过表达STAT1与CD74CD44促进结肠癌细胞粘附和迁移的相关性

目的 探讨信号转导和转录激活子1(STAT1)与CD74/CD44在结肠癌中异常表达与肿瘤转移的相关性.方法 培养结肠癌细胞株Ls-174-T,待其生长至对数生长期,传至第3代收集肿瘤细胞,各细胞分为3份.1份行RT-PCR、Western blotting方法检测STAT1与CD74/CD44表达情况;1份检测定量粘附细胞数;1份以划痕实验检测细胞迁移能力.统计分析比较STAT1与CD74/CD44在结肠癌细胞中的异常表达情况及与肿瘤迁移和粘附能力的相关性.结果 RT-PCR、Western blotting结肠癌组织中STAT1与CD74/CD44的蛋白及mRNA表达显著高于正常结肠组织,两组相比具有统计学差异(P＜0.05).MTT法检测结果显示,不同作用时间(0、6、12、24、48 h)不同剂量STAT1与CD74/CD44过表达质粒(0.000、0.001、0.010、0.060、0.100 mg/ml)干预后,结肠癌细胞体外粘附能力明显加强,与对照组(0.000 mg/ml各组)相比,差异有统计学意义;Transwell结果显示,不同作用时间(0、6、12、24、48 h)不同剂量STAT1与CD74/CD44过表达质粒(0.000、0.001、0.010、0.060、0.100 mg/ml)干预后,结肠癌细胞体外迁移能力随着时间及剂量的增加而明显加强,与对照组(0.000mg/ml各组)相比,差异有统计学意义.结论 STAT1与CD74/CD44在结肠癌细胞中高表达,从而调节结肠癌细胞粘附和迁移能力的作用,表明STAT1与CD74/CD44在结肠癌发生进展中可能与肿瘤的侵袭和转移密切相关.     

奥沙利铂对二甲肼诱导的结肠癌大鼠CD44V6、VEGF、survivin、Caspase-3和Caspase-7的影响

目的 研究奥沙利铂对结肠癌大鼠治疗的作用机制。方法 将42只SD大鼠均颈背部皮下注射二甲肼,每周注射 1次,连续注射5周。随机抽取2只大鼠切取直肠进行HE染色,病理学观察,确定结肠癌大鼠模型建立。将40只结肠癌大鼠随机分为模型组、奥沙利铂高、中、低剂量组,每组10只。另设正常组SD大鼠10只。奥沙利铂高剂量组（27.2 mg/kg）、中剂量组（13.6 mg/kg）、低剂量组（6.8 mg/kg）,给予1 ml 5%的葡萄糖注射液溶解,尾静脉注射给药,每3周给药一次,连续给药12周。正常组与模型组给予1 ml 5%的葡萄糖注射液代替。末次给药48 h后,通过颈脱位法处死大鼠。显微镜观察结肠组织中异变腺窝病灶(ACF)的个数。通过酶联免疫吸附（ELISA）法检测结肠癌大鼠血清中CD44V6和VEGF的含量变化。免疫蛋白印记（Western blot）法检测结肠癌组织中survivin、Caspase-3和Caspase-7的蛋白水平。结果 与模型组比较,奥沙利铂给药组结肠组织中ACF的数量明显减少。与正常对照组比较,模型组血清中CD44V6和VEGF的含量显著增加（P＜0.05）。与模型组相比,奥沙利铂高剂量组、中剂量组血清中CD44V6和VEGF的含量下降。其中奥沙利铂高剂量的效果最好,差异有统计学意义（P＜0.05）。与正常组相比,模型组、奥沙利铂给药组结肠癌组织中的survivin、Caspase-3和Caspase-7的蛋白水平均上升。与模型组相比,奥沙利铂给药组结肠癌组织中的survivin的蛋白水平降低;Caspase-3和Caspase-7的蛋白水平升高,差异有统计学意义（P＜0.05）。结论 奥沙利铂通过调控CD44V6、VEGF、survivin、Caspase-3和Caspase-7的水平,减少肿瘤血管的生成与转移、调节结肠癌组织中的细胞凋亡,从而达到治疗的目的。     

