低分子肝素对肝癌生长和转移抑制作用的研究

目的　研究低分子肝素对肝癌生长和转移的抑制作用。方法　建立人肝癌裸鼠动物模型 (LCI D2 0 )。术后第一天起分别予腹腔内注射生理盐水 (对照组 )、顺铂 氟尿嘧啶 (化疗组 )、皮下注射法安明 (低分子肝素组 )、顺铂、氟尿嘧啶与法安明联合应用 (联合组 ) ,连续 5周。测量原位肿瘤大小、观察肿瘤腹壁、其他脏器转移及腹水情况 ;肿瘤组织中微血管密度 (microvesseldensity,MVD)、血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)、平滑肌肌动蛋白 (smoothmuscleactin ,SMA) ;测定血清AFP、CEA、CA199。结果　低分子肝素组肿瘤体积、MVD、SMA、肝、肺、腹壁转移率及腹水形成率明显低于对照组 (P <0 0 5 ) ,抑瘤率明显高于对照组 (P <0 0 5 )。结论　低分子肝素对肝癌的生长与转移具有抑制作用 ,该作用与抑制肿瘤血管形成有关。     

低分子肝素对种植性乳腺癌生长和转移的抑制作用

目的 观察低分子肝素在种植性乳腺癌动物模型中对肿瘤生长和转移的抑制作用.方法 制作120例MCF-7乳腺癌细胞移植瘤裸鼠模型,将其随机分为低分子肝素组、生理盐水组、化疗组、内分泌治疗组,每组30只;观察裸鼠一般情况及移植瘤的牛长变化,28 d后统一脱颈椎处死裸鼠,切取移植瘤标本进行常规镜检及应用免疫组织化学检测瘤组织内血管内皮生长因子(VEGF)和微血管密度(MVD)的变化.结果 实验4周后,低分子肝素组、化疗组、内分泌治疗组不仅在移植瘤体积、胸壁浸润及淋巴转移等方面明显优于生理盐水组,其VEGF、MVD的表达亦低于生理盐水组,差异有统计学意义(P<0.01);其中尤以低分子肝素组中VEGF、MVD的表达更低,但与化疗组、内分泌治疗组间对比差异并无统计学意义(P>0.01).结论 低分子肝素在裸鼠MCF-7移植瘤模型中可以通过抑制肿瘤血管形成而抑制移植瘤的生长及转移.     

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...     

普通肝素和低分子肝素对骨代谢的影响

普通肝素和低分子肝素常用来预防和治疗老年骨质疏松骨折伴发的下肢深静脉血栓形成。临床研究上证明了在骨代谢的影响方面,低分子肝素要优于普通肝素。普通肝素可能通过多种途径促进破骨细胞的形成,抑制成骨细胞的成骨作用,从而对骨代谢有不良影响。而低分子肝素也能够抑制成骨细胞的作用,但对破骨细胞的作用明显低于普通肝素,总体上造成骨量流失的作用要低于普通肝素,在骨代谢上显示了更好的安全性。肝素类药物对骨代谢的作用可能涉及到了破骨细胞抑制凝集素、护骨素及硬化素等多种途径。     

低分子肝素早期使用预防断流术后门静脉系血栓形成

目的研究断流术后早期使用低分子肝素对门静脉系统血栓形成的预防作用。方法选取肝硬化门脉高压症患者200例，随机分成低分子肝素组与对照组。每组100例。均行脾切除及贲门周围血管离断术，低分子肝素组术后使用低分子肝素钙治疗（4100 IU，皮下注射。每日1次。连用10d），对照组进行常规治疗。比较两组间血栓发生率、术后再出血情况及生存情况。结果低分子肝素组断流术后门静脉系统血栓发生率（6．25％）明显低于对照组（17．35％，P〈0．05）。低分子肝素组治疗期间无出血顷向等不良反应。门静脉系统血栓形成组再出血率（21．74％）明显高于无血栓形成组（5．26％，P〈0．05）。结论低分子肝素早期使用预防断流术后门静脉系血栓形成，是安全、有效的，且使用方便，值得推广。     

