心脏淋巴管的分布、功能和病理意义

心脏淋巴引流对于维持心肌内微环境稳定起着重要作用。在心肌梗死和心力衰竭等疾病,淋巴管损伤或功能障碍可引起心脏淋巴水肿,从而导致心肌纤维化,加重炎症反应和严重影响心功能。近年来,人们对于心脏淋巴水肿与心脏疾病的相互关系以及心脏淋巴管新生的生理、病理意义的研究非常重视。靶向刺激心脏淋巴管新生可作为缓解心脏淋巴水肿的可靠疗法。然而,刺激心脏淋巴管新生的优化策略有待深入研究。本文主要综述心脏淋巴管的分布和功能特点,讨论心脏淋巴水肿的病理作用,心脏淋巴管新生的机制以及促进心脏淋巴管新生的措施和临床意义。     

血小板内皮细胞黏附分子1、细胞间黏附分子3和CD44在体外淋巴管新生中的作用

目的 探讨内皮黏附分子血小板内皮细胞黏附分子1(PECAM-1)、细胞间黏附分子3(ICAM-3)和CD44对淋巴管新生的作用。方法 用狗的胸导管分离和培养淋巴管内皮细胞。标记内皮细胞的PECAM-1、ICAM-3和CD44，在荧光显微镜和共聚焦激光扫描显微镜下观察。内皮细胞用肿瘤坏死因子(TNF-Ⅱ)或脂多糖(LPS)刺激后，再阻断PECAM-1、ICAM-3和CD44，作细胞计数和计算迁移率。制备三维凝胶淋巴管形成模型，观察管状结构的形成，测量其长度和面积，并在透射电镜下观察其特征。结果淋巴管内皮细胞表达PECAM-1：ICAM-3和CD44。在对照组以及TN-α和LPS刺激组，分别阻断PECAM-1、ICAM-3和CD44后，内皮细胞的迁移率降低，管样结构的长度和面积减少。阻断PECAM-1或CD44后，细胞的增殖数目降低，但阻断ICAM-3后细胞的增殖数目无明显变化。在半薄和超薄切片上，淋巴管内皮细胞形成的管状结构具有毛细淋巴管的形态特征。结论 体外培养的淋巴管内皮细胞表达PECAM-1、ICAM-3和CD44，这些黏附分子参与了淋巴管内皮细胞的增殖、迁移和管腔形成等淋巴管新生过程。     

血管内皮生长因子C、D和受体3在人胰腺癌组织中的表达

目的:通过观察不同临床指标的人胰腺癌组织VEGF-C、VEGF-D、VEGFR-3的表达,来探讨VEGF-C和VEGF-D对人胰腺癌转移的影响,为癌组织中淋巴管的生成机制以及癌的淋巴道转移机制提供理论依据。方法:取人胰腺癌标本33例及癌旁正常胰腺组织15例,用免疫组化的方法观察VEGF-C、VEGF-D及VEGFR-3在人胰腺癌和癌旁正常胰腺组织中的表达。结果:VEGF-C、VEGF-D和VEGFR-3在胰腺癌组织中的表达比例较在癌旁正常胰腺组织中的表达比例明显增高,并且VEGFR-3的表达与VEGF-D的表达具有显著相关性(P<0.01),与VEGF-C的表达不具有相关性(P>0.05)。胰腺癌组织中VEGF-C和VEGF-D的表达与患者的年龄、性别、远处转移无关(P>0.05)。结论:VEGF-C、VEGF-D在胰腺癌组织中的表达明显增高,并有可能通过与VEGFR-3的结合促进了癌组织中淋巴管的生成,从而对癌的淋巴道转移起促进作用。     

血管内皮生长因子-C促进淋巴管内皮细胞的增殖、迁移和F-肌动蛋白重组

目的 研究血管内皮生长因子-C(VEGF-C)对于淋巴管内皮细胞增殖和迁移的作用，探讨VEGF-C促进淋巴管新生的机制。方法 从狗的胸导管分离和培养淋巴管内皮细胞。标记内皮细胞的VEGFR-3和F-肌动蛋白，在荧光显微镜和共聚焦激光扫描显微镜下观察。用VEGF-C刺激后，计数增殖细胞和迁移细胞，测量细胞迁移距离，并与bFGF和VEGF的作用进行比较。结果 淋巴管内皮细胞表达VEGFR-3，静脉内皮细胞为阴性。bFGF和VEGF-C促进淋巴管内皮细胞的增殖，VEGF-C的作用比bFGF强。与对照组相比，bFGF、VEGF和VEGF-C组引起迁移细胞的数目增多和迁移距离增大，VEGF-C的作用最强。在VEGF-C组的迁移细胞，F-肌动蛋白和应力纤维明显增多。结论 淋巴管内皮细胞特异性表达VEGFR-3，VEGF-C促进淋巴管内皮细胞的增殖和迁移，引起F-肌动蛋白的重组和应力纤维形成。     

