galectin-3、HBME-1、CK19及RET在甲状腺肿瘤中的表达情况及其临床价值

目的分析半乳糖凝集素-3(galectin-3)、人骨髓内皮细胞-1(HBME-1)、细胞角蛋白(CK)19及RET在甲状腺良、恶性肿瘤中的表达情况,探讨其在诊断甲状腺肿瘤中的临床价值。方法收集2009～2012年期间我院甲状腺外科经手术切除的131例甲状腺肿瘤患者的临床病理资料,其中甲状腺恶性肿瘤患者45例,甲状腺良性肿瘤患者86例,应用免疫组织化学方法检测galectin-3、HBME-1、CK19及RET在甲状腺良、恶性肿瘤中的表达情况。结果 galectin-3、HBME-1、CK19及RET在45例甲状腺恶性肿瘤患者中的表达阳性率分别为97.8%(44/45)、88.9%(40/45)、100%(45/45)及71.1%(32/45),均明显高于其在86例甲状腺良性疾病患者中的表达阳性率〔分别为9.3%(8/86)、12.8%(11/86)、37.2%(32/86)及8.1%(7/86)〕,差异均有统计学意义(P<0.05)。galectin-3、HBME-1、CK19及RET诊断甲状腺良、恶性疾病的灵敏度分别为97.8%、88.9%、100%及71.1%,特异度分别为90.7%、87.2%、62.8%及91.9%,诊断符合率分别为93.1%、87.8%、75.6%及84.7%。结论 galectin-3、HBME-1、CK19及RET均在甲状腺恶性肿瘤中表达增强,是甲状腺良、恶性疾病病理诊断中有价值的辅助诊断指标,其中galectin-3对甲状腺恶性肿瘤的诊断有较高的参考价值,联合检测可以较大程度上提高甲状腺癌的诊断率。     

D2-40|CK19|galectin-3|VEGF和EGFR在甲状腺乳头状癌中的表达及其临床意义

目的研究甲状腺乳头状癌中D2-40,CK19,galectin-3,VEGF和EGFR的表达及其临床意义。方法应用免疫组化法检测38例甲状腺乳头状癌和12例甲状腺乳头状增生组织中D2-40,CK1 9,galectin-3,VEGF和EGFR的表达水平。结果 D2-4 0,CK1 9,galectin-3,VEGF和EGFR在甲状腺乳头状癌中的阳性表达率明显高于甲状腺乳头状增生组织(P<0.05);D2-40,VEGF,EGFR在甲状腺乳头状癌组织中有淋巴结转移组的表达高于无淋巴结转移组(P<0.05);CK19,galectin-3在甲状腺乳头状癌中的表达在有、无淋巴结转移组之间无统计学差异(P>0.05)。结论D2-40,CK19,galectin-3,VEGF及EGFR的检测有助于甲状腺乳头状癌与甲状腺乳头状增生的诊断和鉴别诊断;D2-40,VEGF和EGFR的表达与甲状腺乳头状癌淋巴结转移有关,对预测淋巴结的转移与否可能有帮助。     

