胃癌组织中T细胞及其亚群ICOS分子的表达及其意义

目的探讨胃癌组织中T细胞共刺激分子ICOS及其亚群的表达及意义。方法应用流式细胞术检测38例胃癌和21例健康人（对照组）外周血T细胞亚群及其共刺激分子ICOS的表达。结果胃癌组与对照组比较：CD3^＋T细胞表达（53．61±13．84）／（72．07±7．83）％,P〈0．01;CD3^＋CD4^＋T细胞表达（29．84±9．71）／（38．79±5．08）％。P〈0．01;CD3^＋ICOS^＋T细胞表达（25．80±10．56）／（0．82±0．98）％,P〈0．01;CD3^＋CD8^＋ICOS^＋T细胞表达（1．57±1．99）／（0．02±0．04）％,P〈0．01;CD3^＋CD8^＋ICOS^-T细胞表达（16．06±6．94）／（20．56±6．54）％,P〈0．05。胃癌组患者手术前和手术后1周外周血T细胞亚群的差异无统计学意义（P〉0．05）。结论胃癌患者T细胞数量明显减少,T细胞共刺激分子ICOS表达增高,CD4^＋T细胞显著减少。     

T细胞亚群测定在胃癌中的临床意义

目的　了解胃癌患者不同期的外周血T淋巴细胞亚群分布的差异 ,探讨其在抗肿瘤免疫中的意义。方法　采用间接免疫荧光法对 72例不同期胃癌患者进行外周血T淋巴细胞亚群测定 ,同时 ,以 6 0例健康患者作为对照。结果　 72例胃癌患者随着病期进展 ,CD4 含量逐渐减低 ,CD4 /CD8比值明显低于正常对照组 (P <0 0 1) ,CD8含量高于正常对照组。结论　胃癌患者分期越高 ,免疫功能越低 ,测定T淋巴细胞亚群有助于判断病情的严重程度 ,提示早治疗 ,减轻瘤负荷是关键。     

胃癌根治术对患者外周血T细胞亚群的影响

本文研究了30例行胃癌根治术前的胃癌患者术及术后T细胞亚群的动态变化。结果表明，胃癌患者术前CD3^ 、CD4^ 均较对照组低，而CD8^ 高于对照组，致CD4^ /CD8^ 比值降低（P＜0.05-0.01)，且术后1周，免疫抑制进一步加重，2周后逐渐恢复，根治术后4周可恢复到正常水平。提示胃癌患者的免疫功能被明显抑制，胃癌根治术引起患者一个短暂的、有意义的、可逆的免疫功能抑制，其间可能为肿瘤扩散提供一个机会。因此应大力开展围手术期免疫保护，预防肿瘤转移扩散。     

胃癌间质T细胞及其亚群和B细胞的免疫组化研究

本实验应用抗T_3、T_4和T_8细胞表面抗原及抗B细胞表面抗原的单克隆抗体、对38例胃癌术后冰冻切片和20例正常胃粘膜活检冰冻切片进行免疫组织化学染色,较为系统地研究了T_3、T_4和T_8细胞及B细胞的分布特点。T_3、T_4和T_8细胞与胃癌病理生物学行为、临床分期和预后的关系。     

慢性萎缩性胃炎和胃癌患者T细胞亚群及NK细胞活性的检测研究

 本文用OKT单抗致敏血球花环法和MTT比色法对慢性萎缩性胃炎(CAG)和胃癌(GC)患者进行外周血T淋巴细胞亚群及NK细胞活性的检测。结果显示CAG患者CD⁺₃亚群及CD₄/CD₈均较健康对照明显降低(P<0.01),NK细胞活性显著低下(P<0.01)。胃癌患者术前CD⁺₃、CD⁺₄亚群及CD₄/CD₈较健康对照明显降低(P<0.01),CD⁺₈亚群显著升高(P<0.01),NK细胞活性明显升高(P<0.01)。与CAG患者比较,胃癌患者术前CD⁺₃亚群及CD₄/CD₈明显降低(P<0.05),CD8+亚群显著升高(P<0.01),NK细胞活性显著低下(P<0.01)。而术后两周,以上指标有不同程度的恢复,说明CAG患者的细胞免疫功能已处于失调状态,而胃癌患者的免疫失调更为严重,但手术切除肿瘤后病人的免疫失调能迅速恢复,一般为两周左右。     

