肝癌发生与转移过程中E—选择素在裸鼠肝、肺、肾微血管内皮细胞的表达

目的：观察肝原位种植肝癌裸鼠模型在肿瘤发生与转移过程中E－选择素在肝、肺、肾组织中的表达。方法：将人肝癌组织块直接种植于裸鼠肝内,术后15、17、19、21、40天取材,免疫组化法观察。结果：肝癌种植后第15－17天,肝、肺、肾组织中微血管内皮细胞E－选择素呈弱阳性表达,种植后第19天,肝血窦内皮细胞呈强阳性表达。种植后第19天,肺组织内E－t选择素表达增强。至40天时,表达最强,结论：E－选择素的表达和增强与肝癌的发生和转移有关。     

E-选择素及其配体在人卵巢癌细胞与血管内皮细胞粘附中的作用

目的和方法：为进一步阐明肿瘤血路转移的分子机制,采用活性染料玫瑰红摄入法,研究人卵巢癌细胞系ＨＯ－８９１０与激活的人脐静脉内皮细胞（ＨＵＶＥＣｓ）的粘附性以及抗粘附分子Ｅ－选择素及其配体ｓＬｅ＾ｘ单抗对ＨＯ－８９１０细胞与激活的ＨＵＶＥＣｓ粘附的影响。     

E-选择素及其配体在肝细胞癌中的表达

侵袭和转移是恶性肿瘤主要的生物学特性之一。研究表明：肿瘤侵袭转移过程中均存在细胞粘附分子及其介导的粘附行为的改变。对肿瘤细胞与内皮细胞间粘附作用的研究还有助于阐明肿瘤转移的器官特异性的分子机制。Ｅ选择素是粘附分子选择素家族中的一员,其配体ｓＬｅＸ／...     

E-选择素在生殖道沙眼衣原体感染中的作用研究

目的 研究E-选择素在生殖道沙眼衣原体感染中的作用.方法 将64只小鼠生殖道沙眼衣原体感染模型随机分成2组,实验组中的小鼠用人工合成E-选择素干预,对照组中的小鼠用生理盐水进行干预,统计两组在1w,2w,3w,4w不同时间点上的感染小鼠阴道脱落菌量以及沙眼衣原体感染率.结果 成功建立生殖道沙眼衣原体感染的小鼠模型:与对照组相比较,人工合成E-选择素干预后1w和2w的生殖道沙眼衣原体感染率(90.2％vs 77.4％,85.3％vs 70.1％)显著增高,而阴道脱落菌量显著增高(4.758 ±0.225 vs 3.210 ±0.315,2.698±0.177 vs 1.809±0.203),两组间差异具有统计学.在干预后3w两组的沙眼衣原体感染率分别为34％和24％,阴道脱落菌量分别为1.412±0.134和1.201±0.189,两组间差异无统计学意义;两组在干预后4w的沙眼衣原体感染率均为0且无阴道脱落菌量.结论 E-选择素能促进生殖道沙眼衣原体感染的发生率以及增加沙眼衣原体的毒力,本文为进一步阐明生殖道沙眼衣原体感染的发病机制提供实验依据.     

E-钙粘蛋白表达异常在肺癌转移过程中的意义

一、材料与方法1 材料 :正常肺组织标本 2 8份 ,非小细胞肺癌标本 71份 ,分别取自第三军医大学附属第一、二、三医院 1991～ 1998年的石蜡及新鲜手术标本 ,其中 40例伴有淋巴结转移 ,31例不伴有淋巴结转移。患者术前皆未做抗肿瘤治疗。鼠抗人Ｅ 钙粘蛋白 (Ｅ ＣＤ)单抗 (ＨＥＣＤ 1)由日本Ｈｉｒｏｈｓｈｉ教授惠赠。免疫组织化学链霉抗生物素蛋白 过氧化物酶 (ＳＰ)法试剂盒购于福州迈新生物技术开发公司。2 方法 :(1)非小细胞肺癌组织标本Ｅ ＣＤ表达检测 :常规甲醛固定、石蜡包埋的正常肺组织和非小细胞肺癌标本 ,制成 4μｍ厚切片。 7…     

