Comparative Immunohistochemical Assessment of Craniopharyngioma and Related Lesions

Craniopharyngiomas (CP), Rathke’s cleft cysts (RCC), and sellar xanthogranulomas (XG) are closely related lesions. As expression of cytokeratins 8 (CK8) and 20 (CK20) was reported in RCC but not in CP, the present study investigates the reproducibility of immunohistochemical distinction between CP and RCC, attempting to identify the relationship of XG to these lesions. A comparative study of 55 patient specimens (25 CP, 28 RCC, and 2 XG) was analyzed for the histological features of xanthomatous changes and squamous metaplasia, and expression of CK8 and CK20. In the 25 CP cases, xanthomatous changes were seen in 5 (20%), with CK8 reactivity demonstrated in all 25 cases. A prominent xanthomatous component was identified in 13 of 28 RCC (46%), and squamous metaplasia was seen in 11 (39%), 9 of which also contained xanthomatous features. CK8 reactivity was demonstrated in all 28 RCC cases, whereas CK20 was seen only in 9 cases (32%). Of the two cases diagnosed as XG, none contained epithelium, and immunohistochemistry for cytokeratins was not observed. Overall, differential expression of cytokeratins cannot reliably distinguish CP from RCC. Furthermore, expression of CK20 in RCC is generally seen within a background of prominent squamous metaplasia and reactive xanthomatous changes.     

Ectopic salivary gland tissue in a Rathke’s cleft cyst

The presence of salivary gland tissue in the sella turcica has rarely been reported, mainly after pituitary examination at autopsy. Only five symptomatic cases have previously been described, mainly associated with Rathke’s cleft cyst. We report a 17-year-old boy presenting with headaches and hyperprolactinemia. The MRI showed a 19 mm sellar mass that at surgery revealed as a cystic lesion filled with mucinous fluid. The histological examination documented the presence of ectopic salivary gland tissue in the wall of a Rathke’s cleft cyst. The present report focuses on the possible pitfalls when dealing with unusual sellar lesions, and the need of increased awareness of this rare condition.     

米非司酮流产蜕膜组织中白血病抑制因子表达的研究

目的探讨早孕妇女米非司酮药物流产与非药物人工流产的蜕膜组织中白血病抑制因子（LIF）表达的差异,分析米非司酮的致流产作用与LIF维持妊娠作用之间的关系。方法运用免疫组织化学技术检测23例米非司酮流产妇女蜕膜组织LIF蛋白的表达,并与20例非药物人工流产蜕膜组织进行对照。结果LIF蛋白在所有蜕膜标本中均有表达,其表达强度在米非司酮流产蜕膜组织和非药物人工流产蜕膜组织中无明显差异（P〉0.05）。结论米非司酮对早孕蜕膜组织中LIF的表达可能无明显影响。     

白血病抑制因子受体不同亚基细胞内区与HL—60细胞内STAT3激活的关系

目的　观察白血病抑制因子（LIF）受体gp190亚基和gp130亚基胞内区在人白血病细胞系HL-60中与STAT3表达及激活的关系,了解白血病抑制因子（LIF）引发白血病细胞增殖抑制和分化的机制。方法　用基因重组技术将gp130和gp190的细胞内区互换以构成两个嵌合体受体基因（130/190,190/130）并分别在HL-60细胞表达。用免疫组化和免疫印迹杂交方法分析形成受体亚基细胞内区同源性二聚体后的磷酸化STAT3的水平和STAT3的表达水平。结果　转染pED130/190,LIF诱导10min后,HL-60细胞内的STAT3磷酸化增加（P＜0.01）,经LIF诱导的转染pED130/190的HL-60细胞的STAT3磷酸化水平存在时间依赖性,转染pED190/130的HL-60细胞,LIF诱导6h后,STAT3的表达降低。结论　白血病抑制因子受体gp190亚基细胞内区在LIF诱导下参与HL-60细胞中STAT3的激活。     

Lymphocytic Adenohypophysitis Associated with Rathke's Cleft Cyst

During the 8th month of her first pregnancy, a 40-year-old female suffered from visual disturbances. After treatment of pericarditis, which appeared 1 month after a normal delivery, she was referred to the neurosurgical department. She showed bitemporal hemianopsia, disturbance of visual acuity, and hypopituitarism. Initial computed tomography (CT) image showed a solid pituitary mass with suprasellar extension. However, 2 months later, the CT image changed to an enlarged partially cystic lesion. Transsphenoidal exploration of the sella demonstrated lymphocytic adenohypophysitis coexistent with Rathke’s cleft cyst. To our knowledge, such an association has never been reported previously. Presurgical diagnosis of lymphocytic adenohypophysitis still remains difficult and surgical intervention is necessary for definitive diagnosis. However, special attention is needed for the histological diagnosis of this lesion, particularly in clinically atypical cases.     