TI林巴细胞及其亚群在胃癌腹腔冲洗液中含量及临床意义

目的检测胃癌患者腹控冲洗液中T淋巴细胞及其亚群的含量,探讨其与胃癌临床病理因素和腹膜转移相关因素的关系.方法采用流式细胞术(FCM)检测39例进展期胃癌、30例溃疡患者腹腔冲洗液中T淋巴细胞及其亚群的含量.结果胃癌患者腹腔冲洗液中T细胞的含量与良性病变组的含量基本一致(P＞0.05),且与肿瘤的分期无关,CD8+T细胞的含量高于良性病变组的含量,而CD4+T细胞含量低于良性病变组中的含量,但两者均无统计学差异(P＞0.05).结论随着胃癌的进展和腹膜转移的发生,腹腔内的细胞免疫能力下降,CD8+T细胞含量的增加和CD4+/CD8+T细胞比值的下降是晚期肿瘤免疫抑制的一种特征表现.     

胃癌癌周淋巴结网膜及腹膜中T淋巴细胞亚群和NK细胞分布的研究

目的:通过检测胃癌、癌周正常胃粘膜、胃周淋巴结、大网膜、小网膜、腹膜及外周血中T淋巴细胞亚群和NK细胞数以探讨胃癌局部及全身的免疫状况.方法:利用流式细胞术测定40例胃癌患者的癌组织、癌周正常胃粘膜、胃周淋巴结、大网膜、小网膜、腹膜及外周血的CD4 、CD8 及NK细胞的含量.取22例良性疾病患者的胃粘膜和外周血做对照.结果:CD4 、CD8 、NK细胞计数在胃癌组织和胃周淋巴结中最高,均高于癌周正常胃粘膜、大网膜、小网膜、腹膜及外周血(P＜0.05),但癌组织的CD4 /CD8 比值低于淋巴结和大网膜(P＜0.05);良性疾病对照组的胃粘膜、外周血CD4 、CD8 、NK细胞计数和CD4 /CD8 比值均高于胃癌患者(P＜0.01).结论:胃癌患者局部及全身的免疫功能均低于对照组;胃癌组织内CD4 、CD8 、NK细胞较癌周正常胃粘膜、大网膜、小网膜、腹膜高聚集,但免疫功能呈现低下和抑制状态.     

乳腺癌组织中T细胞亚群分布的观察与分析

为了探讨乳腺癌组织局部的免疫反应状态及其临床意义，作者应用抗Ｔ细胞亚群的ＯＫＴ系列单克隆抗体及免疫组化ＡＢＣ技术，对３９例乳腺癌及３０例良性乳腺病变组织中Ｔ细胞亚群表现型进行了原位定量观察。结果发现：乳腺癌组织中ＯＫＴ＾＋８细胞显著多于ＯＫＴ＾４＋细胞，癌巢实质中Ｔ细胞亚群显著少于癌巢间质。癌巢实质，间质中ＯＫＴ＾＋４／ＯＫＴ＾＋８比值均分别显著低于良性病变实质、间质。癌巢实质中Ｔ细胞亚群数量极少     

胃癌患者外周血T淋巴细胞亚群的测定及临床意义

目的分析胃癌患者外周血T淋巴细胞亚群水平的特点、影响因素及临床意义.方法采用流式细胞术(FCM)检测308例胃癌患者外周血中的T淋巴细胞亚群的水平与48例正常对照比较研究.结果患者外周血CD3+、CD4+明显减少,而CD8+明显增加,CD4+/CD8+比值明显下降,与正常组比较差异具有高度显著性(P＜0.01);患者性别、年龄、临床分期不影响其表达,差异无显著性(P＞0.05).结论胃癌患者存在细胞免疫功能紊乱,检测胃癌患者外周血T淋巴细胞亚群的表达对评估患者的细胞免疫功能及疾病的诊断具有一定的临床意义.     

T-lymphocyte subpopulations in patients with gastric cancer]

T-lymphocyte subpopulation profile in peripheral blood of gastric cancer patients proved abnormal. The disbalance became more apparent with progression of disease. A decrease in T gamma-lymphocyte level was observed after radical surgery. T gamma- and T mu- lymphocyte levels proved significantly altered following combined treatment including surgery and chemotherapy with ftorafur or pyrogenal immunotherapy.     

