两种源于胶原Ⅳ非胶原区具有抑制血管形成和肿瘤生长的功能肽

Tum statin和 Canstatin是继 Restin、angiostatin和 endostatin之后最新发现的基底膜来源人胶原 肿瘤血管生成抑制因子。 Tumstatin来源于胶原 α3链 ,其 N-端 5 4～ 132氨基酸功能肽能够抑制内皮细胞增殖和诱导内皮细胞凋亡 ,N -端 197～ 2 15氨基酸 [α3( ) NC1185～ 2 0 3氨基酸 ]功能肽能够抑制多种恶性肿瘤细胞的增殖。 Canstatin是来源于 型胶原α2链的 2 4 k D的血管生成和肿瘤生长抑制因子 ,它能剂量依赖性抑制内皮细胞管状结构的形成 ,有效抑制内皮细胞的增殖和迁移 ,并能诱导内皮细胞凋亡。在小鼠移植瘤模型体内实验中 ,Tum-statin和 Canstatin都显示出对实体瘤生长的显著抑制作用     

血管生成抑制因子与肿瘤转移的抑制

新生血管形成是肿瘤生长和转移的重要环节，是肿瘤细胞进入血液的主要通道，受到血管生成刺激因子和抑制因子（ 如ａｎｇｉｏｓｔａｔｉｎ 和ｅｎｄｏｓｔａｔｉｎ） 等物质的调节。血管生成抑制因子通过抑制内皮细胞的生成和迁移而显示出强烈的抗肿瘤作用，其毒性低、不易产生耐药性，具有广泛的应用前景     

血管新生与血液系统恶性肿瘤

血管新生（Ａｎｇｉｏｇｅｎｅｓｉｓ）是指通过内皮细胞的增殖和迁移,从先前存在的血管处以发芽或非发芽（又称套迭）的形式生成新的毛细血管［１］,是近年来新兴的一个医学研究领域,几乎涉及到医学领域的各个学科。血管新生受一系列刺激和抑制因子调节,这些因子控制着内皮细胞的增殖和迁移,对血管新生具有调节作用［２＿４］。其中主要的血管新生剌激因子有碱性纤维蛋白生长因子（ｂＦＧＦ）和血管内皮生长因子（ＶＥＧＦ）,主要的血管新生抑制因子有血管抑素（ａｎｇｉｏｓｔａｔｉｎ）、内皮抑素（ｅｎｄｏｓｔａｔｉｎ）、血小板第４…     

高血压患者肾蒂小动脉外膜组织学观察研究

目的：在血管重塑过程中血管平滑肌细胞（ＶＳＭＣ）和成纤维细胞的增殖和迁移常伴有细胞外基质成分的变化。既往的研究多以大鼠为研究对象,本文以肾切除术患者的肾蒂小动脉为研究对象,探讨高血压患者血管外膜组织学病变及胶原含量的变化。方法：取手术切除术的肾脏组织,按有无高血压病病史分为两组（高血压组６例,血压正常组７例）,用ＶａｎＧｉｅｓｏｎ染色法对肾蒂小动脉外膜进行组织学观察,用免疫组化法检测Ｉ、Ｖ型胶原在     

哮喘青春期缓解者外周血可溶性血管细胞粘附分子-1的测定

血管细胞粘附分子 1(ＶＣＡＭ 1)主要表达于活化的内皮细胞 ,它介导了炎症细胞与血管内皮细胞的粘附和跨内皮转移 ,在气道粘膜的嗜酸粒细胞 ,淋巴细胞的选择性聚集、浸润中起重要作用[1] 。可溶性血管细胞粘附分子 1(ｓＶ ＣＡＭ 1)是存在于血清中的从血管内皮细胞上自然脱落的ＶＣＡＭ 1分子 ,是反映体内ＶＣＡＭ 1表达水平的可溶性标志物。临床上某些哮喘儿童到青春期会自然缓解甚至痊愈是个普遍现象[2 ] ,其机制尚未阐明。本实验通过对哮喘青春期缓解组、哮喘组和正常对照组的外周血ｓＶＣＡＭ 1水平的测定和比较 ,探索其中的规律。1　…     