E-选择素在胚胎着床过程中小鼠子宫内膜的表达规律

目的：研究E-selectin在胚胎着床及早期分化中的作用。方法：用RT—PCR、Immunoblot、Western blot法检测小鼠胚胎着床前后蜕膜组织E-selectin的表达。结果：E-选择素在孕4天的小鼠子宫内膜中的表达出现升高，第5天达到峰值，随后妊娠第6、第7天E-selectin蛋白的表达则逐渐下降至正常水平。结论：提示E-选择素可能参与了胚胎着床过程。     

选择蛋白及其配体在肿瘤转移中的作用

选择蛋白 (selectin)在生理状态下参与白细胞运行过程的调节 ,在炎症反应过程中与白细胞的渗出密切相关。近期研究发现 ,在肿瘤的转移过程中 ,选择蛋白及其配体也可发挥重要的作用 ,甚至是导致肿瘤发生转移的信号分子之一 ,而阻断选择蛋白及其配体间的相互作用有可能抑制肿瘤转移的发生     

肝细胞癌唾液酸化的路易斯寡糖-X抗原和E-上皮钙粘蛋白的表达及其意义

探讨唾液酸化的路易斯寡糖 X抗原 (sialylLewis X ,SLeX)和E 上皮钙粘蛋白 (E cadherin ,ED)表达与肝细胞癌(HCC)转移和预后的关系。应用免疫组织化学方法 ,检测分析 110例HCC组织中SLeX及ED蛋白表达 ,结合随访资料分析。结果显示 ,在HCC中 ,SLeX和ED阳性表达率分别为 39 1%和 4 4 5 %。SLeX阳性表达的HCC转移率高(P <0 0 5 )、分化程度和患者 >5年生存率低 (P <0 0 5 ) ;ED阳性表达的HCC转移率低 (P <0 0 5 )、分化程度和患者>5年生存率高 (P <0 0 5 )。SLeX表达与ED表达呈负相关 (r =- 0 5 3,P <0 0 0 1)。SLeX和ED表达与HCC转移和患者生存期密切相关 ,检测SLeX和ED蛋白的表达可作为判断HCC预后的参考指标     

IL-1β诱导新生牛脑微血管平滑肌细胞表达E-选择素

Ｅ选择素是细胞粘附分子中选择素（Ｓｅｌｅｃｔｉｏｎ）家族的主要成员之一,属人类白细胞分化抗原ＣＤ６２Ｅ,为１１０ｋＤ的跨膜糖蛋白［１］;大多数研究认为,Ｅ选择素只表达在受细胞因子作用后的血管内皮细胞［２］,但近来有文献报道,非内皮源性的细胞经细胞因子或脂多糖诱导后也可表达Ｅ选择素［３,４］。本研究将观察新生牛脑微血管内皮细胞（ＢＣＭＳＭＣ）经ＩＬ１β诱导后是否表达Ｅ选择素。１　材料与方法１１　动物　新生牛,雄性,购自上海光明乳制品公司奶牛场;Ｗｉｓｔａｒ大鼠,雌雄兼用,本校实验动物中…     

Tumor-associated carbohydrate antigens in primary pulmonary adenocarcinomas and their metastases.

