甘糖酯对实验糖尿病大鼠粘附分子-CD54、CD106、CD62p的影响

目的观察糖尿病大鼠肾脏、主动脉等粘附分子的变化及甘糖酯干预的影响,为早期防治糖尿病并发症提供科学依据.方法实验分正常对照、糖尿病对照、高、低剂量甘糖酯共4组,通过免疫组织化学方法观察大鼠肾脏和主动脉CD54和/或CD106的表达,应用流式细胞仪测定血中单个核细胞表面CD54、血小板表面CI)62p的表达水平;应用甘糖酯治疗8周后,观察上述指标的变化.结果(1)血单个核细胞表面CD54测定表明高剂量甘糖酯组有明显降低,(CD54高=36.04±11.01%,VS CD54DM=65.09±14.92%,P＜0.05),而低剂量甘糖酯组降低不明显;甘糖酯时血小板表面CD62P表达影响不大;(2)肾脏和主动脉CD54、CD106免疫组化显示甘糖酯能降低其表达并减轻组织病理变化,且与剂量有关.(3)甘糖酯有降低血糖的作用,并与剂量有关(高剂量组BG治疗前=20.93土4.22mmol@L-1,BG治疗后=15.76±2.39mmol@L-1,P＜0.05;低剂量组BG治疗前=17.35±1.13mm0l@L-1,BG治疗后=13.52±6.24mmol@L-1,P＞0.05).结论糖尿病粘附分子的增加可能是糖尿病肾病和大血管病变的重要发病因素,甘糖酯可降低CD54、CD106对糖尿病并发症有延缓和改善作用.     

西洛他唑对磷脂多糖诱导的粘附及粘附分子释放的影响

目的　研究磷酸二酯酶 3型抑制剂西洛他唑对磷脂多糖 (LPS)诱导的粘附及血管内皮细胞 (ECs)释放可溶性细胞粘附分子 (sCAMs)的影响。方法　体外培养第 4～ 6代人脐静脉血管内皮细胞 (HUVECs) ,以LPS(5mg·L- 1)刺激 ,并与西洛他唑 (1～ 10 μmol·L- 1)共培养 2 4h ,观察西洛他唑对由LPS诱导的HUVECs与中性粒细胞之间的粘附的影响 ;另取培养上清 ,以ELISA法测定HUVECs释放可溶性血管细胞粘附分子 1(sVCAM 1)、细胞间粘附分子 1(sICAM 1)以及E 选择素 (sE selectin ,sELAM 1)。结果　西洛他唑抑制由LPS诱导的HUVECs与中性粒细胞之间的粘附以及HUVECs释放sVCAM 1,而对sICAM 1和sE 选择素无影响。并且 ,该药对于sVCAM 1的抑制作用被蛋白激酶A(PKA)抑制剂H 89所阻断。结论　西洛他唑对由细胞因子LPS诱导的粘附反应以及ECs释放sVCAM 1有抑制作用 ,后者可能与PKA依赖性通路相关     

Hyperoxia-induced apoptosis of AEC Ⅱ in premature rats by inhibiting expression of focal adhesion kinase

Objective To explore the role of focal adhesion kinase (FAK) in hyperoxia-apopto- sis of type Ⅱ alveolar epithelial cells (AEC Ⅱ s) of premature rats. Methods AEC Ⅱ from prema- ture rat lungs were cultured and randomly assigned to air group and hyperoxia group. After exposed to hyperoxia for 6, 12, 24 and 48 h, apoptosis rate of AEC Ⅱ were analyzed by flow cytometry with an- nexin-Ⅴ/propidium iodine (PI) double staining. FAK mRNA and FAK and fAK-Tyr397 peptide were detected by RT-PCR and Western blot, respectively. Results Positive cells of Annexin-Ⅴ+ / PI- in AEC Ⅱ after 6,12,24 and 48 h of hyperoxia exposure were significantly decreased, and the maximal apoptosis rate of AEC Ⅱ (stained of Annexin-Ⅴ+ / PI- ) was found in the hyperoxia group at 12 h (23.83%±4.43%). Compared to the air group, the expression of FAK mRNA and of FAK de- creased markedly and progressively in hyperoxia groups at 12, 24 and 48 h(P<0. 05). Conclusions Decreased expression of FAK induced by hyperoxia is likely to contribute to the apoptosis and neco-z sis of AEC Ⅱ.     

Prognostic value of E-cadherin immunoexpression in patients with primary ovarian carcinomas.

