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Cyanobacterial Exopolysaccharides: Their Nature and Potential Biotechnological Applications 蓝藻胞外多糖:它们的性质和潜在的生物技术应用
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648020
Pengfu Li, S. Harding, Zhi-li Liu
Cyanobacteria (blue-green algae) are photosynthetic prokaryotic organisms which are unicells or filaments. Of great significance biologically is the fact that certain cyanobacteria can fix elemental nitrogen (Carr and Whitton, 1982). Some cyanobacteri a are capable of movement by gliding when in contact with the substrate (Bold and Wynne, 1985). Some cyanobacteria have the ability to survive desiccation and extremes of temperature, and can grow at high pH and salinity (Flaibani et al., 1989). Cyanobacteria occur in most environments on earth. Their distribution in freshwater and marine environment is cosmopolitan. Cyanobacteria are also commonly found in the soil and in rocks from the tropics to polar regions, and from temperate climates to extreme arid deserts, where they sometimes participate in the formation of microbial crusts or mats (Bold and Wynne, 1985; Mazor et al., 1996). A number of diazotrophic cyanobacteria grow easily in association or symbiosis with certain green algae, liverworts, water ferns, and angiosperms (Bold and Wynne, 1985). Cyanobacteria have been known, for a long time, to produce large amounts of exopolysaccharide (Drews and Weckesser, 1982). Recently, this massive production has received increasing attention due to the potential applications of these substances as industrial gums, bioflocculants, soil conditioners and biosorbants, and to their participation in symbiotic processes in plants, in the gliding movement, and in the general interactions between microorganisms and their habitats (Bertocchi et al., 1990; Painter. 1993; Morvan et al, 1997; De Philippis and Vincenzini, 1998).
蓝藻(蓝绿藻)是单细胞或细丝的光合原核生物。具有重要生物学意义的是,某些蓝藻可以固定元素氮(Carr和Whitton, 1982)。一些蓝藻在与底物接触时能够通过滑动运动(Bold and Wynne, 1985)。一些蓝藻具有在干燥和极端温度下生存的能力,并且可以在高pH和高盐度下生长(Flaibani et al., 1989)。蓝藻存在于地球上的大多数环境中。它们在淡水和海洋环境中的分布是世界性的。蓝藻也普遍存在于从热带到极地的土壤和岩石中,从温带气候到极端干旱的沙漠,在那里它们有时参与微生物结壳或垫的形成(Bold和Wynne, 1985;Mazor et al., 1996)。许多重氮营养蓝藻很容易与某些绿藻、苔类、水蕨类和被子植物结合或共生生长(Bold and Wynne, 1985)。长期以来,人们都知道蓝藻可以产生大量的胞外多糖(Drews和Weckesser, 1982)。最近,由于这些物质作为工业胶、生物絮凝剂、土壤调节剂和生物吸附剂的潜在应用,以及它们参与植物的共生过程、滑动运动和微生物与其栖息地之间的一般相互作用,这种大规模生产受到了越来越多的关注(Bertocchi等,1990;画家。1993;Morvan等人,1997;De Philippis和Vincenzini, 1998)。
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引用次数: 99
Biotechnological Approaches to Fight Pathogens at Mucosal Sites 在粘膜部位对抗病原体的生物技术方法
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648018
C. Kelly, D. Medaglini, Justine S. Younson, G. Pozzi
Most interactions between host and pathogens occur at the host mucos al surfaces. Many pathogens, such as the human immunodeficiency virus (HIV), gain entry via the mucosa while others, including Candida, Streptococcus mutans and Helicobacter pylori , must become established at the mucosa to cause damage to the host. Strategies aimed at controlling pathogens at mucosal surfaces and infectious diseases in general are summarized in Figure 13.1. These include primarily vaccination and the use of antimicrobial chemotherapy, particularly antibiotics, which have both had an enormous impact on infectious disease (Cohen, 2000). Passive immunization has been used less with the advent of vaccines and antibiotics but is of increasing importance for treatment of immunocornpromised patients (Hammarstrom, 1999) whilst the development and use of topical microbicides is regarded as a potentially important means of preventing infection with HIV (Lange et al., 1993). Pathogens at mucosa( sites, however, present particular problems for these measures, e.g. antibiotics can be very effective in clearing systemic infections while being unable to affect mucosal carriage of the pathogen. A limited number of vaccines induce protective mucosal responses and vaccines are not yet available for several microorganisms that infect rnucos al surfaces. These observations, together with concern over the spread of antibiotic resistance (Hawkey, 1998; Irvin and Bautista, 1999), have stimulated investigation of additional antimicrobial strategies as well as refinement of existing approaches.