To better understand the metastatic behavior of pulmonary adenocarcinoma, we studied the differences in carbohydrate antigens between primary tumors and their metastases using three monoclonal antibodies (FH-2 defining Lewis [Le]x, AH-6 defining Le(y), and FH-6 defining sialyl Le(x-i)) on 56 autopsy cases (including 15 cases in which primary tumors were surgically resected) and 116 cases of surgically resected pulmonary adenocarcinoma. Metastatic lesions were divided into two groups according to the route of metastasis: group 1 comprised lymphatic metastases, such as lymph node and contralateral lung metastases, and group 2 comprised hematogenous metastases, such as extrathoracic spread. Both primary tumors and metastatic lesions with well-differentiated glandular patterns showed higher positive rates for Le(y) than the poorly differentiated lesions. Such a difference in the antigen expression in relation to tumor differentiation was barely demonstrated for Le(x) and sialyl Le(x-i). Discordance in antigen expression between primary and metastatic lesions (ie, positive primary tumors with negative metastatic lesions and negative primary tumors with positive metastatic lesions) was observed in the following order of frequency: extrathoracic metastatic lesion, contralateral lung, mediastinal lymph node (N2), and ipsilateral peribronchial and hilar (N1) lymph nodes. This study revealed increased biologic diversity of pulmonary adenocarcinoma in cell surface antigens following tumor progression, especially in extrathoracic metastasis.     

Tumor-associated antigens and biomarkers in cancer and immune therapy

Cancer has currently overtaken heart disease as the major cause of mortality in the United States. The Human Genome Project, advances in informatics, miniaturization of sample collection, and increased knowledge of cell signaling pathways has revolutionized the study of disease. Genomics, proteomics, and metabolomics are currently being used to develop molecular signatures for disease diagnosis, prognosis, and therapeutic efficacy. Tumor-associated antigens discovered by these methods are being used to develop passive (humoral) as well as active immunotherapy strategies to stimulate the immune system. Development and validation of biomarkers on a parallel track with therapeutics can speed development times by accurate screening of patient populations and substituting surrogate markers that correlate well with clinical outcomes.     

Tumor-associated antigens in effusions of malignant and benign origin

Summary We determined the concentration and effusion/serum ratio of mucin-like carcinoma-associated antigen (MCA) in comparison to carcinoembryonic antigen, carbohydrate antigen 19-9, cancer antigen 125, and cancer antigen 15-3 in 80 sera and 99 effusions from 64 patients with histologically confirmed malignancies (4 patients out of this group showed various effusions simultaneously, which were analyzed separately) and 31 patients with various nonneoplastic diseases. Tumor cells were detected by cytological examination in 41 effusions (60.3%) from patients with neoplastic diseases, while in another 27 cases this method failed to demonstrate the malignant origin of the effusion. Of the cytological positive malignant effusions 90% were also correctly identified by an elevated MCA concentration at a cutoff level of 10 U/ml, whereas only one effusion of benign origin (3%) showed a slightly elevated MCA concentration of 10.5 U/ml. In 33% of cytologically negative effusions of patients with neoplastic diseases, the MCA concentration was also elevated, with a maximum of 453 U/ml. Increased MCA levels in cytologically confirmed malignant effusions were not restricted to metastatic breast cancer. All 17 cytologically positive non-breast cancer effusions were correctly identified by their MCA concentrations. None of the other tumor markers reached this high sensitivity at the same level of specificity. The ratio of effusion/serum concentration of all tumor markers as well as the concentration of cancer antigen 125 in effusions was of little diagnostic value. Our results indicate that the MCA concentration in an effusion correlates very closely with its malignant origin and is superior to all the other antigens tested. Accordingly, the concurrent MCA determination could improve the diagnostic accuracy of the cytological examination of effusions.Abbreviations MCA mucin-like carcinoma-associated antigen - CEA carcinoembryonic antigen - CA 15-3 cancer antigen 15-3 - CA 125 cancer antigen 125 - CA 19-9 carbohydrate antigen 19-9     

