穴位注射卡介菌多糖核酸治疗支气管哮喘疗效观察

目的:观察卡介菌多糖核酸不同给药途径对支气管哮喘疗效的差异。方法:将60例支气管哮喘患者随机分为穴位注射组30例和肌肉注射组30例。穴位注射组将卡介菌多糖核酸注射液于双侧肺俞穴处行穴位注射,前15d每日1次,双侧肺俞穴各注射1mL,15d以后隔日注射1次,连续用药3个月;肌肉注射组将卡介菌多糖核酸注射液2mL注射于一侧臀部,给药时间同穴位注射组。比较治疗后两组肺功能及免疫球蛋白情况及停药3个月后两组症状、体征积分及哮喘控制测试(ACT)得分。结果:两组治疗后肺功能、IgE、IgG、症状体征积分、ACT得分均较治疗前改善(P0.01),但穴位注射组的改善作用优于肌肉注射组(P0.01,0.05),停药3个月后穴位注射组症状体征积分、ACT得分仍优于肌肉注射组(P0.01)。结论:穴位注射较肌肉注射卡介菌多糖核酸能更快速、持久控制患者症状、体征,能更显著改善肺功能、降低IgE,是治疗支气管哮喘的有效方案。     

Expression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) in human urinary bladder transitional cell carcinoma

The objective of this study was to evaluate the expression pattern of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) and its clinical significance in human bladder cancer (BC).     

Recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells

Interleukin 7 (IL-7) has an important function in the development and maintenance of IL-17A+ γδ T cells. We here constructed a recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing antigen 85B (Ag85B)-IL-7 fusion protein (rBCG-Ag85B-IL-7). The Ag85B-IL-7 fusion protein and IL-7 were detected in the bacterial lysate of rBCG-Ag85B-IL-7. rBCG-Ag85B-IL-7 was the same in number as control rBCG expressing Ag85B (rBCG-Ag85B) in the lung at the early stage after intravenous inoculation, whereas the numbers of IL-17A+ γδ T cells and Ag-specific Th1 cells were significantly higher in the lungs of mice inoculated with rBCG-Ag85B-IL-7 than those inoculated with rBCG-Ag85B. The Ag-specific Th1 cell response was impaired in mice lacking IL-17A+ γδ T cells after inoculation with rBCG-Ag85B-IL-7. Thus, rBCG-Ag85B-IL-7 increases the pool size of IL-17A+ γδ T cells, which subsequently augment the Th1 response to mycobacterial infection.     

Evaluating the need for transurethral bladder biopsy at first follow up after intravesical BCG therapy for superficial bladder cancer: Preliminary data

IntroductionPatients with high-risk superficial transitional cell carcinoma (TCC) of the bladder have a lifelong risk of progression and require particular attention. Intravesical Bacillus Calmette-Guerin (BCG) is recommended as a first-choice adjuvant treatment to reduce the risk of progression of high-grade tumors and carcinoma in situ (CIS).ObjectivesTo evaluate the need for routine transurethral bladder biopsy from the site of previously resected tumor three months following intravesical BCG therapy, even if the urine cytology and cystoscopy were both negative.Subjects and methodsA prospective study was carried out on 45 patients of both genders presenting with superficial bladder cancer. All patients received a six-week course of intravesical BCG. The mean age of the patients was 59 (range 33–80) years. Three months following resection, urine cytology was negative in all patients. Cystoscopy was then performed and although it was negative for any suspicious lesions, a routine biopsy from the previous resection site was taken.ResultsThe indication for BCG instillation was T1G1 in 20 patients (44%), T1G2 in 12 patients (27%) and TaG2 in eight patients (18%). Three patients (7%) had a positive bladder biopsy for malignancy at follow-up despite the negative cystoscopy and cytology. There were no statistically significant differences between patients with positive and those with negative biopsies with regard to the stage and grade of the tumor before resection or the number of resected lesions. The original pathology of the three positive patients was T1G1 (two patients) and T1G2 (one patient). The pathology after BCG treatment was the same as before instillation, T1G1 (two patients) and T1G2 (one patient).ConclusionUntil more studies on larger numbers of patients are done, a routine biopsy from the site of previously resected tumor at the time of check cystoscopy may improve the detection of tumor recurrence.     

MicroRNA expression profiling of PPD-B stimulated PBMC from M. bovis-challenged unvaccinated and BCG vaccinated cattle

There is an urgent need to identify additional diagnostic biomarkers for bovine TB to complement existing read-out systems such as interferon-gamma and for predictive markers of vaccine efficacy to accelerate vaccine development. To evaluate the potential of miRNAs as such biomarkers, we have analysed their expression in bovine PPD stimulated PBMC isolated from unvaccinated and BCG vaccinated cattle before and following Mycobacterium bovis (M. bovis) infection. Using a bovine microRNA microarray, miR-155 was found to show a significant up-regulation in expression in early (week 2) and late (week 11) M. bovis post-infection samples from unvaccinated cattle, while in BCG vaccinated cattle up-regulation was observed only in late post-infection samples. No differential expression of miR-155 was observed in pre-infection samples from unvaccinated and vaccinated cattle. These observations suggest that miR-155 could be exploited as a marker distinguishing vaccinated from infected animals (DIVA). Analysis by TaqMan RT-PCR, verified the up-regulation of miR-155 in unvaccinated cattle post-infection. Significant correlation was found between the degree of pathology and miR-155 induction in the experimentally infected cattle, suggesting miR-155 is a biomarker of disease development and/or severity. Induction of miR155 expression in cattle sourced from farms with confirmed bTB that tested positive in the tuberculin skin or interferon-gamma blood test was found to be significantly higher in cattle presenting with more advanced pathology (defined by the presence of visible TB lesions) compared to infected cattle without visible pathology and thus likely to be of lower infectivity than those with more advanced disease. In conclusion, our data indicate that miR-155 has potential both as a diagnostic and prognostic biomarker that could be used to identify animals with advanced pathology and as a DIVA test read-out. Its role in the immune biology of bovine TB will also be discussed.     

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