骨髓干细胞与消化系统肿瘤

骨髓干细胞有强大的可塑性,且与肿瘤细胞有许多相似之处,有很强的自我更新能力;巨大的增殖潜能等,因此骨髓干细胞很可能与肿瘤的发生发展有着密切的关系。此文就骨髓干细胞的可塑性和消化系统肿瘤的关系作一综述。     

消化系统肿瘤转移的诊断方法及评价

消化系统肿瘤是最常见的肿瘤,可通过浸润区域淋巴结,或进入门静脉循环转移到全身各部治疗的关健在于早期发现,并对已有转移的患者及时调整治疗计划;新发现的肿瘤患者经过初次治疗后,也应该行全面检查以确定有无转移此外目前临床所谓的“肿瘤早期”不一定意味着肿瘤没有转移,近几年来随着免疫学和分子生物学的发展,已经开始从分子和基因水平诊断消化系统肿瘤的微转移与传统的影象学技术和肿瘤标志物检测相比,这些方法能发现更早期的转移本文综述了近年来诊断消化系统肿瘤转移的常用方法及其效果评价,供临床医生选择参考１影象学技术…     

细胞粘附分子与癌侵袭转移

癌是老年人常见顽症。癌的发生、侵袭和转移与细胞粘附分子的表达和功能异常密切相关。本文综述了细胞粘附分子与癌侵袭和转换和的关系，指出细胞粘分子的粘附介导影响着癌细胞的侵袭转移。粘附分子是研究和防治癌侵袭转移的生物学指征之一。     

粘附分子与大肠癌的浸润和转移

细胞粘附分子是细胞之间及细胞与细胞外基质之间的一类粘附物质的总称，与肿瘤的浸润转移有关。本综述了大肠癌浸润转移过程中所涉及到的几种粘附分子，它们以表达的上调、下调和在细胞膜上分布极性的改变影响着癌细胞的侵袭表型，有助于阐明转移的分子机制，并且为临床上治疗癌转移提供了新的思路。     

外泌体在消化系统肿瘤中的研究进展

近年来,消化系统肿瘤的高发病率和高病死率已引起国内外学者的广泛关注。外泌体作为一种可以包裹药物的载体,目前已被应用于肿瘤的靶向治疗。研究表明,外泌体可以携带蛋白质和miRNA在细胞之间转运,可作为肿瘤标志物,并且可以作为消化系统肿瘤治疗药物运输的载体,诱导抗肿瘤免疫反应,从而在促进消化系统肿瘤的发展、侵袭转移中发挥重要的作用。     

蛋白质组学在消化系统肿瘤中的研究进展

蛋白质组学是系统研究分子体系、亚细胞系、细胞、组织、器官乃至整体等生物体系内蛋白质组成及其活动规律的科学。近些年来,它已成为全面分析蛋白质表达变化的有力研究工具,并被广泛应用到各种疾病研究之中。此文旨在介绍蛋白质组学的相关研究技术及其在消化系统肿瘤中的应用。     

水通道蛋白在消化系统肿瘤中的表达及其意义

水通道蛋白广泛存在于生物体内的各组织部位,影响机体水代谢过程,并参与恶性肿瘤的生长、浸润和转移。随着分子生物学技术的进步,水通道蛋白相关基础研究已较为深入和成熟。本文对水通道蛋白在消化系统肿瘤中的表达及其意义进行概述,以期利用相关研究成果,为阐释消化系统肿瘤的发病机制以及寻找新的治疗途径提供可能的思路。     

肿瘤干细胞与消化系统肿瘤

近年来的研究表明肿瘤中只有少量细胞具有发生肿瘤以及持续的自我更新能力,这类具有干细胞特性的肿瘤细胞被定义为肿瘤干细胞（CSC）。越来越多的证据提示了多种实体肿瘤中CSC的存在。消化系统肿瘤是常见的恶性肿瘤,其中是否存在肿瘤干细胞一直备受关注,本文就消化系统肿瘤中肿瘤干细胞的研究进展进行讨论。     

