Yes相关蛋白在小细胞肺癌中的表达及意义

目的:探讨YAP(Yes-associated protein,YAP)蛋白在小细胞肺癌组织中的表达及其临床意义.方法:应用免疫组织化学检测106例小细胞肺癌组织标本和25例癌旁组织标本,分析其与患者临床病理特征及预后的关系.结果:小细胞肺癌组织中YAP阳性表达率为68.9%(73/106),癌旁组织中YAP阳性表达率为12%(3/25),差异具有统计学意义(P<0.05).在小细胞肺癌组织中,YAP表达与临床分期(P=0.021)、淋巴结转移(P=0.032)、转移病灶数目(P=0.007)、血清NSE水平(P=0.034)和血清LDH水平(P=0.037)有关.单因素生存分析显示,临床分期(P<0.001)、淋巴结转移情况(P=0.018)、病灶转移数目(P=0.004)、心包浸润(P=0.009)、血清NSE水平(P=0.01)、血清LDH水平(P=0.008)和YAP表达(P=0.001)与预后相关.进一步多因素分析显示,临床分期(P=0.001)、淋巴结转移(P=0.012)、心包浸润(P=0.009)和YAP表达(P=0.003)为总生存期的独立预测因子.结论:YAP在小细胞肺癌中具有较高的表达率,其表达情况与肿瘤的进展密切相关.YAP 蛋白表达可作为判断小细胞肺癌患者预后的一个预测指标.     

低氧对恶性黑素瘤A375细胞中Nodal及细胞迁移相关蛋白表达的影响

目的 探讨低氧对恶性黑素瘤A375细胞中Nodal及细胞迁移相关蛋白表达的影响.方法 对恶性黑色素瘤A375细胞进行体外培养,细胞分为空白对照组、CoCl2组、SB-431542阻断组和CoCl2+SB-431542组,以氯化钴(CoCl2)诱导构建A375细胞内的低氧环境,SB-431542阻断Nodal信号通路,应...     

YAP1在食管癌KYSE30和EC9706细胞侵袭和转移中的作用机制探讨

目的探讨Yes相关蛋白(YAP)在食管癌KYSE30和EC9706细胞侵袭转移中的作用。方法将不做任何处理空白食管癌KYSE30和EC9706细胞分别作为A组和E组,将只添加Lipofectamine 2000转染试剂的食管癌KYSE30和EC9706细胞分别作为B组和F组,将转染无义干扰小RNA(siRNA)和YAP1 siRNA的食管癌KYSE30细胞和EC9706细胞分别作为C组、D组和G组、H组。逆转录聚合酶链反应(RT-PCR)和蛋白质印迹(Western blot)法检测基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、血管内皮生长因子(VEGF)和YAP1 mRNA及其对应蛋白的相对表达量,CCK8法、Transwell小室和划痕实验检测各组细胞增殖、侵袭和迁移能力。结果 D组细胞中MMP2、VEGF、YAP1 m RNA和蛋白的相对表达量均低于A、B和C组细胞(P﹤0.05),H组细胞MMP2、VEGF、YAP1 mRNA和蛋白的相对表达量均低于E、F和G组细胞(P﹤0.05)。转染48、72 h后,D组细胞OD值低于A、B和C组(P﹤0.05),H组细胞OD值低于E、F和G组细胞(P﹤0.05)。D组穿膜细胞数少于A、B和C组细胞(P﹤0.05),划痕愈合距离小于A、B和C组细胞(P﹤0.05);H组穿膜细胞数少于E、F和G组细胞(P﹤0.05),划痕愈合距离小于E、F和G组细胞(P﹤0.05)。结论 YAP1可能通过抑制MMP2和VEGF的表达,抑制食管癌细胞的侵袭和转移,有望成为抑制食管癌恶性进程的有效靶点。     