宿主与病原体之间的相互作用大多发生在宿主粘膜表面。许多病原体,如人类免疫缺陷病毒(HIV),通过粘膜进入,而其他病原体,包括念珠菌、变形链球菌和幽门螺杆菌,必须在粘膜上建立,才能对宿主造成损害。图13.1概述了控制粘膜表面病原体和感染性疾病的总体策略。这些措施主要包括接种疫苗和使用抗微生物化学疗法,特别是抗生素,这两种方法都对传染病产生了巨大影响(Cohen, 2000年)。随着疫苗和抗生素的出现,被动免疫的使用越来越少,但对于治疗免疫能力低下的患者越来越重要(Hammarstrom, 1999年),而局部杀微生物剂的开发和使用被认为是预防艾滋病毒感染的潜在重要手段(Lange等人,1993年)。然而,粘膜部位的病原体对这些措施提出了特殊的问题,例如,抗生素可以非常有效地清除全身感染,但不能影响病原体的粘膜携带。有限数量的疫苗可诱导保护性粘膜反应,目前还没有针对感染所有表面的几种微生物的疫苗。这些观察结果,加上对抗生素耐药性蔓延的担忧(Hawkey, 1998;Irvin和Bautista, 1999)刺激了对其他抗菌策略的研究以及对现有方法的改进。
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引用次数: 7
Kinetic Analysis for Analyte-Receptor Binding and Dissociation in Biosensor Applications: a Fractal Analysis 生物传感器应用中分析物-受体结合和解离的动力学分析:分形分析
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648007
A. Sadana
To acquire an understanding of biological processes at the molecular level requires two basic approaches: structural and functional analysis. Under ideal conditions these should complement each other and provide a complete picture of the molecular processes. Electron microscopy, sequence analysis, mass spectroscopy, X-ray and electron diffraction studies are routinely employed as structural techniques. These provide information about the atomic organization of individual as well as interacting biomolecules, but these have the disadvantage of being static and ’frozen’ in time. Functional investigation techniques like affinity chromatography, immunological techniques, and spectrophotometric techniques give valuable information on the conditions and the specificity of the interaction, but are (a) unable to follow a process in time, or (b) are too slow to be rendered suitable for most biospecific interactions. Moreover, these techniques demand some kind of labelling of interactants which is undesirable as it may interfere with the interaction and this will necessitate purification of the interactants in large quantities. A promising area in the investigation of biomolecular interactions is the development of biosensors. These biosensors are finding application in the areas of biotechnology, physics, chemistry, medicine, aviation, oceanography, and environmental control. These sensors or biosensors may be utilized to monitor the analyte—receptor reactions in real time (Myszka et al., 1997), besides some techniques like the surface plasmon resonance (SPR) biosensor do not require radiolabelling or biochemical tagging (Jonsson et al., 1991), are reusable, have a flexible experimental
要了解分子水平上的生物过程,需要两种基本方法:结构分析和功能分析。在理想的条件下,这些应该相互补充,并提供分子过程的完整图像。电子显微镜,序列分析,质谱,x射线和电子衍射研究通常被用作结构技术。它们提供了关于个体原子组织以及相互作用的生物分子的信息,但它们具有静态和“冻结”时间的缺点。功能调查技术,如亲和层析、免疫学技术和分光光度法技术,提供了有关相互作用条件和特异性的有价值的信息,但(a)无法及时跟踪过程,或(b)太慢,无法适用于大多数生物特异性相互作用。此外,这些技术要求对相互作用进行某种标记,这是不希望的,因为它可能干扰相互作用,这将需要大量纯化相互作用。生物传感器是研究生物分子相互作用的一个有前途的领域。这些生物传感器正在生物技术、物理、化学、医学、航空、海洋学和环境控制等领域得到应用。这些传感器或生物传感器可用于实时监测分析物-受体反应(Myszka等人,1997年),除了一些技术,如表面等离子体共振(SPR)生物传感器不需要放射性标记或生化标记(Jonsson等人,1991年),是可重复使用的,具有灵活的实验
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引用次数: 2
Regulation of Muscle Glycogen Phospfaorylase by Physiological Effectors 肌糖原磷酸化酶的生理效应调控
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648016
N. Chebotareva, S. V. Klinov, B. Kurganov