乳腺癌CD44v6和Survivin的表达与临床预后的相关性研究

研究CD44v6和Survivin的表达与乳腺癌临床病理特征和生存率的关系以及在乳腺癌和良性乳腺疾病的表达差异。方法:用免疫组化法检测64例乳腺癌标本和12例良性乳腺（对照组）标本CD44v6和Survivin表达。将乳腺癌病例按表达分成A组（双阳性组）、B组（单阳性组）和C组（双阴性组）,随访生存情况。结果:乳腺癌组和对照组中CD44v6阳性率分别为57.81%和25.00%（P=0.037）,Survivin阳性率分别为73.43%和8.33%（P<0.001）。乳腺癌组织中CD44v6和Survivin表达均高于对照组。CD44v6和Survivin的表达与年龄、肿瘤大小、组织学分级和分类均无明显相关（P>0.05）,但与临床分期和淋巴结转移明显相关（P<0.05）。A、B、C组的平均生存期分别为（84.07±6.69）、（103.89±6.77）、（115.50±7.42）个月。64例乳腺癌患者的平均生存期为（97.43±4.59）个月。A、B、C组的5年总生存率分别为74.19%、90.91%、100.00%;10年总生存率分别为35.48%、59.09%和72.73%（P=0.043）。结论:CD44v6和Survivin表达分布存在组织特异性。两者过量表达与年龄、肿瘤大小、组织学分级及组织学分类之间均无统计学差异,但与临床分期和淋巴结转移存在显著性差异。两者均阳性表达患者5年和10年生存率最低。CD44v6和Survivin均是乳腺癌的预后因素,有助于指导治疗和预测预后。      

Quantitative Analysis of Multidrug-resistance mdr1 Gene Expression in Head and Neck Cancer by Real-time RT-PCR

Progression of head and neck cancer is always associated with changes of gene expression profile. In this study, we characterized the expression of multidrug‐resistance mdr1 gene, which may play a role in tumorigenesis and multidrug resistance in head and neck cancer. A TaqMan one‐step RT‐PCR with a linear range for quantification across at least a 5 log scale of concentration of mdr1 mRNA was designed to determine the level of mdr1 expression in 50 pairs of normal vs. malignant head and neck tissues. Both the absolute level of mdr1 mRNA in tumor (T) and the relative mdr1 expression between tumor and its normal counterpart (T/N) were measured and their associations with several clinical variables were analyzed. Among the clinical variables analyzed, only the clinical stage of tumor was found to be associated with mdr1 expression. The distribution of clinical stages differed significantly (P<0.01) among the 27 specimens that had a T/N>1, with 59.3%, 22.2%, 14.8% and 3.7% in stage IV, III, H, and I, respectively. In addition, 76% of stage IV and 75% of stage III tumors had a T/N>1 compared to 25% of stage II and 20% of stage I tumors (P=0.004). Multivariate logistic regression analysis also indicated a significant difference of mdr1 expression between the early (I and II) and advanced (III and IV) stages tumors. The adjusted odds ratios (95% confidence intervals) were 1.477 (1.084–2.012) and 1.001 (1.000–1.002) for T/N (P<0.05) and T (P<0.05) treated as continuous variables, and 15.521 (3.414–70.550) and 5.074 (1.154–22.311) for T/N (P<0.001) and T (P<0.05) treated as binary variables, respectively. Taken together, the data presented here indicated that real‐time RT‐PCR provides a quantitative way to monitor mdr1 gene expression. The differential expression of mdr1 between early and advanced stages of head and neck cancer may shed light on the process of tumorigenicity and offer clues to the planning of new treatments.     

CD44v和透明质酸介导的细胞游走受体在多阶段胃癌发生中的表达特点

目的 探讨透明质酸（ＨＡ）受体ＣＤ４４和透明质酸介导的细胞游走受体（ＲＨＡＭＭ）在多阶段胃癌发生过程中的表达情况及其肿瘤学意义。方法 以非癌粘膜,各类癌前病变和胃癌标本为研究对象,采用常规和组织选择性方法提取样本ＲＮＡ和蛋白质,进而分析其ＣＤ４４和ＲＨＡＭＭ基因表达的特点,结果 含变异型外显子/５的ＣＤ４４广泛存在于各类组织中,ｖ７常见于非癌细胞,但随癌前病变的进展而趋降低,ｖ８～ｖ１０仅见于部分肠     

CD44在胰头癌中的表达及其临床意义

目的 研究CD44与胰头癌各临床病理参数、生存期和预后的关系.方法 收集48例胰头癌原发灶.记录48例胰头癌病例的临床病理学资料如性别、年龄、组织学分型、肿瘤所在部位、淋巴结转移情况等.结果 CD44在48例胰头癌中阳性表达率为64.6%(31/48).单因素分析显示,胰头癌患者的T分期、TNM分期、淋巴结转移情况与CD44的阳性率表达相关(P<0.05),而年龄、性别、脉管侵犯、神经侵犯、分化程度、肿瘤部位等与CD44的阳性率表达无关(P>0.05).Cox模型分析显示CD44、淋巴结转移情况可作为独立的预后因子.结论 胰头癌中CD44呈高表达,且与胰头癌的恶性程度有关.     

