cyclin E与p27在乳腺癌中的研究进展

细胞周期调控紊乱是乳腺癌重要发病机制之一,而cyclin E和p27是细胞周期最重要的调节因子.研究表明,cyclin E和p27具有评估乳腺癌预后的能力,且与其他生物学指标相比,与乳腺癌预后相关性更大.     

乳腺癌组织SULT1E1蛋白表达与临床病理学特征及预后相关性的研究

目的:探讨乳腺癌组织SULT1E1的表达,并分析其与临床病理学特征及预后因素的相关性.方法:采用免疫组织化学二步法检测129例乳腺癌组织和癌旁正常组织SULT1E1的表达情况,应用Kaplan-Meier法行单因素生存分析SULT1E1的表达与临床病理学特征及预后的关系.结果:乳腺癌组织中SULT1E1的阳性表达率(25.6％)明显低于癌旁组织(45.0％),差异有统计学意义,P＜0.05；SULT1E1的表达与乳腺癌患者年龄、肿瘤大小、淋巴结转移和病理类型以及是否有远处转移等无明显相关性,P＞0.05.Kaplan-Meier生存分析曲线显示,SULT1E1阳性表达患者的术后无复发生存率较阴性表达患者明显增高,x2=4.943,P＜0.05.结论:乳腺癌组织SULT1E1低表达者提示预后不佳,SULT1E1检测有可能成为判断乳腺癌分期和预后的重要分子标志,并成为重要的预后因素.     

真核起始因子 4E 在乳腺癌中的研究进展

真核起始因子 4E (elF4E)是真核细胞翻译起始因子,在蛋白质的翻译起始阶段起重要作用,并且与多种恶性肿瘤的发生、发展、浸润密切相关.近年来发现eIF4E与乳腺癌的预后、放疗敏感性都有显著相关性,进而可能成为一个影响治疗策略制定的一个指标,同时elF4E也有可能成为乳腺癌靶向治疗的新靶点.     

原癌基因eIF4E与bFGF在乳腺癌中的表达及其临床意义

目的 探讨eIF4E与bFGF在人类乳腺癌组织中的表达、相关性及其春临床意义.方法 采用免疫组化方法对75例乳腺和12例乳腺良性病变中eIF4E与bFGF基因表达的水平进行研究.结果 eIF4E与bFGF在乳腺癌组织中表达的阳性率分别为89.3%和58.7%.乳腺癌中eIF4E与bFGF阳性率明显高于生存期≥5年组(P＜0.05),与生存期成负相关.bFGF在有腋淋巴结转移组阳性表达率明显高于无腋淋巴结转移组(P＜0.01),而eIF4E的表达与有无腋淋巴结转移无关(P＞0.05).两者均与患者年龄、肿块大小、病理类型、临床分期、ER、PR、CerbB-2表达状态无关(P＞0.05).eIF4E与bFGF表达有相关性(P＜0.01),两者呈显著正相关(r=0.473).结论 eIF4E与bFGF在乳腺癌的发生发展及预后中起着重要作用,联合检测eIF4E与bFGF的表达可以成为临床上判断乳腺癌预后的参考指标.     

原发星形细胞瘤中TP53、PDGF、EGFR的表达及与临床病理特征和预后的相关性

目的 探讨TP53、PDGF、EGFR在原发星形细胞瘤中的表达,分析其与临床病理特征和预后的相关性.方法 回顾性收集90例原发星形细胞瘤患者临床病理资料,采用免疫组织化学检测原发星形细胞瘤组织样本中TP53、PDGF、EGFR表达,随访患者生存情况,Cox回归分析影响预后的因素.结果 TP53表达于细胞核,PDGF、E...     

E-cadherin及其相关蛋白在食管鳞癌的表达与预后的关系

目的　研究食管鳞状细胞癌中钙粘附蛋白 (E cad)、连接蛋白 (cat)α、β、γ的表达与预后关系。方法　免疫组化法检测 6 2例食管癌手术标本E cad、α cat、β cat、γ cat蛋白的表达 ,结合临床资料进行分析。结果　γ cat蛋白缺失表达与淋巴结转移有显著相关性 (P <0 .0 5 ) ;术后三年生存率E cad保留表达和缺失表达组分别为 10 0 %和 5 6 % ,γ cat保留表达和缺失表达组分别为 78%和 4 8% ,统计学差异均有显著性。结论　E cad、γ cat缺失表达提示肿瘤细胞恶性程度高 ,可能为食管癌预后差的因素之一。     