合并微小乳头状癌不同组织中的表达半乳糖凝集素-3和细胞角蛋白-19在桥本甲状腺炎

目的探讨半乳糖凝集素-3(galectin-3,Gal-3)和细胞角蛋白-19(cytokeratin-19,CK-19)在桥本甲状腺炎(HT)合并微小甲状腺乳头状癌(PTMC)不同组织中的表达及其临床意义。方法收集25例HT合并良性结节患者(HT合并良性结节组)、25例PTMC患者(PTMC组)及25例HT合并PTMC患者(HT合并PTMC组)的肿瘤结节组织、距离肿瘤0.5 cm以远的正常甲状腺组织及对侧叶正常甲状腺组织,采用免疫组织化学法检测不同组织中Gal-3和CK-19的表达。结果①PTMC组和HT合并PTMC组的结节组织中Gal-3和CK-19的表达阳性率均明显高于HT合并良性结节组(P<0.05)。②HT合并良性结节组和HT合并PTMC组的对侧叶组织中Gal-3和CK-19的表达阳性率均明显高于PTMC组(P<0.05)。③HT合并良性结节组和HT合并PTMC者的距肿瘤0.5 cm组织中Gal-3和CK-19的表达阳性率均明显高于PTMC组(P<0.05)。④在HT合并PTMC组的距肿瘤0.5 cm组织中Gal-3和CK-19表达中阳性和强阳性率均分别明显高于HT合并良性结节组和PTMC组(P<0.05)。结论①Gal-3和CK-19联合检测可作为鉴别甲状腺良、恶性肿瘤指征;②伴HT疾病中Gal-3和CK-19的表达水平明显高于不伴HT疾病的正常甲状腺组织中的表达情况,提示HT疾病易癌变;③Gal-3和CK-19联合检测有助于HT恶性变倾向的判断和甲状腺癌的早期诊断,特别在其强阳性表达中应视为已恶变;④HT合并PTMC时,应扩大手术范围,以行侧叶加对侧叶大部分切除或全叶切除为宜。     

Galectin-1表达对LoVo细胞凋亡的影响

目的 观察galectin-1对LoVo细胞生长的影响.方法 构建galectin-1真核表达载体转染LoVo细胞,观察LoVo细胞生长情况.用免疫细胞化学方法检测转染后细胞galectin-1蛋白表达水平,免疫印迹检测转染后细胞Bc1-2表达的变化.结果 成功构建了 galectin-1真核表达载体pEGFP-C1/GAL1(p-GAL1),并建立了稳定的空载体(LoVo)细胞和真核表达载体转染细胞(P-LoVo细胞和p-GAL1-LoVo细胞).p-GAL1细胞可表达galectin-1,而另2组细胞则不能.galectin-1表达可降低LoVo细胞Be1-2的表达,诱导的细胞凋亡增加,3组细胞凋亡率分别为(9.61±0.56)%,(3.56±0.53)%和(3.46±0.46)%(P<0.001).而细胞生长曲线表明,P-GAL1-LoVo细胞增殖与P-LoVo和LoVo细胞相似.结论 galectin-1可促进LoVo细胞凋亡可能与galecfin-1可降低LoVo细胞Be1-2的表达有关.     

Galectin-9基因不同亚型对结肠癌LoVo细胞株体外黏附侵袭能力的影响

目的 构建galeetin-9基因不同亚型的真核表达载体,观察galectin-9对结肠癌LoVo细胞体外黏附侵袭能力的影响.方法 构建galectin-9基因不同亚型的真核表达载体后,用脂质体法转染结肠癌LoVo细胞,逆转录-聚合酶链反应(RT-PCR)和Western blot方法验证转染效果.LoVo细胞分别在转染galectin-9、转染galectin-9+抗体(5 mg/L)和转染galectin-9+β-L糖(30 mmol/L)条件下进行体外细胞-基质黏附实验和体外细胞侵袭实验.结果 测序结果证实载体上插入的galectin-9三种剪接体碱基序列正确,同时载体成功转染LoVo细胞.体外细胞-基质黏附实验中,转染空载体,转染galectin-9L,galectin-9M和galectin-9S组平均吸光度分别为:0.74±0.04、1.14±0.12、1.12±0.10和1.15±0.13,表明galectin-9促进LoVo细胞黏附于细胞外基质(P＜0.05).galectin-9抗体和β-乳糖可抑制该作用,但转染galectin-9L和galectin-9S LoVo细胞的黏附作用受β-乳糖抑制更明显(P＜0.05).体外侵袭实验未发现galectin-9对LoVo细胞侵袭力有影响.结论 galectin-9促进LoVo细胞与细胞外基质的黏附,这可能与结肠癌侵袭转移相关,但其三种亚型发挥作用的机制不全相同.     