肝深淋巴管的分布及其与肝浅淋巴管的交通

目的：探讨肝浅淋巴管和深淋巴管的交通，以及肝淋巴管的交通在肝脏病理学方面的意义。材料和方法：采用普鲁士蓝注射、厚片透明和组织切片的方法，在５２例小儿和８例胎儿的肝脏对肝淋巴管作了形态学观察。结果：肝深淋巴管包括小叶间淋奥管和小叶下淋巴管，分别位于门管区的疏松结缔组织和小叶下静脉的外膜内。星状浅淋巴管和少数区域洒巴管经肝表面的小凹或裂隙注入小叶间淋巴管。阻断肝深淋巴管时，注射剂经肝深淋巴管返流人肝浅     

淋巴管新生及其在相关疾病发生和治疗中的意义

淋巴管在维持体内微环境衡定、免疫反应和肿瘤淋巴转移等方面起着重要作用,淋巴管新生与胚胎发育、外伤修复、炎症转归和肿瘤转移密切相关.在趋化因子和生长因子的作用下,淋巴管内皮细胞迁移、增殖和构成管腔,形成新的淋巴管.近年来发现淋巴管内皮祖细胞参与淋巴管新生.淋巴管内皮特异表达Prox-1、podoplanin、VEGFR-3和 LYVE-1等,这些因子和受体调控淋巴管新生.VEGF-C/VEGFR-3或VEGF-D/VEGFR-3信号途径在淋巴管新生过程中起着重要作用.VEGF-C、VEGF-D和VEGFR-3可作为基因治疗的靶点,有望治疗淋巴管新生障碍性疾病以及抗移植后免疫排斥和抗肿瘤淋巴管转移.本文主要综述了胚胎发育、先天性淋巴水肿、炎性病变和肿瘤等状态下淋巴管新生的变化及其机制、淋巴管内皮祖细胞参与淋巴管新生的过程、淋巴管内皮细胞特异性转录因子和受体对于淋巴管新生的调控作用.     

出血性休克时小肠固有层内血管、间质和淋巴管间的液体流动

以大鼠为对象，由颈动脉放血，血压维持在５．３ｋＰａ，处于休克状态。由静脉快速注射０．５％荧光素钠０．２５ｍｌ。结果：出血性休克组荧光素钠通过微血管壁向固有层间质弥散的时间为３１±８ｓ，明显小于正常对照组的９７±３３ｓ。显示休克时小肠绒毛微血管通透性增加。小肠绒毛固有层内荧光素钠集中后进入初始淋巴管，测量淋巴管的面积、灰度，出血性休克组与正常对照组无明显差别，但集中和排除时间都明显快于正常对照组。这一结果说明休克时淋巴形成和排除过程明显快于正常对照组。荧光素钠经小肠绒毛淋巴管排除后，残留在绒毛固有层间质的数量，休克组远少于正常组。     

胃癌组织淋巴管LYVE-1、钙粘蛋白的表达及其与癌转移的关系

目的：探讨胃癌组织钙粘蛋白的表达与癌淋巴道转移的相关性。方法：取胃癌标本14例，正常胃组织标本2例。通过E-cadherin、β-catenin和LYVE-1免疫组化方法，观察肿瘤淋巴管的表达。结果：LYVE-1在正常和癌组织淋巴管阳性表达，正常淋巴管E．cadherin、β-catenin表达阴性，β-catenin在胃癌淋巴管表达弱阳性，β-catenin在淋巴管的表达与肿瘤的分化程度及有无转移有负相关性。结论：LYVE-1在淋巴管特异性表达，E-cadherin／β-catenin复合物在淋巴道转移过程中，对肿瘤细胞与淋巴管内皮细胞的粘附起一定的作用，但不是主要作用。     

复杂性淋巴管异常4例临床病理学分析

目的探讨复杂性淋巴管异常的病理特征、临床表现及鉴别诊断。方法收集2010年1月至2021年12月北京协和医院诊治的4例复杂性淋巴管异常患者临床及病理信息, 并进行总结分析。结果 4例病例包括1例Gorham-Stout综合征及3例泛发性淋巴管异常, 男女比为3∶1, 年龄7～32岁。活检部位骨活检3例, 支气管黏膜活检1例, 镜下均可见弥漫分布的扩张或增生的淋巴管结构, Gorham-Stout综合征病例中可见明显的成骨现象。影像学上Gorham-Stout综合征可见骨皮质破坏, 而泛发性淋巴管异常均为髓内溶骨性改变, 3例泛发性淋巴管异常均合并凝血功能障碍, 其中2例合并乳糜性浆膜腔积液。结论复杂性淋巴管异常病理形态上以弥漫性分布的畸形淋巴管为特点, 其诊断需结合临床及病理综合考虑。此类疾病治疗和预后上有所差别, 因此需了解其临床及病理特点并进行鉴别诊断。     

