分枝杆菌细胞壁成分的免疫学活性

本世纪六十年代Mathe等倡导BCG免疫治疗人癌,取得了成效。但临床治疗需要反复注射较大剂量,因此副反应很重,有时造成BCG感染扩散、潜在结核病复发以及过敏反应,偶可引起死亡。由于重复使用BCG治疗不够安     

重组卡介苗

卡介苗（BCG）已成为可同时表达多种病原体重组抗原的新疫苗载体。本文概述了重组BCG研究进展，分别介绍了抗病毒、 细菌、寄生虫病重组BCG的构建和在动物中的免疫应答，分泌细胞因子的重组BCG用于抗肿瘤免疫治疗，重组的BCG也可发展为抗分枝杆菌感染的新疫苗,并提出了今后研究方向。     

BCG与细胞因子在膀胱肿瘤中联合应用的基础与临床研究进展

膀胱癌是我国目前泌尿系统最常见的恶性肿瘤 ,据统计大约75 %病例为浅表性膀胱癌 ,其中95 %为高危浅表性肿瘤。高危浅表性肿瘤术后若不给予药物治疗 ,其近期复发率为60 %～90 %。预防膀胱肿瘤术后复发、治疗残余瘤及原位癌是当前临床亟待解决的问题。BCG(BacillusCalmette -Guerin)是一种生物免疫调节剂。膀胱腔内灌注BCG在预防肿瘤复发、治疗残存肿瘤和原位癌等方面已经取得了较满意的临床疗效 ,但仍有30 %～45 %患者对BCG灌注治疗无效 ,此外 ,BCG灌注所致膀胱局部和全身的毒副作用使临床应用受到一定的限制。因此 ,开始研究BCG与…     

减毒活菌卡介苗对哮喘TLR4表达的影响

目的观察减毒活菌卡介苗（BCG）对哮喘小鼠肺组织TLR4表达的影响,以探讨BCG对哮喘治疗的可能作用机制。方法昆明小鼠建立哮喘模型并多次BCG接种,Western Blotting检测肺组织TLR4的表达。结果 BCG干预组小鼠TLR4基因表达量与空白对照组以及哮喘发病组相比增强。结论卡介苗对哮喘的治疗作用可能与肺组织TLR4上调有关。     

生物免疫调节剂在浅表性膀胱肿瘤治疗中的应用

目的：观察卡介苗（BCG）和干扰素（IFN）治疗浅表性膀胱肿瘤的临床疗效。方法随机选取2010年6月～2011年6月诊治的78例浅表性膀胱肿瘤患者,随机分为对照组和研究组各39例,对照组给予膀胱内灌注卡介苗（BCG）治疗,研究组给予干扰素（IFN）联合卡介苗（BCG）进行治疗,记录并分析两组相关数据和情况。结果治疗后,研究组的复发率和症状改善情况明显优于对照组,比较差异均有统计学意义（P＜0.05）。结论应用干扰素（IFN）联合卡介苗（BCG）治疗浅表性膀胱肿瘤效果更加显著,值得临床推广。     

卡介苗性淋巴结核10例报道及分析

目的探讨卡介苗(BCG)接种后异常淋巴结反应的原因及处理方法。方法回顾2006年收集的10例患儿BCG接种后出现异常淋巴结反应,淋巴结病理诊断均为结核病。9名患儿接种BCG 3~7个月后无结核中毒症状,生长发育正常;另一名患儿接种6个月后,诊断为全身广泛性的播散症。结果10例患儿在全身抗结核的同时给以局部治疗。结论提高BCG接种的质量和最大限度减少并及时处理BCG接种后异常反应,是BCG接种工作中值得关注的重要问题。     

卡介苗治疗原发性肾炎的临床观察和实验研究

我们以灭活卡介苗(BCG)联合其他药物治疗肾病型的原发性肾小球肾炎(PGN),60例(大部对激素不敏感)中完全和基本缓解者分别为32和16例。对病理类型和临床表现相仿者,BCG 组疗效远胜于对照组。随访1～2年以上的15例中,13例完全缓解。对24例 PGN 病人单核细胞吞噬功能检查的结果表明,PGN 组明显低于正常对照组,经 BCG 接种3周后可使之恢复正常。对家兔改良的慢性血清病肾炎(呈系膜增殖性)模型接种 BCG 的结果显示,BCG 组肾小球炎症明显轻于对照组。以上结果提示 BCG 接种有助于 PGN 的治疗。     

艾灸联合西药治疗多发性跖疣的疗效观察

目的观察艾灸联合西药治疗多发性跖疣的疗效及安全性。方法 106例患者随机分为治疗组53例和对照组53例。两组均使用卡介菌(Bacillus Calmette-Guerin,BCG)多糖核酸注射液(以下简称BCG注射液)和左旋咪唑片。治疗组采用温和灸法,对照组外贴鸡眼膏。疗程8周。观察两组治疗前后皮损变化及不良反应情况。据此进行意向性治疗分析。结果治疗组有效率83.02%,对照组58.49%,差异有统计学意义(P<0.05)。结论艾灸联合BCG注射液、左旋咪唑治疗多发性跖疣有效、安全、简便、可行。     

人 IL-2与 HBsAg融合基因重组卡介苗的构建与鉴定

目的:构建人 IL-2与 HBsAg融合基因并转化到BCG中构建重组BCG(recombinant BCG,rBCG),为制备治疗和预防乙型肝炎和结核病的二联疫苗奠定基础。 方法:以IL-2 pMalLP质粒和HBsAg pMalLP质粒为模板,设计引物,利用PCR技术扩增 ...     