Immunohistochemical assessment of splenic lymphocyte and macrophage subpopulations in patients with gastric cancer

In order to assess the effects of malignant tumors on the immune system, 25 spleens from patients with gastric carcinoma were studied by in situ immunohistochemical methods for lymphocyte subsets and cells of the mononuclear phagocyte system. Highly significant reductions of CD4+ T cells (P less than 0.001), Ki M2+ and Ki M-3+ MPS cells (P less than 0.02 and P less than 0.05), and a stage-dependent reduction of Ki 67+ B cell proliferation activity (P less than 0.05) were seen in spleens of patients with gastric cancer. These results, which were obtained by morphologic methods in a noninvolved lymphatic organ, reflect the systemic immunosuppressive and immunodepleting effects of malignant tumors that are probably mediated by tumor-associated cytokines.     

ICOS+ Foxp3+ TILs in gastric cancer are prognostic markers and effector regulatory T cells associated with Helicobacter pylori

Regulatory T cells (Tregs) have an immunosuppressive role in the tumor microenvironment. Since effector Tregs (eTregs), which have highly suppressive functions, are located in a subpopulation of Foxp3⁺ CD4⁺ Tregs, the TCR‐inducible costimulatory receptor (ICOS) was applied as a marker of eTregs that infiltrated gastric cancer tissue and the induction pathway of ICOS⁺ Foxp3⁺ cells was analyzed by flow cytometry and immunohistochemistry. In tumor‐infiltrating lymphocytes (TILs), ICOS⁺ Foxp3⁺ CD4⁺ T cells were abundantly observed in the late stages of gastric cancer. ICOS⁺ CD4⁺ TILs exhibited the ability to produce IL‐10, but not IFN‐γ, TNF, or IL‐17 and also to suppress the proliferation of CFSE‐labeled responder CD8⁺ T cells. With the agonistic ICOS‐L protein (rICOS‐L Ig), ICOS⁺ Foxp3⁺ cells were efficiently induced from naive CD4⁺ T cells under a stimulation with TGF‐β and CD3/CD28 mAbs. Furthermore, when A*0201 PBMCs were cultured with the CMV or Melan‐A antigenic peptide and rICOS‐L Ig, the induction of CMV or Melan‐A tetramer‐binding CD8⁺ T cells, respectively, was inhibited. The expression of ICOS in Foxp3⁺ cells was closely related to plasmacytoid dendritic cells (pDCs) and their expression of ICOS‐L and TLR9 as well as Helicobacter pylori infection. Collectively, our results demonstrate the potential of ICOS as a promising target for direct Treg‐targeting therapeutic agents for gastric cancer, and that of eradicating therapy for H. pylori as an indirect immune therapy for gastric cancer.     

Effect of therapy on T cell subpopulations in patients with chronic lymphocytic leukemia

We have previously demonstrated functional and quantitative imbalances in two human thymic (T) cell subpopulations. Tγ and Tμ, in chronic lymphocytic leukemia (CLL) patients. Serial evaluations of the numbers of Tγ and Tμ subsets in CLL were performed in order to delineate more completely the patterns of T cell abnormalities. Two groups of CLL patients were studied: (1) previously untreated (n = 3) and (II) stable CLL on chemotherapy (n = 12). In Group I, two of three patients had significantly increased percentages of Tγ cells (mean ± S.E.M. = 57 ± 5 vs 18 ± 2 for controls). There was defective in vitro appearance of Tμ cells in both groups. In Group II, repeated studies of T cell subsets revealed persistently elevated Tγ cells despite various modes of oral chemotherapy. In three CLL patients who required splenectomy a dramatic decrease in the percentages of Tγ, cells was noted post-splenectomy (51 ± 3 to 15 ± 3). In all cases the spleen was diffusely involved with CLL. These findings indicate: (1) abnormalities of T cell subsets are present early in CLL. (2) chemotherapy does not affect the levels of Tγ cells in stable patients and (3) removal of infiltrated CLL spleens results in a dramatic decrease in the proportion of Tγ cells. This latter finding plus the increase in Tγ cells in progressive disease post-splenectomy suggest Tγ cells may be an important determinant of the course of CLL.     