自身免疫性甲状腺炎患者降钙素储备功能的测定

目的 为探讨AITD患者降钙素储备功能。方法 采用钙负荷一降钙素兴奋试验观察33例AITD患者CT基础值及其储备功能的改变，并与25例健康女性进行比较。AITD患者以具有典型的甲状腺机能减退的临床症状，甲状腺肿大，化验检查证实血清总T3、总T4降低和(或)FT3、FT4n降低并伴有TSH明显增高，甲状腺球蛋白抗体(TGAb)和甲状腺微粒体抗体(TMAb)阳性为诊断标准。血清钙采用电极法测定，CT采用放免法测定，所有资料均输入微机，用SPSS软件包进行统计学处理。结果 AITD患者CT基础值及其储备功能均低于对照组。结论 AITD患者在甲状腺滤泡细胞受损的同时，其C细胞也同时受到损伤，使CT分泌及储备功能减少。     

LncRNA SNHG15在甲状腺癌细胞中的表达及作用

目的:探讨LncRNA SNHG15在甲状腺癌细胞中的表达及作用。方法:qRT-PCR检测人未分化甲状腺癌FRO细胞、人甲状腺鳞癌SW579细胞、人甲状腺导管癌TT细胞及正常甲状腺HT-ori3细胞中Lnc RNA SNHG15表达水平;将FRO细胞分别转染SNHG15 siRNA及阴性对照siRNA后,CCK8实验和克隆形成实验检测细胞增殖,流式细胞术检测细胞凋亡,Western Blot检测凋亡相关蛋白的表达。结果:Lnc RNA SNHG15在FRO细胞、SW579细胞和TT细胞中的表达量均明显高于正常甲状腺HT-ori3细胞,且在FRO细胞中表达量最高(均P0.05);与转染阴性对照si RNA的FRO细胞比较,转染SNHG15 si RNA的FRO细胞增殖能力与克隆形成率均明显降低、细胞凋亡率明显增高、caspase-3与Bax蛋白表达量明显上调,而Bcl-2蛋白表达量明显下调(均P0.05)。结论:Lnc RNA SNHG15在甲状腺癌细胞中表达升高,且细胞分化程度越低表达越高,沉默Lnc RNA SNHG15表达可抑制抑制甲状腺癌细胞增殖并促进凋亡。     

甲状腺Hurthle细胞肿瘤19例诊治分析

目的 探讨甲状腺Hurthle细胞肿瘤的诊断和治疗.方法 回顾性分析我院1994年至2008年收治的19例甲状腺Hurthle细胞肿瘤,并进行随访.结果 本组均行手术治疗.术后病理检查甲状腺Hurthle细胞腺瘤16例,Hurthle细胞腺癌3例,伴颈部淋巴结转移2例;切除标本中合并甲状腺滤泡型腺瘤2例、桥本甲状腺炎3例.16例患者获得随访,随访时间3个月至13年,中位随访时间5年,未发现肿瘤复发或转移.结论 选择适宜的手术方式,甲状腺Hurthle细胞肿瘤患者可获较好的预后.     

甲状腺肿瘤中Bcl—2及p53基因产物的表达及意义

Ｂｃｌ－２及ｐ５３基因可以调控细胞凋亡。我们应用Ｂｃｌ－２及ｐ５３基因产物单克隆抗体，标记５３例甲状腺腺瘤及４１例甲状腺癌。结果发现，甲状腺癌和部分甲状腺腺瘤有Ｂｃｌ－２及ｐ５３基因产物表达。阳性产物分别定位于肿瘤细胞浆和细胞核。在甲状腺癌、二种基因产物阳性表达率在恶性度较高的未分化癌和滤泡状癌或临床ＴＮＭ分期Ⅲ、Ⅳ期的病例增高显著。提示Ｂｃｌ－２及突变型ｐ５３基因产物与甲状腺肿瘤的发生，发展及预     