BCG治疗膀胱肿瘤有效率接近80%

美国国立癌症研究所的研究人员说,对动物皮肤黑素瘤模型皮内注射卡介苗(BCG)在肿瘤治疗中是一个显著进展。目前开始用BCG作膀胱内输注治疗复发性表浅膀胱肿瘤和原位膀胱癌。美国波士顿大学的泌尿科副教授Babayan说“BCG的效力大于我们使用的任何药物,保护作用似可持续到疗程结束后至少2年”。迄今,Babayan治疗了100多例患者,并公布了其中77例患者的治疗情况——其     

Leukocytes and cytokines in the urine of superficial bladder cancer patients after intravesical immunotherapy with bacillus Calmette-Guerin.

The urine of superficial bladder cancer patients treated intravesically with BCG was examined for the presence of leukocytes and cytokines. The number of leukocytes was markedly increased 24h and 48h after five or more BCG instillations. Flow cytofluorometric analysis revealed that, in addition to large numbers of granulocytes, monocytes/macrophages and T-lymphocytes were clearly detectable. The T cells were predominantly CD4+ and probably activated, since they expressed IL2 receptors and HLA-DR. The cytokines IL1, IL2, IL6 and TNF alpha were also increased after BCG instillations. These cytokines and leukocytes may play a role in the antitumor activity of BCG.     

Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 Murine Bladder Tumor cells

Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.     

Oxidative stress of red blood cells during Bacillus Calmette-Guerin intravesical instillations

Although Bacillus Calmette-Guerin (BCG) intravesical instillation is widely accepted as a very effective modality in treating bladder carcinoma in situ, and in preventing superficial bladder cancer recurrence, its mechanism of action is not yet fully understood. The antitumor effects of BCG are mostly related to local immunological events but a systemic activation of the immune system cannot be excluded. The objective of the present study was to estimate the systemic production of oxidants during intravesical BCG treatment. Systemic production of oxidants was estimated by assessing the red blood cells (RBC) oxidative stress in twelve patients undergoing BCG immunotherapy for bladder carcinoma in situ. RBC oxidative stress induced by peroxynitrite was determined by luminol-enhanced chemiluminescence. During the treatment period, the RBC oxidative stress revealed a biphasic curve of changes: after an initial 5-fold increase, it dropped to pretreatment levels following the 4th instillation. Intravesical BCG administration induced systemic production of oxygen free radicals that may reflect a systemic activation of the immune system.     

Study of recombinant human IFN-α-2b bacilli Calmette-Guerin activated killer cells and against bladder cancer cell in vitro

Presently, one of the most potent immunotherapies is the application of bacillus Calmette Guerin (BCG) to prevent recurrences of the superficial bladder cancer. Despite its successful use, nonresponders and certain side effects remain a major obstacle. Therefore, current studies aim at developing recombinant BCG (rBCG) strains secreting Th1-like cytokines to improve the effectiveness of the therapy. In this study, a new type of rBCG strain constructed by Tianjin institute of Urology was tested for its immunostimulatory capacity in vitro. Peripheral blood monocytes (PBMC) were stimulated by recombinant BCG and transformed into bacilli Calmette-Guerin activated killer (BAK) cells, and the effect of anticancer BAK cells was studied. Recombinant IFN-α-2b-BCG, wild-type BCG (wBCG), wild-type BCG and IFN-α-2b were coincubated with PBMCs respectively in vitro, and the proliferation of PBMC was detected with MTT in different time. BAK cells have the ability to kill bladder tumor cells, and the antitumor activity of effecter cells was determined by LDH release assay. The result of MTT showed that the proliferation of PBMC in the recombinant BCG group was more powerful than in the other two groups (P < 0.05). The result of LDH release assay showed that the antitumor activity of BAK cells stimulated by Recombinant BCG was the highest in all groups. We conclude that the recombinant BCG can activate more PBMCs to anti-bladder cancer in vitro than wild-type BCG does. __________ Translated from Tianjin Medical Journal, 2007, 35(1): 1–3 [译自: 天津医药]     

