塞来昔布对鼻咽癌细胞株HNE-1增殖与侵袭能力、VEGF表达及放疗敏感性的影响

目的探讨环氧化酶-2(COX-2)选择性抑制剂塞来昔布(Celecoxib)对鼻咽癌细胞株HNE-1增殖与侵袭能力、血管内皮生长因子(VEGF)表达及放疗敏感性的影响。方法HNE-1细胞经不同浓度塞来昔布处理后,采用MTT法检测各组细胞的增殖水平,细胞侵袭试验检测细胞的侵袭转移能力,RT-PCR及ELISA分别检测细胞VEGF mRNA的转录水平及蛋白的表达水平,克隆形成试验检测细胞对放疗的敏感性。结果不同浓度的塞来昔布均可显著抑制HNE-1细胞的增殖与侵袭能力,并显著下调HNE-1细胞VEGF在mRNA及蛋白水平的表达,且均呈剂量依赖性,差异具有统计学意义。克隆形成试验结果表明,125μmol/L的塞来昔布与放疗联用对HNE-1细胞有明显的协同抗肿瘤效应。结论塞来昔布对HNE-1细胞的增殖与侵袭能力及VEGF的表达均有明显的抑制作用;经塞来昔布处理可增强HNE-1细胞对放疗的敏感性。     

Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)^y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.     

Significant Roles of Regulatory T Cells and Myeloid Derived Suppressor Cells in Hepatitis B Virus Persistent Infection and Hepatitis B Virus-Related HCCs

The adaptive immune system, including type1 helper T cells (Th1 cells), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs), plays an important role in the control of hepatitis B virus (HBV). On the other hand, regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) suppress the immune reaction in HBV and hepatocellular carcinoma (HCC). Excessive activation of immune suppressive cells could contribute to the persistent infection of HBV and the progression of HCC. The frequency and/or function of Tregs could affect the natural course in chronic hepatitis B patients and the treatment response. In addition to the suppressive function of MDSCs, MDSCs could affect the induction and function of Tregs. Therefore, we should understand in detail the mechanism by which Tregs and MDSCs are induced to control HBV persistent infection and HBV-related HCC. Immune suppressive cells, including Tregs and MDSCs, contribute to the difficulty in inducing an effective immune response for HBV persistent infection and HBV-related HCC. In this review, we focus on the Tregs and MDSCs that could be potential targets for immune therapy of chronic hepatitis B and HBV-related HCC.     

Incidence of adenoviruses in raw and treated water

Adenoviruses are of major public health importance and are associated with a variety of clinical manifestations, i.e. gastroenteritis, eye infections and respiratory infections. The importance of water in the epidemiology of adenoviruses and the potential health risks constituted by adenoviruses in water sources and supplies are widely recognised. This study was conducted to assess the incidence of human adenoviruses in raw and treated water systems. Various raw and treated water were routinely monitored for the presence of adenoviruses, over a 1-year period (July 2000-June 2001). The supplies were derived from acceptable quality surface water sources using treatment processes, which conform to international standards for the production of safe drinking water. Adenoviruses were detected by firstly amplifying the viruses in cell cultures and then amplifying the extracted nucleic acids of these viruses using molecular techniques (nested PCR). The results indicated human adenoviruses present in 13 (12.75%) of the raw and 9 (4.41%) of the treated water samples tested. The combination of cell culture and nested PCR has proved to be a quick and reliable method for the detection of adenoviruses in water environments.     

Livin在人喉癌细胞中的表达及白毛藤多糖的干预作用

研究白毛藤多糖对人喉癌细胞生长的抑制作用以及Livin表达的影响。将白毛藤多糖以不同浓度加入到人喉癌细胞,用M1Tr比色法检测细胞增殖抑制率;荧光定量PCR检测LivinmRNA的表达。结果表明,白毛藤多糖可诱导Livin基因的表达,Livin可能参与白毛藤多糖抑制人喉癌细胞的增殖。     