PURPOSE: To analyse the negative versus positive immunoexpression of E-cadherin in patients with primary ovarian carcinomas, and determine its significance in relation to clinicopathological features, overall and recurrence-free survival (RFS). PATIENTS AND METHODS: The protein expression of E-cadherin was immunohistochemically evaluated in formalin-fixed, paraffin-embedded samples in 104 patients with primary ovarian carcinomas. The clinicopathological factors studied were age, FIGO staging, histological type, tumour differentiation, the appearance of the ovarian capsule, peritoneal implants and residual tumour after cytoreductive surgery. Overall survival and RFS were evaluated using the Kaplan-Meier method, and multivariate analysis was completed using the Cox regression model. RESULTS: Of the 104 carcinomas, negative E-cadherin immunoexpression was observed in seven (7%) cases, and positive immunoexpression in 97 (93%). E-cadherin categorised into negative versus positive expression did not associate with any of the established clinicopathological parameters. However, negative E-cadherin expression significantly predicted a poorer overall survival when compared with positive expression (P=0.006). In the multivariate analyses, negative E-cadherin and the presence of residual tumour after cytoreductive surgery were independent prognostic factors for survival (P=0.014 and P=0.034, respectively). CONCLUSIONS: The presence of residual tumour after primary cytoreductive surgery and negative E-cadherin expression seem to be useful markers in patients with ovarian carcinomas likely to have an unfavourable clinical outcome. The assessment of E-cadherin immunoreactivity may be a useful prognostic indicator in ovarian cancer, complementary to established prognostic factors.     

高温对人舌癌细胞粘附性影响的实验研究

[目的]观察高温外理前、后的人舌癌细胞(Tca鄄8113)对层粘连蛋白(Ln)和纤维粘连蛋白(Fn)的粘附能力的影响,探寻高温治癌的机理。[方法]采用结晶紫染色法分别测定在37℃条件下培养24小时和在43℃条件下加热40分钟后继续培养24小时的Tca鄄8113细胞对Ln和Fn的粘附能力。[结果]加温后的人舌癌细胞粘附在包被了Fn和Ln孔板上的数量、密度明显减小;通过酶标仪测定光密度OD值,发现加温组的OD值均低于未加温组的OD值,两组相比,具有显著性差异(P<0.01)。[结论]高温能够降低人舌癌细胞对Fn、Ln的粘附能力,从而降低肿瘤细胞对基底膜的浸润、转移力,达到治疗肿瘤的目的。     

Homotypic Adhesion through Carcinoembryonic Antigen Plays a Role in Hepatic Metastasis Development

We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of liver-metastatic cells in SCID mice. This cell line strongly expressed CEA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay. Further, to study the role of CEA in the hepatic metastasis of cells with high metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the inhibition of hepatic metastasis after splenic injection in vivo was examined. There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated (100 μg/ml) LS-LM4 cells under a Ca²⁺-free condition as compared with the control ( P <0.01). Anti-CEA antibody (100 μg/ml) inhibited cell aggregation under a Ca²⁺-free condition ( P <0.05). Treatment with anti-E-cadherin antibody (60 μ/ml) plus anti-CEA antibody (100 μg/ml) inhibited cell aggregation more potently than anti-E-cadherin antibody treatment alone in the presence of Ca²⁺. In vivo , there was a 75% decrease in the number of hepatic metastatic nodules in the G125 anti-CEA antibody-treated group as compared with the control group ( P <0.01). Similarly, there was a 40% decrease in the diameter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated group as compared with the control ( P <0.01). These results suggest that increased metastatic potential to the liver is at least partly due to increased homotypic binding mediated by CEA.     

CD73 and Adhesion of B-Cells to Follicular Dendritic Cells

CD73, otherwise known as ecto-5'-nucleotidase, is a lymphocyte maturation marker which is involved in intracellular signalling, lymphocyte proliferation and activation. In addition, we have demonstrated that CD73 is involved in mediating lymphocyte binding to in vitro cultured endothelial cells and in controlling adhesion between freshly isolated germinal center B-cells and follicular dendritic cells (FDC). In secondary lymphoid tissues, CD73 is expressed on FDC in the light zone of the germinal center as well as on small, resting mantle zone B-cells but not on B-cells within germinal centers. In this review article, the potential role of CD73 in controlling B-cell-FDC interactions and B-cell maturation will be discussed.     

