The Effect of Targeted Magnetic Nanopaticles on Hepatoma and the Expression of bcl-2/bax Protein

The effect of targeted magnetic nanoparticles on hepatoma and the underlying mechanism were examined. Nude mice transplanted with a human hepatoma cell line （HepG2 cells） were randomized into 5 groups, including： （1） group A, receiving normal saline, （2） group B, receiving 5-fluorouracil （5-Fu）, （3） group C, receiving magnetic nanoparticles containing 5-Fu, （4） group D, consisting of treatment with magnetic nanoparticles containing 5-Fu and inside magnetic field and （5） group E, receiving pure magnetic nanoparticles and inside magnetic field. Morphological features of transplanted tumors in mice in each group were observed under transmission electron microscope （TEM）. The expression of bcl-2/bax protein was immunohistochemically detected by SABC method. The results showed that a large number of apoptotic tumor cells were found in group B and group D under TEM. The expression of bcl-2 protein was significantly decreased and the expression of bax protein increased significantly in both group B and D as compared with those in group A, C and E （P〈0.01 for all）. The decrease in bcl-2 and the increase in bax were more in group D as compared with group B （P〈0.01）. It is concluded that the targeted magnetic nanoparticles containing 5-Fu can improve the chemotherapeutic effect of 5-Fu by decreasing bcl-2 expression, increasing bax expres- sion and inducing apoptosis of the liver cancer cells.     

Inhibitory Effects of Parthenolide on the Angiogenesis Induced by Human Multiple Myeloma Cells and the Mechanism

The inhibitory effects of parthenolide （PTL） on angiogenesis induced by multiple myeloma （MM） cells in vitro and the mechanism were investigated. Human MM line RPMI8226 cells were cultured in vitro. The effects of MM culture supernatant on the migration and tubule formation ability of human umbilical vein endothelial cells （HUVECs） treated with PTL were observed. By using Western blot, the expression of p65 and IкB-α in MM cells was detected. RT-PCR was used to assay the expression of VEGF, IL-6, MMP2 and MMP9 mRNA in MM cells. ELISA was used to measure the levels of VEGF and IL-6 in MM cell culture supernatant. The expression of MMP2 and MMP9 in MM cells was examined by immunohistochemistry. （1） In 3.5, 5.0, 7.5 and 10 μmol/L PTL groups the number of migrated cells was 310±56, 207±28, 127±21 and 49±10 respectively, which was significantly different from that in positive control group （598±47） （P〈0.01）. In 3.5 and 5.0 μmol/L PTL groups the areas of capillary-like structures were 0.092±0.003 and 0.063±0.002 mm2, significantly less than in positive control group （0.262±0.012 mm2） （P〈0.01）, but in 7.5 and 10 μmol/L PTL groups no capillary-like structures were found; （2） After treatment with different concentrations of PTL for 48 h, the expression of p65 protein was gradually decreased, while that of IкB-α was gradually enhanced with the increased concentration of PTL; （3） After treatment with 3.5, 5.0, 7.5 and 10 μmol/L PTL for 48 h, the VEGF levels in the supernatant were 2373.4±392.2, 1982.3±293.3, 1247.0±338.4 and 936.5±168.5 pg/mL respectively, significantly different from those in positive control group （2729±440.0 pg/mL） （P〈0.05）. After treatment with 7.5 and 10 μmol/L PTL, the IL-6 levels in the culture supernatant were 59.6±2.8 and 41.4±9.8 pg/mL respectively, signifi- cantly lower than in positive control group （1287.3±43.5 pg/mL） （P〈0.05）; （4） RT-PCR revealed that PTL could significantly inhibit the expression of V     

