阳江高本底和对照地区癌亡病例对照研究

本研究的目的是探索高本底和对照两地区癌亡与环境诱变因素问的关系, 以进一步分析造成两地区癌症死亡率差异的原因和正确地估价高本底辐射在其中的作用。所研究的肝癌、胃癌和肺癌病仞高本底地区分别为64、28和17例, 对照地区分别为75, 36和13例。病例和对照数的比例肝癌为1:1, 胃癌和肺癌为l:2.研究的因素包括职业, 受教育程度, 经济收入、居住史和居住条件等一般社会经济状况, 农药使用, 吸烟、饮酒、饮食以及医用诊断x线照射情况等。     

Synthesis and structure-activity relationship studies for hydantoins and analogues as voltage-gated sodium channel ligands

We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing an effective non-hydantoin ligand. To further understand structural features that result in optimum binding, here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [3H]-batrachotoxinin A 20-alpha-benzoate ([3H]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore, which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.     

Cyclooxygenases in cancer: progress and perspective

Aspirin has been used to control pain and inflammation for over a century. Epidemiological studies first associated a decreased incidence of colorectal cancer with the long-term use of aspirin in the early 1980s. Near the same time the first reports showing regression of colorectal adenomas in response to the non-steroidal anti-inflammatory drug (NSAID) sulindac were reported. In subsequent years, the use of other NSAIDs, which inhibit cyclooxygenase (COX) enzymes, was linked to reduced cancer risk in multiple tissues including those of the breast, prostate, and lung. Together these studies resulted in the identification of a new cancer preventive and/or therapeutic target-COX enzymes, especially COX-2. Meanwhile, the overexpression of COX-2, and less consistently, the upstream and downstream enzymes of the prostaglandin synthesis pathway, was demonstrated in multiple cancer types and some pre-neoplastic lesions. Direct interactions of prostaglandins with their receptors through autocrine or paracrine pathways to enhance cellular survival or stimulate angiogenesis have been proposed as the molecular mechanisms underlying the pro-carcinogenic functions of COX-2. The rapid development of safe and effective inhibitors targeting individual COX enzymes not only dramatically improved our understanding of the function of COX-2, but also resulted in discovery of COX independent functions of NSAIDs, providing important hints for future drug design. Here we review the fundamental features of COX enzymes, especially as related to carcinogenesis, their expression and function in both animal tumor models and clinical cancers and the proposed mechanisms behind their roles in cancer.     

Alpha-methylacyl-CoA racemase as an androgen-independent growth modifier in prostate cancer

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in beta-oxidation of branched-chain fatty acids and bile acid intermediates. Recent work has identified AMACR as a new diagnostic marker for prostate cancer (PCa). The data from the present study suggest that AMACR is also functionally important for the growth of PCa cells. Overexpressed AMACR from both clinical tissues and PCa cell lines is wild type by sequence analysis and functionally active by enzymatic assay. Correspondingly, enzyme activity of AMACR increases approximately 4-fold in PCa in comparison with adjacent normal prostate. Small interference RNA (siRNA) against AMACR, but not the control inverted siRNA, reduced the expression of AMACR and significantly impaired proliferation of the androgen-responsive PCa cell line LAPC-4. No effect was observed in HeLaS3 cells, which express AMACR at a low level. Cell cycle analyses revealed a G(2)-M cell cycle arrest in LAPC-4 cells treated with siRNA compared with mock treatment or control inverted siRNA. Expression of a siRNA-resistant form of AMACR in LAPC-4 cells protects the cells from growth arrest after AMACR-specific siRNA treatment. Data from Western blotting and luciferase-based reporter assays suggest that the function and expression of AMACR are independent of androgen receptor-mediated signaling. Moreover, simultaneous inhibition of both the AMACR pathway by siRNA and androgen signaling by means of androgen withdrawal or antiandrogen suppressed the growth of LAPC-4 cells to a greater extent than either treatment alone. Taken together, these data suggest that AMACR is essential for optimal growth of PCa cells in vitro and that this enzyme has the potential to be a complementary target with androgen ablation in PCa treatment.     

