Galectin-3鉴别良、恶性甲状腺结节的研究进展

随着分子生物学技术的发展和不断完善，用于鉴别良、恶性甲状腺结节的许多潜在的肿瘤分子标志物被发现，如galectin-3(Gal-3)、细胞角蛋白19(EK19)、二肽酶Ⅳ(DPPⅣ)、粘蛋白-1(MUC1)、细胞周期蛋白D1、甲状腺转录因子-1(TTF-1)等。其中，Cal-3经国内外多项研究显示它是鉴别甲状腺良、恶性结节的良好标志物，尤其对甲状腺乳头     

乳腺癌组织Ezrin表达及其与临床病理特征关系的研究

目的:研究Ezrin表达与乳腺癌临床病理特征的关系。方法:应用组织芯片技术和免疫组织化学方法检测117例浸润性乳腺癌和41例乳腺良性增生中,Ezrin、ER、PR、c-erbB-2、MMP-2及MMP-9的表达。结果:Ezrin在91.89%(34/37)的乳腺良性增生中表达于导管腔缘上皮顶膜,在细胞质内无表达;在76.99%(87/113)的乳腺癌组织中,Ezrin表现为细胞质中弥散表达,未见顶膜表达,两者差异有统计学意义,P=0.000。在乳腺癌组织中,Ezrin表达与肿瘤最大直径、TNM分期、淋巴结转移以及基质细胞中MMP-2和MMP-9的表达呈正相关,P值分别为0.016、0.002、0.036、0.007和0.002;而与年龄、组织学分级、ER、PR、c-erbB-2、肿瘤细胞中MMP-2及MMP-9表达无明显相关性。结论:Ezrin在乳腺良恶性病变中有明显不同的亚细胞定位,其表达情况对乳腺病变性质的判断具有重要价值。高表达Ezrin的乳腺癌具有更高的侵袭性和淋巴结转移能力,在乳腺癌组织中检测Ezrin的表达能为患者的预后和淋巴结转移风险评估提供重要参考。     

乳腺癌组织磷酸化STAT3表达及其与淋巴结转移关系的研究

目的：研究乳腺癌组织中磷酸化STAT3（pSTAT3）的表达情况,及其与病变性质、淋巴结转移、雌激素受体（ER）、孕激素受体（PR）和c-erbl3-2表达的关系。方法：选择乳腺浸润性导管癌45例和乳腺癌旁组织12例,应用Envision免疫组化法对其进行pSTAT3蛋白的检测,并进行相关统计分析。结果：pSTAT3在乳腺癌组织中的阳性表达率（60．0％）明显高于癌旁组织中的阳性表达率（16．7％）,P〈0．01。pSTAT3在有淋巴结转移患者癌组织中的阳性表达率（77．8％）比没有淋巴结转移患者癌组织中的阳性表达率（48．10A）明显升高,P〈0．05。pSTAT3在PR阳性患者癌组织中的阳性表达率（72．3％）比PR阴性的阳性表达率（37．5％）明显升高,P〈0．05。pSTAT3的表达与乳腺癌患者年龄、肿瘤大小及ER和c-erbB-2的表达未见相关性,P〉0．05。结论：pSTAT3蛋白的表达增强可能与乳腺癌淋巴结转移以及PR有关,提示STAT3基因可能参与了乳腺癌的发生、发展和预后过程。     

组织蛋白酶D在乳腺癌中的表达及其与转移的相关性研究

目的探讨组织蛋白酶Ｄ（ｃａｔｈｅｐｓｉｎＤ，ＣＤ）在乳腺癌中的表达及其与转移的关系。方法应用ＣＤ多克隆抗体对７２例乳腺浸润性导管癌（以下简称乳腺癌）进行了免疫组织化学研究。结果乳腺癌ＣＤ阳性细胞的分布极不一致，可能与乳腺癌的生长方式及异质性有关；腋下淋巴结阳性病例组中ＣＤ高表达者明显多于腋下淋巴结阴性（ｎｏｄｅ－ｎｅｇａｔｉｖｅｂｒｅａｓｔｃａｎｃｅｒ，ＮＮＢＣ）病例组（Ｐ＜０．００５）；乳腺癌术后复发及远处转移者均为高水平ＣＤ表达；３４例ＮＮＢＣ的ＣＤ表达差异颇大，其中有１０例ＣＤ完全阴性，８例低表达，１６例高表达。结论ＣＤ表达与乳腺癌转移密切相关，ＣＤ高表达者术后复发、远处转移的可能性大。     

CD44V6表达与乳腺癌侵袭转移的关系

目的 研究乳腺癌中CD44V6的表达及其与乳腺癌侵袭转移的关系。方法 应用免疫组织化学和RT-PCR方法，检测30例乳腺癌和10例乳腺良性肿瘤组织中CD44V6表达。结果 CD44V6在乳腺癌组织中的表达明显高于良性组织；CD44V6在Ⅲ-Ⅳ期乳腺癌中表达明显高于Ⅰ-Ⅱ期，有淋巴结转移乳腺癌组织中CD44V6表达显著高于无淋巴结转移者；CD44V6的表达与乳腺癌的病理类型无关。结论 CD44V6的表达，有助于预测乳腺癌进展程度和对淋巴结转移的判断。     

nm23基因在人乳腺癌中的表达及与淋巴结转移的关系

应用免疫组织化学抗生蛋白链菌素－生物素标记法，对１２２例乳腺部ｎｍ２３基因的表达及其与淋巴结转移的关系进行了研究。结果显示：１２２例乳腺癌ｎｍ２３基因性阳性率为５１．６％，而有腋窝淋巴结转移的５３例乳腺癌，其阳性率为２８．３％，无腋窝淋巴结转移的６９例，阳性主６９．６％，两者有非常显著差异。     

乳腺癌组织CCR5和c-erbB-2表达与腋窝淋巴结转移的相关性研究

目的:检测乳腺癌组织中趋化因子受体5(CCR5)和c-erbB-2的表达情况,分析CCR5与c-erbB-2及腋窝淋巴结转移的关系.方法:采用免疫组化SP法检测72例乳腺癌组织标本中CCR5和c-erbB-2的表达,结合临床资料进行统计学分析.结果:72例乳腺癌组织标本中有61例(84.7%)CCR5表达阳性,其中伴有淋巴结转移者46例;CCR5与腋窝淋巴结转移(χ2=4.982,P=0.026)和c-erbB-2过度表达(χ2=4.583,P<0.05)均呈正相关.结论:CCR5可作为乳腺癌发生、发展及判断预后的一种新型的生物学标志.     

乳腺癌淋巴结转移与免疫组化检测的意义

本文对813例乳腺癌淋巴结转移的分析,提出国人乳腺癌的淋巴结转移与肿瘤部位、肿瘤大小、病理类型及5年和10年生存率相关(P 值<0.001)。应用许良中免疫酶标ABC 法,检测159例乳癌组织的 ER、PR 水平,检测147例 LeuM_1及 CEA 水平,石蜡切片,DAB 显色。结果:淋巴结转移率随 ER、PR 水平的增高而降低。LeuM_1及 CEA 水平的升高,淋巴结转移个数增加。四项检测各组淋巴结转移均有显著差异(P 值<0.05-0.001)我们提出检测乳癌组织 ER、PR、LeuM_1及CEA 水平,可以作为预测乳癌予后的指标。     

PTEN蛋白表达与乳腺癌增殖、侵袭转移的相关性

目的：研究乳腺癌组织中抑癌基因PTEN编码蛋白的表达与肿瘤细胞增殖、侵袭转移的关系,探讨PTEN蛋白的表达在乳腺癌发生发展过程中的作用机制。方法：选取福州市第一医院病理科存档的乳腺癌标本86份和乳腺良性病变组织标本30份,应用免疫组织化学法检测乳腺癌组织和乳腺良性病变组织中PTEN表达情况与Ki67增殖指数,分析PTEN表达与乳腺癌Ki67增殖指数以及患者年龄、肿瘤大小、组织病理学分级、淋巴结转移、临床分期等临床病理学参数之间的关系。结果：乳腺癌组PTEN的阳性表达率为52.3%,良性对照组为93.3%;乳腺癌组Ki67增殖指数为（31.5±20.6）%,对照组为（9.7±6.9）%,比较均具有显著差异（P〈0.01）。乳腺癌PTEN表达与Ki67增殖指数、组织病理学分级、腋窝淋巴结转移及临床分期呈负相关（P〈0.05或P〈0.01）,与患者年龄、肿瘤大小未见显著相关（P〉0.05）。结论：PTEN蛋白的表达与乳腺癌细胞增殖及侵袭转移具有相关性,是判断肿瘤生物学行为和患者预后的重要参考指标之一。     

Kiss-1及nm23表达与乳腺癌淋巴结转移的关系

背景与目的:Kiss-1和nm23是肿瘤转移抑制基因,其蛋白表达与乳腺癌的转移密切相关.本研究探讨Kiss-1及nm23蛋白在乳腺癌中的表达与腋窝淋巴结转移的关系.方法:用免疫组化技术检测70例乳腺癌中Kiss-1及nm23蛋白表达.结果:乳腺癌中Kiss-1与nm23蛋白的阳性表达率分别为62.86%和68.57%,其中有淋巴结转移者的阳性表达率分别为38.46%和50.00%,明显低于无淋巴结转移者的阳性表达率77.27%和79.55%(P(0.05).Kiss-1与nm23蛋白表达均阳性患者的淋巴结转移率(14.29%)明显低于其他患者(P＜0.05). 结论:Kiss-1与nm23具有抑制乳腺癌淋巴结转移的作用,可能成为预测乳腺癌淋巴结有无转移的生物学标志.     

Relationship between galectin-3 expression and TRAIL sensitivity in breast cancer

Evaluation of: Mazurek N, Byrd JC, Sun Y, Ueno S, Bresalier RS. A galectin-3 sequence polymorphism confers TRAIL sensitivity to human breast cancer cells. Cancer DOI: 10.1002/cncr.26078 (2011) (Epub ahead of print).

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to death receptors expressed on cancer cells and induces apoptosis. Triple-negative breast cancer cell lines are more sensitive to TRAIL or TRAIL-death receptor agonistic monoclonal antibody-induced apoptosis compared with HER-2/neu-overexpressing or luminal cell lines. The paper under evaluation sought to determine whether the His64/Pro64 polymorphism of galectin-3, which is associated with breast cancer incidence, affects sensitivity to TRAIL. None of five breast cancer cell lines homozygous for Pro64 galectin-3 were sensitive to TRAIL, but two out of two homozygous His64 cell lines and one out of two heterozygous His64 cell lines were sensitive. Transfection of galectin-3 null BT549 breast cancer cells with His64 galectin-3 rendered them sensitive to TRAIL, while Pro64 galectin-3-transfected cells remained resistant to TRAIL. This article highlights that galectin-3 receptor expression and genotype may be useful markers in predicting TRAIL or agonistic antibody sensitivity of breast cancer patients.     

Chemically modified,non-anticoagulant heparin derivatives are potent galectin-3 binding inhibitors and inhibit circulating galectin-3-promoted metastasis

Concentrations of circulating galectin-3, a metastasis promoter, are greatly increased in cancer patients. Here we show that 2- or 6-de-O-sulfated, N-acetylated heparin derivatives are galectin-3 binding inhibitors. These chemically modified heparin derivatives inhibited galectin-3-ligand binding and abolished galectin-3-mediated cancer cell-endothelial adhesion and angiogenesis. Unlike standard heparin, these modified heparin derivatives and their ultra-low molecular weight sub-fractions had neither anticoagulant activity nor effects on E-, L- or P-selectin binding to their ligands nor detectable cytotoxicity. Intravenous injection of such heparin derivatives (with cancer cells pre-treated with galectin-3 followed by 3 subcutaneous injections of the derivatives) abolished the circulating galectin-3-mediated increase in lung metastasis of human melanoma and colon cancer cells in nude mice. Structural analysis using nuclear magnetic resonance and synchrotron radiation circular dichroism spectroscopies showed that the modified heparin derivatives bind to the galectin-3 carbohydrate-recognition domain. Thus, these chemically modified, non-anticoagulant, low-sulfated heparin derivatives are potent galectin-3 binding inhibitors with substantial potential as anti-metastasis/cancer drugs.     

Relationship between galectin-3 expression and TRAIL sensitivity in breast cancer

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to death receptors expressed on cancer cells and induces apoptosis. Triple-negative breast cancer cell lines are more sensitive to TRAIL or TRAIL-death receptor agonistic monoclonal antibody-induced apoptosis compared with HER-2/neu-overexpressing or luminal cell lines. The paper under evaluation sought to determine whether the His64/Pro64 polymorphism of galectin-3, which is associated with breast cancer incidence, affects sensitivity to TRAIL. None of five breast cancer cell lines homozygous for Pro64 galectin-3 were sensitive to TRAIL, but two out of two homozygous His64 cell lines and one out of two heterozygous His64 cell lines were sensitive. Transfection of galectin-3 null BT549 breast cancer cells with His64 galectin-3 rendered them sensitive to TRAIL, while Pro64 galectin-3-transfected cells remained resistant to TRAIL. This article highlights that galectin-3 receptor expression and genotype may be useful markers in predicting TRAIL or agonistic antibody sensitivity of breast cancer patients.     

