Inhibition of sensitized leukocyte's in vitro reactivity by circulating immune complexes in prostate cancer

Summary Circulating immune complexes in the sera of patients with confirmed histological diagnosis of carcinoma of the prostate, were found to interfere in the sensitized leukocyte's in vitro reactivity to prostate cancer associated antigen as evaluated by tube leukocyte adherence inhibition assay, thereby suggesting an inhibitory role of such serum factors in host's anti tumor cell mediated immune responses.4 November 1986     

Is chlamydial heat shock protein 60 a risk factor for oncogenesis?

Heat shock protein 60 (HSP60) plays an important role in the protein folding of prokaryotic and eukaryotic cells. Most of the papers published on chlamydial HSP60 concern its role in immune response during infection. In the last decade, exposure to Chlamydia trachomatis has been consistently associated with the development of cervical and ovarian cancer. Moreover, it has been suggested that chlamydial HSP60 may have an anti-apoptotic effect during persistent infection. We hypothesize that the accumulation of exogenous chlamydial HSP60 in the cytoplasm of actively replicating eukaryotic cells may interfere with the regulation of the apoptotic pathway. The concomitant expression of viral oncoproteins and/or the presence of mutations may lead to the ability to survive apoptotic stimuli, loss of replicative senescence, uncontrolled proliferation and, finally neoplastic transformation.Received 15 August 2004; received after revision 1 October 2004; accepted 7 October 2004     

Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells

Cancer cell metabolism is characterized by limited oxidative phosphorylation in order to minimize oxidative stress. We have previously shown that the flavonoid flavone in HT-29 colon cancer cells increases the uptake of pyruvate or lactate into mitochondria, which is followed by an increase in O₂^−.. production that finally leads to apoptosis. Similarly, a supply of palmitoylcarnitine in combination with carnitine induces apoptosis in HT-29 cells by increasing the mitochondrial respiration rate. Here we show that flavone-induced apoptosis is increased more than twofold in the presence of palmitoylcarnitine due to increased mitochondrial fatty acid transport and the subsequent metabolic generation of O₂^−. in mitochondria is the initiating factor for the execution of apoptosis. Received 12 August 2005; received after revision 12 October 2005; accepted 14 October 2005     

Genetic analysis of the kinome and phosphatome in cancer

Protein phosphorylation is a well-characterized biochemical process for reversible regulation of protein activity. Protein kinases and protein phosphatases are the key complementary players in this process, and through their coordinated activity cell homeostasis is tightly controlled. If these enzymes display aberrant activity, cells may undergo unrestrained growth, thus giving rise to complex diseases such as cancer. The technological platform gathered during the Human Genome Project recently allowed the systematic identifi cation of the genetic alterations present in the kinase (the kinome) and the phosphatase (the phosphatome) gene families. These studies suggest that most if not all human tumors carry genetic alterations in at least one phosphatase or kinase gene. Here we integrate the biochemical knowledge on the properties of these molecules with the information collected through their systematic genetic analysis in cancer. We also analyze why the molecular profi ling of the kinome and phosphatome in individual cancers is revolutionizing basic and clinical oncology.Received 13 May 2005; received after revision 30 May 2005; accepted 22 June 2005     

莪术油对胃癌细胞SGC-7901增殖和凋亡的影响

研究莪术油影响人胃癌细胞SGC-7901增殖及凋亡的机制。采用台盼蓝拒染法检测不同剂量莪术油对胃癌细胞SGC-7901的生长抑制率;光学显微镜观察细胞的形态学变化;琼脂糖凝胶电泳检测细胞DNA片段化情况;流式细胞术检测细胞线粒体膜电位的改变、细胞凋亡率以及细胞周期分布。实验结果表明：作用48h时,最佳浓度为110μg／mL,IC50值为104．958μg／mL。DNA电泳可见有梯状条带出现,流式细胞术法显示有凋亡峰出现。莪术油可诱导胃癌SGC-7901细胞凋亡。     