非肌层浸润性膀胱癌的免疫治疗

膀胱癌是泌尿生殖系统常见的恶性肿瘤,中、高危非肌层浸润性膀胱癌的标准治疗方式为单纯经尿道膀胱肿瘤切除术＋膀胱灌注治疗。在众多膀胱灌注药物中,BCG膀胱灌注以其明显的抗肿瘤疗效得到广泛使用。但部分高危患者即使进行了BCG标准灌注治疗,仍会发生膀胱癌复发和/或进展,且后续可供选择的治疗方式很少。近几年随着肿瘤免疫学研究的进展,新型免疫治疗药物的开发为膀胱癌的治疗带来了重大突破。此文对非肌层浸润性膀胱癌TURBT术后BCG等免疫调节剂膀胱灌注及其失败后的免疫治疗方法进行综述。     

卡介苗DNA抗肿瘤免疫的实验研究

目的探讨卡介苗DNA抗肿瘤免疫的效果及其免疫机制。方法纯化提取卡介苗菌DNA,建立荷瘤裸鼠模型,将24只荷瘤裸鼠随机分为3组,每组8只。于接种A549细胞株后第15d,分别腹腔注射TES液、BCG液、DNA液各0-3ml,隔2d1次,共8次。结果DNA、BCG可抑制肿瘤生长,DNA增强NK／Mφ杀伤活性,提高荷瘤裸鼠血清IFN—γ和TNF—α水平。结论DNA与卡介苗都具有抗肿瘤免疫效果,DNA比卡介苗抗肿瘤效果更强。     

Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is used for the treatment of bladder cancer. The recruitment of neutrophlis to the bladder after BCG instillation exerts anti-tumor activity against bladder tumor. We have recently demonstrated that interleukin (IL)-17A produced by γδ T cells played a role in the recruitment of neutrophlis to the bladder after BCG instillation. IL-15 is known to play an important role in neutrophil migration during inflammation. We previously constructed a recombinant BCG strain expressing the fusion protein of IL-15 and Ag85B (BCG-IL-15) for prevention of Mycobacterium tuberculosis infection. Here we compared the efficacy of the BCG-IL-15 in protection against bladder cancer with that of rBCG-Ag85B (BCG).Six-week-old female C57BL/6 mice were inoculated with MB49 bladder tumor cells in the bladder and subsequently intravesically inoculated with BCG or BCG-IL-15.BCG-IL-15 treatment significantly prolonged survival of mice inoculated with bladder cancer cells compared with BCG treatment. Infiltration of neutrophils was significantly elevated in BCGB-IL-15 treated mice accompanied by increased chemokines (MIP-2 and MIP-1α) in the bladder. Thus, BCG-IL-15 exerted additive effect on Infiltration of neutrophils in the bladder. BCG-IL-15 may be a promising drug for non-muscle invasive bladder cancer.     

吡柔比星及卡介苗膀胱灌注预防膀胱癌术后复发的临床观察

目的评价吡柔比星(THP)膀胱灌注及卡介苗(BCG)膀胱灌注预防膀胱癌术后复发的效果.方法患者随机分成两组,一组患者膀胱灌注THP(52例),另一组膀胱灌注卡介苗(47例),各组均灌注6～48个月,期间观察复发情况及不良反应.结果THP膀胱灌注组复发率为11.5%,无全身不良反应例子;卡介苗膀胱灌注组复发率为21.2%,68.1%患者出现膀胱刺激症状,两组比较THP组略好于.结论THP及卡介苗均是有效的预防膀胱癌术后复发的药物,THP膀胱灌注操作简单,全身不良反应小,是一种安全有效的膀胱局部化疗药物.     

α-干扰素＋丝裂霉素C膀胱灌注预防膀胱癌术后复发的疗效观察

目的分析浅表性膀胱癌患者行经尿道膀胱肿瘤电切术（TURBT）后分别采用α-干扰素＋丝裂霉素C和卡介苗进行膀胱灌注预防肿瘤复发的疗效。方法将64例浅表性膀胱癌术后患者随机分为观察组34例和对照组30例。观察组采用α-干扰素＋丝裂霉素C治疗,对照组给予卡介苗作膀胱灌注,观察其不同疗效。结果所有病例随访12～24个月,平均18个月。观察组复发率为11.76%低于对照组的16.67%,差异有统计学意义（P〈0.05）,且不良反应小。结论α-干扰素＋丝裂霉素C疗效优于卡介苗,且不良反应小,耐受性好,可以作为临床一线用药。     

基因重组卡介苗高效电转化条件的实验研究

目的探讨卡介苗(BCG)电转化中影响转化效率的因素。方法利用电转化仪将穿梭质粒pYL-hB7-2转入BCG中,考察其影响因素并优化转化条件。转化子利用卡那霉素抗性筛选和聚合酶链反应(PCR)及酶链免疫吸附试验(ELISA)鉴定。结果重组BCG获得较高的转化效率,最高可达8/9。外加电场强度和质粒浓度是决定电转化效率的关键因素,感受态细胞的状态,如生长期和冰浴时间均可影响转化效率。结论成功解决了基因重组BCG构建过程中电转化的问题。