PLOD2、VSIG4在结肠癌中的表达及临床意义96例分析

[目的]探讨结肠癌患者癌组织中赖氨酸羟化酶2(PLOD2)、巨噬细胞表达共刺激分子VSIG4表达及意义。[方法]收集经病理确认的Ⅰ～Ⅳ期结肠癌患者，应用免疫组化方法检测癌组织及其癌旁组织中的PLOD2、VSIG4表达，分析两者表达的相关性及与患者临床病理特征的关系。随访并探讨PLOD2、VSIG4表达与患者5年总生存率关系。Kaplan-Meier法绘制生存曲线，应用单因素及多因素Cox回归分析影响患者5年总生存率的因素。[结果]结肠癌癌组织及其癌旁组织中PLOD2表达阳性率分别为68.75%(66/96)、25.00%(24/96)(P<0.05),VSIG4表达阳性率分别为56.25%(54/96)、18.75%(18/96)(P<0.05)。Spearman相关性分析显示，结肠癌癌组织中PLOD2与VSIG4表达呈正相关(r=0.363,P=0.041)。PLOD2表达与肿瘤分化程度、浸润深度、淋巴结转移、TNM分期相关(P<0.05);VSIG4表达与肿瘤浸润深度、淋巴结转移、TNM分期相关(P<0.05)。PLOD2阳性表达者5年总生存率为18.03%...     

VSIG4在乳腺癌中的表达及其与免疫浸润和预后的相关性

目的 分析M2型巨噬细胞在乳腺癌组织中的浸润丰度,探索VSIG4与M2型巨噬细胞的相关性及调控乳腺癌侵袭和迁移的潜在机制。方法 下载TCGA-BRCA的RNA-seq数据,CIBERSORT评估样本的免疫细胞浸润丰度,构建预后风险预测模型。分析M2型巨噬细胞及VSIG4对乳腺癌患者预后的影响,基因集富集分析VSIG4参与的信号通路,并预测其上游调控miRNA。结果 M2型巨噬细胞的浸润丰度与年龄、PR状态、病理分期共同参与构建风险预测模型,模型预测性能较好（AUC=0.816）。M2型巨噬细胞的高浸润（HR=1.35, P<0.05）及VSIG4的高表达（HR=1.4, P=0.039）提示乳腺癌患者预后较差。VSIG4受上游miR-29a-3p调控,与Toll样受体、细胞黏附、细胞因子的生成及释放等通路显著相关。结论 VSIG4与乳腺癌患者预后及M2型巨噬细胞浸润丰度显著相关,受上游miR-29a-3p调控,VSIG4促进乳腺癌细胞的侵袭和迁移,可作为乳腺癌的潜在预后标志物。     

调节性T细胞与妇科恶性肿瘤免疫研究进展

调节性T细胞(regulatory T cell, Treg)是一群具有抑制其他免疫细胞功能的负调控细胞,包括CD4+ Treg、CD8+ Treg、自然杀伤T细胞(natural killer T cell,NKT)和双阴性Treg(double negative Treg,DN Treg)细胞等4大类。Treg细胞在妇科恶性肿瘤免疫抑制及逃逸机制中起重要作用。肿瘤可诱导生成特异性Treg细胞,CD4+ CD25+ T细胞向Treg细胞的转化可能是引起肿瘤微环境中Treg细胞数量增多的原因。本文就CD4+ CD25+ Treg细胞与妇科恶性肿瘤免疫抑制及逃逸之间的关系进行综述。     

恶性肿瘤患者外周血CD4+CD25+调节T细胞的检测及其临床意义

目的探讨恶性肿瘤外周血CD4+CD25+调节T细胞水平的特点及其临床意义.方法采用流式细胞术检测53例恶性肿瘤患者外周血CD4+CD25+调节T细胞水平及淋巴细胞亚群,并进行分层分析.结果外周血淋巴细胞亚群分析显示恶性肿瘤患者CD4、CD16阳性细胞比例在早期(Ⅰ+Ⅱ期)患者即低于对照组,但差异无显著性意义(P＞0.05),CD4/CD8亦低于对照组,差异有显著性意义(P＜0.05);随着疾病进展(Ⅲ、Ⅳ期)CD4、CD4/CD8、CD16阳性细胞比例减低明显,差异有显著性意义(P＜0.05);各期CD8、CD19、CD3与对照组接近(P＞0.05).外周血CD4+CD25+调节T细胞比例健康对照组CD4+CD25+T细胞水平为(14.49±4.69)%,恶性肿瘤53例CD4+CD25+T细胞比例为(19.61±8.17)%,统计学有差异(P＜0.05);进一步分层分析显示随疾病进展外周血CD4+CD25+T细胞水平升高,在肿瘤进展期(Ⅳ期)尤其明显,统计学有极显著差异(P＜0.01).结论恶性肿瘤患者外周血CD4+CD25+调节T细胞水平的升高,与恶性肿瘤免疫功能低下及肿瘤的发生发展密切相关.去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供一种新的方法.     

