大鼠胰腺癌微环境诱导未成熟树突状细胞功能的变化

Objective To study the effect of pancreatic cancer microenvironment on maturation of dendritic cells ( DCs), and to investigate the mechanism by which tumors escape from immune recognition. Methods DCs were cultured with rmGM (40μg/L) ,rmIL-4 (40μg/L) ,and the supernatant of cell line AR42J cells was added on the day 6, then a large number of DCs was gained. DCs cultured and in-duced by routine methods were used as controls. The expression of surface molecules CD86, and CD80 in DCs was detected to observe whether this intervention could delay or block maturation of DCs and this effect could be reversed by stimulation with lipopolysaccharide (LPS). T cell stimulatory effects were also determined. Results Compared to normal DCs, CD86 and CD80 expression positive rate was significantly decreased in DCs induced by AR42J supernatant from (70.88±3.60)% to (7.15±0.71 )%. After stimulation with LPS, the expression of CD86, and CD80 in DCs was still low, suggesting the AR42J super-natant could block the maturation of DCs. The allostimulatory capacity of the immature DCs stimulated with the AR42J superoatant was significantly lower than that of the normal immature DCs. Conclusion The supernatant from pancreatic cancer ceils in rats could inhibit the maturation of DCs, which was not easily reversed.     

Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263-272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation in four patients carrying HLA-B27. In three of these patients the mutation occurred late, coinciding with disease progression. In another it occurred within 1 yr of infection and was associated with a virus of syncytium-inducing phenotype. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. After the loss of the cytotoxic T lymphocyte (CTL) response to this epitope and in the presence of high viral load, reversion to wild-type sequence was observed. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. Phylogenetic analyses indicated that these substitutions emerged under natural selection rather than by genetic drift or linkage. Outgrowth of CTL escape viruses required high viral loads and additional, possibly compensatory, mutations in the gag protein.     

抗Fas锤头状核酶阻抑小鼠急性粒-单核白血病细胞免疫逃逸的研究

为了研究抗Fas锤头状核酶对T细胞Fas表达及其凋亡的影响和探讨增强供者淋巴细胞输注时移植物抗白血病（GVL）效应的新策略，构建可有效切割Fas mRNA的锤头状核酶真核质粒，用电穿孔法将其导入小鼠CTL细胞株CTLL-2之后，借助RT—PCR和Western blot检测其Fas的表达，同时检测转染前后其胱冬酶-3（Caspase-3）活性和凋亡（Annexin V—FITC法）的改变，并用MTT法检测空白对照组、空载体转染组及pU6-RZ596转染组CTLL-2细胞的增殖情况和体外杀伤小鼠急性粒-单核白血病细胞（WEHI-3）的活性。结果表明：构建的U6嵌合型锤头状核酶RZ596在细胞内能有效切割Fas，明显降低小鼠活化CTLL-2的Fas水平，与高表达Fas配体的WEHI-3孵育后，其存活率和体外杀伤WEHI-3活性明显高于对照组。结论：抗Fas核酶能显著降低小鼠活化CTLL-2的Fas表达，使其免于WEHI-3的膜Fas配体经Fas途径所致的凋亡，并提高CTL对小鼠急性粒-单核白血病细胞的杀伤力，从而阻抑小鼠急性粒-单核白血病细胞的免疫逃逸。     

The evolving landscape of N6-methyladenosine modification in the tumor microenvironment

1. Download : Download high-res image (125KB)
2. Download : Download full-size image

     

Expression of calreticulin is associated with infiltration of T-cells in stage ⅢB colon cancer

AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage ⅢB colon cancer. METHODS: Sixty-eight pathologically-confirmed speci-mens were obtained from stage ⅢB (T3N1M0) colon cancer patients who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University, Guangzhou, China. Immuno-histochemical analysis was performed to show infiltration of lymphocytes and expression of calreticulin in colon cancer. Associa...     