桥本甲状腺炎治疗及预后分析

目的:探讨桥本甲状腺炎的临床诊断、治疗方法及其预后.方法:106例桥本甲状腺炎患者中,内科治疗40例,经甲状腺自身抗体检测或细针穿刺细胞学检查确诊,口服甲状腺素片治疗.手术治疗66例.随访时间0.5～6年,中位时间3年.结果:内科治疗组新增甲状腺功能下降18例,外科治疗组新增甲状腺功能下降15例.结论:对于桥本甲状腺炎患者,严格遵守手术指征,对有气管压迫症状和无法排除合并恶性结节的患者选择适当手术方式,术后规律服药及监测甲状腺功能变化,可取得良好疗效.     

Galectin-3 expression in papillary thyroid carcinoma: relation to histomorphologic growth pattern, lymph node metastasis, extrathyroid invasion, and tumor size

BACKGROUND: Galectin-3 has been recently recognized as a promising presurgical marker of thyroid malignancy. METHODS: Galectin-3 expression was examined immunohistochemically in 202 specimens of papillary thyroid carcinoma (PTC) in relation to histomorphologic subtypes and clinicopathologic data. RESULTS.: The sensitivity of galectin-3 immunostaining versus conventional histology was 98% (100 of 102) for classical PTC, 85.2% (46 of 54) for follicular variant, and 50% (23 of 46) for follicular/solid variant of PTC. All cases (n = 36) involving lymph node metastases and 42 of 45 cases with extrathyroid invasion expressed galectin-3. However, among the galectin-3-positive cases (n = 169), 133 were without lymph node metastases, and 127 were without extrathyroid invasion. Galectin-3 expression was not related to the size of intrathyroid PTC. CONCLUSIONS: Galectin-3 immunohistochemical expression itself is not an indicator of local metastatic spread or extrathyroid invasion of PTC, thus being irrelevant clinically from this aspect. Galectin-3 is an excellent marker for classical PTC but must be used with caution in diagnosing unconventional variants of PTC because of the possibility of false-negative results.     

Diagnostic value of galectin-3 as a marker for malignancy in follicular patterned thyroid lesions

BACKGROUND: The determination of malignancy in follicular patterned thyroid lesions is based on postoperative histologic findings. Therefore, affected patients are referred for surgery, although only 20% will have a final diagnosis of malignancy. The aim of this study was to investigate the potential of galectin-3 as a marker of malignancy in these lesions. METHODS: Fifty-four tissue specimens of follicular patterned thyroid lesions were immunohistochemically stained for galectin-3. Area and intensity scores were recorded. RESULTS: Significant differences were found between the benign and malignant lesions. The sensitivity, specificity, positive predictive values, and negative predictive values of galectin-3 staining were 82%, 68%, 75%, and 77%, respectively (p=.0002). Significant differences were also found between the subgroups of benign and malignant lesions (p < or =.05). CONCLUSIONS: Galectin-3 staining is highly sensitive for malignancy in follicular patterned thyroid lesions. Diagnostic problems may arise in the presence of Hurthle cell proliferation or minimally invasive follicular carcinoma.     

Is galectin‐3 a good method for the detection of malignancy in patients with thyroid nodules and a cytologic diagnosis of “follicular neoplasm”? A critical appraisal of the evidence

BACKGROUND: Thyroid nodules are the most common surgical disease of the thyroid. Fine-needle aspiration biopsy (FNAB) is the most commonly employed tool for establishing a diagnosis. However, 15% to 25% of FNAB reports yield inconclusive results. Immunostaining of cytological smears from FNAB with galectin-3 has been proposed as a tool for differentiating between benign and malignant nodules. We performed a systematic review to evaluate the utility of galectin-3. METHODS: Prospective studies of nodules with FNAB reports of "follicular neoplasm" and with a definitive diagnosis confirmed by histopathology were selected. Calculations of individual sensitivity, specificity, and positive and negative likelihood ratios were made. RESULTS: The articles selected were those with the best methodological quality. CONCLUSION: Galectin-3 could be a good tool to guide therapeutic decision in patients with thyroid nodules and FNAB results of follicular neoplasm, but available information has methodological flaws that precludes a definitive answer about galectin-3 utility in the clinical setting.     