淋巴管阻断对大鼠睾丸影响的自动图像分析

目的 :研究淋巴管阻断后对睾丸的定量组织学影响。方法 :用电灼法将双侧睾丸淋巴管阻断 ,对双侧睾丸淋巴管阻断术后 2天、6天、1 2天、2 4天和 48天的 2 5只大鼠进行研究。另 2 5只大鼠为假手术对照。将睾丸组织切片输入TAS plus型自动图像分析仪进行定量组织学测定。结果 :在睾丸淋巴管阻断术后 6天、1 2天和 2 4天 ,睾丸间质的面积占总面积的比值增加 ,而生精小管的面积占总面积的比值则减少。在睾丸淋巴管阻断术后 2天、6天、1 2天、2 4天和 48天 ,生精上皮的面积占总面积的比值均减少 ,而间质面积与生精上皮面积的比值则均增加 ,生精小管的直径和生精上皮的厚度均变小。结论 :以上结果表明睾丸淋巴管阻断对生精上皮的影响比对间质的影响更为明显。     

基于小鼠肥大细胞瘤P815模型的肿瘤免疫学研究进展

肿瘤动物模型是研究肿瘤免疫学、临床前期评价肿瘤治疗方案有效性和安全性的重要前提.P815肿瘤模型是一种较为成熟的小鼠肿瘤研究模型,因其具有某些独特的优点而被研究者广泛采用.近年来,在已鉴定出P815AB、P815E等肿瘤抗原的基础上,基于该模型的肿瘤疫苗及相关肿瘤免疫学研究都有了相当大的进展.     

The pros and cons of chemokines in tumor immunology

Innate and adaptive immune cells can intervene during tumor progression at different stages including initiation, angiogenesis, local spreading and distant metastasis formation. The net effect can be favorable or detrimental to tumor development, depending on the composition and activation status of the immune infiltrate. Chemokines can determine the distribution of immune cells in the tumor microenvironment and also affect stroma composition. Here we consider how a complex network of chemokines plays a key role in dictating the fate of a tumor. Although the field is in its infancy, we also highlight how targeting chemokines offers a tool to modulate the tumor environment with the aim of enhancing immune-mediated rejection of cancer.     

Cyclooxygenase-2 and thromboxane synthase in non-endocrine and endocrine tumors: A review

Prostaglandins (PG) are members of a large group of hormonally active fatty acids derived from free fatty acids. They are formed from arachidonic acid—the major PG precursor. Cyclooxygenase (COX)-1 and -2 are the rate-limiting steps in PG synthesis. COX-2 is overexpressed in many human non-endocrine and endocrine tumors including colon, breast, prostate, brain, thyroid, and pituitary. COX-2 has an important role in angiogenesis and tumor growth. Thromboxane synthase (TS) catalyzes the synthesis of thromboxane A2 (TXA2), which is derived from arachidonic acid and prostaglandin H₂ and is a vasoconstrictor and inducer of platelet aggregation. TXA2 stimulates tumor growth and spread of some tumors and TS appears to have a critical role in tumorigenesis in some organ systems. In this review, we examine the role of COX-2 and TS in various non-endocrine tumors, especially colon, breast, prostate, and brain as well as in endocrine tumors. The accumulating evidence points to an increasingly important role of COX-2 and TS in tumor progression and metastasis.     

肿瘤疫苗的研究现状

肿瘤在体内的排斥/控制主要依赖于肿瘤抗原特异性T淋巴细胞.T淋巴细胞通过TCR与肿瘤细胞表面表达的HLA-抗原肽复合物的相互作用来识别其靶分子.与特异性HLA-抗原肽复合物有价值的相互作用诱导了淋巴细胞克隆的扩增以及一系列的免疫反应.目前,从理论上已经提出了以整个肿瘤细胞,或纯化的肿瘤抗原作为疫苗(包括整个蛋白质分子和抗原肽及纯化的DNA分子)来提高免疫系统对肿瘤的识别和排斥.本文从免疫系统对肿瘤细胞的识别、疫苗诱导的体内抗肿瘤免疫的假设机制、疫苗接种所诱导的抗肿瘤反应以及临床结果几个方面,对当前肿瘤疫苗的研究现状作一简要综述,并对肿瘤疫苗研究中尚待解决的问题作了简单的归纳.     

Oncocytic non-functioning endocrine tumor of the pancreas

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.     