Expression of calreticulin is associated with infiltration of T-cells in stage IIIB colon cancer

AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage IIIB colon cancer.METHODS: Sixty-eight pathologically-confirmed specimens were obtained from stage IIIB (T3N1M0) colon cancer patients who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University, Guangzhou, China. Immunohistochemical analysis was performed to show infiltration of lymphocytes and expression of calreticulin in colon cancer. Association between calreticulin expression, infiltration of lymphocytes, and 5-year survival rate of patients was assessed.RESULTS: The expression level of calreticulin was lower in cancer nest than in its adjacent normal epithelium since 61.8% (42/68) of the samples were stained with calreticulin in colon cancer. The expression of calreticulin in colon cancer was associated with the infiltration of CD45RO+ cells rather than with that of CD3+ cells. In addition, the stronger expression of calreticulin and the higher infiltration of CD3+ and CD45RO+ cells in colon cancer were associated with the higher 5-year survival rate of patients.CONCLUSION: Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.     

加速性房性或房室交接区逸搏心律动态心电图心率分析

目的探讨加速性房性或房室交接区逸搏心律的24h动态心电图变化特征。方法选取加速性房性或房室交接区逸搏心律患者53例．采用24h动态心电图分别测定和比较窦性最快和最慢心率、加速性房性或房室交接区逸搏心律的最快和最慢心率。结果窦性心律的心率变化范围（57．92±7．58）～（125．85±25．87）次／min．明显大于房性或房室交接区心律的心率变化范围（59．82±9．13）～（88．42±17．36）次／min,两者最快心率比较差异有显著统计学意义（P〈0．01）,最慢心率比较差异无统计学意义（P〉0．05）。结论窦性心律和房性或房室交接区心律的重叠部分基本为前者心律的最低至后者心律的最高心率。节律转换时的心率相近,易出现竞争心律或房性融合波,房性或房室交接区性心率在一定时间内节律相对较稳定。     

高危型HPV感染与宫颈癌组织中IDO表达的相关性研究

目的探讨吲哚胺2,3-二氧酶（IDO）在宫颈癌发生发展中的作用及其与高危型人乳头状瘤病毒（HR—HPV）感染之间的关系。方法我院经宫颈活检病理确诊为CINⅢ和宫颈浸润癌患者43例,同时期因子宫肌瘤行全子宫切除宫颈正常患者30例作为对照。采用第2代杂交捕获法（HC-2）HR-HPVDNA检测高危型HPV DNA,免疫组化染色方法检测IDO的表达。结果IDO和HR—HPV阳性率在宫颈原位癌和浸润癌组均显著高于正常宫颈组（P〈0．01）。HR—HPV感染与IDO表达呈正相关（rs=0．759,P〈0．01）。结论在HR—HPV感染的CINⅢ和宫颈浸润癌中,IDO出现过表达,可能与肿瘤免疫逃逸有关。IDO可能成为宫颈癌预后的预测因子及治疗靶点。     

56例胸腰椎骨折的临床效果分析

目的：探讨56例胸腰椎骨折的临床治疗效果。方法：采用回顾性分析的方法,分析本院收治的56例胸腰椎骨折患者临床资料,依据治疗方式不同分为观察组和对照组。结果：观察组手术时间、术中出血量、术后引流量、住院时间均明显低于对照组,观察组伤椎平均高度、Cobb角度均明显优于对照组,观察组术后疼痛缓解总有效率明显高于对照组,P〈0.05,差异均有统计学意义。结论：经后路器械固定间接减压治疗胸腰椎骨折临床效果良好,值得临床推广应用。     

肿瘤来源的外体及其在肿瘤中的作用

外体（exosome）是由细胞内多泡体（multivesicular body,MVB）与细胞膜融合而释放到细胞外的纳米大小的膜性小囊泡,具有一定的免疫调节功能。造血细胞以及非造血细胞都可以分泌外体。肿瘤来源的外体（tumor-derived exosome,TEX）存在于肿瘤细胞培养上清液、肿瘤患者血浆或者恶性渗出液中,包含天然的肿瘤相关抗原,并能将其呈递给T细胞,可有效地促进细胞毒T淋巴细胞（cytotoxic T lymphocyte ,CTL）的活化,产生抗瘤免疫。近年来,也有文献报道外体可诱导免疫耐受,甚至产生免疫抑制作用而使得肿瘤逃逸宿主免疫系统对它的免疫监视,并能促进肿瘤细胞的增殖。这些功能的不一致与外体的表型密切相关。