N-去硫酸基团肝素与低分子肝素对造模肠穿孔诱发急性肺损伤治疗作用的对比研究

目的:在幼猪肠穿孔脓毒症诱发急性肺损伤(ALI)的动物模型基础上,比较N-去硫酸基团肝素与低分子肝素的治疗效果.方法:23只雄性幼猪随机分为:A组为假手术对照组(n=5),B组为模型组(n=6),C组为N-去硫酸基团肝素治疗组(n=6)及D组为低分子肝素治疗组(n=6).于建立肠穿孔脓毒症诱发急性肺损伤模型后,在机械通气基础上,即刻在C组予静脉注射N-去硫酸基团肝素12 mg/kg,D组予静脉注射低分子肝素抗Xa因子300 IU/kg,观察比较动脉血气、肺动态顺应性、呼吸系统阻力、血流动力学、肺干湿重比、病理组织检查.结果:C组PaO2/FiO2、肺干湿重比相对较B组明显改善,呼吸系统阻力下降,肺动态顺应性下降不明显,肺组织病变减轻.D组仅肺干湿重比减轻,其他指标未见明显好转.结论:N-去硫酸基团肝素对肠穿孔脓毒症诱发的急性肺损伤有一定治疗作用,相对于低分子肝素在采用实验剂量下的治疗作用不明显.     

乙酰肝素酶与蛋白尿性肾脏疾病的关系

蛋白尿是众多肾脏疾病的主要临床表现，肾小球滤过屏障的完整性决定着对蛋白质的选择通透特性。肾小球基底膜中硫酸乙酰肝素在电荷屏障的维持中起重要作用。乙酰肝素酶作为新近克隆出来的一种内切糖苷酶，与肿瘤的转移浸润密切相关。近年来研究发现其通过选择性降解肾小球基底膜硫酸乙酰肝素侧链，也参与蛋白尿的发生。本文就其分子学特点、调控以及与蛋白尿性肾脏疾病的关系作一综述。     

低分子肝素对脊柱脊髓术后预防下肢深静脉栓塞的临床疗效及安全性分析

[目的]探讨低分子肝素对脊柱脊髓术后预防下肢深静脉栓塞的临床疗效及安全性.[方法]自2008年9月～ 2010年7月,共收治单纯脊柱损伤患者58例,合并有脊髓损伤者51例,脊柱退变患者73例.所有患者随机分为两组,对照组和低分子肝素组.实验组于术后12 h低分子肝素2 500单位皮下注射,次日起一日2次低分子肝素2 500单位皮下注射.术后低分子肝素应用时间为7～21 d,平均11d.观察切口引流量、失血量及失血指数.[结果]对照组中,83例患者有3例发生下肢深静脉血栓形成,低分子肝素组中,所有患者均未出现下肢肿胀等不良反应.两组切口引流量、失血量及失血指数相比,作配对t检验,P＞0.05,差别无显著性意义.[结论]低分子肝素对脊柱脊髓术后深静脉血栓的预防是安全、有效的.     

低分子肝素与黄芪联用治疗难治性肾病综合征临床研究

目的:探讨低分子肝素与黄芪注射液联用对难治性肾病综合征的治疗作用.方法:65例难治性肾病综合征患者随机分成两组,对照组进行常规治疗,治疗组在常规治疗的基础上加用低分子肝素和黄芪注射液.然后进行疗效观察,并通过实验室检查评价低分子肝素与黄芪对肾功能和凝血功能的作用.结果:两组疗效比较,治疗组明显优于对照组(P＜0.05);其血清蛋白、尿蛋白、BUN、Cr、Fg、FⅡa、FX a、AT-Ⅲa、血白细胞计数等实验室检查指标,治疗组与治疗前比较有统计学差异(P＜0.05),与对照组治疗后比较亦有统计学差异(P＜0.05),其疗效与病理类型有关.结论:低分子肝素与黄芪注射液可降低血液的高凝状态,联合应用治疗难治性肾病综合征疗效显著.     