乌体林斯注射液合并化疗治疗恶性肿瘤的临床研究

 目的　探讨乌体林斯注射液在恶性肿瘤综合治疗中的作用。方法　采用乌体林斯注射液配合化疗与单用化疗对照治疗恶性肿瘤病人 133例 ,并对疗效、1年生存率、生存质量及免疫功能进行评价。结果　治疗组近期有效率及 1年生存率均高于对照组 ,有显著性差异 (P <0 .0 5 ) ;治疗组生活质量的提高也高于对照组 ,有非常显著性差异 (P <0 .0 1) ;治疗组治疗后T细胞亚群及NK细胞活性和免疫球蛋白明显高于治疗前 ,有非常显著或显著性差异 (P <0 .0 1或 0 .0 5 ) ,而对照组治疗后T细胞亚群及NK细胞活性和免疫球蛋白低于治疗前 ,无统计学意义 (P >0 .0 5 )。结论　乌体林斯可通过提高恶性肿瘤患者的细胞免疫和体液免疫功能 ,增强机体对化疗药物的耐受性 ,从而发挥治疗的协同作用 ,达到提高治疗效果和生存质量 ,值得临床进一步推广应用。     

肿瘤患者周围血T淋巴细胞亚群研究进展

本文着重从临床角度,对肿瘤患者周围血T淋巴细胞亚群的研究进展作一综述。 一、T亚群及其功能 应用单克隆抗体,可把T淋巴细胞分为两大亚群,一类表现有T_4表面抗原,即T辅助及诱导细胞亚群(T_h);另一类有T_5、T_8表面抗原,即抑制细胞(T_s)或细胞毒性细胞(T_c)亚群。在人体周围血中,Th占50～60％,T_s占20～30％。T_s能抑制B细胞产生免疫球蛋白及抑制混合淋巴细胞反应(MIC)中自体T     

免疫卡控点抑制剂在肺癌治疗中的研究进展

肺癌是发病率和死亡率增长最快,对人群健康和生命威胁最大的恶性肿瘤之一。尽管近年来化疗、放疗以及分子靶向治疗均取得了不错的进展,但其5年生存率仍无显著提高。免疫卡控点抑制剂作为肿瘤治疗的新方向,以其高效、低毒的特点引起了极大的关注。目前细胞毒性T细胞相关蛋白4、程序性细胞死亡蛋白1／程序性细胞死亡受体1、T细胞免疫球蛋白黏蛋白3等免疫卡控点抑制剂的研究均已在肺癌治疗中有序的展开。本文就其研究现状展开综述。     

晚期恶性肿瘤患者化疗前后T细胞亚群变化的临床分析

目的 探讨恶性肿瘤患者化疗前后T细胞亚群的变化.方法采用流式细胞术分别对26例晚期恶性肿瘤患者化疗前和化疗后外周血T细胞及亚群进行检测.结果晚期恶性肿瘤患者化疗前后CD3+T细胞百分数分别为(71.35+ 16.82)%、(70.49+16.82)%,差异无统计学意义(P＞0.05);CD3+ CD4+比值分别为(31...     

妇科肿瘤免疫治疗的新靶点

虽然作用于程序性细胞死亡蛋白1/程序性死亡配体 1（PD-1/PD-L）和细胞毒性 T淋巴细胞抗原4（CT- LA4）的抗体已成功应用于晚期实体瘤的治疗，但其疗效仍不够高。需寻找新的免疫靶点以便为难治性肿瘤患者寻求替代治疗。根据受体与配体结合后发挥的作用，可将免疫靶点分为共刺激分子和共抑制分子，共抑制分子包括∶T细胞免疫球蛋白黏蛋白-3（TM-3）、含免疫球蛋白及 ITM 结构域的T 细胞免疫受体（TGIT）、淋巴细胞活化基因3（LAG-3）、T细胞激活抑制物免疫球蛋白可变区结构域（VISTA）以及 B7家族的 B7-H3 和 B7-H4;共刺激分子包括 CD27、OX40、4-1BB、CD40，糖皮质激素诱导的肿瘤坏死因子受体（GITR）和诱导共刺激因子（ICOS）等。本文就新兴的免疫靶点在妇科恶性肿瘤的临床前和临床研究进展作一简要阐述。     