白血病抑制因子在妊娠输卵管黏膜中的表达

目的探讨白血病抑制因子(LIF)与输卵管妊娠的关系。方法选择输卵管妊娠组25例、正常输卵管组28例及正常宫内早孕组30例,采用免疫组织化学染色技术及半定量病理图像分析系统检测输卵管妊娠黏膜组织、正常输卵管黏膜组织及正常宫内早孕组子宫蜕膜组织中LIF的表达。结果 LIF阳性表达在正常宫内早孕组最高,在输卵管妊娠组中较高,在正常输卵管组中最低,三组两两比较差异均有有统计学意义(P<0.05)。结论 LIF可能参与了输卵管妊娠发病过程,且与输卵管妊娠缺乏蜕膜化反应有关。     

Leukemia inhibitory factor: an important regulator of endometrial function

PROBLEM: Leukemia inhibitory factor (LIF) is multifunctional cytokine that displays biological activities in different cells, including endometrial cells. The aim of this study is to describe implications of LIF on a physiological function of endometrium. METHOD OF STUDY: The role of LIF in the endometrial function is reviewed and summarized from the available literature. RESULTS: LIF plays an important role in a physiological function of endometrium. In human endometrial LIF expression depends on cellular localizations, steroid hormones, menstrual stages and a local cytokine network. Stronger LIF expression exists in an endometrial epithelium during a luteal phase of the menstrual cycle, which coincides with the time of an implantation. The impairments of the endometrial LIF expression may play a significant role in the pathological processes involving implantation and the infertility. CONCLUSIONS: There is a substantial evidence that LIF is a potential regulator of the endometrial function and might be one of the factors that play a key role in human reproduction.     

白血病抑制因子在小鼠子宫内膜不同部位的表达研究

目的探讨白血病抑制因子(LIF)在着床窗口期小鼠子宫内膜不同部位的表达。方法运用半定量逆转录聚合酶链反应(RT-PCR)和免疫组化技术,分别从mRNA水平和蛋白质水平检测LIF在孕4d小鼠子宫内膜着床位点及着床旁组织表达量及位置的分布。结果LIFmRNA及蛋白在胚泡着床位点较着床旁组织表达明显增高(P<0.05)。免疫组化检测结果显示LIF蛋白表达于子宫内膜间质细胞及腺上皮细胞胞桨。结论在着床窗口期,LIF作用的发挥主要是通过在着床位点高表达而促进胚泡着床、胚胎发育。     

白血病抑制因子及其受体在早产胎盘组织及蜕膜组织中的表达及临床意义

目的探讨早产胎盘及蜕膜组织中的白血病抑制因子(LIF)及其受体(LIFR)的表达。方法应用免疫组织化学方法检测白血病抑制因子(LIF)及其受体(LIFR)在30例早产(实验组)、30例人工流产(对照组)胎盘和蜕膜组织中的表达。用卡方检验(Chi-Square Test)检测LIF、LIFR在早产和人工流产中的表达是否有差异。结果 LIF、LI-FR在早产胎盘组织中阳性率分别为6.7%和10%,在蜕膜组织中阳性表达率分别为10%和13.3%,结论白血病抑制因子(LIF)及其受体(LIFR)对晚期妊娠的维持有待进一步研究。     

The impact of leukemia inhibitory factor in uterine flushing on the reproductive potential of infertile women--a prospective study

PROBLEM: To determine the value of leukemia inhibitory factor (LIF) assessment for predicting the reproductive outcome. METHOD OF STUDY: Two phase study. Phase I: assessment of LIF in uterine flushing. Phase II: 1,5 years after examining the last patient, a questionnaire was sent to all participants of the phase I. Phase I: Uterine flushing and endometrial samples were collected during implantation window from infertile patients with stage I/II endometriosis (n = 14), patients with idiopathic infertility (n = 27), luteal phase deficiency (n = 13), and fertile control (n = 21). LIF was assessed in uterine flushings in all patients by ELISA. In endometrium, semiquantitative RT-PCR was performed for LIF mRNA expression. Phase II: questionnaire has been sent to all infertile women taking part in the first phase of the experiment, regarding their reproductive outcome. RESULTS: 65.4% patients who had returned the questionnaire did get pregnant. LIF concentration at a cut-off point of 2.31 pg/ml had a 95.7% sensitivity and 81.8% specificity in predicting the reproductive outcome. CONCLUSION: This prospective study for the first time in literature indicates that the LIF assessment can be used as a predictor of reproductive success.     