黑素瘤相关抗原-A9和-A11在食管鳞状细胞癌组织中的表达及其临床意义

目的：探讨黑素瘤相关抗原（melanoma antigen,MAGE）-A9 和-A11在食管鳞状细胞癌组织中的表达情况,分析其与食管癌患者临床病理学特征及其预后的关系。方法：选取河北医科大学第四医院2010年9月至2010年11月住院手术切除的食管癌组织及距癌组织边缘5 cm以上且病理诊断证实为正常组织的癌旁组织标本各60例,同时选取5例该院前列腺癌住院患者术后的睾丸组织作为阳性对照,应用免疫组织化学法检测食管鳞状细胞癌组织及相应癌旁组织中MAGE-A9和-A11蛋白的表达。结果： 食管鳞状细胞癌组织中MAGE-A9和 MAGE-A11 蛋白的阳性表达率分别为 45%（27/60）和66.67%（40/60）,而相应的癌旁组织未发现MAGE-A9和-A11蛋白的表达。MAGE-A9蛋白的表达与食管鳞状细胞癌患者的年龄、临床分期、肿瘤大小、淋巴转移均无相关性（P>0.05）,但与组织学分级相关（P<0.05）;MAGE-A11蛋白表达与食管鳞状细胞癌患者的年龄、组织学分级、淋巴转移均无相关性（P>0.05）,但与临床分期、肿瘤大小呈正相关（P<0.05）。Log-Rank检验显示,MAGE-A9 （P=0.037）和-A11（P=0.039）蛋白表达阳性的食管鳞状细胞癌患者和贲门腺癌患者的生存期均显著低于其表达阴性的患者。Cox多因素分析提示,MAGE-A9(P=0.026)和MAGE-A11(P=0.038)蛋白表达、组织学分级(P=0.026)、临床分期(P=0.008)及淋巴结转移(P=0.010)可作为整体生存的独立预后因素。结论： MAGE-A9和-A11蛋白是食管鳞状细胞癌的特异性抗原,似可作为食管鳞状细胞癌预后不良的预测指标。     

PKCι/YAP1在宫颈癌中的表达及其临床意义

目的 探讨蛋白激酶Cι（PKCι）、Yes相关蛋白1（YAP1）与高危型人乳头瘤病毒（HPV）感染在宫颈癌局部免疫微环境中的相关性。方法 选择宫颈正常组织（NCT）、宫颈低级别鳞状上皮内病变（LSIL）、宫颈高级别鳞状上皮内病变（HSIL）以及宫颈鳞状细胞癌（SCC）各80例。收集4组蜡块组织,实时荧光PCR法测定4组组织高危型HPV感染率;免疫组织化学法检测4组组织中PKCι、YAP1、CD4及CD8表达水平并进行相关性以及临床病理分析。结果 NCT、LSIL、HSIL以及SCC各组间高危型HPV感染率、PKCι、YAP1、CD4、CD8阳性率差异均有统计学意义（P<0.05）;宫颈病变级别与高危型HPV感染、PKCι、YAP1及CD8阳性表达均呈正相关（P<0.05）,与CD4阳性表达呈负相关（P<0.05）;在SCC中HPV感染、PKCι、YAP1以及CD8阳性表达相互之间的均呈正相关,而与CD4阳性表达均呈负相关（P<0.05）;HPV感染、PKCι、YAP1及CD8阳性表达在SCC不同分化程度及有无脉管瘤栓之间差异均有统计学意义（P<0.05）。结论 宫颈病变患者常伴有高危型HPV感染与PKCι、YAP1、CD4及CD8表达异常,相互之间可能存在协同作用,造成SCC的局部免疫抑制微环境,为SCC的发病机制研究及其诊治提供可能的策略。     

siRNA沉默YAP1对宫颈癌Hela细胞增殖和侵袭的影响

目的:用小干扰RNA(siRNA)沉默宫颈癌Hela细胞中YAP1基因的表达,观察YAP1表达降低对细胞增殖和侵袭能力的影响,初步探讨YAP1在宫颈癌中的作用。方法:qRT-PCR和Western blot方法检测宫颈癌Hela细胞及正常宫颈上皮细胞H8中YAP1的表达,siRNA YAP1转染Hela细胞沉默YAP1表达,并以转染control siRNA的细胞作为对照,转染48h后,分别用qRT-PCR和Western blot方法检测沉默效果。用MTT法检测沉默后细胞增殖情况。Transwell 检测细胞侵袭能力。结果:YAP1在宫颈癌细胞中高表达。siRNA能够有效沉默Hela细胞中YAP1的mRNA 及蛋白的表达。沉默YAP1表达能够明显抑制Hela细胞的增殖及侵袭能力。结论:YAP1蛋白在宫颈癌细胞中高表达并具有促进细胞增殖及侵袭的能力。     

