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Mycobacteria-Derived Agents for the Treatment of Urological and Renal Cancers 分枝杆菌衍生药物治疗泌尿和肾癌
Pub Date : 2017-12-20 DOI: 10.5772/INTECHOPEN.69659
Estela Noguera-Ortega, E. Julián
Mycobacteria are the unique group of bacteria that are currently used in antitumoral immunotherapy. Specifically, intravesical instillation of viable cells of Mycobacterium bovis Bacillus Calmette-Guérin (BCG), after transurethral resection of non-muscle invasive bladder cancer, is the most efficacious treatment for avoiding recurrence and progression of the disease. BCG has been used for the last 35 years for bladder cancer treatment, but other mycobacteria or mycobacteria components are currently under pre- clinical and clinical studies for the immunotherapeutic treatment of non-invasive bladder cancer and also of other types of tumors located at the urinary system. Those are, for instance, cell wall extracts or heat-killed forms from BCG or other mycobacteria such as Mycobacterium phlei or Mycobacterium indicus pranii (MIP) or even viable cells from non-pathogenic mycobacteria such us Mycobacterium brumae . A review of the literature in which mycobacteria components, non-viable mycobacteria, and viable mycobacteria have been used for these different cancers will be performed. In this chapter, the func-tion of mycobacteria as antitumor agents will be then analyzed, awarding the audience a broad knowledge of one of the beneficial applications of mycobacteria, which are usually introduced as dangerous microorganisms. bacterial cell wall components are responsible for the antitumor effect but other fractions also triggered the production of Th1 cytokines and stimulated the cytotoxic activity against T24 BC cells by peripheral blood cells. Antigens from different cell fractions are recognized by surface-located receptors present in antigen-presenting cells.
分枝杆菌是目前用于抗肿瘤免疫治疗的独特细菌群。具体而言,经尿道非肌肉浸润性膀胱癌切除术后,膀胱内灌注牛分枝杆菌卡介苗活细胞是避免疾病复发和进展的最有效治疗方法。在过去的35年里,卡介苗一直用于膀胱癌的治疗,但其他分枝杆菌或分枝杆菌成分目前正在临床前和临床研究中,用于非侵袭性膀胱癌和其他类型的泌尿系统肿瘤的免疫治疗。例如,这些是来自卡介苗或其他分枝杆菌(如细菌性分枝杆菌或indicus pranii分枝杆菌(MIP))的细胞壁提取物或热杀灭形式,甚至是来自非致病性分枝杆菌(如布鲁氏分枝杆菌)的活细胞。将对分枝杆菌成分、非活分枝杆菌和活分枝杆菌用于这些不同癌症的文献进行回顾。在本章中,将分析分枝杆菌作为抗肿瘤剂的功能,使读者对分枝杆菌的有益应用有一个广泛的了解,分枝杆菌通常被介绍为危险的微生物。细菌细胞壁成分负责抗肿瘤作用,但其他部分也触发Th1细胞因子的产生,并刺激外周血细胞对T24 BC细胞的细胞毒活性。来自不同细胞组分的抗原被存在于抗原呈递细胞中的表面受体识别。
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引用次数: 5
Drug Resistance in Mycobacterium tuberculosis 结核分枝杆菌的耐药性
Pub Date : 2017-12-20 DOI: 10.5772/INTECHOPEN.69656
K. Peñuelas-Urquides, F. Castorena-Torres, B. Silva-Ramírez, Mario Bermúdez de León
Tuberculosis (TB) remains to be a serious health problem worldwide. There is an increased transmission of Mycobacterium tuberculosis strains with drug resistance, hence complicat‐ ing TB control. The deciphering of the M. tuberculosis genome, together with the imple‐ mentation of new molecular biology tools, has allowed the identification of changes in nucleic acid sequences with a functional impact. These mutations have become important in the design of early‐diagnostic kits to identify the resistance profile of M. tuberculosis . Since the conventional methods to determine the identity of M. tuberculosis strains based in cultures are laborious, time‐consuming and performed by specialized technicians, the result is generated until 4 months after receiving the samples. During this time, patients with TB are not adequately treated, and resistant strains may be transmitted to the rest of the population. In this chapter, we describe the most relevant mutations in genes associ‐ ated with drug resistance in M. tuberculosis , the analysis of gene expression to identify new markers of drug resistance strains, and the development of new antituberculosis drugs against drug‐resistant strains.