单核/巨噬细胞在血管生成和侧枝血管生长中的作用

血 管生成 (Ａｎｇｉｏｇｅｎｅｓｉｓ)是指毛细血管的增生和发芽 ,即血管形成 ,包括基质溶解、细胞转移、粘附、增生和管腔形成 ;侧枝血管生长 (ＣｏｌｌａｔｅｒａｌＶｅｓｓｅｌＧｒｏｗｔｈ)是指已有的连接侧枝动脉的微动脉原位增生形成肌型动脉 ,或者原有的侧枝血管形成。虽然毛细血管的形成可缓解缺血组织的灌注不足 ,但只有侧枝动脉能提供足够的血液到缺血区[1] 。在缺血区二种血管生长方式都存在 ,在不同的部位和条件常以一种生长方式为主[1,2 ] 。单核细胞系统的细胞在成人主要来源于骨髓造血干细胞 ,骨髓中的髓样干细胞受细胞因子…     

恶性肿瘤转移过程的研究进展

用活体内显微摄像技术（ＩＶＶＭ）观察了多种肿瘤细胞由血路转移到实质脏器的情况发现，不同转移力的瘤细胞在微循环中停滞过程相似，游出血管外的过程和时间与侵袭力无关，未见明显的血小板凝聚和血管基底膜破坏。肿瘤细胞都是向脏器实质内适合生长部位迁移。不同转移力的肿瘤细胞在转移脏器中形成克隆的差异不是瘤细胞游出能力的差异造成，而是瘤细胞在脏器内生长潜力不同造成的。因此，控制肿瘤细胞游出血管外后在脏器中的生长潜力是治疗肿瘤转移的关键     

银屑病患者治疗前后血清Ⅳ型胶原和层粘连蛋白测定的意义

Ⅳ型胶原 (ＣｏｌｌａｇｅⅣ ,Ⅳ .Ｃ)是细胞外基质的重要成分 ,在正常情况下分布在血管、胆管的基底膜中。层粘连蛋白(Ｌａｍｉｎｉｍ ,ＬＮ)为细胞外间质中的非胶质糖蛋白 ,广泛分布于基底膜的透明层 ,与Ⅳ型胶原结合构成基底膜的骨架 ,影响细胞粘附、迁移、调节细胞的生长与分化 ,并与纤维化、肿瘤等疾病密切相关[1] 。国内尚少见有银屑病患者治疗前后血清Ⅳ型胶原和层粘连蛋白测定的报道 ,为此 ,我们进行了探讨 ,现将结果报告如下。对象和方法一、对象 :(一 )正常人 :35人 (男 2 5 ,女 10 ) ,均为我院预防保健科体检合格的健康者 ,均无…     

人内皮抑素克隆表达及对血管内皮细胞生长的抑制 …

目的 获得具有抑制血管内皮细胞生长活性的重组人内皮抑素（ｒｅｃｏｍｂｉｎａｎｔ ｈｕｍａｎ ｅｎｄｏｓｔａｔｉｎ）。方法 从肝细胞中分离总ＲＮＡ,经反转录多聚酶链反应（ＲＴ－ＰＣＲ）得到ｅｎｄｏｓｔａｔｉｎ全基因。用原核细胞表达载体构建了ｐＢＶ２２０／ｅｎｄｏｓｔａｔｉｎ重组质粒,经ＤＮＡ测序确认后,将其转化大肠杆菌ＤＨ５α进行表达、初步纯化及活性测定。结果 经ＳＤＳ－ＰＡＧＥ分析,表达产物相对分     

环氧-二十碳三烯酸：一类内皮衍生性超极化因子

自从 1 980年Ｆｕｒｃｈｇｏｔｔ等[1 ] 发现内皮细胞释放内皮衍生性舒张因子 (ｅｎｄｏｔｈｅｌｉｕｍｄｅｒｉｖｅｄｒｅｌａｘｉｎｇｆａｃｔｏｒ,ＥＤＲＦ )以来 ,血管内皮细胞在调节血管舒缩方面的作用引起极大关注。随着对ＥＤＲＦ研究的深入 ,发现在内皮完整的离体血管上 ,抑制一氧化氮 (ｎｉｔｒｉｃｏｘｉｄｅ ,ＮＯ)和前列环素 (ｐｒｏｓｔａｇｌａｎｄｉｎ ,ＰＧＩ2 )合成之后 ,乙酰胆碱等物质所致血管舒张并未完全消除 ,这说明内皮细胞还可产生另外一类舒血管物质。Ｃｈｅｎ等[2 ] 研究了乙酰胆碱所致离体平滑肌舒张机制 ,发现…     