妇科肿瘤免疫治疗的新靶点

虽然作用于程序性细胞死亡蛋白1/程序性死亡配体 1（PD-1/PD-L）和细胞毒性 T淋巴细胞抗原4（CT- LA4）的抗体已成功应用于晚期实体瘤的治疗，但其疗效仍不够高。需寻找新的免疫靶点以便为难治性肿瘤患者寻求替代治疗。根据受体与配体结合后发挥的作用，可将免疫靶点分为共刺激分子和共抑制分子，共抑制分子包括∶T细胞免疫球蛋白黏蛋白-3（TM-3）、含免疫球蛋白及 ITM 结构域的T 细胞免疫受体（TGIT）、淋巴细胞活化基因3（LAG-3）、T细胞激活抑制物免疫球蛋白可变区结构域（VISTA）以及 B7家族的 B7-H3 和 B7-H4;共刺激分子包括 CD27、OX40、4-1BB、CD40，糖皮质激素诱导的肿瘤坏死因子受体（GITR）和诱导共刺激因子（ICOS）等。本文就新兴的免疫靶点在妇科恶性肿瘤的临床前和临床研究进展作一简要阐述。     

Characterization of malignant and non-neoplastic cell phenotypes in highly malignant non-Hodgkin lymphomas

Malignant and non-neoplastic cells in 38 cases of highly malignant non-Hodgkin lymphomas: 3 centrocytic anaplastic, 18 centroblastic, 13 immunoblastic and 4 lymphoblastic (according to the Kiel classification) were immunophenotyped in cryosections and cell suspensions by means of monoclonal antibodies. Additionally, cell cycle analysis on cell suspensions was performed by DNA flow cytofluorometry. In 33 (87%) lymphomas the malignant cells expressed monoclonal surface immunoglobulin (Ig), which indicated B-cell origin of tumors. In 7 of the 19 B-cell lymphomas tested by the peroxidase-antiperoxidase method, cytoplasmic Ig was found. Four lymphomas were of T-cell and one of non-B/non-T-cell origin. In II B-cell and 2 lymphoblastic non-B-cell tumors, common acute lymphoblastic leukemia antigen (CALLA) was found. In 25 of 30 studied NHL the malignant cells expressed receptor for transferrin and in 19 of 28 cases a high percentage of cells in S-phase (greater than 10.85%) was found. Number and distribution as well as type of non-B-cells infiltrating B-cell-derived lymphomas varied considerably from case to case. Among these cells Leu 3+ (T helper/inducer) cells predominated. Leu 2+ (T suppressor/cytotoxic) and Leu 7+ (natural killer and killer) cells constituted less numerous groups. Correlation of cytodiagnostic analyses with clinical observations indicates that high content of infiltrating T cells may be a favorable prognostic feature in highly malignant B-cell lymphomas.     

ICAM-1在肿瘤中的研究进展

细胞间黏附分子(Intercellular adhesion molecule-1,ICAM-1)又称CD54,是免疫球蛋白超家族的一种跨膜糖蛋白,参与肿瘤细胞免疫调节、血管生成、侵袭和远处转移。国内外诸多研究证明ICAM-1在多种恶性肿瘤中异常高表达,促进了肿瘤的发生、发展并影响其预后,同时对预测个别肿瘤放化疗敏感性有一定的作用。因此ICAM-1可能为恶性肿瘤的诊断和治疗提供参考依据。本文就近年来ICAM-1在恶性肿瘤中的研究做一综述。     

Evaluation of galectin-3 expression by sarcomas,pseudosarcomatous and benign lesions of the soft tissues. Preliminary results of an immunohistochemical study

Galectin-3 is an endogenous galactose-binding protein that is expressed in several normal and neoplastic tissues and is thought to play a role in a variety of biological processes. In this study we have examined the immunohistochemical expression pattern of galectin-3 in the most representative categories of soft tissue tumors consisting of 162 patients' specimens. Lesions were classified according to histogenetic criteria into 13 major categories. Overall, there were 18 fibrous tumors (13 benign, 4 intermediate and 1 malignant), 21 fibrohistiocytic tumors (5 benign, 11 intermediate and 5 malignant), 22 lipomatous tumors (14 benign and 8 malignant), 20 smooth muscle tumors (12 benign, 5 intermediate and 3 malignant), 2 skeletal muscle tumors (2 malignant), 19 vascular tumors (9 benign and 10 malignant), 6 perivascular tumors (5 benign and 1 malignant), 7 synovial tumors (4 benign and 3 malignant), 3 benign mesothelial tumors, 27 neural tumors (25 benign and 2 malignant), 7 cartilaginous and osseous tumors (4 benign and 3 malignant), 8 miscellaneous tumors and 2 high grade unclassified sarcomas. Galectin-3 was constantly expressed by almost all the major categories of benign, pseudosarcomatous and malignant soft tissue tumors. At this time no data are available in the literature about the expression of galectin-3 distribution in a wide range of soft tissue tumors. In the present work we discuss the significance and the possible usefulness of such findings.     

