Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant

There is increasing evidence showing the involvement of CD4(+) T cells in initiating and maintaining antitumor immune responses. NY-ESO-1 is expressed by various tumors but not normal tissues except testis. We conducted a cancer clinical trial by using full-length NY-ESO-1 protein formulated with ISCOMATRIX adjuvant and injected into patients intramuscularly. Autologous dendritic cells pulsed with NY-ESO-1 ISCOMATRIX in combination with overlapping synthetic peptides were used to identify immunodominant T cells from a vaccinated patient. We show here the identification and characterization of two novel CD4(+) T cell epitopes. T cells specific to these epitopes not only recognized autologous dendritic cells loaded with NY-ESO-1 but also NY-ESO-1-expressing tumor cell lines treated with IFN-gamma. One of the two responses identified was greater than the previously identified immunodominant HLA-DP4-restricted response and correlated with NY-ESO-1-specific CD8(+) T cell induction after vaccination. This T cell response was vaccinated in most patients who expressed HLA-DR2. This study has systematically surveyed patients vaccinated with full-length tumor antigen for a vaccinated CD4 helper T cell response.     

Autophagy is involved in oral rAAV/Aβ vaccine-induced Aβ clearance in APP/PS1 transgenic mice

The imbalance between β-amyloid(Aβ) generation and clearance plays a fundamental role in the pathogenesis of Alzheimer 's disease(AD). The sporadic form of AD is characterized by an overall impairment in Aβ clearance. Immunotherapy targeting Aβ clearance is believed to be a promising approach and is under active clinical investigation. Autophagy is a conserved pathway for degrading abnormal protein aggregates and is crucial for Aβ clearance. We previously reported that oral vaccination with a recombinant AAV/Aβ vaccine increased the clearance of Aβ from the brain and improved cognitive ability in AD animal models, while the underlying mechanisms were not well understood. In this study, we first demonstrated that oral vaccination with rAAV/Aβ decreased the p62 level and up-regulated the LC3BII/LC3B-I ratio in APP/PS1 mouse brain, suggesting enhanced autophagy. Further, inhibition of the Akt/m TOR pathway may account for autophagy enhancement. We also found increased anti-Aβ antibodies in the sera of APP/PS1 mice with oralvaccination, accompanied by elevation of complement factors C1 q and C3 levels in the brain. Our results indicate that autophagy is closely involved in oral vaccination-induced Aβ clearance, and modulating the autophagy pathway may be an important strategy for AD prevention and intervention.     

Addition of adjuvant tamoxifen to cyclophosphamide,methotrexate and 5-fluorouracil for premenopausal women with oestrogen receptor-positive breast cancer

OBJECTIVE: To study the value of adjuvant tamoxifen (TAM) in premenopausal women with oestrogen receptor (ER)-positive breast cancer who received adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) polychemotherapy. METHODS: Four hundred and two premenopausal ER-positive breast cancer patients who received CMF chemotherapy between January 1990 and December 1999 were retrospectively studied. Disease-free survival (DFS) and overall survival (OS) were used to evaluate the clinical value of TAM therapy. The relationships between nodal status and TAM were also analysed. RESULTS: After a mean of 41 months of follow-up, 43 (13.7%) patients died of breast cancer and 68 (19.9%) patients suffered recurrence. There was a significant difference between TAM and non-TAM treatment groups for DFS (p=0.0058), but no significant difference for OS. For node-negative patients, there was no significant difference between the TAM and non-TAM treatment groups for either DFS or OS. For node-positive patients, the difference between TAM and non-TAM treatment groups was significant for both DFS and OS (p=0.0497 and p=0.0285, respectively). CONCLUSION: TAM resulted in additional benefit to premenopausal patients with node-positive ER-positive breast cancer who received the CMF polychemotherapy regimen.     

