术前中性粒细胞淋巴细胞比率（NLR）预测胃癌预后的临床意义

目的：探讨术前中型粒细胞-淋巴细胞比例（NLR）在评估术后胃癌患者预后方面的临床意义。方法：选取2003年1月至2006年1月于我院行胃癌根治术（D2）患者344例做回顾性研究,其中男性231例（67.2%）,女性113例（32.8%）,平均年龄67.6岁（24岁-83岁）,远端胃大部切除203例,近端胃大部切除45例,全胃切除76例,全胃加联合脏器切除患者20例。收集患者术前中性粒细胞计数,淋巴细胞计数,血小板计数,计算中性粒细胞淋巴细胞比率（LNR）,以LNR=3为临界点将患者分为高LNR组和低LNR组,术后定期随访,将相关的临床病理因素行单因素及多因素分析。结果：高LNR组患者5年生存率明显较低LHN组差（51%vs 74%,P〈0.001）,无病生存率也有明显差异（67%vs 85%,P〈0.001）,肿瘤浸润超过肌层,淋巴结转移,远处转移,分化差患者NLR较高（P〈0.001）,影响预后的相关临床病例因素的单因素分析结果提示：肿瘤浸润深度,淋巴结转移,远处转移,分化差是影响预后的高风险因素,多因素分析显示高NLR是影响术后肿瘤患者预后的独立危险因素（HR1.768-2.174,P〈0.001）。结论：术前NLR可能会成为预测胃癌术后复发的简便的生物标记。     

GNA14在子宫内膜癌组织中的表达及临床意义

目的:检测GNA14在子宫内膜癌组织中的表达,并探讨其与临床病理及预后的关系。方法:选取2013年01月至2014年08月我院行子宫内膜癌手术切除的93例子宫内膜癌组织及同期40例子宫内膜增生组织样本进行研究。采用免疫组化法检测子宫内膜癌组织中GNA14表达水平;分析GNA14表达水平与临床病理特征及预后的关系。结果:子宫内膜癌组织中GNA14高表达率（52.6％）显著高于子宫内膜增生组织（15.0%）（P＜0.05）。GNA14表达水平与淋巴结转移和临床分期相关(P＜0.05),与年龄、血压、肌层浸润及病理类型无关(P＞0.05)。GNA14低表达组患者预后5年生存率优于GNA14高表达组患者（P＜0.05）。单因素分析显示,病理类型、临床分期、淋巴结转移和GNA14蛋白表达与子宫内膜癌患者不良预后有关（P＜0.05）。多因素分析显示,GNA14蛋白表达、临床分期、淋巴结转移是影响子宫内膜癌患者不良预后的独立因素（P＜0.05）。 结论:GNA14在子宫内膜癌组织中高表达,其与临床分期和淋巴结转移密切相关,是影响子宫内膜癌患者预后不良的因素之一,可作为临床诊断及治疗的靶基因和生物标志物。     

火殃簕、铁海棠、扭曲藤和红背叶对3-甲基胆蒽诱发小白鼠皮肤肿瘤的作用

作者研究了火殃簕,铁海棠,扭曲藤和红背叶对致癌物质3—甲基胆蒽(3—met—hycholanthrene,3—MC)诱发小白鼠背部皮肤肿瘤的促进作用。实验结果表明,小鼠在用药30周后,背部皮肤出现数量不等的乳头样肿瘤。火殃簕、铁海棠,扭曲藤和红背叶的促肿瘤发生率分别为10％,15％,13％和17％。而对照巴豆油组的肿瘤促发率为43％。单—3—甲基胆蒽组的肿瘤诱发率为0％。研究结果证明,火殃簕,铁海棠,扭曲藤和红背叶是一类较弱的促癌物质     

乳管镜用于乳腺导管内乳头状瘤的临床诊治研究

目的:评价纤维乳管镜对乳管内乳头状瘤类疾病的诊断及治疗作用。方法:选取我科2009年8月-2011年8月经乳管镜诊断为导管内乳头状瘤患者144例,其中血性溢液78例,褐色溢液51例,深黄色溢液15例。回顾性分析其术前诊断及治疗过程。结果:所有病例在乳管镜下可见导管内肿物,并经镜下定位行病变腺叶切除,术后病理132例诊断为乳管内乳头状瘤,7例诊断为原位癌,3例为早期浸润性癌。结论:纤维光导乳管镜可准确诊断乳管内乳头状瘤,并进行定位切除。对此类疾病的诊治有重要应用价值。     

MG132和DDP联合应用对人鼻咽癌细胞CNE-1凋亡影响及其机制的探讨

目的:研究蛋白酶体抑制剂MG132与顺铂(DDP)联合应用对人鼻咽癌细胞株CNE-1细胞凋亡的影响,观察细胞中凋亡相关蛋白Bcl-2和Bad表达的变化。方法:体外培养的CNE-1细胞分别暴露于MG132和DDP、单独MG132或者DDP,24h后,流式细胞术(FCW)检测CNE-1细胞的凋亡率,蛋白质印迹法测定CNE-1细胞中Bcl-2和Bad蛋白的表达情况。结果:流式细胞术检测结果显示,MG132和DDP联合用药组CNE-1细胞凋亡率(53±3.2)%较单独应用MG132组(20±1.7)%、DDP组(18±2.3)%的凋亡率显著增加。蛋白质检测结果显示,与MG132组、DDP组比MG132和DDP组Bcl-2的表达减少约3倍,而Bad的表达增加约2倍。结论:MG132和DDP联合应用可能通过降低Bcl-2同时增强Bad的表达而进一步诱导CNE-1细胞的凋亡。因此,我们可以认为MG132能够增强DDP对CNE-1细胞凋亡的作用。     