醋酸催化下枸杞多糖的硒化修饰及抗肿瘤活性

制备硒化枸杞多糖,初步了解其结构及体外抗肿瘤活性。利用亚硒酸钠对枸杞多糖进行修饰,通过将无机硒转化为有机硒,为得到高含硒量的枸杞多糖进行探索,找出最佳反应条件为:2mL冰醋酸作为催化试剂,硒化试剂硒酸钠用量为2g,室温下反应时间48h。通过紫外光谱、红外光谱分析,并进行了体外抗肿瘤的初步试验研究。结果:确定了硒化枸杞多糖的分子结构中存在亚硒酸基团,人宫颈癌细胞抑制率可达到26.1%。硒化枸杞多糖对人宫颈癌细胞存在一定的抑制作用。     

Effects of ready to drink teas on AhR- and PXR-mediated expression of cytochromes P450 CYP1A1 and CYP3A4 in human cancer cell lines and primary human hepatocytes

A variety of xenobiotics are taken in the diet and they can interfere with regulatory pathways of drug metabolizing enzymes in humans. This can result in food-drug interactions, which is undesirable clinical situation where drug pharmacokinetics are influenced by dietary compounds. Xenobiotics-mediated food-drug interactions include the induction of drug metabolizing cytochromes P450. The expression of the most important inducible cytochromes CYP1A and CYP3A4 are regulated by xenoreceptors PXR and AhR.We examined extracts from 17 different flavoured ready to drink teas (RDTs) for their capabilities to activate PXR and AhR receptors and to induce CYP3A4 and CYP1A genes. Primary cultures of human hepatocytes and cancer cell lines HepG2 and LS174T were used as in vitro models. Gene reporter assays, RT-PCR and Western blots were performed.We identified three RDTs that induced CYP3A4 mRNA and protein, implying a potential for food-drug interactions. Several RDTs slightly elevated CYP1A1 expression or activated AhR.     

MPPA光动力作用诱导人鼻咽癌细胞凋亡的实验研究

为观察MPPa光动力作用对鼻咽癌细胞凋亡的影响,应用AnnexinV—PI双染结合流式细胞仪分析MPPa光动力作用后人鼻咽癌细胞株CNE2细胞发生凋亡和继发性坏死的比率。结果显示MPPa光动力作用实验组人鼻咽癌细胞株CNE2细胞发生凋亡和继发性坏死的比率分别增加到16.43 %和4.64 % ,且均显著高于单纯光照射组、单纯MMPa光敏剂处理组和假照射组(P <0 .0 1) ,而三对照组间无明显差异(P >0 .0 5 )。表明MPPa光动力作用能有效诱导低分化人鼻咽癌细胞株CNE2细胞凋亡的发生。这也可能是MPPa光动力作用杀伤鼻咽癌的重要机制之一。     

鼻咽癌放射治疗对听力的影响

本文探讨鼻咽癌患者放疗后对听力的影响,着重测试放疗前、放疗后鼻咽癌患者的听力变化。结果表明：放疗对内耳感音功能无明显影响,而对中耳传音功能有明显的改善作用。使听力得以恢复。     

晚期肾细胞癌靶向药物治疗后孤立转移灶手术切除的疗效

目的　探讨靶向药物治疗的转移性肾细胞癌患者远处孤立转移病灶行手术切除的疗效。方法　回顾性收集2007年12月至2013年12月在北京协和医院接受靶向药物治疗的126例转移性肾细胞癌患者资料，其中16例对远处孤立转移灶予以手术切除。患者均有明确的肾细胞癌病理诊断，口服靶向药物索拉非尼、舒尼替尼或依维莫司，直至孤立转移灶稳定且评估为可切除。对手术治疗的安全性和远期效果进行评价。结果　接受远处孤立转移灶切除术的16例患者中，男11例，女5例，中位年龄51岁（37~72岁）；其中肾透明细胞癌14例，肾乳头状细胞癌2例；肺转移5例，骨转移2例，肾上腺转移5例，脑转移2例，肝转移1例，腹壁转移1例。患者围术期均恢复良好，无严重并发症发生。术后肿瘤相关症状明显缓解，一般情况有所好转。16例患者1、3、5年生存率分别为75.0%、43.8%和31.3％。无手术相关的死亡。结论　经靶向药物治疗的晚期肾细胞癌患者有远处孤立转移灶时可从手术治疗中获益，取得较长时间生存。。