大肠癌中CD44V6、CD44s表达与nm23-H1表达相关性及临床意义

目的　了解CD4 4V6 、CD4 4s、nm2 3-H1 在结直肠癌组织、移行粘膜及正常粘膜间的表达 ,探讨它们与结直肠癌侵袭与转移的关系。方法　运用免疫组化SABC法测定CD4 4V6 、CD4 4s、nm2 3-H1 在癌组织、癌远端 3cm处的移行组织及正常结直肠组织中的表达 ,同时记录有关的临床病理指标。结果　CD4 4V6 、、CD4 4s、nm2 3-H1 阳性表达率分别在癌组织中为 70 .18%、4 2 .11%及 5 4 .39%与移行组织中 12 .0 2 %、89.4 7%、91.2 %及正常结直肠组织中 0、10 0 %、94 .74 % ,其差别有显著性 (P <0 .0 5 )。CD4 4V6 表达与肿瘤侵袭深度、Dukes分期及淋巴结转移正相关 ,nm2 3-H1 表达与Dukes分期、淋巴结转移呈负相关 (P <0 .0 5 )。CD4 4s在移行粘膜与正常组织表达有显著差别 (P <0 .0 5 )。结论　结直肠癌组织CD4 4V6 表达增多 ,CD4 4s及nm2 3-H1 表达降低。CD4 4V6 及nm2 3-H1 与结直肠癌的侵袭与转移有关 ,CD4 4V6 变化较nm2 3-H1 在前。直肠癌手术时癌远端至少应切除 3cm长的肠管     

Increased expression of CD44 in hypertrophied ligamentum flavum and relevance of splice variants CD44v5 and CD44v6

Background  

The most common spinal disorder in the elderly is lumbar spinal stenosis (LSS), which results in part from ligamentum flavum (LF) hypertrophy. Although prior histologic and immunochemical studies have been performed in this area, the pathophysiology of loss of elasticity and hypertrophy is not completely understood. The purpose of this immunohistological study is to elucidate the role of CD44 and its splice variants CD44v5 and CD44v6 in the hypertrophied LF obtained from patients with lumbar spinal stenosis (LSS).     

原发性肝癌组织中粘附分子CD54,CD44及E-cadherin的表达及意义

目的 探讨粘附分子表达与原发性肝癌生物学行为的关系。方法 应用免疫组化技术观察粘附分子ＣＤ５４、ＣＤ４４和Ｅ－ｃａｄｈｅｒｉｎ及增殖细胞核抗原（ＰＣＮＡ）在４９例肝细胞癌组织中的表达。结果 非癌组肝细胞均见Ｅ－ｃａｄｈｅｒｉｎ阳性表达,ＣＤ５４,ＣＤ４４均呈阴性染色。肝癌组织中ＣＤ５４和ＣＤ４４表达增加,阳性率分别为８５．７％（４２／４９）和８１．６％（４０／４９）,Ｅ－ｃａｄｈｅｎｉｎ表达明显减     

前列腺癌CD44及nm23-H1基因表达

目的　探讨在前列腺癌中CD44和nm2 3 H1基因表达的意义。　方法　应用免疫组织化学、银染单链长度构相多态性半定量逆转录聚合酶链式反应及免疫印迹杂交法分别检测 32例前列腺癌石蜡标本及 15例新鲜标本中CD44、nm2 3 H1基因的突变、表达情况。　结果　前列腺癌组织中nm2 3 H1蛋白及mRNA高水平表达 ,转移组nm2 3 H1蛋白表达强度高于非转移组。前列腺癌组织中存在nm2 3 H1基因突变 ,突变检出率为 13 3% (2 / 15 )。前列腺癌转移组中 ,CD44s蛋白表达水平下降。CD44smRNA在癌及非癌对照组织中全部表达 ,但 86 7% (13/ 15 )的癌组织中同时表达CD44v。　结论　nm2 3 H1基因的高表达和CD44v/CD44s基因的表达失衡可能在前列腺癌的恶性进展中共同发挥作用。     