Cellular localization of CD44 correlates with cell proliferation and liver metastasis in colon cancer

Background. The functional heterogeneity of the cell adhesion molecule family CD44 is explained by differences in its activity, which is regulated by alterations in the distribution of its cellular localization. The aim of the current study was to evaluate the functional differences in cancer cells according to variations in the cellular localization of CD44. Methods. Paraffin-embedded tissue sections of 34 colon cancers (obtained from 17 patients with liver metastasis and 17 without liver metastasis) were investigated. These tumors were classified according to the predominant pattern of cellular localization of CD44 (the isoforms CD44H, CD44v6, and CD44v9). For each CD44 isoform, the functional differences were investigated for a correlation between localization patterns and Ki-67 labeling index (to indicate cell proliferative activity), and for a correlation between localization patterns and liver metastasis. Results. On staining for CD44H, tumors displayed three localization patterns. One pattern, in which CD44H was expressed on the basal or basolateral side of the plasma membrane in cancer cells, showed a higher Ki-67 labeling index than other localization patterns (P < 0.01), and a higher rate of the basolateral localization pattern was observed in patients with liver metastasis than in those without (P = 0.02). On staining for CD44v6 and CD44v9, tumors showed four and three localization patterns, respectively. No significant differences in localization patterns were found in analyses of the Ki-67 labeling index and liver metastasis for either CD44v6 or CD44v9. Conclusions. A functional correlate of CD44H localization patterns was detected. In particular, cancer cells in which CD44H was localized at the basal or basolateral membranes were closely associated with high proliferative activity and high liver metastatic potential. Received: February 27, 1998 / Accepted: November 16, 1998     

Predictive Value of CD44 for Prognosis in Patients with Breast Cancer

Background: Breast Cancer (BC), is one of the most common malignancies around the world. CD44 expression correlates with cell proliferation, infiltration, angiogenesis, metastasis and prognosis in breast cancer but the exact mechanism of CD44 function is still not clear. The present study evaluates the expression of CD44 in primary HER2-positive breast cancer. The results can be used to determine the disease-free and overall survival of patients with breast cancer. Methods: We studied specimens from 100 patients with HER2-positive invasive breast cancer between March 2011 and June 2019. Immunohistochemical staining for CD44 was performed in all the specimens. Their CD44 association with clinicopathologic parameters and prognosis was evaluated. Results: The high CD44 was expression in 68(68%) of the patients and Low expression in 32(32%). CD44 expression was significantly associated with stage (p=0.007). There were no significant associations between the DFS, OS and other clinicopathologic parameters except for the stage, respectively (HR= 3.67, 95% CI =1.16-11.56, P = 0.03) (HR= 0.8.56, 95% CI =2.22-32.90, P = 0.002).20% of patients had died by the end of the follow-up. There were no significant association between DFS, OS and CD44 expression, respectively. (Log-rank p=0.13). (Log-rank p=0.10). Conclusion: The results from this study suggest that CD44 is clinically associated with stage of breast cancers. From the survival analysis, there was no statistical difference in overall survival and disease free survival with respect to CD44 expression. Further studies larger sample sizes are recommended for further investigation.     

Expression of CD44 Variants and Its Association with Survival in Pancreatic Cancer

Since the CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, we examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 variants was evaluated immunohistochemically in paraffin-embedded pancreatic cancer tissues from 42 patients who were confirmed surgically and histologically to have received curative resection. An indirect immunoperoxidase method was used with monoclonal antibodies against epitopes of the standard (CD44s) portion, v6 and v2. Protein expression data were evaluated statistically for any correlations with the length of survival or with histological parameters. The expression of CD44v6 and v2 was observed only in tumor cells, if at all. On the other hand, expression of total CD44 (including CD44v, as well as CD44s) was observed in both tumors and adjacent normal sites. Tumor tissue from 21 (50%) and 16 (38%) patients showed positive immunoreactivity with mAb 2F10 (anti-CD44v6) and mAb M23.6.1 (anti-CD44v2), respectively. The expression of CD44v6 and v2 was correlated with decreased overall survival ( P =0.0160 and P =0.0125, respectively). A significant correlation was obtained between CD44v2 peptide expression and vessel invasion ( P =0.026). These results suggest that CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer.     