Decreased galectin-3 expression in prostate cancer

BACKGROUND: Galectin-3 is a carbohydrate-binding protein whose level of expression has been shown to be correlated with metastatic potential in a number of different tumor types. The purpose of this investigation was to examine galectin-3 expression in several tumorigenic and nontumorigenic prostate cell lines and prostate tissue samples. METHODS: The expression of galectin-3 in cell lines and tissue samples was evaluated by tissue immunohistochemistry and Western blot analysis. RESULTS: Human cell lines PC-3M, PC-3, DU-145, PrEC-1, and MCF10A demonstrated the presence of galectin-3. Galectin-3 was not detected in TSU-pr1 and LNCaP by Western blot analysis. We furthered our studies by examining a series of human prostate tissue samples for expression of galectin-3. Overall, approximately 60-70% of the normal tissue examined demonstrated heterogenous expression of galectin-3. In stage II tumors, however, there was a dramatic decrease in galectin-3 expression in both PIN and tumor sections, with only 10.5% (2/19) of these samples expressing this protein. Stage III tumors also demonstrated a decreased expression of galectin-3, although this downregulation was not as dramatic, with 35% of PIN samples and 52% of tumor tissue expressing galectin-3 (P < 0.01). CONCLUSIONS: These data demonstrate that galectin-3 is downregulated in prostate cancer. The altered downregulation pattern of galectin-3 observed between tumor stages suggests different roles for galectin-3 in the progression of prostate cancer.     

Clinicopathological significance of decreased galectin-3 expression and the long-term prognosis in patients with breast cancer

Purpose

Galectin-3 expression is modulated in cancer cells, and that finding has led to the recognition of galectin-3 as a diagnostic or prognostic marker for various cancers, including breast cancer. This study investigated the correlation between galectin-3 expression and the clinicopathological features in patients with breast cancer, in order to determine the relevance and role of galectin-3 in breast cancer progression.

Methods

Galectin-3 expression was investigated immunohistochemically in 116 patients with breast cancer, and a statistical analysis was performed.

Results

Galectin-3 expression in breast cancer was significantly associated with tumor vascular invasion. However, galectin-3 expression was not associated with Ki-67 expression, which reflects tumor proliferation. Disease-free survival and long-term overall survival were significantly shorter for patients with reduced galectin-3 expression.

Conclusions

This study demonstrated that the galectin-3 expression was associated with tumor vascular invasion and metastasis, suggesting that galectin-3 plays a critical role in tumor progression via an invasive mechanism but not via proliferation in breast cancer. Furthermore, reduced expression of galectin-3 is useful for predicting a long-term poor prognosis in patients with breast cancer.     

Differential expression of galectin-3 in papillary projections of malignant and non-malignant hyperplastic thyroid lesions

Galectin-3 is a a beta-galactoside binding protein recently proposed to be a promising presurgical molecular marker for distinguishing benign from malignant thyroid neoplasms. We analyzed galectin-3 expression immunohistochemically in papillary areas of hyperplastic lesions of benign thyroid tissue in comparison with malignant papillary projections of papillary thyroid carcinoma (PTC). A monoclonal antibody to galectin-3 and ABC immunohistochemical technique were used to evaluate galectin-3 expression in 26 cases of benign papillary hyperplasia (8 cases of hyperplastic adenoma, 8 cases of hyperplastic colloid goiter, 10 cases of Graves disease) in comparison with 25 cases of PTC. Immunohistochemical results showed no reactivity for galectin-3 in papillary areas of benign hyperplastic lesions. Strong cytoplasmic galectin-3 immunoreactivity was found in all 25 cases of PTC. These results show that galectin-3 expression is a feature of malignant papillary projections but not of benign papillary hyperplasia. Thus, the immunohistochemical evaluation of galectin-3 might contribute to differential diagnosis between malignant and benign thyroid lesions with papillary projections.     