Circulating galectin-3 in the bloodstream: An emerging promoter of cancer metastasis

Increased concentrations of free circulating galectin-3 are commonly seen in the blood circulation of patients with many types of cancers including colorectal cancer. Recent studies have shown that changes in circulating galectin-3 levels in cancer patients may contribute significantly to the metastatic spread of disseminating cancer cells by enhancing their ability to adhere to blood vessel endothelium and by helping their avoidance of immune surveillance. Thus, targeting the galectin-3 actions in the circulation may hold significant promise for future development of novel therapeutic agents to prevent metastasis and reduce cancer-associated fatality.     

NGAL表达与乳腺癌进展、转移及预后的关系

目的 探讨中性粒细胞相关载脂蛋白(NGAL)在乳腺癌组织中的表达及与乳腺癌进展、转移及预后的关系.方法 应用免疫组化方法检测NGAL在127例乳腺癌,20例乳腺良性肿瘤组织中的表达,分析其与乳腺癌临床病理特征及预后的关系.结果 NGAL在乳腺癌组织中的阳性表达率为40 2%,明显高于在乳腺良性肿瘤中的表达(χ2＝6 816,P＝0 009),NGAL表达与乳腺癌组织学分级(χ2＝6 269,P＝0 012)和病理类型(χ2＝14 213,P＝0 001)有关,与TNM分期(r=0 192,P=0 031)、淋巴结转移(r=0 257,P=0 004)和HER-2(r=0 287,P=0 001)呈正相关,与ER(r=-0 197,P＝0 026)呈负相关.NGAL表达阳性组和阴性组的5年特异生存率分别为38 4%和63 4%,差异有显著性(P＝0 016).结论 NGAL阳性表达提示乳腺癌预后不良.NGAL可作为评价乳腺癌预后新的生物学指标,为乳腺癌综合治疗提供依据.     

Involvement of galectin-3 expression in colorectal cancer progression and metastasis.

Galectin-3 is a beta-galactoside-specific lectin that binds to laminin sugar-sites and is involved in tumor malignancy. Galectin-3 expression in relation to primary tumor and liver metastasis of colorectal cancer was examined to determined its involvement in cancer progression and metastasis. Immunohistochemical staining of galectin-3 was performed on 117 primary lesions and 15 liver metastases of colorectal cancer using TIB166 monoclonal antibody. The expression of galectin-3 was evaluated by grading the intensity of the staining as either negative, weakly positive, or strongly positive. Normal mucosa of all patients were strongly positive for galectin-3, but the staining in these tissues was still significantly less than in the primary lesions of the cancer (31.6%). Galectin-3 expression in the primary lesions was significantly increased, correlating with the progression of clinical stage (p=0. 0224), liver metastasis (p<0.0001), venous invasion (p=0.0048), and lymph node metastasis (p=0.0289). Liver metastatic lesions also showed up-regulated levels of galectin-3 compared to the primary lesions (p=0.0030). The group showing strongly positive galectin-3 had a significantly poorer prognosis than the negative/weakly positive group in terms of disease-free survival (p=0.0224). The strong expression of galectin-3 in colorectal cancer correlates with cancer progression, liver metastasis, and poor prognosis for patients.     

Prognostic significance of the expression levels of T-cell immunoglobulin mucin-3 and its ligand galectin-9 for relapse-free survival in triple-negative breast cancer

