的HPLC回归方程.结果显示,在阿奇霉素投入量为10%时微球具有较好的形态,而且包封率达到90%;药物的释放为两相释放,第一阶段为暴释,第二阶段为溶蚀释放.研究结果为聚乳酸药物缓释微球进一步应用提供技术和参数支持.