上皮钙粘着蛋白与肿瘤

上皮钙粘着蛋白(E—cadherin)是一种重要的细胞粘附分子和信号转导分子，参与组织形态发生、胚胎发育过程。研究发现E-cadherin与肿瘤发生、发展密切相关：近年来有报道血清可溶性E-cadherin与恶性肿瘤临床预后有相关性，有可能成为一种肿瘤标志物，以及评估疗效和预后的新指标。现综述近年来E—cadherin与肿瘤的研究进展。     

乳腺癌中cyclin E的表达及其预后意义

目的：研究细胞周期素E蛋白在乳腺癌中的表达，并探讨其临床预后意义。方法：总结67例乳腺癌病例的临床病理特点，同时运用免疫组化技术检测cyclinE蛋白的表达，分析其临床病理特点及预后的相关性。结果：cyclinE蛋白的表达与乳腺癌的预后关系密切，同时与乳腺癌的组织学分型相关；与乳腺癌的受体情况，肿瘤大小，淋巴结转移情况以及是否绝经无明显相关性。结论：cyclinE蛋白的表达是有效的预后预测因子。     

E-cd/γ-cat复合体在膀胱癌中的表达及临床意义

 目的　探讨上皮钙黏蛋白 /γ -连接素 (E cd/γ cat)复合体在膀胱癌中的表达及临床意义。方法应用免疫组织化学法 (S P法 )检测 72例膀胱癌和 5例正常膀胱黏膜石蜡包埋标本中E cd/γ cat复合体的表达情况。结果　所有 5例正常膀胱黏膜E cd/γ cat复合体正常表达。E cd、γ cat异常表达率分别为 4 1/ 72 (5 6 .9% )、31/ 72 (4 3.1% )。E cd和γ cat表达具有显著相关性 (P <0 .0 1)。E cd/γ cat复合体异常表达率与膀胱癌的病理分级和临床分期密切相关 (P <0 .0 5 )。γ cat异常表达与膀胱癌的预后密切相关 (P <0 .0 1)。结论　E cd/γ cat复合体的异常表达与膀胱癌的分化和侵袭程度密切相关。γ cat是判断膀胱癌预后的有价值指标     

甲状腺乳头状癌BRAF V600E基因突变 及相关蛋白的表达

背景与目的:BRAF V600E基因突变可作为甲状腺乳头状癌靶向治疗的靶点,因此检测患者BRAF基因状态对于能否应用靶向药物治疗具有重要意义.观察BRAF V600E基因突变及突变蛋白VE1在甲状腺乳头状癌中的表达情况,并分析其与甲状腺乳头状癌的临床病理特征及其预后的关系.方法:采用DNA测序法及免疫组织化学法分别检测108例甲状腺乳头状癌、54例甲状腺腺瘤和54例结节性甲状腺肿标本中BRAF基因突变及其相关蛋白VE1的表达.结果:108例甲状腺乳头状癌基因突变率为67.6%,VE1表达率为64.8%,与甲状腺良性病变相比差异有统计学意义(P<0.05),与临床病理参数间无相关性.结论:甲状腺乳头状癌BRAF V600E基因突变率和BRAF V600E蛋白表达水平增高,可以作为鉴别甲状腺良、恶性肿瘤的有效指标.免疫组织化学法检测甲状腺乳头状癌BRAF V600E蛋白的表达与其基因突变的一致性高,可间接有效地反映BRAF V600E基因突变的状态.BRAF V600E基因突变及突变蛋白的表达与甲状腺乳头状癌患者预后无关.     

乳腺癌手术前后血浆前列腺素E2水平变化及意义

目的　研究血浆前列腺素E2 (ProstaglandinE2 ,PGE2 )水平与乳腺癌的诊断和预后的关系。方法　应用放射免疫分析法测定 80例乳腺癌患者、10例正常献血员的血浆PGE2 水平。结果　乳腺癌患者血浆PGE2 水平显著高于正常对照组 (P <0 .0 1) ,转移性乳腺癌患者的血浆PGE2 水平显著高于无转移者 (P <0 .0 1) ,术后血浆PGE2 水平较术前下降显著 (P <0 .0 1)。结论　乳腺癌组织产生PGE2 并释放入血 ,血浆PGE2 水平与乳腺癌的转移有密切的关系。     

Alcohol,smoking, and risk of Her2‐overexpressing and triple‐negative breast cancer relative to estrogen receptor‐positive breast cancer