The enzyme from rabbit skeletal muscle contains 842 amino acid residues and the essential cofactor pyridoxa1-5’-phosphate is linked through its aldehyde group to the &amino group of Lys680. The polypeptide chain can be divided in two domains, both of them having an-sheet core surrounded by a-helices. The main oligomeric form of the enzyme is a dimer. The interactions between identical subunits are relatively few in dephosphorylated form of the enzyme (phosphorylase b). The main contacts involve the cap (residues 36 to 45) and the tower (residues 260 to 276) of symmetryrelated subunits. X-ray crystallographic studies reveal four ligand-binding sites: catalytic site, allosteric effector site, glycogen storage site, and nucleoside inhibitor site (Figure 11.1). The catalytic site is buried in the centre of the subunit where the domains come together. Access to this site is achieved through a narrow channel which is some 1.2 nm long. The access is restricted mostly by the 280s loop (residues 282 to 286). The residues from the 280s loop are displaced upon transition to catalytically active state following motion of the symmetry-related towers. The allosteric effector site is located near the subunit interface and is separated by a distance of 3.2 nm from the catalytic site. The glycogen storage site is 3.0 nm apart from the catalytic site and at a distance of 4.0 urn from the allosteric effector site. The
兔骨骼肌酶含有842个氨基酸残基,其必需辅因子pyridoxa1-5′-磷酸通过其醛基与Lys680的&氨基相连。多肽链可以分为两个结构域,它们都有一个被a-螺旋包围的片核。酶的主要低聚形式是二聚体。在去磷酸化形式的酶(磷酸化酶b)中,相同亚基之间的相互作用相对较少。主要接触涉及对称相关亚基的帽(残基36至45)和塔(残基260至276)。x射线晶体学研究揭示了四个配体结合位点:催化位点、变构效应位点、糖原储存位点和核苷抑制剂位点(图11.1)。催化位点埋在亚基的中心,这些区域聚集在一起。通过一条约1.2纳米长的窄通道进入该站点。访问主要受280s环(残基282 ~ 286)的限制。280s环的残基在对称塔运动后转变为催化活性态时发生位移。变构效应位点位于亚基界面附近,与催化位点相距3.2 nm。糖原储存位点距离催化位点3.0 nm,距离变容效应位点4.0 nm。的
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引用次数: 16
Bioconjugation for Enzyme Technology 酶技术的生物偶联
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648015
O. Kwon, Yoshihiro Ito
Enzymes play important roles in all living cells. They possess remarkable catalytic properties in terms of high catalytic activity, exclusion of undesirable side-reactions such as racemization, and operations under mild conditions. The most specific features of enzyme function are the high substrate specificity including regioselectivity and stereospecificity. As a consequence, enzymes have been used in various industrial and medical fields. Bioconjugation has expanded the possibility of application of enzymes towards bioreactor catalyst, bioreactor sensor and medical drug technologies. Immobilization of enzymes onto solid matrices has enabled the recyclization of enzymes: immobilization of enzymes onto sensing devices including electrodes and optodes has also provided the basis for biochemical sensors. Bioconjugation of medical enzymes extracted from animals with an amphiphilic polymer, polyethylene glycol, has been shown to reduce the immuno-reaction induced by the application of sensor or therapeutic enzymes into the human body. Various bioconjugations of biological molecules are very important in the biomedical fields (Aslam and Dent, 1998). Bioconjugation is divided into two categories in the present review. One is geneengineered bioconjugation, and the other chemically engineered bioconjugation (Figure 10.1). Gene-engineered modification has been used for the alteration of enzymatic activity, such as thermal stabilization (Bryan et al., 1986), alteration of
酶在所有活细胞中起着重要的作用。它们具有催化活性高、不发生外消旋等不良副反应以及在温和条件下操作等显著的催化性能。酶功能最具体的特点是高底物特异性,包括区域选择性和立体特异性。因此,酶已被用于各种工业和医疗领域。生物偶联扩大了酶在生物反应器催化剂、生物反应器传感器和医疗药物技术方面应用的可能性。将酶固定在固体基质上可以实现酶的再循环;将酶固定在传感设备上,包括电极和光电器件,也为生化传感器提供了基础。从动物中提取的医用酶与两亲性聚合物聚乙二醇的生物偶联,已被证明可以减少应用于人体的传感器或治疗酶引起的免疫反应。生物分子的各种生物偶联在生物医学领域非常重要(Aslam和Dent, 1998)。本文将生物偶联分为两类。一种是基因工程生物偶联,另一种是化学工程生物偶联(图10.1)。基因工程修饰已被用于改变酶的活性,如热稳定(Bryan et al., 1986)
