eIF4E在乳腺癌中表达的研究进展

真核细胞翻译起始因子是调节蛋白质翻译的关键因素，作为mRNA帽结合磷蛋白，过度表达能使一些肿瘤相关恶性基因的蛋白质表达量发生变化，引起致癌性改变。笔者就elF4E在乳腺癌中的表达、作用以及治疗研究的最新研究进展作一综述。     

eIF4E在乳腺癌中表达的研究进展

真核细胞翻译起始因子是调节蛋白质翻译的关键因素，作为mRNA帽结合磷蛋白，过度表达能使一些肿瘤相关恶性基因的蛋白质表达量发生变化，引起致癌性改变。笔者就eIF4E在乳腺癌中的表达、作用以及治疗研究的最新研究进展作一综述。     

PSA在乳腺癌的研究进展

复习近年来的相关文献，综述前列腺特异性抗原(KA)在乳腺癌的研究近况。PSA是具有胰蛋白酶和糜蛋白酶活性的一种丝氨酸糖蛋白酶，并非前列腺特有。编码PSA的基因是人腺体激肽释放酶基因家族成员之一。它不仅是判断乳腺癌患者预后的一个新的指标，而且对其研究可洞察乳腺癌组织中医体类受体状况以预测辅助治疗的效果。     

乳腺癌免疫治疗的研究进展

免疫治疗是继传统化疗、放疗、内分泌治疗等非手术治疗之后的乳腺癌重要治疗方法,其作为一种乳腺癌新的治疗策略,具有强大的发展前景。笔者就乳腺癌免疫治疗的研究现状与进展做一综述。     

microRNA在三阴型乳腺癌中的研究进展

microRNA（miRNA）是一种小分子RNA,对细胞的增殖、分化、凋亡以及应激等生物过程有广泛的调节作用。miRNA通过多种方式参与乳腺癌的发生及进展,笔者就其在三阴型乳腺癌（TNBC）中的研究进展作一综述。     

联合检测多基因在乳腺癌组织中的表达及其临床意义

乳腺癌是女性中最常见的恶性肿瘤，在全球范围内其发病率有逐渐增高的趋势。在我国发病率也逐年增高。目前，对乳腺癌有了进一步的认识，治疗方法也日趋完善。但是目前对乳腺癌的易患人群(high-risk patient with breast canser)的研究却重视不够。只有加强对乳腺癌易患人群的研究，降低这类人群患乳腺癌的风险，才能降低乳腺癌发病率，真正做到预防为主。     

乳腺癌保乳手术治疗研究进展

随着对乳腺癌生物学特性的进一步认识及诊疗水平的提高，保乳手术终将逐步取代改良根治术而成为主要术式。笔者就乳腺癌治疗观念的改变、保乳手术及其适应证、保乳治疗的技术保障等方面进行综述。     

乳腺癌基因分型的研究进展

利用基因芯片及组织微阵列等技术,通过对乳腺癌基因表达谱的检测分析,最近提出了乳腺癌的5个基因亚型,即Luminal A,Luminal B,ERBB2+,Basal-like和normal breast-like亚型。笔者对乳腺癌各基因亚型的免疫表型和基因表达特点、临床特征、预后分析以及靶向治疗等作一综述。     

肿瘤相关成纤维细胞在乳腺癌内分泌治疗中作用的研究进展

内分泌治疗是激素受体阳性乳腺癌患者的基础治疗,可显著减少复发和病死率。然而,并非所有患者能从中获益,如何进一步提高内分泌治疗疗效具有重要临床意义。肿瘤相关成纤维细胞(CAF)是乳腺癌间质中的主要细胞成分,具有不同于正常成纤维细胞的促肿瘤特性。CAF可改变肿瘤细胞的微环境,从而影响乳腺癌细胞生物学行为和内分泌治疗疗效。近年来,一些以CAF为治疗靶点的研究逐渐开展,并证实可提高乳腺癌内分泌治疗疗效。笔者对CAF在乳腺癌内分泌治疗中作用以及如何针对CAF改善内分泌治疗疗效进行综述。     