气球状细胞痣的病理诊断及鉴别诊断

目的:探讨皮肤气球状细胞痣的病理诊断及鉴别诊断。方法:对1 例皮肤气球状细胞痣应用免疫组化SP（streptavidin-perosidase）法观察,并进行临床病理分析。结果:皮肤组织真皮内见胞浆透亮的细胞排列成大小不等由胶原纤维分隔的小叶,痣细胞绝大部分为体积较大、胞质丰富且呈透明状或细颗粒状气球状痣细胞。胞核小而圆,大小一致,多位于细胞的中央,无异型性及核分裂像。免疫组化染色提示气球状细胞痣S-100(++)、Vimentin(++)、Melan-A（++）、Ki-67＜5%,HMB-45仅在真皮浅层的灶性气球状细胞浆呈弱阳性表达。结论:气球状细胞痣极为罕见,需要与皮肤的多种透明细胞肿瘤进行鉴别,正确诊断主要依赖组织病理及免疫组化结果。     

PTEN基因蛋白在恶性黑素瘤中的表达及意义

目的探讨PTEN基因蛋白在恶性黑素瘤中的表达及其意义.方法采用免疫组化EnVision检测PTEN基因蛋白在51例恶性黑素瘤以及30例皮内痣组织中的表达情况.结果恶性黑素瘤组织中PTEN表达强度低,总体阳性率52.9%(27/51),其中Ⅰ、Ⅱ、Ⅲ各期阳性率分别为59.4%(17/32)、38.5%(5/13)、33.3%(2/6);而皮内痣中PTEN均呈强阳性,表达阳性率为100%(30/30),二者差异具有显著性(P＜0.01).结论恶性黑素瘤的发生可能与PTEN基因蛋白的低表达有关,PTEN基因蛋白表达缺失或低下者更易发生远处转移,标记PTEN可作为判断黑素瘤预后的一项指标.     

TIPE1在皮肤鳞状细胞癌中的表达及意义

目的:研究TIPE1在皮肤鳞状细胞癌中的表达变化情况。方法:采用免疫组化方法检测31例皮肤鳞状细胞癌组织和31例正常皮肤组织中TIPE1的表达情况。结果:在正常皮肤组织中,TIPE1弱表达于表皮基底层及棘层下部,在表皮全层表达的阳性率为23.20%。在皮肤鳞状细胞癌中,可见TIPE1高表达于大部分的癌细胞中,阳性率为77.41%。TIPE1在皮肤鳞状细胞癌中的表达显著高于正常皮肤组织(P＜0.05)。结论:TIPE1可能参与皮肤鳞状细胞癌的发生和发展。     

黑素瘤干细胞在黑素瘤转移中的研究进展

黑素瘤是一种恶性程度极高的恶性肿瘤,具有高侵袭力和转移能力,早期可转移至肺和脑等部位,晚期则可扩散至全身.既往研究认为,黑素瘤干细胞(melanoma stem cells,MSCs)是引起黑素瘤侵袭、转移和复发的潜在原因之一.MSCs可表达多种细胞标志物,包括CD133、ATP结合盒亚家族B成员5(ATP-bindi...     

High nevus counts confer a favorable prognosis in melanoma patients

A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5‐ and 10‐year melanoma‐specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21–0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08–0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.     

A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes

An abnormal nevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual nevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify the risk better and to determine whether relative risk is varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with nevus characteristics. Participants with whole body nevus counts in the highest of 4 population-based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 11.2) for those aged<50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged>or=50). The pOR for presence compared with absence of any clinically atypical nevi was 4.0 (95% CI: 2.8, 5.8). The pORs for 1-2 and >or=3 large nevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of nevus phenotype, except for the analysis of nevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal nevus phenotype is associated most with melanomas on intermittently sun-exposed sites. The presence of increased numbers of nevi, large nevi and clinically atypical nevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes.     