Protein content and functional characteristics of serum‐purified exosomes from patients with colorectal cancer revealed by quantitative proteomics

Tumor cells of colorectal cancer (CRC) release exosomes into the circulation. These exosomes can mediate communication between cells and affect various tumor‐related processes in their target cells. We present a quantitative proteomics analysis of the exosomes purified from serum of patients with CRC and normal volunteers; data are available via ProteomeXchange with identifier PXD003875. We identified 918 proteins with an overlap of 725 Gene IDs in the Exocarta proteins list. Compared with the serum‐purified exosomes (SPEs) of normal volunteers, we found 36 proteins upregulated and 22 proteins downregulated in the SPEs of CRC patients. Bioinformatics analysis revealed that upregulated proteins are involved in processes that modulate the pretumorigenic microenvironment for metastasis. In contrast, differentially expressed proteins (DEPs) that play critical roles in tumor growth and cell survival were principally downregulated. Our study demonstrates that SPEs of CRC patients play a pivotal role in promoting the tumor invasiveness, but have minimal influence on putative alterations in tumor survival or proliferation. According to bioinformatics analysis, we speculate that the protein contents of exosomes might be associated with whether they are involved in premetastatic niche establishment or growth and survival of metastatic tumor cells. This information will be helpful in elucidating the pathophysiological functions of tumor‐derived exosomes, and aid in the development of CRC diagnostics and therapeutics.     

数字乳腺断层融合X线摄影与常规影像学检查诊断效能的对比研究

背景与目的:乳腺癌已成为女性最常见的恶性肿瘤,乳腺X线摄影新技术的出现对乳腺癌诊断起重要作用;该研究旨在对比数字乳腺断层融合X线摄影(digital breast tomosynthesis,DBT)与常规影像学检查诊断乳腺良、恶性病变的效能.方法:收集2015年3月—2015年12月在复旦大学附属肿瘤医院就诊且经临床或超声检查怀疑乳腺病变的227例患者.所有患者均行B超、全屏数字乳腺X线摄影(full-field digital mammog-raphy,FFDM)、DBT和MRI检查.高年资影像医师双盲阅片,参照2013版BI-RADS分类标准,以病理结果为金标准,采用受试者工作特征(operating characteristic,ROC)曲线分析各种检查方法的诊断效能,并利用Z检验比较DBT与其他检查方法的统计学差异.结果:30例患者因图像不符合诊断要求而排除,剩余197例患者共发现205个病灶,其中良性病灶73例,恶性病灶132例.B超、FFDM、DBT、DBT+FFDM和MRI基于BI-RADS分类诊断乳腺良、恶性病变的ROC曲线的曲线下面积(area under the curve,AUC)分别为0.8308、0.8592、0.9167、0.9198和0.9354;两两比较结果显示,DBT的AUC高于B超和FFDM,且差异均有统计学意义(比B超相比,Z=7.36,P=0.0067;与FFDM相比,Z=4.89,P=0.0271);DBT与MRI、DBT+FFDM的AUC差异无统计学意义(与MRI相比,Z=0.02,P=0.9002;与DBT+FFDM相比,Z=0.69,P=0.4048).结论:DBT较B超、FFDM能显著提高乳腺良、恶性病灶的诊断效能;并与MRI诊断效能相当.DBT作为乳腺X摄影新技术,具有良好的应用前景.     

Characterization of the GNMT‐HectH9‐PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma

The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N‐methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT‐interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9‐mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation. An elevated PREX2 protein expression accompanied by activation of AKT was observed in the liver of Gnmt knockout mice. PREX2 protein expression was upregulated in 54.9% of human HCC samples, while its mRNA level was comparable in tumor and tumor‐adjacent tissue, suggesting a post‐translational alteration of PREX2 expression. Higher level of PREX2 in the tumor tissues was associated with poorer survival. These results reveal a novel mechanism in which GNMT participates in AKT signaling and HCC tumorigenesis by promoting HectH9‐mediated PREX2 degradation.     

Reduction of Foxp3+ T cell subsets involved in incidence of chronic graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation

Foxp3+ T cells (CD4+ Tregs and CD8+ Treg) have been demonstrated to play roles in the maintenance of tolerance after allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). We have found that Foxp3+ γδTCR+ Treg cells (γδTregs) exerted regulatory functions. In the current study, patients were recruited and divided as non‐cGVHD, limited cGVHD and extensive cGVHD groups. Healthy volunteers were recruited as healthy group. Treg cells were evaluated by flow cytometry. Serum cytokine levels of IL‐2, tumour necrosis factor‐α, interferon‐γ and transforming growth factor‐β1 (TGF‐β1) were evaluated by ELISA. The results showed that percentages of CD4+ Tregs, CD8+ Tregs and γδTregs were all significantly increased in non‐cGVHD group compared with those in healthy group, limited cGVHD group and extensive cGVHD group. Moreover, compared with extensive cGVHD group, percentages of these three types of Tregs were significantly increased in limited cGVHD group. The levels of TGF‐β1 increased dramatically in non‐cGVHD group compared with other groups. Spearman's correlation analysis revealed that the increased levels of TGF‐β1 and IL‐2 were positively associated with increased Treg subsets, indicating that TGF‐β1 and IL‐2 participated in the expansion process of Foxp3+ Tregs in vivo. Our findings support that increasing the number of Tregs following allo‐HSCT would be a preferential strategy for controlling cGVHD. Copyright © 2015 John Wiley & Sons, Ltd.