细胞角蛋白19、半乳糖凝集素3、HBME-1和BRAF V600E表达在甲状腺结节的临床应用价值

目的探讨甲状腺结节患者中细胞角蛋白19（CK19）、半乳糖凝集素3（Galectin-3）、HBME-1、BRAF V600E的表达水平,从而分析4种分子标志物在鉴别甲状腺结节良恶性和甲状腺乳头状癌（PTC）的临床应用价值。 方法用免疫组织化学法检测746例甲状腺恶性结节（恶性组）及287例甲状腺良性结节（良性组）患者术后病理标本中CK19、HBME-1、Galectin-3和BRAF V600E的表达,评估各标志物单独及联合检测对PTC的诊断效能及意义。 结果（1）CK19、HBME-1、Galectin-3及BRAF V600E在恶性组的表达阳性率明显高于良性组（P<0.05）。（2）单独诊断PTC时,Galectin-3敏感度和准确性最高,BRAF V600E特异度最高;CK19+HBME-1+Galectin-3联合检测敏感度和准确性最高,分别为93.60%、94.49%。（3）CK19、Galectin-3、HBME-1及BRAF V600E表达阳性率均与PTC合并甲状腺良性病变呈正相关（r_s>0,P<0.05）。CK19、Galectin-3及BRAF V600E表达与病灶数目相关（P<0.05）,且Galectin-3、BRAF V600E表达与微小癌病灶大小呈负相关（r_s<0,P<0.05）。BRAF V600E表达与淋巴结转移、促甲状腺激素水平相关（P<0.05）。（4）与单纯PTC比较,合并良性病变的PTC不易发生淋巴结转移,合并桥本甲状腺炎的PTC多灶癌所占比例较高。 结论CK19、Galectin-3、HBME-1、BRAF V600E是甲状腺良恶性结节鉴别诊断重要的辅助指标,也是诊断PTC的肿瘤标志物,其中Galectin-3诊断效能最高,CK19、Galectin-3、HBME-1联合检测可提高PTC的诊断准确性。     

Effects of galectin-3 expression on growth and tumorigenicity of the prostate cancer cell line LNCaP.

BACKGROUND: Galectin-3 is a beta-galactoside-binding vertebrate lectin. In human prostate cancer, galectin-3 expression has been shown to decrease with progression of disease. In the present study, we further investigated the role of galectin-3 in this malignancy by examining the phenotype of galectin-3-transfected prostate cancer cells. METHODS: Stably transfected galectin-3-expressing cell lines were developed from the prostate cancer cell line LNCaP, which does not constitutively express this molecule. Transfected cells lines were analyzed for alterations in morphology and growth rates, and for ability to form tumors in nude mice. RESULTS: Morphologically, when compared to the parental LNCaP cells, the galectin-3 transfectants had broader, flatter cell bodies, shorter and less finely branched dendritic processes, and large nuclei with pronounced and often multiple nucleoli. The galectin-3 lines were found to proliferate at a slower rate in vitro than either the vector control-transfected lines or parental LNCaP. When injected subcutaneously in nude mice, four of six galectin-3 lines formed tumors at a slower rate than control lines. Twenty-four tumors that formed from the transfected cell lines were examined by immunohistochemistry for galectin-3 expression. Only one tumor was found to express galectin-3, suggesting that the transfected cells which formed tumors were those which successfully down-regulated galectin-3 expression. CONCLUSIONS: In contrast to an apparent stimulatory role in some tumor types, galectin-3 is an inhibitory molecule for prostate cancer.     

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Galectin-1, a β-galactoside–binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1–silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-κB (NF-κB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-κB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease.