MDR-selective microbial-based therapy: A novel approach to cancer treatment

Microbial-based therapy of cancer is one of the earliest non-surgical anticancer therapies. The main limitation of such therapies is the toxicity of the therapeutic dose. This article discusses a novel approach that exploits cancer multidrug resistance (MDR) to provide a safer microbial-based therapy. As multidrug resistant cells can only contain limited amounts of a variety of susceptible drugs including certain antibiotics, we can take advantage of MDR to create a micro-environment (antibiotic free) that favors growth of intracellular bacteria within cancer cells. Thus, this approach targets cancer cells and spares normal cells (shielded by antibiotic): providing a more selective thus safer anticancer treatment. This article also explores the potentials of Chlamydia pneumoniae as an anti-cancer agent in this MDR-selective microbial-based therapy: its unique life cycle and the immune response to its infection suggest that it could be used directly, in the proposed approach, without any pre-requirements.     

Comparison between bacillus Calmette-Guérin and the A60 mycobacterial antigen complex used as cancer-preventive immunotherapies

Preparations of live or lysates ofMycobacterium bovis strain Calmette-Guérin (BCG) have long been used as treatments for a variety of cancer types, especially those involving the urinary tract, with varying success. This study was conducted to compare the antitumoral activity of BCG and the thermostable macromolecular antigen complex of BCG (A60) when used as preventive treatments, in conjunction with or without tumor antigens, against growth and dissemination of the EMT6 murine tumor cell line. It was demonstrated that tumor antigens alone did not significantly alter the oncological indexes, although a slight increase in both T lymphocyte and macrophage activations was found. It was further demonstrated that A60 induces a protective activity up to 40% greater than that of live BCG and that this protection was not accompanied by any of the adverse effects sometimes observed during BCG immunotherapy.Abbreviations BCGMycobacterium bovis strain Calmette-Guérin - A60 the thermostable macromolecular antigen complex ofM. bovis BCG - EMT6 murine transplantable mammary adenocarcinoma - ELISA enzyme-linked immunosorbent assay     

Ag85b-卡介苗重组疫苗的构建及鉴定

目的构建结核分枝杆菌Ag85b-卡介苗重组疫苗,研究其免疫原性及抗结核作用,以期获得结核病预防性和治疗性疫苗。方法通过基因工程重组技术将结核分枝杆菌保护性抗原Ag85b的编码基因与穿梭质粒载体pYUB295重组,通过电穿孔技术导入卡介苗中,应用PCR扩增、PAGE电泳鉴定重组卡介苗。结果通过PCR扩增获得Ag85b基因,与穿梭表达载体pYUB295重组后,通过PCR扩增、限制性内切酶酶切、DNA测序鉴定表明成功地构建了Ag85b基因pYU295重组质粒。将重组质粒通过电穿孔导入卡介苗,重组卡介苗在抗性培养基上生长良好。pYUB295-Ag85b重组卡介苗基因组DNA的PCR扩增以及培养上清液的PAGE电泳表明：Ag85b-卡介苗重组疫苗构建正确,Ag85b蛋白在卡介苗中分泌表达。结论成功构建了Ag85b-卡介苗重组疫苗。     

海珠益肝胶囊对小鼠免疫性肝损伤的影响

目的:进一步证实海珠益肝胶囊对肝损伤小鼠的保肝降酶作用。方法:来用卡介苗 脂多糖(BCG LPS)造成免疫性肝损伤模型小鼠,观察本品对血清中ALT、AST活力单位、肝脾脏器系数和肝脏病理组织学损伤程度的影响。结果:药物能降低血清中ALT、AST活力单位(P<0.01);减小肝脾肿大及脏器系数(P<0.01);减轻肝组织病理损伤程度。结论:海珠益肝胶囊对BCG LPS所致肝损伤小鼠有明显保肝降酶作用。     

荞麦中芦丁对免疫性肝损伤小鼠肝脏超微结构的影响

目的观察荞麦中芦丁(RBFL)对卡介苗(BCG)和脂多糖(LPS)联合诱导的免疫性肝损伤小鼠肝脏的超微结构的影响。方法于尾静脉注射BCG和LPS,建立小鼠免疫性肝损伤模型。取♂昆明小鼠90只,随机均分为正常组、模型组、RBFL低、中、高剂量组及联苯双酯组。除正常组和模型组ig蒸馏水外,其余各组均ig给予对应药物干预,即40、80、160 mg·kg-1·d-1RBFL及联苯双酯200 mg·kg-1·d-1,gd,连续12 d。剖取肝脏、脾脏、胸腺,计算脏器指数,电镜下观察各组小鼠的肝脏超微结构变化。结果模型组小鼠的肝脏体积增大,肝脏指数较正常组的显著增大(P<0.01),各免疫器官脏器的指数增大,RBFL各剂量有抑制作用。结论 RBFL对BCG和LPS联合诱导的小鼠肝脏超微结构损伤具有保护作用。     

卡介菌多糖核酸干预豚鼠急性过敏反应的研究

目的:研究卡介菌多糖核酸对豚鼠急性过敏反应的作用及可能的机制,探讨卡介菌多糖核酸的质量控制效力模型的提高方法。方法:建立牛血清白蛋白诱导豚鼠产生急性过敏反应模型。激发后30 min内观察豚鼠全身反应,并根据致敏性症状评分标准分级。取血用ELISA法测致敏前、攻击前及攻击后豚鼠血清总Ig E和组胺水平。结果:攻击后,模型组和卡介菌多糖核酸低剂量组豚鼠出现不同程度的急性过敏反应症状,而卡介菌中、高剂量组豚鼠急性过敏反应症状明显缓解。模型组在攻击前、后采集的血清总Ig E水平分别为1.637 0±0.158 6,1.683 1±0.228 1μg·ml-1,较正常对照组显著升高(P<0.01),而同时给予卡介菌多糖核酸后,卡介菌高剂量和中剂量处理组在攻击前、后采集的血清总Ig E水平与模型组比较均显著降低(P<0.01)。经牛血清蛋白致敏后,在攻击前后,模型组血清中组胺水平分别为1.499 7±0.133 1,1.512 1±0.050 6μg·ml-1,与阴性对照组相比均显著升高(P<0.01),而同时给予卡介菌多糖核酸后,卡介菌高、中、低各剂量处理组在攻击前、后采集的血清中组胺水平与模型组比较有明显降低(P<0.01)。结论:卡介菌多糖核酸可剂量依赖性抑制牛血清蛋白引起的急性过敏反应。其抗急性过敏反应的可能机制与降低血清总Ig E和组胺水平有关。