多弹头射频治疗肝脏恶性肿瘤对机体T淋巴细胞亚群的影响

目的探讨多弹头射频治疗肝脏恶性肿瘤对患者T淋巴细胞亚群的影响.方法采用APAAP法测定65例肝脏恶性肿瘤患者治疗前、后及治疗后2个月T淋巴细胞亚群数值.结果治疗后与治疗前T淋巴细胞亚群比较,CD3 、CD4 下降,CD8 上升,CD4 /CD8 下降,但差异无显著性(P＞0.05).治疗后2个月与治疗前T淋巴细胞亚群比较CD3 、CD4 明显上升,CD8 明显下降,CD4 /CD8 明显上升,差异有显著性(P＜0.01).讨论肝脏恶性肿瘤多弹头射频治疗后细胞免疫功能进一步受到损害,治疗后2个月细胞免疫功能明显恢复、提高,提示多弹头射频治疗肝脏恶性肿瘤可恢复和刺激机体细胞免疫功能.     

Analysis of MUC4 mucin expression in lung carcinoma cells and its immunogenicity

BACKGROUND: MUC4 has been cloned from tracheobronchial mucosa cDNA and reportedly is highly expressed in some human malignancies, including lung carcinoma. However, little is known about molecular and biologic characteristics. The authors analyzed expression levels of MUC4 mRNA and protein in lung carcinoma cells and analyzed the immunogenicity of this mucin. METHODS: Nine cultured lung carcinoma cell lines and 29 tumor samples from patients with lung carcinoma were examined by Northern hybridization for MUC4 mRNA expression and by flow cytometry or an immunohistochemical staining for its protein expression. Sera from the patients were examined for their reactivity with MUC4 by enzyme-linked immunosorbent assay. RESULTS: Forty-four percent of the cell lines and 72% of the tumor samples showed high levels of MUC4 mRNA expression. Although MUC4 protein was not detected in any live carcinoma cell lines by flow cytometry using rabbit antisera reactive with the MUC4 core, pretreatment with paraformaldehyde and sialidase resulted in successful detection of the protein in 50% of the cell lines. An immunohistochemical study revealed that 67% of the tumors exhibited MUC4 protein expression without any digestion. In 29% of the patients, high levels of anti-MUC4 immunoglobulin M or immunoglobulin G were detected. CONCLUSIONS: MUC4 protein expression was elevated in lung carcinoma tissues because of the increase in its mRNA expression and deglycosylation on its core. This mucin is sufficiently immunogenic to elicit humoral and cellular immunity specific for MUC4 in patients with malignant disease. MUC4 is expected to be useful as a target antigen in immunotherapy for patients with carcinoma of the lung.     

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

The epidermal growth factor receptors, HER1, HER2, HER3 and HER4 play a key role in the growth of malignant tumors. The receptors of the EGF receptor family are not cancer-specific proteins since these receptors are expressed to some extent in both normal and benign tissue, but this is not elucidated in detail in ovarian tissue. High tumor-to-normal-tissue concentration ratios would be favorable for molecular targeted anti-cancer treatment. The primary aim of the study was to analyze the potential differential protein content and gene expression of the four receptors in benign and malignant ovarian tumors. Tissue from 207 patients (101 malignant, 19 borderline, 64 benign ovarian tumors and 23 normal ovaries) were analyzed by quantitative ELISA for HER1-HER4 protein concentrations and by real-time PCR for HER1-HER4 gene expression. HER2 was also analyzed by immunohistochemistry. The HER2-4 receptor protein content and the median gene expression level was significantly higher in ovarian cancer patients compared to patients with benign ovarian tumors and normal ovaries (p<0.0000001). The protein content of the HER1 receptor was significantly lower in ovarian cancer compared to borderline tumors (p=0.012), benign ovarian tumors (p=0.049) and to normal ovaries (p=0.000069). A sound correlation between the protein levels and gene expressions was documented. In conclusion, decreased concentration of HER1 protein and increased HER2, HER3 and HER4 protein concentration were observed, as also elevated HER2-HER4 gene expression levels in ovarian cancer patients with barely any overlap of the HER3 and HER4 expression in malignant ovarian tumors compared to benign ovarian tissues.