VEGF、EGFR、CD44V6、Cath-D及nm23-H_1在结直肠癌组织中的表达及意义

目的 探讨血管内皮生长因子(VEGF)、表皮生长因子受体(EGFR)、CD44V6、Cath-D、nm23-H1在结直肠癌组织中的表达及临床意义.方法 选择2000年1月至2001年12月行根治性手术的131例结直肠癌病例,应用免疫组化SP法检测肿瘤组织中VEGF、EGFR、CD44V6、Cath-D及nm23-H1的表达情况,分析其与术后复发转移的关系.结果 全组术后复发转移率为31.3%(41/131),VEGF、EGFR、CD44V6、Cath-D、nm23-H1阳性率分别为62.6%(82/131)、58.0%(76/131)、52.7%(69/131)、55.0%(72/131)、72.5%(95/131),VEGF阳性组、EGFR阳性组、CD44V6阳性组、Cath-D阳性组、nm23-H1阴性组术后复发转移率较高(P值均<0.05).根据VEGF、EGFR、CD44V6、Cath-D、nm23-H1的表达情况对患者进行评分再分成3组,3组间的术后复发转移率两两间存在统计学差异(P值均<0.05).结论 VEGF、EGFR、CD44V6、Cath-D、nm23-H1 与结直肠癌术后复发转移有关,合并这些不良预后因素越多,患者的预后越差.     

The expression patterns of CD44 and CD45RB on peripheral blood T lymphocytes in the rejection of allogeneic murine skin transplantation

Until now, the rejection was diagnosed through a biopsy, but this method of diagnosis reflected the advanced tissue damage of the transplanted organ and contained the innate problem of being invasive. In relation, our research attempted to evaluate the viability of analyzing the surface antigens of the peripheral blood activated T lymphocytes after murine skin transplantation as a non-invasive and early diagnostic tool for diagnosis of rejection. After mouse skin was transplanted, the expression patterns of activated T lymphocyte markers, CD44 and CD45RB were analyzed along with T lymphocyte markers, CD3, CD4 and CD8 using flow cytometry. The skins from the tails of allogeneic BALB/c(H2d) mice and syngeneic C57BL/6J mice were transplanted to C57BL/6J(H2b) mice as test and control groups, respectively. Peripheral blood, which was sampled from the tail every other day from day 3 to day 15 was stained with anti-CD44 (or CD45RB), anti-CD4 (or CD8) and anti-CD3 monoclonal antibodies simultaneously, and analyzed by 3-color FACS. Rejection occurred only in the test group from day 8 to day 13 (median: day 10). Although the proportions of CD3(+) lymphocytes, CD4(+) lymphocytes and CD8(+) lymphocytes showed no difference, the total number of peripheral blood lymphocytes and the number of CD3(+) lymphocytes and CD8(+) lymphocytes decreased more sharply in the control after day 7. The proportion and the number of CD44(+)CD3(+)-lymphocytes, CD44(+)CD4(+)-lymphocytes and CD44(+)CD4(+)CD3(+)-lymphocytes began to increase after day 7, to peak on day 11, and then to decrease, showing a significant difference. The proportion and number of CD44(+)CD8(+)-lymphocytes and CD44(+)CD8(+)CD3(+)-lymphocytes showed similar trends. No significant difference was observed in any subsets of the CD45RB antigen. The analysis of the expression patterns of surface antigen CD44 on peripheral blood T lymphocytes using flow cytometry is sensitive, safe, easily repeatable and controllable, and, therefore, can be considered a promising tool for the diagnosis of rejection. However, the clear change in CD44 occurred between day 9 and day 13, when rejection was observed grossly. Therefore, it is regarded more useful as a screening test or follow-up indicator rather than as an early diagnostic tool.     

CD25, CD28 and CD38 expression in peripheral blood lymphocytes as a tool to predict acute rejection after liver transplantation