62例鼻咽癌中Ki67和CD44v6表达及意义

[目的]研究鼻咽癌中Ki67和CD44v6的表达及其关系。[方法]采用免疫组化S-P法检测23例鼻咽慢性炎、62例鼻咽癌（38例伴有淋巴结转移）组织中Ki67和CD44v6的表达情况。[结果]鼻咽慢性炎和鼻咽癌中Ki67阳性表达率分别为71.0%、13.0%,差异有统计学意义（P〈0.05）。CD44v6在鼻咽癌和鼻咽慢性炎中的阳性率分别为77.4%、17.4%,差异有统计学意义（P〈0.05）。鼻咽癌转移组Ki67和CD44v6的阳性率分别为84.2%、89.5%,明显高于非转移组的50.0%、58.3%（P〈0.05）。鼻咽癌中Ki67和CD44v6表达呈正相关（r=0.452,P〈0.05）。[结论]Ki67和CD44v6在鼻咽癌中的高表达协同参与了鼻咽癌的增殖和转移。     

CO_2气腹对结肠癌SW480细胞株生长周期及CD44表达的影响

[目的]探讨CO2气腹对体外培养的结肠癌细胞生长增殖的影响。[方法]采用CO2气体建立模拟气腹条件,对照组不作气腹处理。CO2组、Ar组处理结肠癌SW480细胞株气压均为15mmHg维持30min,观察其细胞生长周期变化及细胞表面黏附分子CD44表达情况。[结果]CO2气腹处理SW480结肠癌细胞24h后S期细胞比例无明显变化,与对照组比较无显著性差异;48h后S期细胞比例降至7.2%,显著性低于对照组的37.2%;72h后S期比例回升至25.7%,与对照组相比无显著性差异（25.7%vs31.1%,P〉0.05）。而CO2组CD44表达在24h后降低至1.2%,低于对照组的13.4%（P〈0.01）;48h和72hCD44表达均高于对照组（26.4%vs13.4%,P〈0.01;39.7%vs13.4%,P〈0.01）。[结论]CO2气腹对体外培养的结肠癌SW480细胞的生长有短暂可逆的抑制作用。     

CD44v6、MUC1及VEGF在三阴性乳腺癌组织中的表达及其临床意义

[目的]探讨CD44v6、MUC1及VEGF在三阴性乳腺癌中的生物学特征及其对预后评估的意义。[方法]采用免疫组织化学SP法检测CD44v6、MUC1及VEGF在104例三阴性乳腺癌、168例非三阴性乳腺癌中的表达。[结果]CD44v6及MUC1在三阴及非三阴性乳腺癌中的表达无明显差异．VEGF在非三阴性乳腺癌的表达明显高于三阴性乳腺癌（P〈0．05）。在三阴性乳腺癌中,CD44v6、MUC1及VEGF表达与年龄、组织学分级、肿瘤大小、临床分期、淋巴结转移均无明显相关性：在非三阴性乳腺癌中,除CD44v6在无淋巴结转移组表达明显高于转移组（P〈0．05）外,CD44v6、MUC1及VEGF表达与其他临床病理参数均未见明显相关性。CD44v6、MUC1及VEGF联合检测,阳性率明显增加。但不同组合中三阴性乳腺癌及非三阴性乳腺癌的表达仍无差别。[结论]未发现CD44v6、MUC1及VEGF在三阴性乳腺癌中存在表达优势,且与预后参数如临床分期、组织学分级、淋巴结转移情况无明显相关性,其预后价值有待进一步验证。     

胃癌及癌旁组织Fas蛋白和CD44V6蛋白的表达及其临床意义

目的　探讨Fas蛋白、CD44V 6蛋白在胃癌及癌旁组织的表达及其临床意义。方法　采用免疫组化SP法分别检测5 7例胃癌组织 ,5 7例癌旁组织和 2 0例正常胃黏膜组织中Fas蛋白、CD44V 6蛋白的表达。结果　 5 7例胃癌组织中Fas蛋白表达的阳性率为 35 .0 9% ,5 7例癌旁组织为 70 .18% ,正常胃黏膜为 85 .0 0 % ,胃癌组织与癌旁组织 ,正常胃黏膜组织Fas蛋白的表达比较均有非常显著性差异 (P <0 .0 1)。CD44V 6蛋白的表达 ,胃癌组为 66.67% ,癌旁组为 2 2 .81% ,正常胃黏膜为 10 .0 0 % ,胃癌组织与癌旁组织 ,正常胃黏膜组织之间的CD44V 6蛋白的表达均有非常显著性差异 (P <0 .0 1)。结论　Fas蛋白、CD44V 6蛋白的表达对阐明胃癌的发生机制、预后和转移均有重要意义     

CD44+/MyD88+卵巢癌转移、化疗耐药及预后的研究进展

卵巢癌是妇科三大恶性肿瘤之一,其死亡率居妇科恶性肿瘤首位,利用卵巢癌细胞表面标志分子的特异性,使化疗药物选择性地与卵巢癌细胞结合,可有效地消除肿瘤复发和抑制肿瘤耐药。寻找卵巢癌转移相关分子标记物并对其进行靶向治疗已成为研究热点,目前研究发现MyD88与CD44在卵巢癌中均有表达,并且在卵巢癌的发生发展和侵袭转移、耐药过程中起重要作用,本文着重对CD44+/MyD88+卵巢癌细胞的转移、化疗耐药及预后的研究进展进行综述。