结核病仍然是世界范围内一个严重的健康问题。耐药结核分枝杆菌菌株的传播有所增加,从而使结核控制复杂化。结核分枝杆菌基因组的破译,加上新的分子生物学工具的简单实施,使得鉴定具有功能影响的核酸序列的变化成为可能。这些突变已成为设计早期诊断试剂盒以确定结核分枝杆菌耐药谱的重要因素。由于在培养物中确定结核分枝杆菌菌株身份的传统方法费力、耗时且需由专业技术人员执行,因此直到收到样品后4个月才能得出结果。在此期间,结核病患者没有得到充分治疗,耐药菌株可能会传播给其他人群。在本章中,我们描述了与结核分枝杆菌耐药相关的基因中最相关的突变,基因表达分析以鉴定耐药菌株的新标记,以及针对耐药菌株的新抗结核药物的开发。
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引用次数: 179
Virulence Factors and Pathogenicity of Mycobacterium 分枝杆菌的毒力因子和致病性
Pub Date : 2017-12-20 DOI: 10.5772/INTECHOPEN.72027
G. Echeverría-Valencia, S. Flores-Villalva, C. Espitia
Virulence, is referred as the ability of a pathogen to cause disease, and for mycobacteria it depends on their ability to reside within host cells and evade the microbicidal mechanisms of macrophages. The outcome of tuberculosis (TB) infection is highly variable and it seems that the closest relationship between the Mycobacterium genre and humans has shaped the mycobacterial genome to encode bacterial factors that reflects a highly evolved and coordinated program of immune evasion strategies that interfere with both innate and adaptive immunity causing disease even in fully immunocompetent host. Although Mycobacterium tuberculosis (MTB) does not have classical virulence factors, it has described many virulence-associated genes and virulence lifestyle genes from Mycobacterium tuberculosis complex (MTBC). In this chapter, we describe the most important gene/molecule involved in the host defense modulation response, also the plethora of strategies to evade immune mechanisms of macrophage. We review the main genes whose inactivation in the mycobacterial genome leads to a measurable loss in virulence in the different validated TB models.
毒力是指病原体引起疾病的能力,对于分枝杆菌来说,它取决于它们在宿主细胞内生存和逃避巨噬细胞杀微生物机制的能力。结核(TB)感染的结果是高度可变的,分枝杆菌类型与人类之间最密切的关系似乎塑造了分枝杆菌基因组来编码细菌因子,这些细菌因子反映了高度进化和协调的免疫逃避策略程序,即使在完全免疫能力的宿主中也会干扰先天和适应性免疫导致疾病。虽然结核分枝杆菌(MTB)没有经典的毒力因子,但它已经描述了许多来自结核分枝杆菌复合体(MTBC)的毒力相关基因和毒力生活方式基因。在本章中,我们描述了参与宿主防御调节反应的最重要的基因/分子,以及逃避巨噬细胞免疫机制的过多策略。我们回顾了分枝杆菌基因组中失活导致不同验证结核模型中可测量的毒力损失的主要基因。
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引用次数: 16
The Existence of Mycobacterium tuberculosis in Microenvironment of Bone 骨微环境中结核分枝杆菌的存在
Pub Date : 2017-12-20 DOI: 10.5772/INTECHOPEN.69394
R. Jabir, Andriansjah Rukmana, Ifran Saleh, T. Kurniawati
Mycobacterium tuberculosis is an obligate aerobe bacteria requiring oxygen in its metabolism. In normal condition, bones have pH of 6.9–7.4 and temperature of 37°C. With the composition mentioned, bones fall in the group of tissue with less rich oxygen (<35%) which theoretically means, M. tuberculosis is hard to grow in the bone environment. Bone microliving environment is formed by the cells constructing the bone itself and the active cells which periodically interact with the bone cells. Activation of these cells gives impact to the temperature, pH, gas concentration, and liquid concentration, and at the same time triggers calcium, phosphor, and other minerals to be deposited in the bone. In the process of new bone formation, the osteoblast cells produce matrix and release them to the microenvironment that needs a high concentration of calcium and phosphor. The survival of M. tuberculosis in the microenvironment of bone is reflected in interaction of the bacteria and the non-immune cells, the bacteria and the organic environment, and the bacteria and the inorganic environment. In addition, the immune system also threatens the survival of M. tuberculosis. The results of these interactions will affect the lives of bacteria and has an impact on the bone microenvironment.
结核分枝杆菌是一种专性需氧细菌,在其代谢过程中需要氧气。正常情况下,骨骼的pH值为6.9-7.4,温度为37°C。根据上述成分,骨骼属于含氧量较低的组织组(<35%),理论上意味着结核分枝杆菌很难在骨骼环境中生长。骨微生活环境是由构成骨自身的细胞和与骨细胞周期性相互作用的活性细胞形成的。这些细胞的激活会对温度、pH值、气体浓度和液体浓度产生影响,同时触发钙、磷和其他矿物质沉积在骨骼中。在新骨形成过程中,成骨细胞产生基质并释放到需要高浓度钙和磷的微环境中。结核分枝杆菌在骨微环境中的生存表现为细菌与非免疫细胞、细菌与有机环境、细菌与无机环境的相互作用。此外,免疫系统也威胁到结核分枝杆菌的生存。这些相互作用的结果将影响细菌的生命,并对骨微环境产生影响。
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引用次数: 5
Unique Biochemical Features of the Cytokinetic Protein FtsZ of Mycobacteria 分枝杆菌胞动力学蛋白FtsZ的独特生化特征
Pub Date : 2017-12-20 DOI: 10.5772/INTECHOPEN.70540
Prabuddha L. Gupta, Atul Pradhan, P. Ajitkumar
FtsZ, the bacterial cytokinetic protein, a structural homologue of mammalian β-tubulin, is present in bacteria of diverse genera, including mycobacteria. The FtsZ protein of Mycobacterium tuberculosis ( M . tuberculosis FtsZ), the causative agent of tuberculosis, is the most studied among the mycobacterial FtsZ proteins as it is a potential anti-tuberculosis drug target. M . tuberculosis FtsZ possesses many unique biochemical features, which include slow polymerisation kinetics, presence of charged amino acids in the C-terminal domain that interacts with a variety of other cell division proteins, and the presence of specific amino acids at unique locations that makes it distinct from the FtsZ of other mycobacterial species and of other bacterial genera. On the other hand, although the FtsZ of Mycobacterium leprae ( M . leprae FtsZ), the causative agent of leprosy, shows high level of conservation with M . tuberculosis FtsZ, it has biochemical properties that are very differ- ent from those of M . tuberculosis FtsZ due to the difference in specific amino acid residues at critical locations on the protein. The present review focuses on these structural features of M . tuberculosis FtsZ and M . leprae FtsZ, as studied by others and by us, in comparison to those of the FtsZ of other mycobacterial species and of other bacterial genera.