Abstract: Background/Aim: The aim of this study was to determine whether the expression of CD25, CD28 and CD38 (which reflects the degree of T‐cell activation) by peripheral blood mononuclear cells constitutes a useful means of measuring the immune status of liver transplant recipients. Methods: Fifty‐two patients enrolled in a prospective randomized study comparing cyclosporine and tacrolimus as the principal immunosuppressive drugs were monitored prospectively. The expression of CD25, CD28 and CD38 was analyzed on CD3‐, CD4‐ and CD8‐positive cells from whole blood using flow cytometry. The prognostic value of baseline and day 14 measurements regarding acute rejection was examined using Kaplan–Meier estimates for univariate analyses and the Cox model for multivariate analyses. Results: The mean frequencies of CD28 and CD38‐expressing T cells were significantly higher in patients with acute rejection (p = 0.01 and p = 0.001, respectively), whereas the frequency CD25‐expressing T cells did not differ significantly. Under univariate analysis, baseline CD25 levels, the type of calcineurin inhibitor, as well as the CD28 and CD38 frequencies obtained at day 14 were associated with the subsequent development of acute rejection. Under multivariate analysis, only CD28 and CD38 frequencies obtained at day 14 were independently associated with acute rejection. Conclusions: The evaluation of CD28 and CD38 expression in peripheral blood lymphocytes is a simple marker that could be used routinely in clinical practice to assess the level of immunosuppression.     

Impact of pneumoperitoneum on expression of E-cadherin, CD44v6 and CD54 (ICAM-1) on HT-29 colon-carcinoma cells

INTRODUCTION: The mechanism of potential tumor cell spread and growth during laparoscopy is poorly understood. Nevertheless, different experimental studies reported a stimulation of tumor cell growth and an increased metastatic potential of carcinoma cells using carbon dioxide as an insufflation medium. Adhesion molecules do play an important and regulatory function in the process of metastatic spread and invasion of cancer cells. Therefore we investigated the influence of CO2 and Helium insufflation on the in-vitro expression of E-Cadherin, CD44v6 and CD54 (ICAM-1) on HT-29 colon carcinoma cells. METHODS: HT-29 carcinoma cells were exposed to either CO2 or helium insufflation. Expression of E-Cadherin, CD44v6 and CD54 (ICAM-1) on HT-29 colon carcinoma cells were measured 1, 12, 24, 48 and 96 h after CO2 and helium insufflation using flowcytometry (FACScan). Data were analyzed by Friedman-test. RESULTS: HT-29 cell line showed a short decrease in E-Cadherin expression after CO2 exposure while helium insufflation had no influence. In contrasts to these findings the expression of CD44v6 and CD54 on HT-29 cells were not influenced significantly by either CO2 or helium. CONCLUSION: CO2 seems only to have a minor influence on the expression of E-Cadherin while expression of other adhesion molecules did not change after CO2 incubation. The alternative gas helium did not cause any significant changes of the expression of either E-Cadherin, CD44v6 and CD54. Further investigations are needed to elucidate the changes of the metastatic potential of tumor cells after laparoscopic and open procedures.     

Patterns and significance of CD44 expression in lung allografts.

BACKGROUND: Lung allograft rejection involves the interplay of multiple cellular populations, soluble mediators, and extracellular matrix proteins. The CD44 family of cell surface glycoproteins mediates a variety of cell-cell and cell-matrix interactions including lymphocyte homing to sites of antigenic challenge and fibroblast migration and invasion into extracellular matrix, processes integral to lung allograft rejection. METHODS: We performed immunohistochemical staining for CD44 on biopsies from allograft recipients with differing rejection experiences: Group 1 (n = 5 patients/10 biopsies) never exceeded Grade A1 or B2 acute rejection (AR); Group 2 (n = 7 patients/26 biopsies) had 2 or more episodes of Grade A2 or higher AR and no obliterative bronchiolitis (OB); Group 3 (n = 6 patients/17 biopsies) had clinical and pathologic OB. Nine infected allograft biopsies, 8 near-normal lung sections (non-transplant controls), and 13 non-transplant biopsies showing bronchiolitis obliterans organizing pneumonia (BOOP), organizing diffuse alveolar damage (DAD), or usual interstitial pneumonia (UIP) were also studied. RESULTS: Allograft biopsies demonstrated significantly more CD44 staining among lymphocytes, macrophages, Type II pneumocytes, and respiratory epithelial cells than non-transplant controls, while staining of lymphocytes, macrophages, and Type II pneumocytes did not differ significantly between allograft groups. Fibroblast CD44 staining in Group 3 biopsies significantly exceeded that of controls and Groups 1 and 2, and biopsies with AR and/or OB showed more fibroblast staining than biopsies with BOOP, organizing DAD, or UIP. Alveolar CD44-positive fibroblasts did not predict development of OB, while bronchial CD44-positive fibroblasts were followed in one case by OB. CONCLUSIONS: These findings suggest that CD44 expression is characteristic of graft-infiltrating inflammatory cells and resident parenchymal cells, and may be related to the initiation and evolution of AR and OB.     