The role of vascular endothelial cells in tumor metastasis

Vascular endothelial cells (VECs) are an integral component of the inner lining of blood vessels, and their functions are essential for the proper functioning of the vascular system. The tight junctions formed by VECs act as a significant barrier to the intravasation and extravasation of tumor cells (TCs). In addition to that, the proliferation, activation, and migration of VECs play a vital role in the growth of new blood vessels, a process known as tumor angiogenesis, which is closely related to the malignant progression of tumors. However, during tumor progression, VECs undergo endothelial-to-mesenchymal transition (EndMT), which further promotes tumor progression. Furthermore, VECs act as the first line of defense against effector immune cells and help prevent immune cells from infiltrating into tumor tissues. VECs also secrete various cytokines that can contribute to regulating the stemness of tumor stem cells. Thus, it has been increasingly recognized that dysfunction of VECs is one of the key driving forces behind tumor metastasis, and therapeutic strategies targeting VECs have the potential to be an effective means of antitumor therapy. This review aims to present a comprehensive overview of the role and mechanisms of VECs in regulating tumor progression and metastasis, providing insights into the possibilities for the development of novel antitumor therapies that target VECs.     

Tumor-associated antigens: from discovery to immunity

There is a renewed enthusiasm for therapeutic vaccination as a viable treatment for patients with cancer. Early tumor vaccines were comprised of whole tumor cells, fragments of tumor cells, or protein lysate from tumor cells. Limited results with these approaches led investigators to begin developing the next generation of cancer vaccines based on defined tumor-associated antigens (TAAs). Defining and characterizing TAAs for human cancer, development of new approaches for identifying TAAs, and novel strategies to deliver the antigens as potent therapeutic vaccines have all been the focus of intense research in the past decade and will continue to be the focus for decades to come.     

Construction of cancer vaccines with carbohydrate and protein (peptide) tumor antigens.

Tumor vaccinology is as old as immunological thought and as young as our rapidly evolving understanding of antigen processing and presentation. The recent availability of carbohydrate and peptide tumor antigens suitable for vaccine construction, conjugate and recombinant vector technologies capable of augmenting helper and cytotoxic T cell activity and potent new immunological adjuvants have combined to produce considerable optimism for the future of tumor vaccines.     

Peptide mimotopes of carbohydrate antigens

Carbohydrate structures have been identified as significant antigens for bacterial, viral, and fungal pathogens as well as targets on human tumor cells. Many of these antigens are poorly immunogenic in humans, requiring extensive adjuvant sublimation. Although conjugate carbohydrate vaccines appear promising, there are limitations of using carbohydrate formulations. An alternative approach is to use surrogate antigens for some carbohydrates. We are developing peptides that mimic carbohydrates which might be further manipulated to induce responses that target biologically important carbohydrates expressed on pathogens and on tumor cells. We have shown that peptide mimotopes of carbohydrates induce immune responses to carbohydrate structures with in vivo and vitro functionality. Model systems include the Neisseria group C meningococcal polysaccharide; the histo-blood group-related antigens expressed on tumor cells; and mannose, sialyl, and histo-blood group-related carbohydrate epitopes expressed on human immunodeficiency virus.     

Tumor-associated fibroblasts recruit blood monocytes into tumor tissue

Tumor-associated fibroblasts (TAF) and tumor-associated macrophages are the main stromal components in desmoplastic breast tumors. These host cell types were extensively studied individually with regard to tumor development and progression but little is known about their reciprocal interactions. To elucidate the role of TAF in the recruitment of monocytes (MO) we designed a 3D co-culture system of multicellular fibroblast spheroids of different origin, co-cultured with MO suspensions from healthy donors. Spheroids of tumor-derived but not of normal fibroblasts were extensively infiltrated by MO. A linear correlation between number of infiltrated MO and number of MO applied per spheroid was shown, indicating a distinct migratory MO subpopulation (approximately 15%) within the peripheral blood MO pool. Our data imply that MO migration into fibroblastic tumor areas may partially result from high expression of CCL2 (monocyte chemotactic protein-1), which was regulated by endogenous IL-6 as shown by neutralization experiments. The effect of CCL2 on MO migration was inhibited by CCL2 neutralizing antibody in tumor-derived fibroblast conditioned media in a Boyden chamber migration assay but not in spheroid culture. While this phenomenon needs further evaluation, our data clearly support the concept of fibroblasts as "sentinel cells" relevant for tumor progression.