T-cell immunoglobulin mucin-3 (TIM-3) expressed at the T-cell surface acts as an immune checkpoint when bound by its ligand galectin-9. Blockade of immunosuppression by the TIM3/galectin-9 signalling pathway may offer novel therapeutic approaches for cancer immunotherapy. Consistent with this, TIM-3 expression is associated with poorer prognosis in several different types of cancer, possibly as a result of suppression of anticancer immunosurveillance. A number of studies have now documented some effectiveness of immune checkpoint blockade even in triple-negative breast cancer (TNBC), which is highly aggressive. However, clinical responses are relatively weak, suggesting that several different pathways may be involved. In this context, the role of the TIM-3/galectin-9 checkpoint in TNBC is not clear. The present study aimed to determine the clinicopathological significance of TIM-3 and galectin-9 expression in this cancer. To this end, 62 patients with TNBC undergoing surgery at Kansai Medical University Hospital (Hirakata, Japan), but not given neoadjuvant chemotherapy, were examined. Tissue microarrays were employed for immunohistochemistry to analyse associations of TIM-3 and galectin-9 expression and their impact on relapse-free survival relative to other poor prognostic risk factors. Galectin-9 expression was detected in 49 of 62 patient samples (79%), and TIM-3 in 30 of them (48.4%). Tumour cell galectin-9 expression was associated with a more favourable prognosis (P=0.027) as was TIM-3 expression on tumour-infiltrating lymphocytes (P=0.007). Multivariate analysis indicated that galectin-9- and TIM-3-double-positivity was significantly associated with a more favourable prognosis compared with galectin-9 and/or TIM-3 negativity (P=0.044). Thus, the TIM-3/galectin-9 signalling pathway may impact anticancer immune reactions in the tumour microenvironment of patients with TNBC. Further investigation will be necessary to determine the molecular mechanisms underlying these relationships.     

早期胃癌组织Galectin-3表达与淋巴结微转移关系的探讨

目的:研究早期胃癌组织中半乳凝素3(Galectin-3)表达水平与淋巴结微转移的关系。方法:采用免疫组化技术检测56例早期胃癌患者胃癌组织Galectin-3的表达水平,采用淋巴结组织HE染色和角蛋白AE1/AE3表达检测判断淋巴结微转移情况分析Galectin-3表达水平与淋巴结微转移的关系。结果:56例早期胃癌患者中,7例患者13枚淋巴结发现AE1/AE3阳性细胞,总阳性率12.5%(7/56),淋巴结总转移率11.67%(14/120);Galectin-3免疫反应在不同病理亚型早期胃癌组织中程度不同,随着分化程度降低而增强,有淋巴结转移或微转移的早期胃癌组织中Galectin-3表达比无淋巴结转移或微转移的早期胃癌组织中Galec-tin-3表达明显增强。结论:胃癌组织Galec-tin-3高表达有较高的淋巴结转移风险,这对判断预后和指导治疗有重要意义。     

Galectin-3 在人乳腺癌组织中的表达及对MCF-7 细胞恶性生物学行为的影响

目的：探讨半乳凝集素-3（galectin-3）蛋白在人乳腺癌组织中的表达规律及沉默galectin-3 基因后对乳腺癌MCF-7 细胞迁移、侵袭和凋亡的影响。方法：收集2014 年2 月至2018 年2 月邢台市人民医院手术切除的15 例乳腺癌患者癌组织及其癌旁组织,另外采集该医院和河北医科大学附属第四医院组织石蜡切片100 份,利用Western blotting 检测15 例乳腺癌患者的癌组织及癌旁组织中galectin-3 蛋白相对表达水平,用免疫组织化学法检测galectin-3 蛋白在100 例乳腺癌石蜡标本切片中的表达水平,并分析其表达与患者临床病理特征的关系。将galectin-3 siRNA 转染至MCF-7 细胞中,用qPCR 法和Western blotting 分别检测galectin-3 mRNA和蛋白的表达水平;用Transwell 小室法和流式细胞术分别检测galectin-3 基因沉默后对MCF-7 细胞迁移、侵袭和凋亡的影响。结果：在乳腺癌组织中galectin-3 蛋白表达水平显著高于癌旁组织（P<0.05）;乳腺癌组织中galectin-3 蛋白阳性表达率为67.00%,其表达水平在淋巴结转移、激素受体（ER、PR）阴性组中显著升高（均P<0.05）,且随TNM分期和组织学分级的升高而升高（均P<0.05）。转染galectin-3 siRNA 后,能显著降低MCF-7 细胞galectin-3 mRNA和蛋白的表达水平、迁移和侵袭能力（均P<0.05）,提高细胞的凋亡率（P<0.05）。结论：Galectin-3 在乳腺癌组织中高表达,沉默galectin-3 表达后抑制MCF-7 细胞的迁移和侵袭、诱导细胞凋亡,可作为乳腺癌生物治疗的一个新靶点。