Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.     

一种假单胞菌SY5降解石油的动力学研究

为了确定石油降解菌对石油污染物的生物降解特性,选用分离得到的一株石油降解菌假单胞菌SY5,对其降解石油污染物的动力学特性进行了研究．研究结果表明,在30℃,pH=7．2的反应条件下,所筛选的SY5菌对石油具有良好的降解能力,降解石油的反应基本符合一级反应动力学,且随石油初始浓度的增大,SY5降解石油的速率减小,降解受到抑制．在生物降解的过程中,SY5的生长曲线具有明显增长和衰减曲线．在生长阶段,产率系数Y值为0．3873．在内源呼吸阶段,衰减系数bd值为0．1805d^-1,SY5菌自身氧化速度比较快．SY5生物降解石油Monod方程的最大比增长速率胁,和半饱和常数Ks分别为1．6d^-1和150mg／L．     

An EGF-pseudomonas exotoxin A recombinant protein with a deletion in toxin binding domain specifically kills EGF receptor bearing cells

We constructed two chimeric toxins; one composed of epidermalgrowth factor (EGF) and pseudomonas exotoxin A (PE), designatedEGF-PE and the other composed of EGF and PE with a deletionof the Ia domain (cell-binding domain), designated EGF-PE (Ia).Both chimeric toxins reacted with anti-EGF and anti-PE antibodies.The cell-killing experiments showed that EGF-PE, but not EGF-PE(Ia),was cytotoxic to the murine fibroblast cell line NR6, whichcarried the PE receptor, but not the EGF receptor. However,after NR6 was transfected with DNA for the expression of humanEGF receptor, the transfected cell line, designated NRHER5,overexpressed human EGF receptors and became sensitive to EGF-PE(IA).The cytotoxicity of EGF-PE(Ia), but not EGF-PE, to NRHER5 canbe completely blocked by an excess amount of EGF. To completelyreverse the cytotoxicity of EGF-PE on NRHER5, both the EGF receptorpathway and the PE receptor pathway need to be blocked. Theseresults suggest that EGF-PE exhibits both EGF and PE bindingactivities, while EGF-PE(IA) possesses only EGF binding activity.Thus, EGF-PE(Ia) may be a better chimeric toxin than EGF-PEin terms of target specificity to EGF receptor bearing cells.We, therefore, examined the cytotoxicity of EGF-PE(Ia) to varioushuman cancer cell lines. We find that human cancer cells containingmore EGF receptors are more sensitive to EGF-PE(Ia).     

鲤鱼假单胞菌生长动力学研究和货架期预测

以0,5,10,15℃条件下有氧冷藏的鲤鱼为研究对象,用Statistica软件拟合不同温度下优势腐败菌——假单胞菌的生长情况。结果表明,修正的Gompertz方程均能较好地描述假单胞菌在0～15℃范围内的生长动态。贮藏温度对Nmax(最大菌数)的影响不大,在4种温度下Nmax的平均值为(6.91±0.13)lg CFU/g。采用Belehradek方程分析发现,温度与μmax(最大比生长速率)和λ(延滞时间)均呈现良好的线性关系。再把鲤鱼贮藏在3,8,12℃来验证所建立的货架期(shelf life,SL)预测模型的可靠性,求得的SL预测值相比实测值的相对误差分别为-9.35%、-9.38%、-8.89%,表明SL预测模型能够较快速实时地预测0～15℃条件下鲤鱼贮藏过程中的鲜度品质和剩余SL。     