No evidence of endometriosis within serous and mucinous tumors of the ovary

Ovarian endometriosis can transform into malignant tumors. The author retrospectively examined HE slides of 112 serous tumors and 75 mucinous tumors for the existence of ovarian endometriosis. When endometriosis is present within the tumors, the term "endometriosis-derived tumor" was applied. When endometriosis is recognized adjacent to the tumor, the term "endometriosis-associated tumor" was used. Of the 112 serous tumors (46 benign, 18 borderline, and 50 malignant), 4 (3.5%) (2 benign and 2 malignant) were endometriosis-associated tumors. None was endometriosis-derived tumor. Of the 75 mucinous tumors (30 benign, 26 borderline, and 19 malignant), 4 (5%) (1 borderline and 3 benign) were endometriosis-associated tumors. No tumors showed endometriosis-derived tumors. The data suggest that endometriosis does not transform into serous and mucous tumors. The author felt the limitation of retrospective survey, because the limited numbers of slides (5 to 15) were obtained from each tumor. The author also felt that endometriosis can be difficult to discern because of degenerative changes and other similar lesions such as fallopian tube, fimbria, inclusion cysts, rete ovarii, paraovarian cyst, and Müllerian ducts remnants. Prospective study using whole ovarian examination is required.     

艾氏腹水瘤全细胞瘤苗诱导的特异性杀伤活性

目的研究艾氏腹水瘤全细胞瘤苗诱导的特异性杀伤活性。方法用40g/L的多聚甲醛处理的艾氏腹水瘤细胞作为全细胞瘤苗免疫Balb/c小鼠,建立瘤苗小鼠模型。用HE染色法对亲本肿瘤细胞皮下再次攻击形成的肿瘤结节进行病理学观察;用51Cr释放法测定瘤苗免疫组、荷瘤组、正常组小鼠脾细胞,对亲本艾氏腹水瘤细胞和Sp2/0细胞的杀伤活性。结果HE染色显示,经瘤苗免疫后亲本肿瘤细胞皮下再次攻击形成的肿瘤结节中,瘤细胞几乎完全坏死,同时在坏死部位有大量炎细胞浸润、纤维母细胞和小血管增生;而对照组则无以上现象。效靶比为200∶1时,免疫小鼠脾细胞体外杀伤亲本艾氏腹水瘤细胞的杀伤率(％)为(42.3±3.2)％,显著高于荷瘤组的(12.1±2.3)％、正常组的(6.1±1.1)％和对Sp2/0细胞的杀伤率(8.8±0.4)％(P均∨0.05)。结论艾氏腹水瘤全细胞瘤苗可诱导机体产生特异性杀伤活性。     

外泌体与肿瘤的关系及其应用

细胞总是在不断的分泌各种不同类型的微泡到细胞外液,包括一些小分子和大分子,其中之一就是外泌体.最近研究表明其在细胞间通讯以及肿瘤中具有重要作用,因此得到了广泛的关注.在肿瘤形成过程中,外泌体能够利用自身的结构、组成优势调节免疫系统功能,形成利于肿瘤形成的微环境,诱发肿瘤恶性行为,外泌体研究也为肿瘤诊断和治疗提供了新方向.     

Secondary tumors of the pancreas: Clinicopathological study of 103 autopsy cases of Japanese patients

To investigate the clinicopathological features of patients with secondary tumors of the pancreas, we reviewed autopsy records and pathological features of 103 cases with pancreatic secondary tumors from 690 cases of malignant tumors (excluding cases of primary pancreatic cancer) over a 10-year period. There were 67 men and 36 women in the study, ranging in age from 2 to 94 years (mean: 61 years). The incidence of pancreatic secondary tumors was 15% in the autopsy cases of malignant tumors, and the majority of the secondary tumors were carcinomas. The stomach was the most common primary tumor site (20%), followed by the lung (18%) and extrahepatic bile duct (13%). Because the total number of each primary carcinoma differed, we paid specific attention to the incidence of pancreatic metastasis in each primary carcinoma. We found that carcinoma of the papilla of Vater showed the highest rate of incidence (75%) of pancreatic metastasis in each type of primary carcinoma. Approximately half of the metastatic lesions were solitary, but the metastatic lesions in the pancreas could not be identified macroscopically in 34 cases (33%). Histologically, the most common carcinoma was adenocarcinoma, followed by large cell carcinoma, small cell carcinoma and neuroendocrine carcinoma. The most common non-epithelial tumor was leukemia, followed by malignant lymphoma. Undifferentiated carcinoma and neuroendocrine carcinoma were often found in cases of extrahepatic bile duct or urinary bladder carcinoma with pancreatic metastasis. As for the microscopic infiltration patterns of tumor cells, 73% of cases showed an interlobular and intralobular infiltration. Fat necrosis was most frequently seen as an associated pathological finding (19%). Our study indicates that secondary tumors of the pancreas can be found in approximately one out of six to seven autopsy cases of malignant tumors, and in Japan, the most common of these is adenocarcinoma of the stomach.