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引用次数: 7
Expression of Insulin in Yeast: The Importance of Molecular Adaptation for Secretion and Conversion 胰岛素在酵母中的表达:分子适应对分泌和转化的重要性
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648010
Thomas Kjeldsen, P. Balschmidt, I. Diers, M. Hach, N. Kaarsholm, S. Ludvigsen
The globular, two...chain and 51 amino acid residue peptide-hormone insulin is produced and secreted by the ~-cellsof the pancreatic islets of Langerhans. Insulin is synthesized as preproinsnlin (110 amino acids). The pre-peptide (signal peptide) is removed upon entrance into the endoplasmic reticulum. Proinsulin folds in the endoplasmic reticulum, is transported to the Goigi apparatus and subsequently processed into the mature insulin molecule that is stored in well-defined storage vesicles (Figure 5.1) (Steiner etaI., 1967, 1986; Dodsonand Steiner, 1998). Proinsulin and insulin have self-assembling properties that play an important role in processing and storage in the J3-cell's secretory pathway and both associate to dimers and in the presence of zinc these further assemble into hexamers (Dodson and Steiner, 1998). In the late Golgi apparatus proinsulin is targeted to acidifying secretory granules and conversion ofproinsulin to insulin occurs by removal of the C-peptide by cleavage at dibasic processing sites by the endoproteases PC3 (or PCl) and pe2 (mammalian
球状的,两个…胰岛素链和51个氨基酸残基肽激素是由朗格汉斯胰岛~-细胞产生和分泌的。胰岛素以原胰岛素(110个氨基酸)的形式合成。前肽(信号肽)在进入内质网时被去除。胰岛素原在内质网中折叠,被运输到Goigi装置,随后加工成成熟的胰岛素分子,储存在明确的储存囊泡中(图5.1)(Steiner等)。1967年,1986年;Dodsonand Steiner, 1998)。胰岛素原和胰岛素具有自组装特性,在j3细胞分泌通路的加工和储存中发挥重要作用,两者都与二聚体相关,在锌存在时,二聚体进一步组装成六聚体(Dodson和Steiner, 1998)。在晚期高尔基体中,胰岛素原以酸化分泌颗粒为目标,通过内源性蛋白酶PC3(或PCl)和pe2(哺乳动物)在二碱性加工位点切割去除c肽,胰岛素原转化为胰岛素
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引用次数: 27
Gene Structures and Catalytic Mechanisms of Microbial Enzymes Able to Blodegrade the Synthetic Solid Polymers Nylon and Polyester Polyurethaoe 微生物酶溶胀降解合成固体聚合物尼龙和聚酯聚氨酯的基因结构和催化机理
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648011
N. Nomura, T. Deguchi, Y. Shigeno-Akutsu, T. Nakajima-Kambe, T. Nakahara
Since the middle of the 20th century, the chemical industry has generated various synthetic compounds as both industrial products and wastes material by-products. Among these synthetic compounds the water-insoluble solid polymers (with the exception of polymers synthesized specifically as biodegradable polymers, such as polylactic acid) are generally the most resistant to microbial attack, an attack which is essentially by enzyme action. An enzyme that is able to catalyze the degradation of a solid polymer must be able to access and bind to the polymer at a specific site, and to catalyze the degradation reaction extracellularly. In general, water-insoluble synthetic polymers are hydrophobic, rigid, and have a small specific surface area as compared to naturally occurring water-insoluble polymers such as cellulose. These properties make the degradation of the water-insoluble synthetic solid polymer difficult. However it has been reported that several water-insoluble synthetic solid polymers are vulnerable to microbial attack. In particular, the characteristics of the genetic sequences and catalytic mechanisms of the microbial enzymes which are able to degrade nylon and polyester polyurethane have been well studied, and this is what we will consider in this review.