肝素在肿瘤治疗中的应用(文献综述)

肿瘤的形成与进展与血管形成有密切的关系 ,抑制肿瘤血管形成就能抑制肿瘤生长。肝素有较明显的抑制肿瘤血管形成作用 ,对肿瘤生长、侵袭、转移等各环节均有抑制作用 ,这为肿瘤治疗提供了新的方法和途径。本文就肝素对肿瘤的抑制作用及其相关机制作一综述。     

岩藻糖在正常人肝细胞、低转移人肝癌细胞和高转移人肝癌细胞表面的含量变化

目的 比较正常人肝细胞、低转移人肝癌细胞及高转移人肝癌细胞表面岩藻糖的含量差异.方法 利用能与岩藻糖特异性结合的异硫氰酸荧光素标记的荆豆凝集素(FITC-UEA),与正常人肝细胞、低转移人肝癌细胞及高转移人肝癌细胞悬液充分结合.而后用流式细胞仪定量检测细胞表面的荧光强度,据此评定正常人肝细胞、低转移人肝癌细胞和高转移人肝癌细胞表面岩藻糖的含量.结果 正常人肝细胞表面的荧光强度低于低转移人肝癌细胞扣高转移人肝癌细胞(P<0.05),高转移人肝癌细胞表面的荧光强度高于低转移人肝癌细胞(P<0.051.结论 细胞表面的岩藻糖含量变化与细胞癌变及癌变细胞的转移潜能有关.细胞癌变后,细胞表面的岩藻糖含量增加,并且癌变细胞的转移潜能越高,其表面岩藻糖含量也越高.     

Tumour-associated host cells participating at invasion and metastasis : targets for therapy?

The 100-year old "seed" and "soil" theory explains key features of cancer metastasis: early initiation; late appearance; organ-specificity. The seed is the cancer cell; it undergoes genetic alterations, disturbing the cellular activities that maintain normal tissue organisation and, so, initiating the formation of invasive and metastatic tumours. The soil consists of tumour-associated host cells: endothelial cells and pericytes forming blood-and lymph vessels attracted to the cancer cells by vascular endothelial growth factor (VEGF); nerve cells; fibroblasts converted into myofibroblasts by cancer cell-released transforming growth factor (TGF)-beta; inflammatory cells, attracted by cancer chemokines; osteoclasts activated by metastatic cancer cells in the bone marrow. All these host cells engage in continuous molecular cross talk with the cancer cells, influencing invasion and metastasis. Tumor-associated host cells are themselves invasive and some of them arrive at the site of metastasis ahead of the cancer cells. The high radiosensitivity of the tumor-associated host cells lead us to speculate that radiotherapy may affect invasion and metastasis. Analgesic effects on bone metastasis and prevention of lung metastasis to the brain by ionizing radiation are possibly due to alterations of host cells. We suggest to consider tumour-associated host cells when developping new strategies for cancer radiotherapy, chemotherapy and surgery.     

肝癌复发和转移的新理念

Cancer metastasis is considered as a complex process involving a series of sequential steps and a variety of molecalar signal transduction pathways.Tumor recurrence and metastasis are major obstacles for long-term survival of Liver cancer patients.Although the prognosis after recurrence and metastasis is dismal,the advancement of molecular researches of metastasis of liver cancer seems promising.In studies of origins of metastasis of liver cancer,the primary cancer cell and corresponding metastatic liver cancer cells share similar gene signature,which indicates that genes favoring metastasis progression are initiated in the primary tumors.The metastasis of liver cancer may be an early event in hepatic carcinogenesis and progression.Some molecular signatures have been developed to classify the metastatic potential of liver cancer.Furthermore,a variety of studies demonstrate that the tumor microenvironment instead of tumor cells plays a more important role in liver cancer metastasis.The pre-metastatic niche composed of non-tumoral cells may promote the cancer cell sedimentation and progression.The theory of cancer stem cell speculates that cancer stem cells were the real source of recurrent or metastatic tumors.Cancer stem cells will be one of the main targets of liver cancer treatment.The prevention and treatment of liver cancer recurrence or metastasis are quite difficult because liver cancer is resistant to traditional chemotherapy.Targeting the molecules involved in the metastasis of liver cancer WOuld be promising to cure those diseases.     

Pathological features of lymph node metastasis. 2) From morphological aspects]

Lymph node metastasis is important because of its early appearance and prognostic significance. In this paper the mechanism of development of metastasis, tissue reaction with metastatic cells, and role of lymph node metastasis in cancer spread are described briefly. Lymph node metastasis proceeds when cancer cells invade lymphatic vessels. These cells lodge in the lymphatic sinus where tumor cells adhere to and breach the sinusoidal walls and migrate into the parenchyma. Integrin(s), CD44, and/or carbohydrates of tumor cells and extracellular matrix components such as laminin and type IV collagen, hyaluronic acid, and lectins of the sinus wall become involved in the adherence of cancer cells. Their binding may induce matrix metalloproteinase production from cancer cells, resulting in degradation of surrounding reticular fibers. Lymph nodes sometimes react with tumors, exhibiting follicular hyperplasia, sinus histiocytosis, lymphoid cell depletion, fibrosis, and angiogenesis of lymph nodes. Such tissue reactions may suppress cancer spread but in turn may augment the aggressiveness of cancer cells. It is not yet possible to determine which reaction will occur. In early cancer, lymph node metastasis occurs based on mainly anatomical-mechanical factor, while in advanced cancer, seed-soil factor plays an important role on development of the metastasis.     