Dysplastic nevus syndrome: association with multiple primary neoplasms

A 65-year-old white man with dysplastic nevus syndrome is presented. The patient also developed an extramammary Paget's disease of the scrotum, two malignant melanomas of the skin of the arm and abdomen, two squamous cell carcinomas in the mouth, and several benign tumors such as lentigo maligna, dermatofibroma, and a cavernous hemangioma. Besides the well-established tendency of patients with the dysplastic nevus syndrome to develop malignant melanomas of the skin, their possible propensity to develop other primary malignant neoplasms is discussed.     

Sun exposure, pigmentary traits, and risk of cutaneous malignant melanoma: a case-control study in a Mediterranean population

The main objective of this study was to assess the influence of sun exposure and pigmentary traits on the risk of cutaneous malignant melanoma (CMM) in a Mediterranean population (Andalusia, southern Spain). Cases and controls were selected from 1988 to 1993. The study population included 105 incident cases with non-familial CMM (ICD-9 code 172) and 138 controls aged 20 to 79 years. Data were collected by personal interview, and melanocytic nevi were counted over the entire body surface. Crude, and multiple-risk factor adjusted, odds ratios (OR) and their 95 percent confidence intervals (CI) were computed. After adjustment, the major constitutional risk factor was skin type I-II (OR=29.8, CI=8.9–100) compared with skin type V. Statistically significant and positive trends were observed between the risk of CMM and occupational sun exposure of the skin (P=0.003), recreational exposure (P<0.001), and cumulative lifetime sun exposure (P<0.001). Several characteristics related to sun exposure during summer increased the CMM risk, e.g., episodes of blistering sunburns and the number of sunbaths in childhood. Use of sunsreens and spending summer holidays in places other than beach were associated with a lower risk of CMM. Regarding pigmentary traits, CMM significantly occurred with more frequency in individuals with a high degree of freckling and quoted numbers of melanocytic nevi. In conclusion, the results support sun exposure and pigmentary traits (skin type, melanocytic nevi, and freckles) as main risk factors for CMM in this population.Drs Rôdenas, Tercedor and Serrano are with the Department of Dermatology, School of Medicine, University of Granada, Granada,Spain. Authors are also affiliated with the Division of Epidemiology and Preventive Medicine, University of Cantabria, Santander, Spain (Dr Delgado-Rodríguez); the Service of Dermatology, Hospital Virgen de las Nieves, Granada, Spain (Dr Tercedor); and the Service of Internal Medicine, Hospital General Universitario Morales Meseguer, Murcia, Spain (Dr Herranz) Dr Ródenas, at present, is affiliated with the Department of Dermatology, Hospital General Universitario Morales Meseguer, Murcia, Spain. Address correspondence to Dr Ródenas, Dermatology Department, Hospital General Universitario Morales Meseguer, Av. Marqués de los Vélez, 30008 Murcia, Spain.     

卵巢癌组织Hippo-Yes相关蛋白表达与临床病理参数及增殖凋亡相关性研究

目的探讨卵巢癌组织中Hippo-Yes相关蛋白(Yes-associated protein,YAP)的表达与临床病理参数的关系,及其对卵巢癌细胞增殖和凋亡的影响。方法免疫组化染色技术检测湖南省肿瘤医院病理科2010-01-01-2013-12-31保存的68例卵巢癌及38例良性卵巢组织中YAP蛋白表达,分析YAP表达与卵巢癌临床病理参数的相关性;逆转录病毒介导的YAP shRNA干扰人卵巢癌EFO-21细胞中YAP表达,蛋白质印迹法检测干扰效率,5-溴脱氧尿嘧啶核苷(5-Bromo-2-deoxy Uridine,BrdU)细胞增殖分析和流式细胞术检测肿瘤细胞增殖和凋亡变化。结果卵巢癌组织YAP蛋白阳性表达率为61.8%(42/68),良性卵巢组织为10.5%(4/38),差异有统计学意义,χ2=26.054,P<0.001。卵巢癌组织中YAP蛋白阳性表达率在高临床分期(χ2=8.600,P=0.003)和高病理分级(χ2=5.688,P=0.017)中显著升高。YAP shRNA显著降低卵巢癌EFO-21细胞中YAP蛋白表达,对照组YAP蛋白表达为0.96±0.16,实验组为0.14±0.04,P<0.001。YAP shRNA导致肿瘤细胞增殖能力显著减弱,对照组细胞增殖水平为121.00±3.19,实验组为55.83±3.56,P<0.001。YAP shRNA并诱导细胞凋亡,对照组凋亡率为(8.75±0.15)%,实验组为(32.75±4.76)%,P<0.001。结论 YAP蛋白在卵巢癌组织中表达异常升高并核内蓄积,其阳性表达与高病理分级和高临床分期显著有关,干扰YAP表达导致肿瘤细胞增殖减弱和凋亡增加,提示YAP通过促进肿瘤细胞生长发挥促癌作用,其可能成为卵巢癌靶向治疗的潜在靶点。     