2004～2005年湖州市食源性致病菌污染状况调查

目的：了解湖州市食品中单增李斯特菌、肠出血性大肠埃希菌、沙门菌、金黄色葡萄球菌、副溶血性弧菌、空肠弯曲菌的污染状况，为食物中毒监测提供科学依据。方法：按国标方法，对6类食品进行单增李斯特菌、肠出血性大肠埃希菌、沙门菌、金黄色葡萄球菌、副溶血性弧菌和空肠弯曲菌分离、生化及血清型鉴定。结果：192份样品中共检出致病菌28株，总检出率为14．6％。其中单增李斯特菌检出10株，检出率为5．2％；沙门菌检出12株，检出率为6．3％；副溶血性弧菌检出6株，检出率为3．1％；未检出金黄色葡萄球菌、肠出血性大肠埃希菌、空肠弯曲菌。结论：湖州市食品中存在食源性致病菌的污染，其中生肉制品和水产品受到的污染最为严重，卫生监督部门应加强对生肉制品和水产品的监督管理，防止食源性疾病的发生。     

抗生育中草药的抗HIV研究现状和展望

近年来，抗HIV药物的研究有了很大的发展，目前美国食品及药品管理局（FDA）已经批准了至少29种用于治疗HIV感染的抗病毒药物，主要包括3大类：核苷类逆转录酶抑制剂（NRTIs），非核苷类逆转录酶抑制剂（NNRTIs）及蛋白酶抑制剂（PIs），它们通过抑制HIV病毒的逆转录酶和蛋白酶发挥抗HIV活性。然而，目前HIV对临床使用的上述抗HIV药物均产生耐药性，因此围绕耐药性问题进行了大量的分子机制研究。与此同时，抗HIV天然药物因其专一性、毒副反应少、方便有效等原因得到了越来越多的重视和研究，包括生物碱类、香豆素类、黄酮类、木脂素类和酚类等化合物。研究发现，在天然药物中，有很多抗生育中草药同时具有抗HIV活性，由于抗生育与抗HIV在免疫机制、基因表达、信号转导和促进细胞凋亡方面的机理具有一定的相关性，同时艾滋病又是一种性传播疾病，因此抗生育与抗HIV结合可能成为临床基础研究的新热点。     

卡介菌多糖核酸对尖锐湿疣患者外周血CD4+T细胞细胞因子表达的调节

目的研究卡介菌多糖核酸（BCG-PSN）对尖锐湿疣（CA）患者外周血CD4^＋T细胞IL-2、IL-4、IL-12，IFN-γ表达的调节作用。方法采用流式细胞仪检测了20例正常对照者和60例CA患者（BCG-PSN组40例，激光术后加用BCG-PSN；病例对照组20例，激光术后未加用BCG-PSN）治疗前后外周血CD4^＋T细胞IL-2、IL-4、IL-12、IFN-γ表达水平。结果治疗前CA患者外周血IL-2、IL-12和IFN-γ阳性CD4^＋T细胞百分率较正常对照组均显著下降（P〈0．01），且Th1／Th2平衡失调（P〈0．01）。治疗后BCG-PSN组患者外周血IL-2、IL-12和IFN-γ阳性CD4^＋T细胞百分率显著升高（P〈0．01），Th1／Th2恢复平衡。病例对照组IL-2、IL-12和IFN-γ阳性CD4^＋T细胞百分率于治疗前后差异均无显著性意义（P〉0．05）；临床观察证实BCG-PSN能够显著提高CA临床治愈率，降低CA的复发率。结论CA患者存在Th1／Th2失调；BCG-PSN通过上调外周血CD4^＋T细胞IL-2、IL-12、IFN-γ的表达，纠正机体细胞因子失调而改善患者的细胞免疫功能，以提高其临床疗效和控制复发。     

超排卵治疗过程中卵泡液促性腺激素、雌二醇和胰岛素样生长因子水平检测

目的: 检测超排卵治疗过程中卵泡液内某些激素以及生长因子的水平,探讨它们与受精后胚胎发育潜能的关系.方法:接受辅助生殖技术治疗的患者,根据胚胎发育状况及治疗结局分为妊娠组、正常未孕组和胚胎质量较差组,超促排卵后在超声引导下经阴道穿刺获得卵泡液,用放射免疫法测定卵泡液中促卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、孕酮(P)、生长激素(GH)以及胰岛素样生长因子1(IGF-1)的水平,比较其与不同胚胎发育状况及治疗结局之间的关系.结果:妊娠组及胚胎发育正常但未妊娠组E2水平明显高于胚胎质量较差组(P＜0.05);妊娠组IGF-1水平明显高于胚胎质量较差组(P＜0.05),正常未孕组居于2者之间,但差异无统计学意义;FSH、LH、P及GH水平在以上3组中差异无统计学意义.结论:超促排卵时卵泡液中E2及IGF-1可能与卵子受精后胚胎发育的潜能有关,测定其水平有助于评估辅助生殖技术治疗后的结局.     

新型药用辅料—泊洛沙姆407兔肝内注射后的动态变化

目的 探讨泊洛沙姆407凝胶肝内注射的可行性,了解其肝内注射后的动态变化。方法 采用超声技术动态观察了兔肝内注射泊洛沙姆407后的变化。结果 兔肝内注射泊洛沙姆407凝胶后数小时才被血流冲尽,相比之下,普通水溶液注射后即刻随血流被冲走。结论 泊洛沙姆407作为抗癌药物肝癌内注射的缓释载体是可行的。