Type I insulin-like growth factor receptor function in breast cancer

Experimental evidence suggests an important role of the type I IGF receptor (IGF-IR) in breast cancer development. Breast tumors and breast cancer cell lines express the IGF-IR. IGF-IR levels are higher in cancer cells than in normal breast tissue or in benign mammary tumors. The ligands of the IGF-IR are potent mitogens promoting monolayer and anchorage-independent growth of breast cancer cells. Interference with IGF-IR activation, expression, or signaling inhibits growth and induces apoptosis in breast cancer cells. In addition, recent studies established the involvement of the IGF-IR in the regulation of breast cancer cell motility and adhesion. We have demonstrated that in MCF-7 cells, overexpression of the IGF-IR promotes E-cadherin-dependent cell aggregation, which is associated with enhanced cell proliferation and prolonged survival in three-dimensional culture.The expression or function of the IGF-IR in breast cancer cells is modulated by different humoral factors, such as estrogen, progesterone, IGF-II, and interleukin-1. The IGF-IR and the estrogen receptor (ER) are usually co-expressed and the two signaling systems are engaged in a complex functional cross-talk controlling cell proliferation.Despite the convincing experimental evidence, the role of the IGF-IR in breast cancer etiology, especially in metastatic progression, is still not clear. The view emerging from cellular and animal studies is that abnormally high levels of IGF-IRs may contribute to the increase of tumor mass and/or aid tumor recurrence, by promoting proliferation, cell survival, and cell-cell interactions. However, in breast cancer, except for the well established correlation with ER status, the associations of the IGF-IR with other prognostic parameters are still insufficiently documented.     

Selection of Human Ovarian Carcinoma Cells with High Dissemination Potential by Repeated Passage of the Cells in vivo into Nude Mice, and Involvement of Lex-determinant in the Dissemination Potential

Cells of the human tumor cell line RMG-1, derived from a clear-cell adenocarcinoma of the ovary, were injected intraperitoneally into nude mice, and the cells obtained from the tumor nodules in the mesenterium were found to form a larger number of, and larger-sized, tumor nodules than the original RMG-1 cells. The RMG-1-h cells, transferred into culture from the tumor nodules after a 4th in vivo passage, showed a dissemination potential as high as that of cells disseminating directly from the tissues, and exceedingly higher than that of RMG-1 cells. To assess the molecular bases of the different biological properties of RMG-1 and RMG-1-h cells, we compared the content and expression of various carbohydrate antigens in both cells. The chromosomal profile of RMG-1-h cells revealed their human origin and was identical to that of the original RMG-1 cells. In contrast to the broad histogram for the Le^x-bearing cells among RMG-1 cells in flow cytometry, the weakly and moderately positive cells toward anti-Le^x antibody were found to be eliminated from the histogram for the RMG-1-h cells, resulting in the enrichment of cells strongly expressing Le^x, which may account for the high dissemination potential. In addition, the adhesion of RMG-1 cells to mesothelial cells was found to be significantly inhibited by pretreatment of the cells with anti-Le^x antibody, indicating Le^x-mediated cell-to-cell interaction between ovarian cancer cells and mesothelial cells. By TLC-immunostaining, two Le^x-glycolipids, III³Fucα-nLc₄Cer and V³Fucα-nLc₆Cer were detected in both RMG-1 and RMG-1-h cells, and their total concentrations were not significantly different from each other. However, the hydrophobic moieties of Le^x-glycolipids in RMG-1-h cells were different from those in RMG-1 cells, suggesting that a difference in the structure of the hydrophobic moieties of Le^x is partly involved in the enhanced reactivity of RMG-1-h cells toward anti-Le^x antibody. Thus, the high dissemination potential of ovarian cancer cells was shown to be mediated by the Le^x-determinant and the Le^x-bearing cells are enriched by repeated in vivo passage of the cells into nude mice.     

细胞间粘附分子-1在肾小球炎症过程中的作用及氯沙坦对其影响

目的：探讨细胞间粘附分子－１（ＩＣＡＭ－１）在肾小腺炎症过程中的作用及氯沙坦对其影响。方法：采用体外肾小球系膜细胞与巨细胞共同培养的方法,观察抗ＩＣＡＭ－１ ＭｃＡｂ对巨噬细胞促进系膜细胞增殖的影响及氯沙坦对其保护作用。结果 抗ＩＣＡＭ－１ＭｃＡｂ对巨噬细胞促进系膜细胞的增殖具有抑制作用,呈现剂量依赖趋势;氯沙坦（０,１,１．０,１０．０μｍｏｌ／Ｌ）可明显抗ＩＣＡＭ－１ ＭｃＡｂ对巨噬细胞促进