高表达缓激肽B2受体的大鼠胶质瘤模型的研究

目的建立高表达缓激肽受体(B2R)的大鼠胶质瘤模型,为研究缓激肽选择性开放血脑屏障的机制及解决目前临床应用中存在的问题提供必要的模型。方法①大鼠B2R的真核细胞的表达和其载体(prB2R)侵染C6胶质瘤细胞株;②Real-timeRT-PCR测定B2R的转录;③WesternBlot法测定B2R的表达水平。结果①大鼠胶质瘤细胞株C6高表达B2R;②Real-timeRT-PCR测定C6-B2R1和C6-B2R2克隆的B2R分别比C6对照高7.6和6.9倍;③C6-B2R1和C6-B2R2克隆的蛋白表达水平高于C6对照克隆的3.8和3.78倍。移植C6-B2R1肿瘤1周后的B2R表达水平高于C6对照肿瘤的3.6倍。结论高表达B2R的大鼠胶质瘤模型已被成功建立。     

Bacillus amyloliquefaciens中性植酸酶基因的原核表达及蛋白纯化和性质

淀粉液化芽孢杆菌Bacillus amyloliquefaciens是一种嗜热细菌，其产生的中性植酸酶具有很好的应用前景．通过TD-PCR技术将Bacillus amyloliquefaciens编码的中性植酸酶基因克隆至原核表达栽体pET-30a( )上，在大肠杆菌BL21(DE3)中得到了高效表达，表达量占大肠杆菌可溶性蛋白的33．5％．采用金属Ni^2 亲和层析对基因表达产物进行纯化，表达产物具有正常的生物学功能．     

CEM／ADM多耐药细胞株的P170－糖蛋白的表达

本文利用免疫荧光法对肿瘤细胞ＣＥＭ，ＣＥＭ／ＡＤＭＰ１７０－糖蛋白进行了检测，结果显示：敏感细胞全部为阴性，而耐药细胞株Ｐ１７０－糖蛋白呈过度表达，其过度表达细胞数随肿瘤细胞对抗癌药物耐受性增强而增加，其中ＣＥＭ／ＡＤＭ多耐药细胞株的Ｐ１７０－糖蛋白过度表达细胞为９２％。     

High prevalence of HER-2/neu and p53 overexpression in inflammatory breast cancer

BACKGROUND: Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. Although the survival of patients with IBC has been greatly improved by the use of combined treatment modalities, women with IBC still have lower survival rates. We have summarized a single-center experience involving IBC patients. Our objectives are to clarify molecular alterations of HER-2/neu and p53 in IBC and to investigate the prognostic factors. METHODS: Between January 1990 and December 2000, 57 patients with IBC were referred to the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The incidence of IBC among primary breast cancers was 1.0% (57/5,757) in our hospital. Forty-six patients meeting Haagensen's criteria for inflammatory breast carcinoma were evaluated. All patients had biopsy-proven carcinomas but no distant metastases at referral. The median age at diagnosis for IBC was 51.8 (range, 28 to 70). All patients underwent a mastectomy. Chemotherapy was performed pre- or post-operatively. Three-year and 5-year survival rates were 56.5%, and 40.7%, respectively. Expressions of HER-2/neu and the p53 protein were determined retrospectively by immunohistochemical (IHC) staining of thin paraffin-embedded sections of primary tumors. RESULTS: Of 46 patients, 23 (50.0%) with tumors testing positive for HER-2/neu fared somewhat worse than those with negative tumors, but the differences were not significant for either overall survival (OS) or disease-free survival (DFS). Of 46 patients, 19 (41.3%) whose tumors were positive for p53 fared somewhat better than patients with negative tumors, with no significant differences in either OS or DFS. Patients presenting with less than ten pathologically involved axillary lymph nodes showed significantly better OS and DFS. CONCLUSIONS: Overexpression of HER-2/neu and the p53 protein were not significant prognostic factors in inflammatory breast cancer. However, the increased incidence of HER-2/neu and the poor outcome of IBC may be of clinical interest, suggesting the need for clinical trials of antibody therapy targeted to HER-2/neu. Moreover, a high prevalence of p53 may be useful in determining the specific use of chemotherapy.     

Caloric restriction and aging but not overexpression of SOD1 affect hippocampal volumes in mice

Caloric restriction (CR) and antioxidants have been proposed as strategies to attenuate age-related brain changes. The hippocampus and its subregions dentate gyrus (DG), CA3 and CA1-2 show vulnerability to aging, with hippocampal volume alterations as a measurable sign. Using design-based stereological techniques, we investigated the volumes of the hippocampus and its subregions in six 12-month-old and six 24-month-old mice that were randomly selected from four aging cohorts of 60 male mice each: (1) wild-type mice (WT) fed with control diet (CD), (2) transgenic mice oxerexpressing normal human SOD1 fed with CD, (3) WT mice fed with CR diet, and (4) SOD1 mice fed with CR diet. Aging reduced the mean volume of the entire hippocampus (−9.5%), grey (−8.7%) and white matter (−9.7%), and CA3 subregion (−13.6%), but not DG or CA1-2 subregion. CR reduced the mean volumes of every hippocampal region investigated (on average −11%) in both 12-month-old, and 24-month-old mice. Overexpression of SOD1 was not associated with any volume alteration. These findings indicate that although aging and CR in mice are both associated with hippocampal volume reductions, the patterns of the volume reductions differ. These morphometric alterations may have impact on the function of the hippocampus during aging and CR.     