乳腺癌内分泌治疗研究进展

乳腺癌是我国常见的一种恶性肿瘤,发病率日渐增加并年轻化,严重威胁着女性身体健康。随着转化医学迅猛发展,综合治疗乳腺癌理念逐渐被公众认可。其中内分泌治疗因其疗效显著、低毒等特点,备受关注。笔者就卵巢功能抑制、抗雌激素药物、孕激素、雄激素、芳香化酶抑制剂、促黄体激素-促黄体激素释放激素类似物等内分泌治疗乳腺癌的研究进展进行综述。     

真核翻译起始因子4E在病理性瘢痕中的表达与作用

目的探讨真核翻译起始因子4E（eukaryotic translation initiation factor4E,eIF4E）在病理性瘢痕组织中的表达及其在病理性瘢痕形成中的作用及机制。方法（1）应用免疫组织化学SP法检测20例正常皮肤、20例成熟瘢痕、14例增生性瘢痕和25例瘢痕疙瘩组织中eIF4E蛋白的表达。（2）应用逆转录-聚合酶链式反应（RT—PCR）测定eIF4EmRNA在8例正常皮肤、8例成熟瘢痕、7例增生性瘢痕和8例瘢痕疙瘩组织中的半定量值。结果（1）病理性瘢痕组织中eIF4E蛋白表达增高,与正常皮肤、成熟瘢痕对照组比较,差异有统计学意义（P〈0．05）。（2）与正常对照组0．99±0．28比较,eIF4EmRNA在病理性瘢痕组织1．73±0．31中的表达显著增高,差异有统计学意义（P〈0．05）。结论eIF4E在病理性瘢痕组织中表达增高,eIF4E与病理性瘢痕的形成密切相关,可能对病理性瘢痕的形成起着重要作用。     

胆管癌组织中真核细胞翻译起始因子4E和基质金属蛋白酶-9的表达及临床意义的研究

目的　探讨在胆管癌组织中真核细胞翻译起始因子4E(eukaryotic initiation factor 4E,eIF4E)和基质金属蛋白酶- 9(matrix metalloproteinase -9,MMP- 9)的表达情况及临床病理意义。方法应用免疫组织化学技术检测62例胆管癌组织及8例正常胆管组织中 eIF4E和 MMP 9 的表达情况,同时结合病人的临床病理资料进行分析。结果　在 62 例胆管癌组织中 eIF4E和 MMP 9 的表达阳性率分别为 100%和 82. 3%,二者的表达具有正相关,而正常胆管组织无 eIF4E 和 MMP -9 表达。eIF4E在胆管癌组织中的表达水平与患者性别、年龄和肿瘤部位无明显相关性,但与肿瘤组织分化程度、手术方式和有无浸润转移明显相关。MMP -9表达与患者性别、年龄、肿瘤部位、肿瘤组织分化程度及手术方式无明显相关,但与有无浸润转移明显相关。结论　过度表达的 eIF4E和 MMP- 9 是胆管癌恶性改变及判断其恶性程度的分子标志,并在胆管癌的侵袭和转移机制中发挥重要作用。     