血清中可溶性CD44v6含量和组织中CD44v6蛋白表达研究

目的　研究胃癌患者外周血中sCD44v6含量及其组织中CD44v6蛋白表达 ,探讨sCD44v6含量 /CD44v6蛋白与临床病理参数之间的关系。方法　应用酶联免疫吸附试验 (ELISA)检测胃癌患者 (术前 )及其中部分术后及健康对照组血清中sCD44v6含量并以 (S P)免疫组织化学法测定相应组织中CD44v6蛋白的表达。结果　 70例胃癌患者血清中sCD44v6含量 (2 .15± 0 .78)μg/L明显高于 16例正常对照组 (1.18± 0 .43 ) μg/L、14例根治性手术后血清中sCD44v6含量(1.2 1± 0 .3 9) μg/L比术前 (2 .67± 0 .83 ) μg/L明显下降 (P <0 .0 1) ,而 6例非根治性手术后(3 .2 9± 0 .41) μg/L比术前 (3 .61± 0 .49) μg/L下降不明显 (P >0 .0 5 )。结论　胃癌患者外周血中sCD44v6含量及组织中CD44v6蛋白表达的变化与转移、临床分期、病理分期有关 ,sCD44v6含量升高可作为胃癌患者淋巴结转移 (尤其是早期转移 )的监测指标。     

Expression profile of CD44s,CD44v6, and CD44v10 in localized prostate cancer: Effect on prognostic outcomes following radical prostatectomy

ObjectivesTo investigate the expression of CD44 standard form (CD44s) and 2 major variant exons (CD44v6 and CD44v10) in localized prostate cancer (PC) to determine the prognostic significance of these markers following radical prostatectomy (RP).Materials and methodsExpression levels of CD44s, CD44v6, and CD44v10 in RP specimens from 160 consecutive patients with clinically localized PC were evaluated by immunohistochemical staining.ResultsOf these 3 markers, expression level of CD44v6 was closely associated with several conventional prognostic factors. Univariate analysis identified CD44v6 expression in addition to serum prostate-specific antigen level, Gleason score, seminal vesicle invasion, and surgical margin status as significant predictors for biochemical recurrence (BR). Of these significant factors, CD44v6 expression, serum prostate-specific antigen level, and surgical margin status appeared to be independently associated with BR on multivariate analysis. We observed significant differences in BR-free survival according to the positive numbers of these 3 independent factors; i.e., BR occurred in 0 (0%) of 42 patients who had negative results for risk factors, 9 (16.7%) of 54 who had positive results for 1 risk factor, and 31 (48.4%) of 64 who had positive results for 2 or 3 risk factors.ConclusionsAssessment of the expression levels of CD44v6 in RP specimens in addition to conventional prognostic parameters would contribute to the accurate prediction of the biochemical outcome in patients with localized PC who underwent RP.     

肝细胞癌组织中MMP-9,CD44V6与nm23-H1表达的相关性及意义

目的 检测肝细胞癌(HCC)组织中MMP-9,CD44V6及nm23-H1的表达水平,了解HCC中MMP-9,CD44V6与nm23-H1表达的相关性及其与HCC侵袭转移的关系. 方法 采用免疫组化SP法检测60例HCC中MMP-9,CD44V6及nm23-H1的表达. 结果 侵袭转移倾向高危组的35例HCC标本中,MMP-9,CD44V6及nm23-H1表达的强阳性率分别为71.4%(25/35),68.6%(24/35)和25.7%(9/35);侵袭转移倾向低危组的25例HCC标本中,MMP-9,CD44V6及nm23-H1表达的强阳性率分别为40.0%(10/25),36.0%(9/25)和60.0%(15/25);MMP-9及CD44V6的表达与HCC侵袭转移倾向呈正相关性(P<0.01),nm23-H1的表达与HCC的侵袭转移倾向呈负相关性(P<0.01),MMP-9与CD44V6的表达呈正相关性,而MMP-9,CD44V6与nm23-H1的表达呈负相关性. 结论 MMP-9,CD44V6及nm23-H1的表达可能作为HCC预后及转移潜能判断的指标.     