Epidemiological evidence is limited on how alcohol consumption and smoking are associated with risk of different subtypes of breast cancer, such as triple‐negative (TN) and human epidermal growth factor receptor 2‐overexpressing (H2E) breast cancers, which may have different etiologies from more common luminal (estrogen receptor [ER+]) breast cancers. In this population‐based case‐case study, we evaluated the association between alcohol, smoking, and risk of H2E and TN breast cancer, compared with ER+ breast cancers, among women aged 20–69 years. Using polytomous regression, associations between alcohol consumption, smoking, and breast cancer risk were evaluated in 909 ER+, 1,290 TN, and 489 H2E breast cancer patients, with ER+ breast cancer patients as the reference group. Current alcohol consumption at diagnosis was associated with a lower risk of H2E breast cancer (odds ratio = 0.74, 95% confidence interval: 0.58–0.92) relative to ER+ cancers. No difference in association was observed by menopausal status. No association between alcohol consumption and TN breast cancer relative to ER+ breast cancer was observed. Women who smoked did not have an altered risk of TN or H2E breast cancer, relative to ER+ cancer. Our results suggest that alcohol is associated with lower risk of H2E breast cancer relative to ER+ breast cancer. This study adds to the body of epidemiologic evidence that breast cancer etiology differs by breast cancer subtype.     

Cyclin E表达对于原代乳腺癌细胞侵袭性的影响

目的:从细胞学角度探讨Cycli E表达水平与原代乳腺癌细胞侵袭之间的关系。方法:手术中无菌条件下切取乳腺癌组织,制备原代乳腺癌细胞悬液,运用Transwell小室进行原代乳腺癌细胞侵袭力实验;获取具有不同侵袭力的原代乳腺癌细胞,再用免疫荧光技术检测不同侵袭能力的原代乳腺癌细胞cyclin E的表达水平,研究两者相关性。结果:具有不同侵袭力的乳腺癌细胞表达不同强度的Cyclin E蛋白,分别计数5个高倍视野,其均数分别为81.11±17.25及31.06±4.43,P<0.05。侵袭性试验结果显示:Cyclin E阳性表达的原代乳腺癌细胞经24小时培养以后浸润到Transwell聚碳酸盐微孔滤膜下的细胞数的均值为:76.32±11.40/高倍视野;而Cyclin E阴性表达的原代乳腺癌细胞的均值为21.56±13.22/高倍视野;P<0.05。结论:Cyclin E的表达差异与原代乳腺癌细胞的侵袭性有关,Cyclin E高表达者其侵袭性显著强于Cyclin E低表达者。     

Cyclin E表达对于原代乳腺癌细胞侵袭性的影响

目的：从细胞学角度探讨Cycli E表达水平与原代乳腺癌细胞侵袭之间的关系。方法：手术中无菌条件下切取乳腺癌组织,制备原代乳腺癌细胞悬液,运用Transwell小室进行原代乳腺癌细胞侵袭力实验;获取具有不同侵袭力的原代乳腺癌细胞,再用免疫荧光技术检测不同侵袭能力的原代乳腺癌细胞cyclin E的表达水平,研究两者相关性。结果：具有不同侵袭力的乳腺癌细胞表达不同强度的Cyclin E蛋白,分别计数5个高倍视野,其均数分别为81.11±17.25及31.06±4.43,P〈0.05。侵袭性试验结果显示：Cyclin E阳性表达的原代乳腺癌细胞经24小时培养以后浸润到Transwell聚碳酸盐微孔滤膜下的细胞数的均值为：76.32±11.40/高倍视野;而Cyclin E阴性表达的原代乳腺癌细胞的均值为21.56±13.22/高倍视野;P〈0.05。结论：Cyclin E的表达差异与原代乳腺癌细胞的侵袭性有关,Cyclin E高表达者其侵袭性显著强于Cyclin E低表达者。     