Detection of eIF4E gene amplification in breast cancer by competitive PCR

Background: Initiation factor eIF4E binds to mRNA as the initial step for protein translation. Overexpression of the eIF4E oncoprotein has been found in breast cancer but not in benign breast tissue. The objective of this study is to determine if eIF4E oncoprotein overexpression is associated with eIF4E gene amplification in breast cancer using Western blots and competitive polymerase chain reaction (PCR). Methods: Unknown concentrations of DNA extracted from breast specimens were amplified by PCR using a set of primers spanning intron 2/exon 3 of the eIF4E gene. In the same PCR tube, an internal control consisting of a known concentration of an eIF4E DNA template with 20-base pair (bp) deletion was used as the competitive reference standard (CRS) for competitive PCR. Gel electrophoresis of the PCR products was performed and the bands quantified by densitometry. eIF4E gene amplification was then determined relative to a nonamplified gene (gastrin). Using an anti-eIF4E rabbit antibody, Western blots were performed on benign and malignant breast specimens. Quantification was accomplished by developing blots with a color assay using nitro blue tetrazolium (NBT) and 5-bromo-4-chloro-3-indolyl phosphate (BCIP), scanned and analyzed by densitometry. Results: Twenty-two breast specimens (14 cancer, 8 control) from patients were examined for eIF4E gene amplification and oncoprotein expression. In all fourteen specimens from stage I–III breast cancer patients, eIF4E overexpression was detected at 3- to 30-fold (16.71±7.83) elevations. Similarly, all 14 specimens demonstrated eIF4E gene amplification by competitive PCR (3.69±1.27). In the eight benign breast specimens examined, all were negative for eIF4E overexpression and gene amplification. Conclusions: Overexpression of eIF4E was associated with eIF4E gene amplification in breast cancer specimens. No overexpression or gene amplification was detected in benign breast tissues. eIF4E gene amplification may be one mechanism for eIF4E oncoprotein overexpression.     

TLK1B is elevated with eIF4E overexpression in breast cancer

INTRODUCTION: The overexpression of eukaryotic initiation factor 4E (eIF4E), a critical component of the "RNA helicase" necessary for the initiation of protein synthesis of mRNAs with long 5' prime untranslated regions (5'UTRs), can result in malignant transformation. In a prospective study on breast cancer outcome of women with stage I to III disease, eIF4E overexpression was an independent predictor of cancer recurrence (RR = 7.3, CI = 1.58-33.9). Dysregulation of Tousled-like kinase 1B (TLK1B), a threonine kinase with a highly conserved gene sequence, has been linked to defects in cell division and DNA replication. In cell lines, TLK1B overexpression has been recently associated with resistance to radiation. The 5'UTR of TLK1B is long (1088 nt) and the structure is complex. Our hypothesis is that TLK1B elevation is correlated with the overexpression of eIF4E in human breast carcinoma. MATERIAL AND METHODS: Eighty-seven patients with invasive breast cancer and 11 patients with benign breast disease were accrued prospectively. Clinical data collected include age, race, stage, grade of tumor, ER, and PR status. TLK1B and eIF4E levels were quantified by Western blot analysis. Statistical analysis was performed using Spearman correlation, paired and unpaired t test, and multivariate analysis. RESULTS: In the 87 cancer specimens from patients with breast carcinoma, eIF4E level was elevated by a mean of 9.5-fold (range = 1.8-48.4), and TLK1B was elevated by a mean of 9.4-fold (range = 1.0-58.0) when compared to the 11 specimens from noncancer patients. Multivariate analysis performed demonstrates the degree of eIF4E overexpression is independent of age, race, tumor grade, and ER or PR status of the tumor. Similarly, the degree of TLK1B elevation is independent of age, tumor grade, and ER or PR status of the tumor. Using the Spearman correlation, the degree of TLK1B elevation was strongly correlated with the degree of eIF4E overexpression (r = 0.39, P = 0.001). CONCLUSIONS: Both eIF4E and TLK1B are elevated in breast cancer specimens but not in benign breast specimens from noncancer patients. The degree of TLK1B elevation is correlated with the degree of IF4E overexpression. Both eIF4E and TLK1B overexpression are independent of tumor grade, tumor stage, and ER and PR status.     