卵巢恶性肿瘤手术及化疗前后外周血免疫细胞亚群的检测

目的:探讨卵巢恶性肿瘤手术及化疗前后外周血免疫细胞亚群的改变及临床意义。方法:采用单克隆抗体和流式细胞仪对208例卵巢恶性肿瘤手术前后、化疗前后和200位正常人对照组进行外周血免疫细胞亚群动态检测并比较活性。结果:肿瘤组手术前CD3、CD4、CD4/CD8和NK显著低于对照组,P值分别为0·000、0·000、0·000和0·009。手术后较手术前IL-2和CD3升高,P值分别为0·000和0·000。化疗后较化疗前CD3、CD4和CD4/CD8升高,P值均为0·000;NK下降,P=0·009。Ⅲ~Ⅳ期较Ⅰ~Ⅱ期CD3、CD4、CD4/CD8和NK下降,P值分别为0·003、0·000、0·000和0·000。不同细胞分化程度术前各项指标差异无统计学意义,P>0.05。结论:卵巢恶性肿瘤患者细胞免疫功能低下,手术创伤可导致免疫力下降。疾病分期晚者免疫力差。手术、化疗后由于肿瘤负荷、抑制因子减少免疫力逐渐上升。     

Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients.

Recent studies (K. Komoto et al., Am. J. Gastroenterol., 93: 1271-1276, 1998) have shown that Helicobacter pylori infection is associated with gastric cancer. However, the mechanism of H. pylori in carcinogenesis has not been clarified. H. pylori infection leads to a sustained production of reactive nitrogen species that may contribute to cause DNA damage. In this study, we examined the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine in gastric mucosa. The expression of iNOS and nitrotyrosine was examined by immunohistochemistry in 93 patients who initially underwent gastric biopsies between 1975 and 1992. Thirty-four individuals were later found to have gastric cancer at least 2 years after the initial biopsies (group A). The other 59 subjects have shown no evidence of gastric cancer during long-term follow-up. Fifty-one of these patients were positive for H. pylori (group B), and eight were negative for H. pylori (group C). The expression of iNOS and nitrotyrosine in the gastric mucosa was significantly higher in H. pylori-positive groups A and B than in H. pylori-negative group C. Among the H. pylori-positive patients, the expression of iNOS and nitrotyrosine was significantly higher in group A than in group B. These results suggest that high production of iNOS and nitrotyrosine in the gastric mucosa infected with H. pylori may contribute to the carcinogenesis of gastric cancer.     

miR-200c在胃癌中的表达水平与患者临床病理特征的关系

目的:探讨miR-200c在胃癌组织中的表达水平与胃癌患者临床病理特征及无病生存期(diease free survial,DFS)的关系.方法:收集河北医科大学第四医院普外科2012年5月至2013年1月64例胃癌手术切除的标本及相关临床资料,采用实时荧光定量PCR技术检测miR-200c在胃癌组织和配对癌旁非癌组织中的表达.回顾性分析miR-200c表达水平与胃癌患者的临床病理特征及DFS相关性.结果:胃癌组织中miR-200c的表达水平显著低于癌旁非癌组织(3.29vs5.91,P＜0.01).miR-200c的表达水平与肿瘤TNM分期、浸润深度、转移和脉管瘤栓呈显著负相关(均P＜0.01).miR-200c高表达组患者中位DFS明显长于低表达组患者(22.0 vs 13.5个月,P＜0.01),其表达水平与患者DFS呈正相关(P＜0.01).结论:miR-200c在胃癌组织中低表达,其表达水平与肿瘤TNM分期、肿瘤浸润深度和脉管瘤栓呈负相关,与DFS呈正相关,在胃癌的发生发展及预后中具有重要作用.     

缺氧诱导因子HIF-1α在胃癌细胞系中的表达和意义

目的研究缺氧诱导因子HIF-1α在人多种胃癌细胞系中的表达及意义。方法分别利用RTPCR和Western blot的方法检测多种胃癌细胞系中HIF—1α的表达水平。结果常氧条件下，在永生化的胃粘膜上皮细胞系GES及多种胃癌细胞系(包括耐药细胞)中均能检测到HIF-1α mRNA的表达，其表达水平无明显差异；对部分细胞系中HIF-1α蛋白表达进行检测，同样发现常氧时即有HIF-1α的表达，但表达水平明显不同。结论常氧时在多种胃癌细胞系及永生化的胃粘膜上皮细胞系中均有HIF-1α的表达；在胃癌细胞系中，HIF-1α的调节可能主要在翻译水平而非转录水平；HIF-1α在常氧时胃癌细胞系的异常表达，提示除缺氧刺激外，非缺氧因素可能也在胃癌的发生、发展中发挥了一定的作用。