FtsZ是细菌细胞动力学蛋白,是哺乳动物β-微管蛋白的结构同源物,存在于包括分枝杆菌在内的多种属的细菌中。结核分枝杆菌(M。结核分枝杆菌FtsZ蛋白是结核的致病菌,是目前研究最多的分枝杆菌FtsZ蛋白,是潜在的抗结核药物靶点。M。结核分枝杆菌FtsZ具有许多独特的生化特征,包括缓慢的聚合动力学,在c端区域存在带电氨基酸,与多种其他细胞分裂蛋白相互作用,以及在独特位置存在特定氨基酸,使其与其他分枝杆菌种类和其他细菌属的FtsZ不同。另一方面,虽然麻风分枝杆菌(M。麻风病病原麻风菌(leprae FtsZ)与M。结核菌FtsZ的生化特性与M。结核FtsZ是由于在蛋白质的关键位置的特定氨基酸残基的差异。本文就M的这些结构特征作一综述。结核病保税区和M。与其他分枝杆菌和其他细菌属的FtsZ相比,我们和其他人研究了麻风杆菌FtsZ。
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引用次数: 1
Diagnosis of Tuberculosis among Children and Adolescents 儿童和青少年结核病的诊断
Pub Date : 2017-12-20 DOI: 10.5772/INTECHOPEN.69227
C. Sant’Anna, M. March, R. Aurilio
The authors discuss the challenging aspects of the diagnosis of tuberculosis in children and adolescents, since there is no gold standard for its diagnosis. The different clinical and radiological presentations and the low bacteriological positivity of tuberculosis in childhood are grounds for confrontation to the present. Immunological tests called inter‐ feron gamma release assays (IGRAs) failed to overcome the tuberculin skin test in prac‐ tice. Advances with nucleic acid amplification tests, on the other hand, have contributed to the diagnosis of tuberculosis among adolescents. Standardized systems for diagnosis can be useful as tools for screening or for decision‐making in childhood tuberculosis.
作者讨论了儿童和青少年结核病诊断的挑战性方面,因为它的诊断没有金标准。不同的临床和放射表现和低细菌学阳性肺结核在儿童是对抗到现在的理由。在实践中,称为干扰素γ释放试验(IGRAs)的免疫试验不能克服结核菌素皮肤试验。另一方面,核酸扩增试验的进步促进了青少年结核病的诊断。标准化诊断系统可作为儿童结核病筛查或决策的有用工具。
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引用次数: 4
Application of Integrated Translational Research as Leprosy Problem Solution in Indonesia 综合转化研究在印尼麻风问题解决中的应用
Pub Date : 2017-12-20 DOI: 10.5772/67967
C. Prakoeswa
In Indonesia, leprosy remains a health problem because its elimination has not achieved. This shows the high Mycobacterium leprae transmission as a result of difficulties in the early detection, termination of the transmission chain, and management evaluation. Integrated translational research has been carried out as a solution for the problem. Dissemination of the various results of the research is conducted by the educational aspects tiered with a variety of learning methods including a textbook based on research findings, scientific papers at various scientific meetings, and published journals, as well as aspects of com ‐ munity service through electronic media, newspapers, and management and counseling with leprosy patients and their contact person, especially in endemic pockets area.
在印度尼西亚,麻风病仍然是一个健康问题,因为它尚未消除。这表明麻风分枝杆菌的高传播是由于在早期发现、终止传播链和管理评价方面存在困难。为解决这一问题,开展了综合转化研究。各种研究成果的传播是由教育方面进行的,采用各种学习方法,包括基于研究成果的教科书、各种科学会议上的科学论文和出版的期刊,以及通过电子媒体、报纸和对麻风病患者及其接触者的管理和咨询,特别是在流行地区的社区服务方面。
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Mycobacterium - Research and Development
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