Animal models of human pituitary tumors

Three animal models of pituitary tumors were compared: the spontaneous prolactinoma in Wistar/Furth (W/Fu) rats, an estrogen-induced transplantable tumor in the Fischer rat (MtTF4), and a spontaneous prolactin transplantable tumor in the W/Fu rat (SMtTW1). The spontaneous prolactinoma in W/Fu rats is interesting in that it resembles the human prolactinoma by its morphological characteristics, its benign nature, and its secretion of prolactin alone. It may be useful to study the initial factors of tumorigenesis but it is very expensive and the variability of tumor growth makes it difficult to plan experiments. The MtTF4 tumor is an easy model to study because it is transplantable but this tumor differs from most human pituitary tumors by its induction by estrogen, its malignancy, its undifferentiated aspect and its secretion of ACTH, GH, and prolactin. The SMtTW1 tumor, a new model of transplantable tumor, is close to the human pituitary tumor because the initial tumor is spontaneous, the transplanted tumors are benign and well differentiated. They secrete prolactin only. These transplantable tumors are valuable for studying the factors of growth. Since no single tumor system is a perfect model, researchers have to work on different models each of which is appropriate for investigating specific problems.     

人直肠粘液腺癌裸鼠移植瘤模型的建立及其生物学特性

A model of transplantable human mucoid adenocarcinoma of rectum in BALB/C nu/nu nude mice (TNB 92), was established and 18 sub-transplantations were performed. The success rate of transplantation was 98% and the average tumor bearing life time of mice was 112 days. Histology and ultrastructures showed that the transplantable tumor retained the original structures of the human tumor. Chromosomal analysis of the tumor cells exhibited the same features of the human carcinoma and it also retained the function of secreting CEA. Frozen tissue of the tumor in liquid nitrogen after rehabilitation could be successfully retransplanted into nude mice again. It seems to be a useful model for further study of human rectal adenocarcinoma.     

Isolation and characterization of human antibodies targeting human aspartyl (asparaginyl) beta-hydroxylase

Over-expression of the enzyme human aspartyl (asparaginyl) beta-hydroxylase (HAAH) has been detected in a variety of cancers. It is proposed that upon cellular transformation, HAAH is overexpressed and translocated to the tumor cell surface, rendering it a specific surface antigen for tumor cells. In this work, twelve human single-chain Fv fragments (scFv) against HAAH were isolated from a human non-immune scFv library displayed on the surface of yeast. Five of the twelve were reformatted as human IgG1. Two of the five IgGs, 6-22 and 6-23, showed significant binding to recombinant HAAH in ELISA, tumor cell lines, and tumor tissues. The apparent dissociation constants of 6-22 and 6-23 IgG were 1.0 +/- 0.2 nM and 20 +/- 10 nM respectively. These two antibodies were shown to target different domains of HAAH, with 6-22 targeting the catalytic domain of HAAH and 6-23 targeting the N-terminal non-catalytic domain of HAAH. 6-22 IgG was further characterized, as it had high affinity and targeted the catalytic domain. 6-22 IgG alone does not exhibit significant cytotoxicity toward the tumor cells. However, 6-22 internalizes into tumor cells and can therefore be employed to deliver cytotoxic moieties. A goat anti-human IgG-saporin conjugate was delivered into tumor cells by 6-22 IgG and hence elicited cytotoxicity toward the tumor cells in vitro. These tumor-binding human antibodies can potentially be used in both diagnosis and immunotherapy targeting HAAH-expressing tumor cells.     