DLL3蛋白在人小细胞肺癌细胞中的功能及其机制

为探讨DLL3(human notch ligand delta-like 3)过表达对人小细胞肺癌细胞的影响及可能的作用机制,通过PCR方法扩增人DLL3基因全长序列,并克隆至慢病毒表达载体Lenti-EFS-FLAG-puro而构建人DLL3基因过表达慢病毒表达质粒,酶切及测序鉴定质粒正确。通过慢病毒包装及感染,构建DLL3稳定过表达的人小细胞肺癌细胞株,并通过Western blot验证DLL3蛋白的表达。采用CCK-8法检测DLL3过表达对人小细胞肺癌细胞的增殖的影响。采用平板克隆实验检测DLL3过表达对人小细胞肺癌细胞的克隆形成的影响。Western blot检测DLL3过表达对细胞周期相关蛋白Cyclin D1,Cyclin D3的表达水平的影响。结果表明:人DLL3过表达慢病毒表达质粒构建成功; CCK-8实验显示DLL3过表达促进人小细胞肺癌细胞的增殖。平板克隆实验显示DLL3过表达提高人小细胞肺癌细胞的克隆形成能力。Western blot结果表明DLL3过表达增加细胞周期蛋白Cyclin D1,Cyclin D3的表达水平。可见DLL3过表达对人小细胞肺癌细胞的增殖具有促进作用。     

利用miR-17的腺病毒载体抑制肺癌细胞系增殖

miR-17是肺癌的新型调节因子,有可能在肺癌发生和进展中发挥作用,但其功能尚不完全清楚。构建miR-17的腺病毒表达载体,检测miR-17对A549细胞体外增殖、锚定非依赖性生长、侵袭和转移的调控作用。利用miR-17的腺病毒载体(Ad-miR-17)在A549细胞中过表达miR-17后,使用MTT实验检测miR-17对NSCLC细胞系A549增殖作用的影响;软琼脂成集落实验检测miR-17对A549细胞锚定非依赖性生长的作用,使用Trans-well实验检测A549细胞的体外侵袭/转移作用(in vitro invasion/in vitro migration);在此基础上共转染miR-17的inhibitor确定miR-17作用的特异性。结果表明,miR-17能够显著下调A549细胞的增殖、锚定非依赖性生长、体外侵袭/转移作用;共转染miR-17的inhibitor能够阻断miR-17的作用。     

癌胚抗原对直结肠偶发高代谢灶良恶性判断

探讨肿瘤标记物癌胚抗原(CEA)测定对~(18)F-FDG PET/CT发现直结肠FDG局灶性高代谢灶癌变判断的临床价值。回顾性分析56例意外探测到结直肠局灶性高摄取灶病例,同时行血清CEA测定,将肠镜及病理结果作为标准分组。各组血清CEA水平数据汇总后行单因素方差分析及计算血清CEA水平测定的诊断效率。结果表明:56例结肠局灶性高代谢病灶中,结肠镜及病理检查出结肠癌及腺瘤共43例,阳性预测值(PPV)为76.8%;其中直结肠癌26例,腺瘤17例,其余13例(23.2%)为炎性及生理性改变。结肠癌组、腺瘤组及良性病变组(炎性和生理性摄取)的血清CEA水平分别为(15.0±17.1)μg/mL,(2.23±0.96)μg/mL,(2.51±0.90)μg/mL,恶性病变组与腺瘤组及正常组之间具有显著性差异,F=8.277,P=0.001。结肠癌组与癌前病变组及生理及炎性组之间P值分别为0.001和0.001。血清CEA水平探测局灶性浓聚灶结肠癌变的敏感性、特异性和准确率分别为:84.6%、83%和83.9%。说明~(18)F-FDG PET/CT偶然发现结肠局灶性高摄取病灶中癌前病变和恶性病变阳性率很高,血清CEA水平对局灶性直结肠偶发FDG浓聚灶的恶变诊断具有高的诊断价值。