应用MTT比色法评价新生小牛血清对培养细胞生长的影响

体外培养细胞成功与否常取决于所选用血清质量,不同批号的血清往往有个体差异,质量不尽一样,细胞长势差别很大,所以在培养细胞之前必须对使用的血清进行质量鉴定。血清质量鉴定方法有定性法、定量法、放射性核苷酸掺入法和MTT比色法,而细胞计数法、克隆形成率测定法和H-TdR掺人法存在操作复杂和放射性污染等缺点。自1983年Mosmann建立MTT比色法以来,经不断改良完善,已成为细胞生物学及相关研究领域一种分析细胞活性、生长增殖等常用方法。基于MTT比色法能定量检测细胞的增殖与生长,本室在细胞培养中应用MTT比色法检测300头新生小牛血清(未饮过初乳)支持细胞生长能力。     

两定点连续缝合技术在后腹腔镜离断式肾盂成形术中的应用

目的比较后腹腔镜离断式肾盂成形术中"两定点连续缝合技术"和"间断缝合技术"的临床应用。方法回顾性分析2011年1月至2014年2月后腹腔镜离断式肾盂成形术107例。根据肾盂输尿管吻合方法分为"两定点连续缝合技术"组27例(A组),"间断缝合技术"组80例(B组)。对总手术时间、肾盂缩窄时间、肾盂输尿管吻合时间、术后住院时间、引流管拔除时间及漏尿等并发症进行比较。结果 A组手术无中转开放;B组2例中转开放。A组和B组总手术时间平均分别为167.7及191.4min(P=0.003);肾盂输尿管吻合时间平均为20.1及41.5min(P0.001);两组肾盂缩窄时间、术后引流管放置时间、术后住院天数比较差异无统计学意义。其中A组围手术期无漏尿病例,B组围手术期漏尿4例。术后3月复查B超提示A组肾积水消失16例,肾积水不同程度减轻11例;B组肾积水消失54例,肾积水不同程度减轻24例。结论后腹腔镜离断式肾盂成形术中采取"两定点连续缝合技术",可以降低输尿管吻合难度、缩短手术时间、减少术后漏尿发生率。     

Prediction of different stages of rectal cancer: Texture analysis based on diffusion-weighted images and apparent diffusion coefficient maps

BACKGROUND It is evident that an accurate evaluation of T and N stage rectal cancer is essential for treatment planning. It has not been extensively investigated whether texture features derived from diffusion-weighted imaging(DWI) images and apparent diffusion coefficient(ADC) maps are associated with the extent of local invasion(pathological stage T1-2 vs T3-4) and nodal involvement(pathological stage N0 vs N1-2) in rectal cancer.AIM To predict different stages of rectal cancer using texture analysis based on DWI images and ADC maps.METHODS One hundred and fifteen patients with pathologically proven rectal cancer, who underwent preoperative magnetic resonance imaging, including DWI, were enrolled, retrospectively. The ADC measurements(ADC_(mean), ADC_(min), ADC_(max)) as well as texture features, including the gray level co-occurrence matrix parameters, the gray level run-length matrix parameters and wavelet parameters were calculated based on DWI(b = 0 and b = 1000) images and the ADC maps.Independent sample t-tests or Mann-Whitney U tests were used for statistical analysis. Multivariate logistic regression analysis was conducted to establish the models. The predictive performance was validated by receiver operating characteristic curve analysis.RESULTS Dissimilarity, sum average, information correlation and run-length nonuniformity from DWI_(b=0) images, gray level nonuniformity, run percentage and run-length nonuniformity from DWI_(b=1000) images, and dissimilarity and run percentage from ADC maps were found to be independent predictors of local invasion(stage T3-4). The area under the operating characteristic curve of the model reached 0.793 with a sensitivity of 78.57% and a specificity of 74.19%. Sum average, gray level nonuniformity and the horizontal components of symlet transform(SymletH) from DWI_(b=0) images, sum average, information correlation,long run low gray level emphasis and SymletH from DWI_(b=1000) images, and ADC_(max), ADC_(mean) and information correlation from ADC maps were identified as independent predictors of nodal involvement. The area under the operating characteristic curve of the model reached 0.802 with a sensitivity of 80.77% and a specificity of 68.25%.,CONCLUSION Texture features extracted from DWI images and ADC maps are useful clues for predicting pathological T and N stages in rectal cancer.