白血病抑制因子及其受体在宫外孕胚胎组织中的表达及临床意义

目的探讨宫外孕胚胎组织中的白血病抑制因子(LIF)及其受体(LIFR)的表达。方法应用免疫组织化学方法检测白血病抑制因子(LIF)及其受体(LIFR)在30例宫外孕、30例人工流产以及30例足月妊娠胎盘组织中的表达。用卡方检验(Chi-Square Test)检测LIF、LIFR在宫外孕、人工流产及足月妊娠胎盘组织中的表达是否有差异。结果 LIF、LIFR在宫外孕胎盘组织中阳性率分别为93%和90%,在人工流产胎盘组织中阳性率分别为93%和90%,在足月妊娠胎盘组织中无阳性表达。结论白血病抑制因子(LIF)及其受体(LIFR)在早期妊娠中,对维持胎盘的功能和胚胎的生长发育具有重要意义,对晚期妊娠的临床意义还有待进一步研究。     

小鼠超排卵胚胎的着床与Lif基因表达水平的关系

目的检测胚胎移植时子宫内膜中自血病抑制因子（1eukemia inhibitory factor，Lif）基因的表达水平，探讨超排卵对小鼠胚胎着床潜能的影响。方法建立超排周期胚胎和自然周期胚胎受体妊娠小鼠模型，比较妊娠率、胚胎着床率与可基因表达水平之间的关系。结果超排周期受体组的妊娠率（20．00％）和胚胎着床率（8．33％）显著低于自然周期组的妊娠率（55．00％）和胚胎着床率（35．00％）。自然周期胚胎和超排周期胚胎受体组内膜中Lif矿基因表达水平相似，妊娠受体组Lif矿基因表达水平显著高于未孕受体组，但单胎妊娠和多胎妊娠受体组内膜中Lif矿基因表达水平相似。结论超排卵可能因影响胚胎的质量而降低具有相同Lif mRNA表达水平的受体鼠的妊娠率和胚胎着床率。     

A role for leukemia inhibitory factor in melanoma-induced bone metastasis

Melanoma is commonly associated with multi-organ metastasis, and bone is a frequent metastatic site for melanoma. However, the mechanism responsible for such melanoma-induced bone metastasis is still poorly understood. In the present study, the intracardiac inoculation of leukemia inhibitory factor (LIF)-producing human melanoma-derived cells (SEKI) developed osteolytic bone destruction in male BALB/cA-nu/nu nude mice. To elucidate the role of LIF in melanoma-induced osteolysis, cells were prepared in which the expression of LIF was reduced using a siRNA technique from the parent SEKI cells. Osteoclastogenesis was induced in the co-culture of LIF and/or SEKI cells with osteoblastic stromal cells in vitro, whereas the LIF-reduced SEKI cells did not induce osteoclastogenesis. The intracardiac inoculation of LIF-reduced SEKI cells resulted in a significant reduction in the incidence and number of bone metastasis in comparison to those in the mice inoculated with the parent SEKI cells. The expression of LIF was found in seven of nine human melanoma-derived cell lines, suggesting that LIF expression is a universal event in melanoma. These findings suggest that a potential role for LIF in the melanoma-induced bone metastasis possibly through the stimulation of osteoclastogenesis. LIF might therefore be a potentially effective drug target in the treatment of bone metastasis in melanoma.     

巨噬细胞移动抑制因子在非IgA系膜增生性肾小球肾炎肾组织中的表达

目的 探讨巨噬细胞移动抑制因子（MIF）在非IgA系膜增生性肾小球肾炎患者肾组织中的表达及其意义。方法 应用免疫组织化学双标记技术检测正常对照组及不同病变程度非IgA系膜增生性肾小球肾炎患者肾组织内MIF和人巨噬细胞标记抗原CD68的表达。结果 在正常对照组和IgA系膜增生性肾小球肾炎患者轻度组仅有少量MIF和CD68表达。随着非IgA系膜增生性肾小球肾炎病变程度的加重,MIF、CD68的表达逐渐增强,重度病变时,MIF、CD68的表达最强,且MIF表达水平与CD68表达呈正相关（r=0.87,P〈0.01）。结论 肾组织内MIF表达上调所导致的巨噬细胞浸润增加可能是非IgA系膜增生性肾小球肾炎进展的重要机制之一。     

Leukemia inhibitory factor promotes tumor growth and metastasis in human osteosarcoma via activating STAT3