Nevus density and melanoma risk in women: A pooled analysis to test the divergent pathway hypothesis

A “divergent pathway” model for the development of cutaneous melanoma has been proposed. The model hypothesizes that melanomas occurring in people with a low tendency to develop nevi will, on average, arise more commonly on habitually sun‐exposed body sites such as the head and neck. In contrast, people with an inherent propensity to develop nevi will tend to develop melanomas most often on body sites with large melanocyte populations, such as on the back. We conducted a collaborative analysis to test this hypothesis using the original data from 10 case–control studies of melanoma in women (2,406 cases and 3,119 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure‐related factors. Higher nevus count on the arm was associated specifically with an increased risk of melanoma of the trunk (p for trend = 0.0004) and limbs (both upper and lower limb p for trends = 0.01), but not of the head and neck (p for trend = 0.25). The pooled odds ratios for the highest quartile of nonzero nevus count versus none were 4.6 (95% confidence interval (CI) 2.7–7.6) for melanoma of the trunk, 2.0 (95% CI 0.9–4.5) for the head and neck, 4.2 (95% CI 2.3–7.5) for the upper limbs and 3.4 (95% CI 1.5–7.9) for the lower limbs. Aggregate data from these studies suggest that high nevus counts are strongly associated with melanoma of the trunk but less so if at all of the head and neck. This finding supports different etiologic pathways of melanoma development by anatomic site. © 2008 Wiley‐Liss, Inc.     

YAP蛋白在甲状腺髓样癌组织中的表达

目的：探讨YAP蛋白在甲状腺髓样癌（ MTC）发生发展中的作用及临床意义。方法采用免疫组织化学方法检测25例MTC、25例正常甲状腺组织中YAP蛋白的表达。结果25例MTC组织中YAP蛋白阳性表达率为88.00%（22/25）,而25例正常甲状腺组织中YAP蛋白表达均为阴性,比较差异有统计学意义（χ2=39.286,P〈0.05）。结论 YAP蛋白在MTC组织中呈明显过表达,在MTC的发生发展中可能起着重要作用,且有望成为具有潜在应用价值的分子标记及治疗靶点。     

Linkage and association analysis of nevus density and the region containing the melanoma gene CDKN2A in UK twins

Rare mutations in the CDKN2A gene are highly penetrant for melanoma. Density of nevi is under strong genetic control and high density is a potent risk factor for melanoma. We used linkage and association analysis in adolescent twins from the UK to examine the hypothesis that the region containing the CDKN2A gene also contains a quantitative trait locus influencing normal nevus development. Five markers in the CDKN2A region were genotyped in 115 dizygotic twin pairs, and one marker (D9S942) was genotyped in 103 monozygotic twin pairs, all of whom had been phenotyped for nevus density. Linkage analysis showed no evidence of a quantitative trait locus influencing nevus density in this chromosomal region. A model partitioning the variation in phenotype into within- and between-twin pair components showed weak evidence of association between higher nevus density and longer mean length of the two D9S942 alleles (P=0.01). This relation, which was also observed in an earlier Australian twin study, could be because of the linkage disequilibrium between D9S942 and a neighbouring functional locus. Further investigation of this region is warranted in large-scale linkage or association studies.