PHAGOCYTOSIS OF LYMPHOBLASTOID CELLS AND CELL DESTRUCTION OF HUMAN MALIGNANT TUMOR CELLS

On the basis of the previous study^8,9 on the cell interaction between malignant tumor cells and other cells, especially with lymphocytes, the present study was carried out by investigating cell to cell interaction of human malignant tumor cells and human lymphoblastoid cells such as T-cell (MOLT-4 cell) and B-cell (Burkftt lymphoma cell).
As a result it has been revealed that live lymphoblastoid cells were not adhered on the cell surface of the tumor cells, nor is it ingested by tumor cells, but in the presence of HVJ (Sendai virus: 2,000 H.A. Units) it adheres slightly on the cell surface of tumor cell but no cell fusion of tumor cells and lymphoblastoid cells is observable. On the other hand, the tumor cell as well as T-cell and B-cell all have receptors to concanavah A (Con.A) on their cell surfaces, and they show a marked cell binding such as tumor cell and T-cell, tumor cell and B-cell, and there can be observed a marked phagocytosis of lymphoblastoid cells by tumor cells. Moreover, the tumor cells that have phagocythd lymphoblastoid cells undergo a marked cell destruction within 4 hours of cell-binding and phagocytosis, which is especially prominent in the case of phagocytosis of E.B cell by tumor cell.     

Establishment of a human hepatoblastoma model in athymic nude mice. Producibility of fatty acid-binding protein, alpha-fetoprotein, and alpha 1-acid glycoprotein.

An athymic nude mouse model of human hepatoblastoma, designated HBL-2, was established. HBL-2 produced alpha-fetoprotein (AFP) and the serum level in tumor-bearing mouse was roughly proportional to the tumor weight. Reactivity of AFP to Concanavalin A and Lens culinaris lectins indicated that it contained predominantly fucosylated, non-bisecting N-acetylglucosamine as a sugar moiety. Alpha 1-acid glycoprotein (AAG) was also found in both HBL-2 tumor extract and sera of tumor-bearing mice. The serum level, however, was not proportional to either the tumor weight or the value of the tumor extract. In addition, fatty acid-binding protein (FABP) was detected in approximately 40% of tumor cells and in tumor extract with polyclonal antibody against liver FABP. Thus, HBL-2 is an unique model of human hepatoblastoma, in that it produces FABP in addition to AAG and AFP.     

Establishment of a Human Hepatoblastoma Model In Athymic Nude Mice

An athymic nude mouse model of human hepatoblastoma, designated HBL 2, was established. HBL 2 produced α -fetoprotein (AFP) and the serum level in tumor-bearing mouse was roughly proportional to the tumor weight. Reactivity of AFP to Concanavalin A and Lens culinaris lectins indicated that it contained predominantly fucosylated, non bisecting N acetylglucosamine as a sugar moiety. Alpha 1 acid glycoprotein (AAG) was also found in both HBL 2 tumor extract and sera of tumor bearing mice. The serum level, however, was not proportional to either the tumor weight or the value of the tumor extract. In addition, fatty acid binding protein (FABP) was detected in approximately 40% of tumor cells and in tumor extract with polyclonal antibody against liver FABP. Thus, HBL 2 is an unique model of human hepatoblastoma, in that it produces FABP in addition to AAG and AFP. Acta Pathol Jpn 42: 255 261, 1992.     

新型双光子荧光染料DMAHAS在人-鼠肝癌模型中的应用

研究一种新型双光子荧光素（DMAHAS）对人肝癌HepG2细胞的毒性及肿瘤细胞标记后的体内示踪。体外细胞毒性分析采用MTT、中性红（NR）、考马斯亮蓝（CB）和流式细胞术（FCM）等方法。DMAHAS标记肿瘤细胞的体内示踪在人肝癌模型中进行,切除的肿瘤异种移植物经荧光成像和传统的组织病理分析。此外,我们建立了一种基于DMAHAS释放的细胞毒性分析方法。研究结果表明DMAHAS对HepG2细胞无明显毒性,它显示出对活细胞很高的穿透性和稳定的细胞质定位。体内细胞示踪实验表明它是一种用于肿瘤示踪和荧光成像的可靠探针。     