大肠癌患者骨髓转移癌细胞的检测及临床意义

作以膜上皮抗原(epithelial membrane antigen.EMA)单克隆抗体为探针.对70例大肠癌患进行了骨髓中癌细胞的检测，70例中查出阳性癌细胞39例.阳性率为55.7％。骨髓内癌细胞的阳性率与肿瘤细胞分化程度、临床病理分期有关，腺癌、粘液癌、未分化癌骨髓内转移癌细胞的阳性率分别为47.9％、68.7％、83.3％,Duke′sA期、B期、C期、D期的阳性率分别为23.1％、53.8％、69.6％和15.0％，单纯手术.手术 化疗以及手术 化疗 免疫治疗骨髓内转移癌细胞的转阴率分别为33.3％、42.9％和50.0％。本研究提示：骨髓内转移瘤细胞的检查可估计肿瘤的转移与复发。指导临床治疗，可做为大肠癌术后复查的一项常规检查。     

骨髓活检在骨髓转移瘤诊断中的价值

骨髓检查是骨髓转移瘤诊断的主要方法。骨髓转移瘤时，特别当骨髓增生低下时，易出现取材稀释，影响检出率，故骨髓穿刺阳性率低。近10年来，骨髓活检取得了突破性进展，新型的活检穿刺针和骨髓不脱钙组织塑料包埋术的开展，使组织切片不但可像涂片一样观察骨髓造血细胞形态，而且弥补了涂片检查的不足。本文回顾分析我院诊断的骨髓转移瘤患者76例，旨在评价骨髓活检在骨髓转移瘤中的诊断价值。     

Expression of adhesion molecules in endothelial cells during allogeneic bone marrow transplantation

Abstract: Endothelial cell activation during allogeneic bone marrow transplantation, mainly in acute graft-versus-host disease (aGvHD) was studied in 23 recipients and 5 controls using anti-von Willebrand factor (vWF) antibody, antibodies to endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and anti-HLA-DQ antibody, by immunohistological staining of skin. vWF extravasation, ELAM-1 and VCAM-1 expression were present in most recipients with a cutaneous rash which was confirmed as an aGvHD by histological examination (documented aGvHD) (p = 0.005 for vWF extravasation and ELAM-1 expression and p = 0.03 for VCAM-1 expression in comparison with the controls). In recipients with a rash, the cases displaying vWF extravasation and ELAM-1 expression were significantly more numerous in those with a documented aGvHD than in those without histological features of aGvHD (p = 0.01). vWF extravasation and ELAM-1 occurred concomitantly (p<0.01). This study demonstrates that, during the course of skin aGvHD following bone marrow transplantation, there is transient expression of ELAM-1 and VCAM-1 by endothelial cells and simultaneous vWF extravasation, indicating an intense inflammation with endothelial cell participation.     

47例骨髓转移癌的临床及血液学特点

目的 研究骨髓转移癌的临床及血液学特点。方法 骨髓活检塑料包埋切片，H-Gmiesa-E,Gomori,PAS,Alcin blue染色。结果 47例患者中24例找到原发灶，其中胃癌15例，前列腺癌4例，肺癌2例，乳腺癌，结肠癌，肝癌各1例，34例做骨髓活检者骨髓均找到转移癌细胞，而其中10例骨髓象未能发现转移癌细胞，临床表现以贫血最常见（91.5%)，其次是血小板减少（64.7%)，骨痛（61.7%)和发热（48.9%)。结论 对于不明显原因的贫血和骨痛患者，骨髓活检对转移癌具有重要诊断价值。     

骨髓转移瘤的病理组织学与临床特点

目的：研究骨髓转移瘤的临床和病理学特点。方法：骨髓活检塑料包埋切片,Ｈ－Ｇｍｉｅｓａ－Ｅ,Ｇｏｍｏｒｉ,ＰＡＳ,Ａｌｃｉｎ ｂｌｕｅ染色。结果：６６例骨髓转移瘤中,低分化腺癌４２例、黏液腺癌６例、黏液细胞癌３例、代分化鳞癌９例、巨细胞癌２例、未分化癌２例、恶性黑色素瘤１例、恶性纤维组织细胞瘤１例。临床表现以贫血最常见（９５,１％）,其次为血小板减少（５９．５％）和骨髓（５７．４％）。临床初诊常误诊     