A20和Caspase 3在异基因CD8~+T细胞致人脐静脉内皮细胞凋亡中的表达及意义

目的 探讨异基因造血干细胞移植时,供体CD8 T细胞致受体人脐静脉内皮细胞(HUVEC)凋亡中A20蛋白及Caspase 3的表达及意义.方法 采用密度梯度法分离人周围血单个核细胞,CD8 T细胞亚群阴性分选柱试剂盒分选出CD8 T细胞.HUVEC细胞株经过5 ng/ml TNF-α处理后与CD8 T细胞进行混合培养.以AnnexinⅤ和PI双标后,流式细胞仪对HUVEC进行凋亡分析,用全波长荧光分光光度计测定凋亡相关蛋白Caspase 3的活性.Western blot法检测HUVEC中A20蛋白的表达.结果 异基因CD8 T细胞在与HUVEC混合后可引起HUVEC凋亡,流式细胞仪检测显示24 h时的早期凋亡率最高,达(83.6±0.42)%.而晚期凋亡相关蛋白Caspase 3活性在48 h时达高峰,荧光强度为(13.585±0.269), 此后显著降低,与对照组比较差异有极显著性意义(P<0.01).A20蛋白的表达与HUVEC的凋亡率呈负相关(r=-0.839, P<0.05).结论 体外供体CD8 T细胞致受体HUVEC凋亡过程中,信号蛋白Caspase 3的激活介导了凋亡的发生,而A20可能对其起负调节作用.     

胃癌组织中细胞凋亡和bcl-2基因蛋白表达的研究

目的:为了探讨细胞凋亡和bcl-2基因蛋白与胃癌之间的关系。方法:采用原位末端标记技术和免疫组化法对40例胃癌、25例胃粘膜组织中细胞凋亡和bcl-2基因蛋白进行检测。结果:胃癌组织中80.0％(32/40)凋亡细胞为( ),7.5％(3/40)为( );胃粘膜组织中80.0％(20/25)为( ),20.0％(5/25)为( )。85.0％(34/40)的胃癌bcl-2基因蛋白表达阳性,64.0％(16/25)的胃小凹底部上皮bcl-2基因蛋白表达阳性,而表面上皮则不表达。结论:细胞凋亡受抑制和bcl-2基因蛋白过表达与胃癌的发生有密切关系。     

Bcl—2和p53基因蛋白在阴茎癌中的表达

为了研究Ｂｃｌ－２和ｐ５３基因蛋白与阴茎癌的关系，应用ＰＡＰ免疫组化法对４６例阴茎癌组织中Ｂｃｌ－２和ｐ５３基因蛋白进行检测。结果显示，正常鳞状上皮基底细胞Ｂｃｌ－２蛋白表达阳性，４６例阴茎癌中有３８例（８２．６％）Ｂｃｌ－２蛋白表达阳性，有１１例（２３．９％）ｐ５３蛋白表达阳性。提示两种癌基因蛋白的过度表达参与了阴茎癌的发生发展过程。     

EFFECTS OF SUPEROXIDE DISMUTASE ON SOME BIOLOGICAL CHARACTERISTICS OF LUNG CANCER CELLS IN VIVO AND IN VITRO

The present study observed the effects of superoxide diamutase (SOD) and its Inhibitor, diethyldithiocarbamate (DDC), on the metastasis of Lewis Lung cancer and some biological characteristics of A548 lung cancer cell line. It was found that SOD and DDC inhibited significantly the metastasis of Lewis lung cancer In C57 BL mice, which the effect of DDC was more significant than that of SOD, and decreased the proliferation of A549 lung cancer cell and its transplantation rate in nude mice.     