聚3–羟基丁酸与4–羟基丁酸共聚物薄膜的微生物降解

以门多萨假单胞菌为降解菌株,研究了聚3–羟基丁酸与4–羟基丁酸共聚物[poly(3HB-co-4HB)]薄膜的微生物降降过程。门多萨假单胞菌对poly(3HB-co-4HB)薄膜的降解可分为慢速降解阶段和快速降解阶段。经10 d的降解,薄膜的降解率可达到94.7%。扫描电子显微镜观察发现,经微生物降解的薄膜表面因降解而形成的孔洞及蚀痕,这些孔洞及蚀痕随着降解时间的增加有着加大和加深的情况。差示扫描量热法分析发现,随微生物降解时间的增加,薄膜的熔点上升,而相对结晶度降低。X射线衍射分析结果也进一步证实了薄膜经微生物降解后相对结晶度的降低。热重分析法也证明薄膜的热稳定性随降解时间增加而下降。     

牙膏抑菌效果分析研究

初步研究牙膏对大肠杆菌、金黄色葡萄球菌、绿脓杆菌三种比较常见致病菌的抑制效果,检验牙膏抑菌合格与否。用"抗菌有效性"方法,研究LP、MP、HP、LP-HE、LP-BA五种牙膏抑菌效果。LP牙膏中三种细菌浓度维持在106cfu/mL以上,其余四种牙膏在第14天后没有细菌生长,其中MP在4个周期5次检验中都没有细菌生长,LP-BA有类似抑菌效果,但第2次检验时,金黄色葡萄球菌和大肠杆菌的浓度分别为4×104cfu/mL和35×104cfu/mL,HP与LP-H有类似抑菌效果,在第2次检验时仅大肠杆菌生长,细菌浓度分别为1×106cfu/mL和2×106cfu/mL。LP牙膏不能对实验细菌起到抑制作用,而其余四种牙膏能有效的抑制细菌增长。     

假单胞菌复合菌剂对高浓度废水中氨氮总氮浓度降解的研究

在修复工程中,利用微生物处理高浓度氨氮废水.通过对填埋场渗滤液坑底活性污泥驯化,筛选出复合菌剂,在异养硝化培养基或基坑废水中培养25 d后,氨氮平均质量浓度从830.42 mg/L降至38.28 mg/L,去除率最高达95.4％;总氮平均质量浓度从930.03 mg/L降至330.68 mg/L,去除率最高达66.2％...     

头孢他啶

头孢他啶对绿脓杆菌的杀灭力很强 ,临床应用前景看好。该药品专利保护已到期 ,国内多数企业进口原料药进行分装。据估计 ,我国头孢他啶原料药的消耗量为 5 0～ 10 0t/a。头孢他啶的合成分为侧链酯的合成和原料药的合成两部分。侧链酯的主要原料是乙酰乙酸乙酯 ,原料药的主要原料是 7 ACA ,原料供应不会制约我国头孢他啶的生产。文章详细介绍了合成路线、产品质量标准及原料成本核算     

假单胞菌转化喜树碱的初步研究

研究3种菌株假单胞B、L、B1x对喜树碱的生物转化作用。结果表明,假单胞菌B1x对喜树碱具有生物转化功能;以浓度0.7%的牛肉膏、1%的蛋白胨及0.5%的NaCl的培养基对假单胞菌B1x进行转化培养,得其最佳转化条件为时间60h、温度28℃、浓度为0.1g/L、pH为6.5,菌种具有最高转化率19.1%。     

海洋假单胞菌pf-6胞外多糖吸湿保湿和抗氧化性研究

海洋假单胞菌pf-6通过液体发酵得到胞外多糖,研究了其吸湿、保湿性和抗氧化性。结果表明：多糖有良好的吸湿保湿性,在相对湿度43%和81%环境中吸湿性优于黄原胶和低聚糖,在相对湿度43%和硅胶环境中保湿性略低于黄原胶,高于低聚糖;多糖有一定的还原力和清除DPPH.的能力,尤其对.OH的清除能力较强甚至高于维生素C,对O_2-.的清除能力也与维生素C相当,当.OH、O_2-.清除率达50%时所需维生素C浓度分别为0.617、0.147mg/mL,而在同等条件下所需多糖浓度分别为0.341、0.149mg/mL。这为微生物多糖抗氧化性的进一步研究和应用奠定了基础。