Different binding mechanisms of myeloid leukemic cells to adhesion molecules on bone marrow stromal fibroblasts induced by TNF-α and IL-4

 To study the mechanisms of adhesion of myeloid leukemic cells to bone marrow stroma, we analyzed the interaction of bone marrow stromal fibroblasts with myeloid leukemic cell lines and the modulation of adhesion molecule expression on stromal fibroblasts by TNF-α and IL-4. Like others, we found up-regulation of VCAM-1 and ICAM-1 on fibroblasts with TNF-α treatment, whereby IL-4 acted synergistically with TNF-α. VCAM-1 expression on the cell surface was maximal after 10 h, while ICAM-1 expression increased up to 48 h. All myeloid leukemic cell lines tested (HL-60, K562, TMM, U937, ML-2, PLB-985, THP-1, KG1a) revealed weak adhesion to untreated bone marrow fibroblasts (≤10% bound cells). TNF-α and IL-4 significantly enhanced adhesiveness of fibroblasts to the cell lines PLB-985, THP-1, and ML-2, with a peak between 6 and 10 h of treatment. Adhesiveness to the cell line TMM was increased up to eightfold in a time-dependent manner for up to 48 h. The enhanced binding of ML-2-, THP-1-, and PLB-985 cells to stimulated fibroblasts was due at least partially to the interaction of VLA-4 with VCAM-1. Increased adhesion of TMM cells was impaired neither by antibodies to VLA-4, LFA-1, or Mac-1 nor by antibodies to their counter-receptors VCAM-1 or ICAM-1, suggesting that adhesion molecules distinct from VCAM-1 or ICAM-1 are involved in enhanced adhesiveness of the fibroblasts to myeloid leukemic cells. Received: July 7, 1997 / Accepted: July 28, 1998     

西妥昔单抗治疗RAS野生型结肠癌骨髓转移二例

结肠癌是我国常见的恶性肿瘤之一,晚期疾病以血行转移为主,常见转移部位为肝脏和肺,其次为淋巴结转移和种植转移,发生骨髓转移者临床上极为少见,对其治疗的相关报道亦较少。本文介绍本科经治的2例RAS野生型结肠癌伴骨髓转移患者,应用西妥昔单抗治疗后有一定疗效,现将临床资料及治疗经过分享给大家。     

Diagnosis of unknown nonhematological tumors by bone marrow biopsy: a retrospective analysis of 10,112 samples

Purpose  To investigate how unselected bone marrow (BM) biopsy examinations could help in the diagnosis of clinically unknown nonhematological tumors. Methods  10,112 plastic-embedded BM biopsy sections were retrospectively analyzed. In the analysis we focused on the following aspects: (1) the frequency of BM involvement arising from clinically unknown nonhematological malignancies, (2) the clinical indication for BM biopsy examination in cases with tumor BM metastasis, (3) the primary sites of the metastatic tumors, and (4) the advantage of plastic-embedded biopsy sections over paraffin-embedded samples and the complementarity of biopsy with aspiration smears. Results  Of the 10,112 BM samples analyzed, 101 (1.0%) were interpreted as being nonhematological tumor metastases. In cases with metastatic tumors, the nonhemocyte-related changes, such as skeletal pain (25%) and bone destruction (5%), were considerably higher than in those without metastasis (3.7 and 0.32%, respectively; P < 0.001). Primary lesions were documented antemortem in 50 of the 101 biopsy-positive cases (49.5%); the most frequent being in the lung, gastric tract, and breast. Using this assay, a higher incidence of metastatic tumors was detected when compared with previously reported paraffin-embedded samples. The frequency of metastatic tumors based on aspiration smears when the positive results for biopsy sections were used as a reference was 74.3%. All the 101 sections with metastatic tumors showed various degrees of myelofibrosis. Conclusions  We concluded that the routine BM biopsy examination is helpful in detecting insidious metastatic nonhematological malignancies. Skeletal pain and bone destruction are critical indications for susceptible patients to undergo BM examination. Plastic embedding of biopsy sections appears to be more sensitive than the paraffin embedding of samples and is an excellent complementation to isolated aspiration smears.     