Augmentation of wound healing with translation initiation factor eIF4E mRNA

BACKGROUND: Initiation of translation is the rate-limiting step in protein synthesis; eIF4E increases translational efficiency by facilitating ribosome scanning. eIF4E is present in cells in rate-limiting amounts; chronic overexpression of eIF4E causes cell transformation by upregulating growth-related proteins. Biolistic delivery of epidermal growth factor (EGF) increases wound healing; transiently increasing wound eIF4E levels with biolistic mRNA transmission may further augment wound healing without oncogenesis. PATIENTS AND METHODS: Midline fascial wounds were created in rats and biolistically treated with gold particles carrying mRNA encoding for hEGF with or without eIF4E prior to suture closure; control animals received blank bullets. The animals were sacrificed at 7 or 14 days for determination of peak wound bursting strength on a tensiometer. Results are expressed as means +/- standard deviation; statistics were via analysis of variance. RESULTS: [Table: see text]. CONCLUSIONS: Simultaneous biolistic delivery of EGF mRNA with eIF4E mRNA significantly increases wound breaking strength compared to that in control animals or treatment with EGF mRNA alone without risk of cellular transformation. Further studies of translational activation to augment wound healing are warranted.     

真核始动因子4E反义寡核苷酸对人膀胱癌BIU-87细胞中eIF4E和肝素酶表达的影响

目的 探讨真核始动因子4E(eIF4E)反义寡核苷酸(ASODN)对人膀胱癌BIU-87细胞株中eIF4E及肝素酶(HPA)蛋白、mRNA表达的影响. 方法 采用脂质体介导方法分别将2.5、5.0及7.5 μg/ml eIF4E ASODN转染膀胱癌BIU-87细胞,并设立细胞对照组(不转染)、空白对照组(转染空脂质体)及无关对照组(转染无关对照ASODN),分别转染24、48及72 h,采用原位杂交、免疫细胞化学方法分别检测各组BIU-87细胞中eIF4E及HPA蛋白、mRNA表达. 结果 eIF4E ASODN各转染组细胞中eIF4E蛋白及mRNA表达量均较对照组降低(蛋白:2.5 μg/ml组分别为3.55±0.52、3.52 ±0.51、3.22 ±0.44;5.0 μg/ml组分别为3.43±0.47、3.41±0.46、3.19±0.41;7.5 μg/ml组分别为2.36±0.39、2.33±0.37、2.05±0.30.mRNA:2.5 μg/ml组分别为3.19±0.41、3.13±0.39、2.90±0.38;5.0μg/ml组分别为3.07±0.39、2.94 ±0.38、2.27±0.37;7.5 μg/ml组分别为2.22±0.37、2.06±0.30、1.95 ±0.29),与细胞对照组、空白对照组和无关对照组相应时间段、相应浓度组两两比较差异均有统计学意义(P＜0.05),且具有时间和浓度依赖性.eIF4E ASODN各转染组细胞中HPA蛋白及mRNA表达量均较对照组降低(蛋白:2.5 μg/ml组分别为4.44±0.55、4.40±0.54、3.99±0.52;5.0μ g/ml组分别为4.41 ±0.55、4.21±0.53、3.77±0.50;7.5 μg/ml组分别为4.02±0.52、3.98±0.52、2.32±0.37.mRNA:2.5μg/ml组分别为4.12±0.51、3.75±0.50、3.63±0.45;5.0 μg/ml组分别为4.00 ±0.51、3.71±0.50、3.54 ±0.44;7.5 μg/ml组分别为3.87±0.52、3.61 ±0.49、2.08 ±0.30),与细胞对照组、空白对照组和无关对照组两两比较差异均有统计学意义(P＜0.05),且具有时间和浓度依赖性.eIF4E ASODN对HPA蛋白、mRNA表达的抑制效应和对eIF4E蛋白、mRNA表达的抑制效应呈正相关关系(HPA蛋白r=9.23,mRNA r=9.59,P值均＜0.01). 结论eIF4E ASODN可下调膀胱癌BIU-87细胞中eIF4E、HPA蛋白及mRNA的表达,抑制肿瘤细胞的生长、浸润及转移.