自20世纪中叶以来,化学工业产生了各种合成化合物,这些化合物既是工业产品,也是废料副产品。在这些合成化合物中,不溶于水的固体聚合物(专门合成为生物可降解聚合物的聚合物除外,如聚乳酸)通常最能抵抗微生物的攻击,这种攻击主要是由酶的作用引起的。一种能够催化固体聚合物降解的酶必须能够在特定的位点接近并与聚合物结合,并在细胞外催化降解反应。一般来说,不溶于水的合成聚合物是疏水性的,刚性的,并且与天然存在的不溶于水的聚合物(如纤维素)相比,具有较小的比表面积。这些性质使得不溶于水的合成固体聚合物难以降解。然而,据报道,一些不溶于水的合成固体聚合物很容易受到微生物的攻击。特别是降解尼龙和聚酯聚氨酯的微生物酶的基因序列特征和催化机理已经得到了很好的研究,这是我们将在本综述中考虑的问题。
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引用次数: 26
Pyrolysis in Biotechnology 生物技术中的热解
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648006
I. Drevin, B. Johansson, Erika Lars Son
Pyrolysis is the thermal decomposition of molecules in an inert atmosphere. The transfer of thennal energy to a polymeric network or to macromolecules causes degradation of the sample into volatile products. The reaction products are characteristic ofthe original structure and much more easily analysed than the original sample. A significant advantage of the pyrolysis technique is the speed of the analysis~ Complex materials that normally require time consuming analysis can be investigated by this technique coupled to gas chromatography (Py-GC) in less than an hour or with it coupled directly to a mass spectrometer (Py-MS) in a couple of minutes. e.G. Williams' article from 1862 is considered to be the first of its kind in the field of pyrolysis. That study identified isoprene as the main pyrolytic product of robber. However, broad use of analytical pyrolysis has had to wait for the development of modern analytical technology. Today, pyrolysis is widely used to study macro.. molecules, including synthetic and natural polymers (see for example Wampler, 1989), to perform degradation and kinetic studies and also for the qualitative and quantitative analysis of complex substances. Examples of material analysed by pyrolysis are synthetic polymers (for a review, see Blazs6, 1997), coating materials (Haken, 1999), rubber (Dubey et aI., 1995), paper and paper coating, plant material (Ralph and Hatfield, 1991) and bacteria. Pyrolysis is also used in forensic science, art and archaeology (Shedrinsky et aI., 1989). This present review focuses on the analytical pyrolysis of biological macromolecules such as proteins, DNA and microorganisms. The first part of the article presents an overview of the pyrolysis techniques available and the methods for analysis of the pyrolytic products, the pyrolysate. The second part presents some applications to illustrate the types ofproblem that researchers have been able to solve using pyrolysis.
热解是分子在惰性气氛中的热分解。将能量转移到聚合物网络或大分子导致样品降解为挥发性产物。反应产物具有原始结构的特点,比原始样品更容易分析。热解技术的一个显著优点是分析速度快~通常需要耗时分析的复杂材料可以在不到一个小时的时间内与气相色谱(Py-GC)耦合,或者在几分钟内直接与质谱仪(Py-MS)耦合。威廉斯1862年的文章被认为是热解领域的第一篇同类文章。该研究确定异戊二烯是强盗的主要热解产物。然而,分析热解的广泛应用必须等待现代分析技术的发展。如今,热解被广泛应用于宏观经济的研究。分子,包括合成和天然聚合物(参见Wampler, 1989),进行降解和动力学研究,也用于复杂物质的定性和定量分析。通过热解分析的材料有合成聚合物(回顾,见Blazs6, 1997),涂层材料(Haken, 1999),橡胶(Dubey et aI)。, 1995)、纸张和纸张涂层、植物材料(Ralph and Hatfield, 1991)和细菌。热解也用于法医学、艺术和考古学(Shedrinsky et aI)。, 1989)。本文对蛋白质、DNA和微生物等生物大分子的分析热解技术进行了综述。文章的第一部分概述了现有的热解技术和分析热解产物的方法。第二部分介绍了一些应用,以说明研究人员已经能够使用热解解决的问题类型。
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引用次数: 2
Industrial Purification of Pharmaceutical Antibodies: Development, Operation, and Validation of Chromatography Processes 药物抗体的工业纯化:色谱法的开发、操作和验证
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648017
R. Fahrner, H. Knudsen, Carol D. Basey, Walter Galan, Dian Feuerhelm, M. Vanderlaan, G. Blank