细胞周期相关因子与乳腺细胞的癌变及生物学特性的相关性研究

目的：研究正常乳腺上皮细胞与乳腺癌细胞之间以及不同恶性程度的乳腺癌细胞之间的细胞周期相关因子的表达异同。方法：采用Western印迹法检测正常乳腺细胞株AG11132A、ER阳性和乳腺癌细胞株MCF－7及ER阴性的乳腺癌细胞株MDA－MB－231之间细胞周期蛋白D1、E及P21蛋白表达的异同及与其生物学特性的关系。结果：（1）正常乳腺上皮细胞株高表达P21蛋白,低表达周期蛋白E。与正常细胞相比,乳腺癌细胞株MCF－7、MDA－MB－231细胞高表达周期蛋白E,其中表达的周期蛋白E中存在异常的你分子量周期蛋白E成分,而正常乳腺上皮细胞不表达这种异常 的周期蛋白E。（2）在乳腺癌细胞株之间,相对ER阳性的MCF－7细胞,ER阴性的MDA－MB－231细胞则高表达周期蛋白E,基本无表达P21蛋白。结论L（1）正常细胞与这间、相对低恶性程度的民相对高恶性和蔼的癌细胞之间的差别是多环节的、质和量异常导致的结果;（2）周期蛋白E及P21均可反映乳腺癌细胞的增殖活性和恶性程度,可能是乳腺癌的临床预后指标。     

Association between Breast Cancer and Vitamin C,Vitamin E and Selenium Levels : Results of a Case-control Study in India

In women, cancer of the breast is generally the most prevalent neoplasm and cause of cancer death. Though a ‍large number of women are affected with breast cancer, very few studies have been undertaken in India on the ‍association between micronutrients and the risk of breast cancer. We conducted a hospital based case- control study ‍to examine the associations of vitamin C, vitamin E and selenium with breast cancer. One hundred and sixty breast ‍cancer patients and an equal number of normal healthy individuals constituted the study population. Venous blood ‍was collected from the cases and controls for estimation of vitamin C, vitamin E and selenium utilizing standard ‍procedures. Univariate logistic regression analysis was carried out to calculate odds ratios and confidence intervals. ‍The mean vitamin C, vitamin E and selenium levels were lower in patients as compared to the controls. There was a ‍84% and 77% lower risk of breast cancer if the levels of vitamin C and vitamin E were increased by 1 unit, respectively. ‍Similarly, there was a 7% lower risk of breast cancer if the level of selenium was increased by 1 unit. The results of ‍the present study thus indicated a strong association of vitamin C, vitamin E and selenium with breast cancer in the ‍Indian population. ‍     

DLG5与34βE12在乳腺癌中表达的相关性及临床意义

目的:探讨细胞极性蛋白DLG5与高分子量角蛋白（34βE12）在乳腺癌中表达的相关性，阐明其在乳腺癌临床诊断中的作用。方法:收集乳腺癌组织，通过免疫组织化学（immunohistochemistry,IHC）分析DLG5的表达情况，以及其与34βE12表达的相关性。利用慢病毒技术敲低DLG5的表达后，Western blot检测DLG5与34βE12的表达。结果:DLG5的表达随乳腺癌恶性程度增加而降低，与雌激素受体/孕激素受体（ER/PR）、34βE12的表达呈现正相关性。在乳腺上皮细胞MCF10A中，敲低DLG5表达后，34βE12的表达显著降低。结论:在乳腺癌中，DLG5可以用于早期诊断、恶性程度判定，并且可以作为ER/PR阳性乳腺癌治疗及预测预后的潜在生物标志物。     

Non-protein bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk

It has recently been found by various authors that despite a normal serum concentration of oestradiol (E2), the percentage of non-protein-bound or free E2 is abnormally high in breast cancer patients. Since it is the free E2 which is considered to be biologically active, confirmation of this finding would be most relevant to the pathogenesis of breast cancer. Using Hammond's centrifugal ultrafiltration dialysis method we have measured free E2 in heparinized plasma from 68 premenopausal women (a) at high familial risk of breast cancer (n = 18), (b) with benign breast disease (n = 17), (c) cured of T1N0M0 breast cancer at least 6 months previously (n = 17) and (d) normal controls matched for age, parity and Quetelet index (n = 16). Sex hormone binding globulin (SHBG) was measured as [3H]-dihydrotestosterone binding capacity. Free E2 and SHBG were also measured in the serum of (e) postmenopausal patients having breast cancer (n = 38) and (f) matched control cancer patients (n = 67). We confirmed a very good inverse correlation between log free E2 per cent and log SHBG (P less than 0.0001). The regression lines for groups (a)-(d) were not statistically different. The regression lines for groups (e) and (f) were identical and ran nearly parallel to those for groups (a)-(d) though somewhat lower. This small difference may be ascribed to menopausal status. Therefore, we found no difference in free E2 percentage, calculated free E2 concentration or SHBG between premenopausal women at risk, women with benign breast disease, patients cured for early breast cancer or having breast cancer and matched controls. However, postmenopausal breast cancer patients had a significantly higher total serum E2 concentration and, by consequence a higher calculated free E2 concentration compared to the carefully matched control group.