Impact of laparoscopic and conventional surgery on Kupffer cells,tumor-associated CD44 expression,and intrahepatic tumor spread

BACKGROUND: The oncologic feasibility of laparoscopic surgery for the cure of colorectal cancer is under debate. The effect of laparoscopic colorectal cancer resection on hepatic tumor spread has not yet been clarified. HYPOTHESIS: Laparoscopic surgery affects cell-mediated immune response and hepatic tumor spread dependent on intraperitoneal insufflation. METHODS: Thirty WAG/Rij rats were randomized into 3 operative groups: carbon dioxide (CO( 2)) laparoscopy (n = 10), "gasless" laparoscopy (n = 10), and laparotomy (n = 10). To induce liver metastases, 50 000 CC531 colon carcinoma cells were injected into the portal vein during either laparoscopy or laparotomy. Twenty-eight days after injection, specimens were explanted, sectioned, and examined immunohistochemically for CC531 tumor cells (monoclonal antibody CC52), CD44v5, v6 (monoclonal antibody OX49), and Kupffer cells (monoclonal antibody HIS36). For quantification, a morphometric analysis system was applied. Data were analyzed using the Kruskal-Wallis, Dunn, and Holm tests. RESULTS: No statistically significant differences in hepatic tumor growth were found between CO(2) laparoscopy and laparotomy (P =.37). However, compared with CO(2) laparoscopy and laparotomy, a significant decrease in intrahepatic tumor growth was found after gasless laparoscopy (P =.02). Kupffer cells had significantly decreased after CO(2) laparoscopy and laparotomy compared with after gasless laparoscopy (P<.001 and P =.002, respectively). CD44v5, v6 expression was significantly increased after CO(2) laparoscopy and laparotomy compared with after gasless laparoscopy (P =.002 and P =.05, respectively). CONCLUSIONS: Hepatic resistance to tumor growth is best preserved by gasless laparoscopy as opposed to CO(2) laparoscopy or laparotomy. The amount of intra-abdominal pressure with circulatory changes rather than the used gas may explain this finding. On the other hand, conventional laparoscopy vs laparotomy did not preserve hepatic immune function.     

CD44v6在骨肉瘤组织中的表达及其临床意义

目的探讨骨肉瘤中CD44v6的表达与其临床及生物学行为的关系.方法应用流式细胞免疫学方法检测40例骨肉瘤、10例骨巨细胞瘤、10例骨软骨瘤石蜡标本的CD44v6表达情况,综合分析检测结果对骨肉瘤侵袭转移及预后的影响.结果 CD44v6在骨肉瘤中高表达,明显高于骨巨细胞瘤及骨软骨瘤.CD44v6表达与骨肉瘤患者的性别、年龄、病程及肿瘤发生部位无关;在Enneking外科分期≥ⅡB期(ⅡB、Ⅲ期)、局部复发、伴有肺转移的骨肉瘤中,其CD44v6表达值明显高于＜ⅡB期(ⅡA期)、局部未复发、无肺转移的骨肉瘤.结论 CD44v6可作为骨肿瘤恶性表型的标志和诊断的辅助指标.CD44v6阳性可能预示骨肉瘤复发或转移的倾向,具有一定的临床价值.     

CD44和 CD54在结直肠癌肝转移中的表达意义

目的探讨结直肠癌肝转移患者血清中CD44和CD54含量与结直肠癌肝转移发生发展的关系,寻找一个稳定的早期诊断结直肠癌肝转移的生物学指标。方法应用酶联免疫吸附测定方法(ELISA)检测38例结直肠癌和21例结直肠癌肝转移患者以及40例健康成人(正常对照组)的血清CD44和CD54含量,并比较血清中CD44和CD54含量在治疗前后的变化。结果结直肠癌肝转移组和结直肠癌组血清中CD44和CD54含量明显高于正常对照组,且结直肠癌肝转移组较结直肠癌组含量也明显增高。结直肠癌肝转移组和结直肠癌组治疗后的血清CD44和CD54含量比治疗前下降。结论CD44和CD54可以作为临床早期诊断结直肠癌肝转移的生物学指标,同时也可以作为监测结直肠癌和结直肠癌肝转移预后的客观指标。