Tiam 1基因在喉癌中的表达和意义

目的研究T淋巴瘤侵袭转移基因Tiam 1(T lymphoma invasion/metastasis 1)表达与喉癌浸润转移的关系.方法应用逆转录聚合酶链反应(RT-PCR)检测30例喉癌组织、12例喉癌转移的颈部淋巴结和10例正常喉部组织Tiam 1 mRNA的表达.结果有颈淋巴结转移和无颈淋巴结转移的喉癌原发灶Tiam 1 mRNA高表达率分别为75%(6/8)和18.2%(4/22),P=0.0072;有癌转移和无癌转移的淋巴结Tiam 1 mRNA高表达率分别为100%(8/8)和25%(1/4),P=0.0182.30例喉癌有10例Tiam 1 mRNA高表达,高表达率为33.3%.结论 Tiam 1 mRNA表达与喉癌浸润转移呈相关关系.     

Cyclooxygenase inhibition in cancer prevention and treatment

Several lines of evidence suggest that the cyclooxygenase enzymes (specifically COX-2) might be an important molecular target for the intervention of cancer at both early and late stages of some cancers, providing an opportunity for both cancer prevention and therapy. COX-2 is overexpressed during carcinogenesis, and appears to have a role in both tumour initiation and promotion and is amenable to intervention. This review discusses the importance of COX modulation via non-specific, as well as COX-2 specific COX inhibitors (NSAIDs and COX-2 selective inhibitors [COXIB]). A brief discussion on the pharmacoeconomic considerations of NSAID and COXIB use and safety issues that have recently been the focus of debate, will be presented.     

FoxM1与胶质瘤的研究进展

FoxM1是Forkhead Box（ Fox）转录因子家族的成员之一。近年来研究发现,FoxM1在脑胶质瘤的发生和发展中起着重要的作用。研究表明,人脑胶质瘤组织中FoxM1的表达明显高于正常脑组织,并且其表达水平与胶质瘤等级相关。同时,FoxM1信号途径参与调节细胞分化、增殖、凋亡、血管生成及维持干细胞自我更新等生理过程,并与多种致瘤信号途径有关。通过下调FoxM1的表达,可以抑制胶质瘤细胞的增殖、分化等生物学行为。因此,FoxM1的靶向治疗将为胶质瘤药物研发治疗提供一个潜在的新的作用靶点。     

Sitosterolemia: a gateway to new knowledge about cholesterol metabolism

Sitosterolemia (OMIM 210250) is a rare, autosomal recessive lipid disorder initially described almost 30 years ago. The disease is characterized by elevated plasma levels of plant sterols due to increased intestinal absorption and reduced biliary secretion of neutral sterols. Patients with sitosterolemia are frequently hypercholesterolemic, and develop xanthomas and premature coronary heart disease (CHD). Hemolysis, arthralgias and arthritis are also frequently associated with the disorder. Recently, sitosterolemia has been revealed to be due to mutations in either of the two ATP‐binding cassette (ABC) half‐transporters, ABCG5 or ABCG8. These two genes are expressed almost exclusively in the liver and intestine, and are co‐regulated by the nuclear hormone receptor, liver X receptor (LXR). Genetically modified mice, which express either high levels or no ABCG5 and ABCG8 have been developed. Analyses of these mice confirm that these two transporters play key roles in regulating the absorption of dietary and biliary sterols, and in mediating the excretion of neutral sterols from the liver to the bile.

?The elucidation of the gene defects responsible for sitosterolemia provides potential therapeutic targets for the treatment of hyperlipidemias in the general population.     

EGFR在三阴乳腺癌中的过表达情况及对其预后的影响

目的探讨EGFR的过表达对于三阴乳腺癌的意义,为深入研究三阴乳腺癌的治疗提供有价值的信息。方法设实验组（TNBC组）42例和参照组（HER2组）40例,通过免疫组化得出EGFR在两组中的表达情况;利用随访信息探讨EGFR过表达对三阴乳腺癌预后的影响。结果 TNBC组,EGFR过表达者24例（57.1%）,HER2组,EGFR过表达者10例（25.0%）;在TNBC组,EGFR过表达患者的无病生存率和总生存率都明显降低（DFS 0.027,OS 0.038）,有统计学意义;在HER2组,EGFR过表达对患者生存率的影响无统计学意义（DFS 0.079,OS 0.055）。结论 EGFR过表达现象明显存在于TNBC中;EGFR过表达与TNBC的预后有着明显的相关性,可做为衡量TN-BC预后的一个有价值的指标。