胃癌细胞多种粘附分子表达与胃癌转移器官选择性的关系

目的评价胃癌细胞中细胞间粘附分子(ICAM-1)、白细胞分化抗原44V6(CD44V6)、白细胞分化抗原28(CD28)、钙粘连素(E-cad)、癌胚抗原(CEA)等多种粘附分子在胃癌转移的器官选择性中的作用。方法在1996年8月至2005年10月中南大学湘雅医院消化科84例门诊及住院胃癌病例中,胃癌无转移病例32例,肝脏、骨髓、淋巴结、肺、肾及腹腔转移胃癌病例共52例,留取手术标本或胃镜钳取组织,进行原代培养细胞单个化,留取细胞滴片作ABC法免疫组化检测5种粘附分子表达情况,记录其阳性表达率。结果ICAM-1在有骨髓、肺转移病例中高表达;而在单纯淋巴结转移病例中表达较低;CD44V6在淋巴结及肝转移病例中有高表达;CD28在肝、肺、肾转移病例中表达增强;E-cad除在骨髓转移病例中高表达外,余各种脏器转移胃癌E-cad表达均降低;CEA在肝脏、淋巴结、腹腔转移胃癌病例中表达较高。结论粘附分子ICAM-1、CD44V6、CD28、E-cad、CEA表达的增强或减弱在胃癌转移器官选择性中起到一定的作用。     

胃癌细胞多种粘附分子表达与胃癌转移器官选择性的关系

目的评价胃癌细胞中细胞间粘附分子（ICAM-1）、白细胞分化抗原44V6（CD44 V6）、白细胞分化抗原28（CD28）、钙粘连素（E—cad）、癌胚抗原（CEA）等多种粘附分子在胃癌转移的器官选择性中的作用。方法在1996年8月至2005年10月中南大学湘雅医院消化科84例门诊及住院胃癌病例中，胃癌无转移病例32例，肝脏、骨髓、淋巴结、肺、肾及腹腔转移胃癌病例共52例，留取手术标本或胃镜钳取组织，进行原代培养细胞单个化，留取细胞滴片作ABC法免疫组化检测5种粘附分子表达情况，记录其阳性表达率。结果ICAM—1在有骨髓、肺转移病例中高表达；而在单纯淋巴结转移病例中表达较低；CD44 V6在淋巴结及肝转移病例中有高表达；CD28在肝、肺、肾转移病例中表达增强；E—cad除在骨髓转移病例中高表达外，余各种脏器转移胃癌E—cad表达均降低；CEA在肝脏、淋巴结、腹腔转移胃癌病例中表达较高。结论粘附分子ICAM-1、CD44 V6、CD28、E—cad、CEA表达的增强或减弱在胃癌转移器官选择性中起到一定的作用。     

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically-verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 +/- 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut-off point of <7.4 fl was found to have significant predictive value according to receiver-operating characteristics curve analysis. This cut-off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20-135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.     

免疫组库技术在消化系统肿瘤中的研究进展

免疫组库(immune repertoire,IR)是指在某一时间,某个个体的循环系统内所有功能多样性T细胞和B细胞的总和.IR测序是以T淋巴细胞及B淋巴细胞为研究对象,应用多重聚合酶链式反应或5’RACE技术扩增决定T细胞受体或B细胞受体多样性的互补决定区,结合高通量测序技术及数据分析,从而评估免疫系统的多样性,深入研究IR与疾病的关系.近年来,IR在肿瘤的生物标记物,治疗靶点,疗效监测及预后分析中研究广泛,本文就IR在消化系统肿瘤的研究进展进行综述.