乙酰肝素酶与肿瘤转移

乙酰肝素酶是一种糖苷内切酶，能特异性的水解位于细胞表面，细胞外基质及基底膜的硫酸乙酰肝素蛋白聚糖为小分子片段。乙酰肝素酶普遍存在于恶性转移性肿瘤细胞中。乙酰肝素酶参与肿瘤血管生成，与肿瘤的侵袭、转移密切相关。本文对此进行了综述。     

肝素酶与肝细胞癌侵袭转移的关系

我们应用逆转录聚合酶链反应 (RT PCR)技术检测 33例原发性肝细胞肝癌 (hepatocellularcarcinoma ,HCC)标本中肝素酶 (heparanase,HPA)的基因表达 ,并结合病人的临床病理学和随访资料 ,以探讨HPA可否作为HCC转移潜能的可靠标志。对象与方法1.研究对象 :新鲜冷冻的标本取自 2 0 0 0年 8月至 2 0 0 1年 4月浙江大学医学院附属第二医院普外科、肿瘤外科手术切除并经病理学检查证实的 33例HCC(包括癌和癌旁肝组织 )和 9例肝脏良性肿瘤 (取瘤旁肝组织作正常对照 )。收集病人临床病理学检查资料 ,HCC组中 ,男 2 8例 ,女 5例 ;年龄2 9～ …     

乙酰肝素酶和血管内皮生长因子在肝癌中的表达及其与血管生成的关系

乙酰肝素酶（Hpa）是一种内切糖苷酶，可降解细胞外基质和基底膜中的硫酸乙酰肝素，破坏其完整性，同时释放在细胞外基质中储存的血管内皮生长因子（VEGF），促进肿瘤血管的生成，从而有利于肿瘤细胞的侵袭和转移。本研究旨在探讨Hpa、VEGF与肝癌的临床病理特征及肿瘤血管新生之间的关系。     

乙酰肝素酶与肿瘤转移

乙酰肝素酶是一种糖苷内切酶 ,能特异性的水解位于细胞表面 ,细胞外基质及基底膜的硫酸乙酰肝素蛋白聚糖为小分子片段。乙酰肝素酶普遍存在于恶性转移性肿瘤细胞中。乙酰肝素酶参与肿瘤血管生成 ,与肿瘤的侵袭、转移密切相关。本文对此进行了综述。     

肾细胞癌血管生成与癌细胞转移的关系

目的：探讨肾细胞癌血管生成及其与肿瘤转移的关系。方法：采用免疫组织化学ＬＳＡＢ法检测肾细胞癌血管内皮生长因子（ＶＥＧＦ）的表达及微血管数（ＭＶＣ）。结果：癌组织中ＶＥＧＦ的表达与ＭＶＣ有关;有肿瘤转移者ＶＥＧＦ表达和ＭＶＣ的等级分布显著高于无肿瘤转移者。结论：肾细胞癌血管生成可能有赖于癌细胞合成分泌的ＶＥＧＦ来调节;ＶＥＧＦ表达和ＭＶＣ均与肿瘤转移有关,有可能作为判断肾细胞癌转移潜能的预后指标。     

乳腺癌浸润和转移与乙酰肝素酶表达的关系

目的 观察乙酰肝素酶(Hpa)在乳腺癌的表达,探讨它们的表达与乳腺癌浸润、转移的关系及临床意义.方法 对60例未行任何化疗、放疗和内分泌治疗的原发性乳腺癌病理标本进行分析,应用苏木素-伊红(HE)染色观察乳腺癌的组织形态和病理学变化;应用免疫组织化学法检测乳腺癌患者癌组织、癌旁2 cm乳腺组织及距癌组织5 cm以上的正常乳腺组织中Hpa的表达.结果 60例乳腺癌病理标本免疫组织化学结果显示,乳腺癌组织Hpa阳性表达率为68.33％ (41/60),癌旁组织(癌旁2 cm)Hpa阳性表达率40.00％(24/60),正常组织Hpa阳性表达率0.00％ (0/60).统计分析结果显示,与正常对照组织比较,Hpa在癌组织和癌旁组织表达升高且差异有统计学意义(P＜0.01).Hpa的表达与乳腺癌临床病理标志的相互关系分析结果显示:Hpa的表达与乳腺癌患者体内瘤块直径、组织学分级、腋下淋巴结状况及临床分期明显相关(P＜ 0.05),与患者年龄无明显相关(P＞0.05).而且具有腋下淋巴结转移的患者Hpa阳性表达率显著高于无腋下淋巴结转移组(P＜0.01).结论 Hpa在乳腺癌中的表达均较高,明显高于癌旁组织及正常乳腺组织;Hpa的表达与乳腺癌肿瘤大小、组织学分级、临床分期、淋巴结转移密切相关,与患者的年龄无明显相关.     

乙酰肝素酶在膀胱移行细胞癌中的表达及临床意义

目的:探讨乙酰肝素酶(Heparanase,HPA)在膀胱移行细胞癌中的表达及临床意义.方法:应用逆转录-聚合酶链反应(RT-PCR)及免疫组织化学方法检测68例膀胱移行细胞癌、24例癌旁组织、15例正常膀胱组织中HPA mRNA的水平及蛋白表达定位,并结合患者临床病理指标及预后进行分析.结果:膀胱移行细胞癌中HPA mRNA检出阳性41例(60.3%),24例癌旁组织中阳性1例(4.2%),1 5例正常膀胱组织中全部阴性,分别与癌组织组比较差异有统计学意义(P<0.01),HPA mRNA的表达在膀胱移行细胞癌不同病理分级、临床分期及淋巴结转移与否分组中显著不同(P<0.01).免疫组织化学结果显示,HPA定位于细胞质及细胞核,阳性率为77.9%(53例),在膀胱移行细胞癌淋巴结转移与否分组中显著不同(P<0.01).结论:HPA在膀胱移行细胞癌的生长浸润、侵袭转移中可能发挥重要作用,可为膀胱移行细胞癌生物学行为和预后的判断提供较客观指标.     

乙酰肝素酶在消化道肿瘤中的研究进展

乙酰肝素酶（HPA）是哺乳动物细胞中唯一能切割细胞外基质（ECM）中硫酸乙酰素蛋白多糖（HSPGs）侧链中硫酸乙酰肝素（HS）的一种葡萄糖醛酸内切酶。大量实验证实HPA在多数恶性肿瘤高表达,并参与肿瘤血管生成、侵袭转移。本文对HPA在消化道肿瘤血管生成、侵袭转移及以HPA为靶点的抗肿瘤药物作一综述。     

乙酰肝素酶在恶性肿瘤中的研究进展

乙酰肝素酶(HPSE)是目前在哺乳动物中发现的可以降解硫酸乙酰肝素蛋白聚糖(heparan sulfate proteoglycans,HSPGs)上的硫酸肝素(HS)糖链的一类β-D糖苷内切酶.其在肿瘤侵袭转移中起着关键作用.本文就HPSE分子结构、生物学特征、在恶性肿瘤中的表达、促进肿瘤转移机制及HPSE抑制剂的应...     

Loss of expression of ZAC/LOT1 in squamous cell carcinomas of head and neck

BACKGROUND: ZAC/Lot1 is a previously identified candidate tumor suppressor gene. The gene maps to the human chromosome 6q24-q25, a region frequently deleted in squamous cell carcinomas of the head and neck and other solid tumors. METHODS: We have used a model of head and neck squamous cell carcinoma (HNSCC) and cell lines to analyze the role of the candidate tumor suppressor gene ZAC/Lot1 in oral carcinogenesis. We analyzed the expression in 11 cell lines, and we performed loss of heterozygosity (LOH)- and sequence analyses in 51 primary tumors. RESULTS: Three (27.3%) of 11 cell lines showed a distinctly reduced expression of ZAC/Lot1 compared with expression levels of the gene in the normal oral mucosa. In addition, we analyzed 51 primary squamous cell carcinomas of the head and neck for LOH with seven microsatellite markers flanking ZAC/Lot1. We detected an average LOH rate of 31.4% in the region of interest. Sequence analysis revealed no mutations for the ZAC/Lot1 coding exons, including the exon/intron boundaries. CONCLUSIONS: These data could suggest a minimal role for ZAC/Lot1 in a subgroup of HNSCC tumors.     

Molecular mediators of metastasis in head and neck squamous cell carcinoma

BACKGROUND: The presence of regional metastasis in patients with head and neck squamous cell carcinoma (HNSCC) is a common and adverse event associated with poor prognosis and high mortality. Although significant improvements in standard therapies have increased the efficacy of local tumor management, the high incidence of tumor recurrence has resulted in limited improvements in overall survival rates. Understanding the molecular mechanisms that mediate HNSCC invasion and metastasis may enable identification of novel therapeutic targets for the prevention and management of tumor dissemination. METHODS: A literature review was performed. RESULTS: Several biologic mediators and mechanisms that have been implicated in HNSCC metastasis, such as cell adhesion molecules, proteolytic enzymes, growth factor signaling, metastasis suppressor genes, and chemokine receptors were reviewed. CONCLUSIONS: Prevention of HNSCC metastasis is an important clinical objective that requires an increased understanding of the molecular mechanisms of tumor invasion and dissemination.     