组织因子对大肠癌细胞侵袭及血行转移的影响

目的分析组织因子（TF）表达对人类大肠癌细胞侵袭和血行转移能力的影响。方法利用构建有正义／反义组织因子cDNA（TFcDNA）的质粒pcDNA3．1／Zeo,以脂质体法转染人类大肠癌细胞HT-29细胞及LoVo细胞;转染成功的HT-29细胞及LoVo细胞采用Western Blot检测TF表达水平,通过裸鼠皮下成瘤观察细胞体内侵袭能力的变化;通过建立裸鼠体内肺转移及肝转移模型观察细胞体内血行转移能力的变化。结果转染了正义TFcDNA的HT-29细胞及LoVo细胞的TF表达水平较未转染的HT-29细胞及LoVo细胞升高,转染了反义TFcDNA的HT-29细胞及LoVo细胞的TF表达水平则降低;转染了正义TFcDNA的HT-29细胞的体内侵袭能力较未转染的HT-29细胞增强,转染了反义TFcDNA的HT-29细胞的体内侵袭能力则减弱;转染了正义TFcDNA的LoVo细胞的体内血行转移能力较未转染的LoVo细胞增强,转染了反义TFcDNA的LoVo细胞的体内血行转移能力能力则减弱。结论TF可以促进人类大肠癌细胞的侵袭和血行转移的能力。     

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目的 研究乳腺癌腋窝淋巴结发生癌转移和未发生癌转移时的免疫功能。方法2004年8月至2005年7月采用流式细胞技术检测乳腺癌病人乳腺癌前哨淋巴结（SLN）与乳腺癌非前哨淋巴结（NSLN）中免疫细胞CD3^＋T、CD4^＋T、CD8^＋T、CD16^＋NK、CD^19^＋B的比例，并相互比较。结果淋巴结未发生癌转移时，SLN与NSLN的免疫细胞CD3^＋T、CD4^＋T、CD8^＋T、CD16^＋NK、CD^19^＋B的比例差异无统计学意义（P〉0．05）；而且当SLN与NSLN发生癌转移后，它们的免疫细胞的比例也无差异。但SLN发生癌转移与未发生癌转移时相比，其CD4^＋T、CD8^＋T、CD16^＋NK的比例发生显著改变（P〈0．05），CD3^＋T、CD19^＋B的比例改变无统计学意义（P〉0．05）。结论 当腋窝淋巴结未发生癌转移时，它仍有正常的免疫功能。当腋窝淋巴结发生癌转移后，它的免疫微环境发生了改变，免疫功能呈现一种抑制状态。     

抑制信号转导与转录激活因子-3基因表达对人胰腺癌细胞转移能力的影响

目的 探讨RNA干扰(RNAi)技术抑制信号转导与转录激活因子-3(STAT3)表达对人胰腺癌细胞株SW1990体内转移能力的影响及其机制.方法 构建STAT3短发卡RNA(shRNA)表达载体,稳定转染SW1990细胞.应用RT-PCR方法 观察STAT3 mRNA表达的改变,EMSA方法 检测STAT3-DNA结合活性的改变.应用裸鼠急性血路转移实验检测细胞体内转移能力的变化,并通过RT-PCR方法 检测基质金属蛋白酶-2(MMP-2)和血管内皮生长因子(VEGF)mRNA表达的改变.结果 STAT3 shRNA表达载体稳定转染SW1990细胞可显著抑制STAT3 mRNA表达和STAT3-DNA结合活性(P＜0.05);裸鼠急性血路转移实验显示,RNAi技术抑制STAT3后,SW1990细胞体内转移能力明显下降(P＜0.05);RT-PCR结果 显示,RNAi技术抑制STAT3后,SW1990细胞中MMP-2和VEGF的mRNA表达明显减低(P＜0.05).结论 RNAi技术能有效抑制STAT3基因表达,并可通过下调MMP-2和VEGF表达抑制胰腺癌细胞体内转移能力.     