The leukemia inhibitory factor (LIF) has been demonstrated to be an oncogene and participated in multiple procedures during the initiation and progression of many human malignancies. However, the role of LIF in osteosarcoma is still largely unknown. Here, we performed a series of in vitro and in vivo experiments to investigate the expression and biological functions of LIF in osteosarcoma. Compared to that in the non‐cancerous tissues, LIF was significantly overexpressed in a panel of 68 osteosarcoma samples (p < 0.0001). Moreover, the overexpression of LIF was significantly correlated with advanced tumor stage, larger tumor size, and shorter overall survival. In addition, knockdown of LIF notably suppressed the proliferation and invasion of osteosarcoma via blocking the STAT3 signal pathway; in contrast, treatment with the recombinant LIF protein significantly promoted the growth and invasion of osteosarcoma through enhancing the phosphorylation of STAT3, which can be partially neutralized by the STAT3 inhibitor, HO‐3867. In conclusion, we demonstrated that LIF was frequently overexpressed in osteosarcoma, which could promote the growth and invasion through activating the STAT3 pathway. Our findings proposed that LIF might be a potent therapeutic target for osteosarcoma.     

神经生长因子和白血病抑制因子上调哮喘大鼠脾淋巴细胞IL-4、IL-5的表达

目的:探讨神经生长因子(NGF)、白血病抑制因子(LIF)对哮喘大鼠脾淋巴细胞IL-4、IL-5表达的影响。方法:16只大鼠随机分为对照组(A组)8只,哮喘组(B组)8只,采用卵蛋白和氢氧化铝腹腔内注射致敏,2周后给予1%卵蛋白雾化吸入激发哮喘。(1%卵蛋白/生理盐水)雾化吸入2周后,24h内体外分离培养对照组大鼠和哮喘组大鼠脾淋巴细胞;通过RT-PCR半定量法和ELISA法测定2组大鼠脾淋巴细胞表达Th2细胞因子IL-4、IL-5mRNA转录水平和分泌蛋白的基础水平,观察外源性NGF和LIF体外干预后淋巴细胞IL-4和IL-5表达随干预浓度的变化。结果:(1)哮喘组IL-4、IL-5mRNA表达及蛋白水平明显高于对照组(P0.05);(2)在外源性不同浓度的NGF、LIF干预下,IL-4、IL-5mRNA和蛋白表达量分别比前一梯度低浓度干预组有显著升高(P0.05),NGF、LIF上调IL-4、IL-5mRNA和蛋白表达呈浓度依赖性。结论:在哮喘大鼠中,NGF、LIF可能通过上调Th2类细胞因子IL-4、IL-5mRNA表达和蛋白分泌,参与促进和放大Th2类细胞因子免疫失衡效应。     

鼻咽癌组织中巨噬细胞移动抑制因子和MMP-2、MMP-9表达的关系

目的　研究巨噬细胞移动抑制因子 (macrophagemigrationinhibitoryfactor,MIF)和MMP 2、MMP 9在鼻咽癌组织中的表达水平及相互关系 ,探讨鼻咽癌细胞早期侵袭转移的机制。方法　收集 4 5例确诊的鼻咽原发癌活检组织标本 ,采用免疫组化LSAB法检测鼻咽癌组织中MIF和MMP 2、MMP 9的表达 ,并分析患者的临床参数的关系。结果　在 4 5例鼻咽原发癌组织中 ,MIF、MMP 2和MMP 9的阳性表达率分别为 77 8% (35 / 4 5 )、6 4 4 % (2 9/ 4 5 )和 71 1% (32 / 4 5 )。其中 ,癌细胞MIF和MMP 9的表达水平均显示与淋巴结转移有关 ,伴有淋巴结转移的癌组织中二者表达水平均高于无淋巴结转移的癌组织 (P值均 <0 0 5 )。MIF阳性组的癌细胞MMP 9的表达 (5 0 2 %± 33 5 % )明显高于MIF阴性病例 (11 7%± 2 2 7% ) ,两者差异有显著性 (P <0 0 1) ,且MIF的表达与MMP 9的表达亦呈正相关 (rs=0 .4 92 ,P <0 0 1) ,但癌细胞MMP 2的表达与MIF、MMP 9的表达以及是否有淋巴结转移则均未显示相关性。以Schmincke型生长方式分布的癌细胞MIF表达水平 (6 7 4 %±35 2 % )也高于以Regaud型方式分布的癌细胞 (32 9%± 2 9 7% ) ,差异有显著性 (P <0 0 1)。结论　鼻咽癌组织中癌细胞的MIF和MMP 9同步过表达 ,可能在鼻咽癌细胞的转移