乙酰肝素酶在膀胱癌中的表达及其与肿瘤血管形成的关系

目的探讨乙酰肝素酶(HPSE)mRNA在膀胱癌中的表达及其与肿瘤临床病理特征和血管生成的关系。方法应用逆转录聚合酶链反应(RTPCR)检测42例膀胱癌及16例癌旁组织中HPSEmRNA的表达,应用免疫组织化学法检测膀胱癌组织的微血管密度(MVD),结合患者临床病理指标及预后进行分析。结果42例膀胱癌中,HPSEmRNA阳性23例(54.8%),16例癌旁组织中表达阳性者2例(12.5%),两组差异有统计学意义(P<0.01);HPSEmRNA的表达与膀胱癌的病理分级、临床分期、肿瘤大小及淋巴结转移有相关性(P<0.05);术后生存3年以下者HPSEmRNA的表达阳性率87.5%,明显高于生存3年以上者之46.9%(P<0.05);HPSEmRNA表达阳性者MVD值为90.8±13.6,表达阴性者肿瘤MVD计数均值为65.8±6.6,两组差异有统计学意义(P<0.01)。结论HPSE在膀胱癌的生长浸润、侵袭转移和血管生成中发挥重要作用,可作为判断膀胱癌生物学行为和预后的客观指标。     

Loss of imprinting and loss of heterozygosity on 11p15.5 in head and neck squamous cell carcinomas

BACKGROUND: IGF2 and H19 are reciprocal imprinted genes with paternal and maternal monoallelic expression, respectively. This is interesting, because IGF2 is known as a growth factor, and H19 encodes a RNA with putative tumor suppressor action. Furthermore, IGF2 and H19 are linked genes located on chromosome 11p15.5, a common site of loss of heterozygosity in human cancers. METHODS: We performed an allelic-typing assay using a PCR-RFLP-based method for identification of heterozygous informative cases in head and neck squamous cell carcinomas. Tumoral total RNA was extracted from each of the heterozygotes and further studied by RT-PCR analysis. RESULTS: We detected the expression of the IGF2 gene in 10 of 10 informative cases. Two cases exhibited LOI of the IGF2 gene as evidenced by biallelic expression, and in another case, LOH was coupled with monoallelic expression of this growth factor. LOI for the H19 gene was observed in 1 of 14 informative samples analyzed. In this case, we also detected parallel monoallelic expression of the IGF2 gene. Down-regulation of the H19 gene was observed in 10 of 14 cases. CONCLUSION: These findings support the hypothesis that H19 may be a tumor suppressor gene involved in head and neck carcinogenesis. Furthermore, our data showed that genetic and epigenetic changes at 11p15.5 could lead to abnormal expression of imprinted genes in HNSCC.     

Galectins as modulators of tumor progression in head and neck squamous cell carcinomas

Head and neck squamous cell carcinomas (HNSCCs) remain a significant cause of morbidity worldwide. Biological therapies able to induce and/or upregulate antitumor immune responses could represent a complementary approach to conventional treatments for patients with HNSCC because, despite advances in surgery, radiotherapy, and chemotherapy, the overall survival rates for these patients have not changed over recent decades. Galectins are involved in the control of cell proliferation, cell death, and cell migration and in the modulation of various functions of the immune system. In this context, galectin-1 is known to protect HNSCCs from the immune system. The present review details the involvement of galectins in HNSCC biology and suggests a number of approaches to reduce the levels of expression of galectin-1 in HNSCCs, with the aim of improving the efficiency of HNSCC immunotherapy.     

动态对比增强磁共振成像鉴别诊断头颈部鳞癌和未分化癌的价值

［摘要］ 目的 评价定量动态对比增强磁共振成像（DCE-MRI）参数鉴别诊断头颈部鳞癌和未分化癌的可行性。方法 收集42名患有头颈部鳞状癌,53名患有未分化癌的患者,平均年龄分别为63±17岁,45±23岁,总共95名患者在治疗前进行MRI检查,对QDCE-MRI定量参数进行评估,分析病理类型和MRI参数,包括体积转运常数（Ktrans）、反向回流速率常数（Kep）、血管外细胞外间隙体积（Ve）、血浆体积分数（Vp）、达峰时间（TTP）、最大浓度（MAXCon）、曲线下面积（AUC）、最大斜率（MAXSlope）之间的关联。结果 HNSCC组Ktrans,Kep,TTP,MAXSlope值分别为0.09620±0.3894 min-1,0.6527±0.2608 min-1,2.9640±0.8409 min,1.8499±0.7698,UC组患者的Ktrans,Kep,TTP,MAXSlope值分别为0.1432±0.0527 min-1,0.8520±0.2166 min-1,2.1055±0.9605 min,2.1543±0.8767,两组间差异有统计学意义（P<0.05）,其余参数无统计学差异。结论 包括Ktrans、Kep、TTP、MAXSlope在内的DCE-MRI定量参数可以用来鉴别头颈鳞癌和未分化癌。