Recombinant monoclonal antibodies are becoming a great success for the biotechnology industry. They are currently being studied in many clinical trials for treating a variety of diseases, and recently several have been approved for treating cancer (Carter et al., 1992; Anderson et al., 1996; Baselga et al~, 1996; Bodey et al., 1996; Longo~ 1996). Although there are several types of antibodies produced in different types ofcel1lines, the most clinically significant antibodies are full-length humanized IgG. produced in CHO cells. This review describes the methods used to purify these antibodies at industrial scale, focusing on chromatography processes~ and with particular reference to recent work at Genentech. Routine laboratory purification ofantibodies has been well described (for example see Scott et aL, 1987), but the considerations for large-scale production of pharmaceutical-grade antibodies are much different than those for laboratory scale. There are extreme purity requirements for pharmaceutical antibodies~ and routine large-scale production requires high yield and process reliability. To gain regulatory approval, the process must be completely validated to run consistently within specified limits, so the process should be designed to facilitate validation, Large-scale production of antibodies as pharmaceutical products is a complex
重组单克隆抗体正在成为生物技术产业的巨大成功。目前正在许多临床试验中研究它们,以治疗各种疾病,最近有几种已被批准用于治疗癌症(Carter et al., 1992;Anderson et al., 1996;Baselga等人,1996;Bodey et al., 1996;Longo ~ 1996)。虽然在不同类型的细胞系中产生了几种抗体,但临床上最重要的抗体是全长人源化IgG。在CHO细胞中产生本文综述了用于工业规模纯化这些抗体的方法,重点介绍了色谱法,并特别提到了Genentech公司最近的工作。抗体的常规实验室纯化已经得到了很好的描述(例如,参见Scott等人,1987),但大规模生产药物级抗体的考虑因素与实验室规模的考虑因素大不相同。药物抗体有极高的纯度要求,常规大规模生产需要高收率和工艺可靠性。为了获得监管部门的批准,该工艺必须经过完全验证,以在规定的限度内持续运行,因此该工艺应设计为便于验证。抗体作为药品的大规模生产是一个复杂的过程
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引用次数: 235
Tumour-Selective Salmonella-Based Cancer Therapy 肿瘤选择性沙门氏菌癌症治疗
Pub Date : 2001-07-01 DOI: 10.1080/02648725.2001.10648014
D. Bermudes, K. Low, J. Pawelek, M. Feng, M. Belcourt, Li-mou Zheng, I. King
Cancer therapies fail for several primary reasons; lack ofdrug effect on the cancerous tissue~ lack of selectivity for the cancerous tissue, andlor inadequate delivery to the target tissue. Drug effect and selectivity can be improved by increased understanding of molecular and cellular differences between cancer and normal tissues, thus enabling the design of drugs that potently affect cancer-specific molecular targets associated with malignant behaviour. Another approach is to improve the selective delivery ofanti-cancer agents to tumours. One approach is to use carriers that bind to cancer...specific targets, such as antibodies (Hall, 1995). However, most targeting approaches, even if selective, tend not to deliver sufficiently high concentrations of the agent to the tumour to induce significant therapeutic effects. Recent findings suggest that the pathogenic bacterium Sallnonella, when genetically modified, can be used to selectively deliver therapeutic agents to solid tumours at high concentrations (Pawelek et ai., 1997; Low et ai., 1999a). These attenuated bacteria are administered either systemically or locally, whereupon they typically replicate 1000 times greater in the tumour than in other tissue. The basis for preferential colonization and accumulation of Salmonella in tumours appears to include some of the same characteristics of tumours that provide resistance to drug and immune-based therapies (Bermudes et aI., 2000a,b). Why tumours are susceptible to Sabnonella is not well understood and probably includes a variety of factors. Poor penetration of components of the immune system, including antibodies, complement, CD8+ T-cells, granulocytes and macrophages
癌症治疗失败有几个主要原因;对癌变组织缺乏药物作用~对癌变组织缺乏选择性,或对靶组织递送不足。通过加深对癌症和正常组织之间的分子和细胞差异的了解,可以提高药物的效果和选择性,从而能够设计出有效影响与恶性行为相关的癌症特异性分子靶点的药物。另一种方法是提高抗癌药物对肿瘤的选择性递送。一种方法是使用与癌症结合的载体……特定目标,如抗体(Hall, 1995)。然而,大多数靶向方法,即使是选择性的,也往往不能向肿瘤提供足够高浓度的药物来诱导显著的治疗效果。最近的研究结果表明,经过基因改造的致病菌小沙门氏菌可用于选择性地向实体肿瘤输送高浓度的治疗剂(Pawelek et ai)。, 1997;Low et ai。, 1999)。这些减毒细菌被全身或局部施用,因此它们在肿瘤中的复制通常比在其他组织中多1000倍。沙门氏菌在肿瘤中优先定植和积累的基础似乎包括肿瘤对药物和免疫疗法产生耐药性的一些相同特征(Bermudes等)。, 2000 a, b)。肿瘤对Sabnonella敏感的原因尚不清楚,可能包括多种因素。免疫系统的组成部分,包括抗体、补体、CD8+ t细胞、粒细胞和巨噬细胞渗透性差
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引用次数: 19
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