Molecular pathological approaches to human tumor immunology

Research on human tumor immunology has greatly advanced in the past two decades. Many immunogenic tumor antigens have been identified, and some of these antigens entered in clinical trials. Consequently, it has been shown that these antigens can inhibit tumor growth in patients to some extent, indicating that they act as potent immunogenic therapeutic vaccines in cancer patients with malignancies originating from various tissues. These patients had antigen‐specific cytotoxic T‐lymphocyte (CTL) responses when assessed on tetramer, enzyme‐linked immunospot (ELISPOT), T‐cell clonotype and CTL induction efficiency. Thus, it has become clear that human tumor vaccines can evoke clinical and immunological anti‐tumor responses in patients. The tumor regression effects of tumor vaccines, however, are generally low, and it is obvious that current vaccination protocols are generally too weak to provide substantial and satisfactory clinical benefits. This means that other drastic and more potent clinical and immunological protocols are required in cancer immunotherapy. To find such efficient protocols the basic immunological and biological properties of cancers must be investigated. In the present review the identification of human tumor antigens recognized on CTL and the clinical trials are introduced. Next, the most recent analysis of human cancer‐initiating cell (cancer stem cell)‐associated antigens is described. These antigens might be able to act as ‘universal, general and fundamental’ tumor antigens. Also present is the authors' recent study for increasing cross‐presentation efficiency in dendritic cells and subsequent enhancement of human leukocyte antigen (HLA)‐class I‐restricted peptide antigenicity by using HSP90 and ORP150 molecular chaperones that act as endogenous Toll‐like receptor ligands. In addition to the aforementioned manipulation of the positive loop of tumor immunity, it is necessary to regulate and intervene in the negative loop. In particular, the potential of the expression of HLA class I molecule regulation by epigenetic mechanisms will be discussed. Finally, the type of basic and clinical tumor immunology research highly required currently, and in the very near future, are described.     

131I标记重组人表皮生长因子体内抑制乳腺癌生长的实验研究

研究 1 31 I标记重组人表皮生长因子 (1 31 I- Recombinant hum an epiderm al growth factor,1 31 I- rh EGF)对荷人乳腺癌裸鼠肿瘤生长的抑制作用。1 31 I- rh EGF在荷人乳腺癌裸鼠体内的组织分布实验证实 1 31 I- rh EGF的生物活性及乳腺癌组织对 1 31 I- rh EGF的摄取 ,通过给药后荷人乳腺癌裸鼠肿瘤的生长实验观察 1 31 I- rh EGF对肿瘤生长的影响 ,用透射电镜和病理组织学检查分别观察 1 31 I- rh EGF治疗后肿瘤细胞的超微结构变化和组织病理学变化。1 31 I-rh EGF的组织分布显示 ,荷人乳腺癌裸鼠的肿瘤组织对 1 31 I- rh EGF有明显摄取。肿瘤生长观察结果显示 ,静脉注射和瘤体内注射 1 31 I- rh EGF均能明显抑制肿瘤的生长 ,抑瘤率 (82 .0 0 %和 80 .70 % )显著大于 1 31 I(7.4 9% )和 1 31 I- HSA(6 .91% ) (P<0 .0 5 )。透射电镜和病理学观察均显示 ,静脉注射和瘤体内注射 1 31 I- rh EGF均能明显杀伤、杀死肿瘤组织细胞。实验表明 ,1 31 I- rh EGF能抑制裸鼠体内的人乳腺癌细胞生长 ,可望成为受体介导放射性靶向治疗乳腺癌的新药物     

Development of a novel recombinant adenovirus containing gfp-zeocin fusion expression cassette for conditional replication in p53-deficient human tumor cells

Two obstacles limiting the efficacy of nearly all cancer gene therapy trails are low gene transduction efficiency and the lack of tumor specificity. Fortunately, a replication-competent, E1B-deficient adenovirus (dl1520) was developed that could overcome these limitations, because it was capable of efficiently and selectively destroying tumor cells lacking functional p53. In an attempt to appraise the efficiency and safety of this approach, a novel recombinant adenovirus, r3/Ad, containing a gfp-zeocin expression cassette was constructed in this work. The study in vitro demonstrated that r3/Ad has the ability to replicate in and lyse only the p53-deficient human tumor cells such as the human glioblastoma cells (U251) and human bladder cells (EJ) but not in the human fibroblast cells (MRC-5) with functional p53. Importantly, this gfp-zeocin fusion gene driven by the bipromoter (CMV and EM-7) could be used as an effective selective marker and reporter in prokaryotic and eukaryotic cells; and also zeocin as a selective marker could minimize contamination of the recombinant virus by the wt-Ad5. Additionally, it was found that the r3/Ad could be useful for studying the selective replication of E1B-deficient adenovirus in vivo, it could be used as a "guide" to study the ability of the recombinant adenovirus to spread and to infect distant tumor cells in any tumor bearing animal model by GFP as a reporter. This may help determine the safety of using any E1B-deficient adenovirus in cancer gene therapy.