15-脱氧-前列腺素J2激活过氧化物酶体增殖物激活受体信号抑制肝癌细胞侵袭转移的实验研究

目的探讨15-脱氧-前列腺素J2(15-d-PGJ2)对肝癌细胞SMMC-7721侵袭转移的影响及其内在的机制。 方法SMMC-7721肝癌细胞经天然配体15-d-PGJ2和(或)抑制剂GW9662处理,用伤口愈合实验和Transwell方法检测细胞的转移侵袭能力,用RT-PCR检测细胞PTEN和MMP-9 mRNA的表达,用Western blotting检测细胞PTEN和MMP-9蛋白的表达。 结果15-d-PGJ2对SMMC-7721细胞的转移侵袭具有抑制作用,并能上调PTEN mRNA和蛋白的表达,下调MMP-9 mRNA和蛋白的表达;单药GW9662无此效应,GW9662与15-d-PGJ2联合能够逆转此效应。 结论15-d-PGJ2是通过激活PPAR信号上调PTEN表达,下调MMP-9表达,抑制肝癌细胞的侵袭转移。     

Spontaneous metastasis of PC-3 cells in athymic mice after implantation in orthotopic or ectopic microenvironments

The ability of subcutaneous, prostatic, and nonprostatic intraabdominal organ microenvironments to influence local tumor growth and metastasis of PC-3 human prostate carcinoma cells in athymic mice was determined. Tumorigenesis and metastasis of PC-3 were evaluated 60 days after subcutaneous and intraprostatic (orthotopic) implantation of 5 × 10⁵ PC-3 cells in 6-week-old, male athymic mice. Intraprostatic implantation of PC-3 cells resulted in paraaortic lymph node metastases in 10 of 10 (100%) mice with prostatic tumors, whereas metastases were present in only 2 of 9 (22%) mice after subcutaneous implantation. Next, we determined whether the urinary bladder (nonprostatic, urogenital microenvironment) or stomach (nonurogenital, intraabdominal microenvironment) would facilitate the metastasis of PC-3 cells in athymic mice. Tumorigenesis and metastasis were 100% after subserosal implantation of PC-3 cells within the wall of the urinary bladder (n = 6 mice). Subserosal implantation of PC-3 cells into the stomach wall (n = 7 mice) also resulted in tumor formation and metastasis to regional lymph nodes in 100% of mice. In all experiments, regional lymph nodes were the most frequent site of metastasis, regardless of implantation site. We conclude that tumor microenvironment factors responsible for the metastasis of PC-3 cells in athymic mice may not be organ-specific, since nonprostatic visceral microenvironments are sufficient for predictable metastasis. Use of these models may further our understanding of how tumor microenvironment modulates expression of the metastatic phenotype by human prostate carcinoma cells.     

Relationship of the distribution of Leu-2+ cells with suppressor cell activities in the spleen and lymph-nodes from gastric cancer

Tissue distributions of Leu-2+ cells in the spleen and draining lymph-nodes in cases of clinical gastric cancer were investigated, with special reference to suppressor cell function. Significantly higher Concanavalin-A (Con-A) induced suppressor cell activities were evident in spleen cells (SCs), as compared with peripheral blood lymphocytes (PBLs). As for the tissue distribution, the proportion of Leu-2+ (cytotoxic/suppressor) cells within Leu-1+ cells was higher in the spleen than in the lymph-nodes without metastasis. On the other hand, in lymph-nodes with metastasis, the enhanced spontaneous suppressor cell activity was noted. In addition, the proportion of Leu-2+ cells within Leu-1+ cells was the greatest in the lymph-nodes with metastasis, among the lymphoid organs tested. In lymph-nodes without metastasis, lower suppressor cell activities were noted, and numerous Leu-3+ (helper/inducer) cells were present, while Leu-2+ cells were less frequent. NK cell activity against K-562 cells was enhanced by elimination of Leu-2+/OKT-8+ cells with complement-mediated lysis. These results suggest that Leu-2+ cells located in the spleen and lymph-nodes with metastasis may predominantly act as suppressor cells and interact with effector cells.