Colles‘骨折固定体位的探讨（附56例疗效分析）

通过对临床实践中正反两方面经验和教训的总结，根据腕部解剖、生理及骨折后的病理特点，分析比较了５６例Ｃｏｌｌｅｓ’骨折患者复位后分别采用腕掌屈前臂旋前位与腕背伸前臂旋后位两种不同固定方法的优劣。结果表明，骨折再移位发生率后者明显低于前者；而功能恢复情况后者明显优于前者（Ｐ＜０．０１）。揭示腕背伸前臂旋后位固定不仅利于骨折复位后的稳定，而且有利于骨折愈合和功能恢复。因此主张摒弃传统的腕掌屈前臂旋前位固定，采用腕背伸前臂旋后位固定。     

Effect of nitrite on endothelial function in isolated lung

Nitrated tyrosine, implicated in protein dysfunction, is increased in various tissues in association with diverse pathological processes. Angiotensin converting enzyme (ACE) is a luminal vascular endothelial enzyme whose dysfunction is an early sign of endothelial injury. ACE contains a tyrosine critical for its enzymatic activity. Others have shown that nitrite exacerbates the ACE dysfunction of cultured endothelial cells in contact with activated polymorphonuclear neutrophils (PMN). We hypothesized that exogenous nitrite would enhance endothelial ACE dysfunction associated with PMN activation in the isolated lung. Rats received lipopolysaccharide (LPS) 2 h prior to isolated lung perfusion with Ficoll containing buffer. Either formyl-Met-Leu-Phe (fMLP, 10(-7) M) or phorbol myristate acetate (PMA, 10(-7) M) was used to activate PMN in lungs treated or not treated with 300-microM nitrite. A first pass indicator dilution method and first order reaction kinetics were used to determine ACE activity, while lung Ficoll content served as an index of vascular permeability. Both fMLP and PMA decreased endothelial ACE activity and increased pulmonary artery pressure, edema and vascular permeability. Exogenous nitrate did not potentiate the decrease in ACE activity, the lung injury or nitrotyrosine immunoreactivity of lung homogenates. In contrast to observations in cultured endothelial cells, our findings in the whole lung are compatible with the speculation of others that the rat lung has an unidentified factor, which minimizes accumulation of nitrated proteins.     

Phase I study of liposomal annamycin

Annamycin is a highly lipophilic anthracycline with the ability to bypass the MDR-1 mechanism of cellular drug resistance. In this phase I study, annamycin entrapped in liposomes was administered by a 1- to 2-h intravenous infusion at 3-week intervals. Thirty-six patients with relapsed solid tumors were treated and 109 courses were administered at doses ranging from 3 to 240 mg/m². The dose-limiting toxicity was thrombocytopenia. Five patients had a probable allergic reaction, requiring discontinuation of treatment in one. Treatment was well tolerated otherwise. No cardiac toxicity was seen on endomyocardial biopsy of four patients studied. There was limited gastrointestinal toxicity and no alopecia. No objective tumor responses were observed. Pharmacokinetic studies at 24, 120 and 240 mg/m² showed a biexponential plasma concentration-versus-time profile. There was a linear relationship between the dose and the maximal plasma concentration with relatively constant plasma clearance values. The maximum tolerated dose (MTD) for liposomal annamycin defined in this study is 210 mg/m². Because of a subsequent change in the formulation of the drug, future studies will use 190 mg/m² as the MTD. Received: 28 December 1999 / Accepted: 29 June 2000     

人正常与结石性胆囊上皮细胞分泌颗粒和溶酶体的定量分析及其意义

作者对２０例胆固醇结石和１５例正常人的胆囊上皮细胞分泌颗粒和溶酶体进行了定量分析，同时测定其胆囊胆汁中的糖蛋白含量，比较两组间的差异。结果显示：结石组胆囊上皮细胞分泌颗粒数、体密度和总面积均明显高于对照组，而溶酶体含量则明显低于对照组；结石组胆汁中糖蛋白含量较对照组高，且胆汁中糖蛋白含量与细胞分泌颗粒数呈正相关，与溶酶体含量呈负相关。作者认为胆囊上皮细胞分泌颗粒影响胆汁糖蛋白量的变化，而溶酶体则可能与细胞内分泌颗粒或蛋白的降解有关，提示胆囊粘膜细胞内结构改变对结石形成起有一定作用。