结直肠腺癌中skp2、p27^kip1、ERK蛋白的表达及意义

目的研究细胞S期激酶相关蛋白2（skp2）、p27k ip1、细胞外调节蛋白激酶（ERK）蛋白在结直肠癌组织中的表达情况及在结直肠腺癌发生发展中的作用。方法应用免疫组化法检测60例结直肠癌组织（A组）、30例腺瘤组织（B组）、20例正常大肠组织（对照组）中skp2、p27k ip1、ERK蛋白的表达,分析其与临床病理因素的关系。结果 3组skp2、p27k ip1、ERK蛋白表达阳性率比较差异均有统计学意义（P〈0.05）;skp2、p27k ip1、ERK蛋白的表达与结直肠腺癌的分化程度、Dukes’分期及淋巴结转移有关（P〈0.05）;skp2、ERK与p27k ip1表达呈负相关（r=-0.723 7、P〈0.01;r=-0.695 2、P〈0.01）,而skp2与ERK表达呈正相关（r=0.652 2、P〈0.01）。结论 skp2、p27k ip1、ERK蛋白的表达可能与结直肠腺癌的发生发展有关,ERK可能参与了skp2-p27k ip1通路的调节。     

P27和skp2在肝细胞癌中的表达及其意义

目的探讨肝细胞癌P27和skp2蛋白的表达情况与临床病理意义。方法用免疫组化二步法检测P27和skp2在60例肝细胞癌及20例癌旁组织中的表达。结果60例肝细胞癌P27的阳性表达率为23％（14／60）,癌旁组织为80％（16／20）,60例肝细胞癌高分化癌阳性表达率为47％（7／15）,低分化癌为16％（7／45）。P27在肝细胞癌中的表达明显低于癌旁组织,P27蛋白的表达随病理分级增高而降低。60例肝细胞癌skp2阳性表达率为47％（28／60）,癌旁组织为15％（3／20）,60例肝细胞癌高分化癌阳性表达率13％（2／15）,低分化癌为58％（26／45）,可见skp2在肝细胞癌中表达明显高于癌旁组织（P〈0．05）,低分化癌明显高于高分化癌（P〈0．01）。结论P27和skp2蛋白的表达情况与肝细胞癌的发生发展及恶性度有关。     

p27在腮腺恶性肿瘤中的表达及意义

腮腺癌是较多见的恶性肿瘤,其患病率逐渐增加,具有一定的侵袭性和转移能力。细胞周期的运行受多种因素所调控,肿瘤的发生与细胞周期失控有关,p27活性的改变直接影响细胞周期进程,进而影响细胞的增殖,与肿瘤的发生密切相关。     

大肠癌患者Skp2、P27kipl及CyclinE表达及意义

采用免疫组化方法检测大肠癌组织和正常大肠黏膜组织中Skp2、P27kipl及CyclinE蛋白的表达.结果 Skp2、P27kipl和CyclinE蛋白的表达在大肠癌和正常大肠黏膜组织中均有统计学差异(P均＜0.05),且其表达与大肠癌分化程度、临床分期及淋巴结转移相关(P＜0.05);大肠癌组织中Skp2及cyclinE蛋白的表达均与P27kipl呈负相关(r=-0.367、-0.557,P均＜0.05),Skp2与CyclinE蛋白的表达不相关.提示P27kipl、Skp2及CyclinE蛋白的表达可能与大肠癌的发生、发展及生物学行为有关,有望成为大肠癌治疗的新靶点.     

p27基因及其与大肠肿瘤的关系

p2 7基因主要功能是作为CDK抑制因子 ,作用于细胞周期的G1期 ,调节细胞周期进程。研究表明 ,p2 7基因能够阻止细胞周期中G1/S期转化 ,一般认为p2 7是一种抑癌基因 ,有研究证实细胞核 p2 7基因表达水平与肿瘤恶性程度呈负相关 ,故可能是一种新的肿瘤标志物及肿瘤预后指标。     

Skp2、p27在急性白血病细胞中的表达及意义

采用免疫组化方法检测了Skp2及p27在32例急性白血病患者（AL组）及10例良性血液病患者（对照组）血细胞中的表达。结果AL组Skp2表达高于对照组,p27表达低于对照组,P均〈0．05。认为Skp2高表达与白血病的发生、发展密切相关,应用其抑制剂可为多靶位治疗白血病提供理论及技术基础。     

p27kip1、Skp2及Survivin在乳腺癌组织中的表达及意义

近期,我们观察了p27^Kip1、S期激酶伴随蛋白2（Skp2）和Survivin蛋白在乳腺癌组织中的表达,并探讨其与临床病理特征的关系。     

p53蛋白在大肠肿瘤组织中表达的意义

ｐ５３蛋白在大肠肿瘤组织中表达的意义陈大伟，高瀚，王元和，陈泳莲，叶挺军笔者用免疫组织化学方法，检测ｐ５３蛋白在正常大肠粘膜、大肠腺瘤和大肠腺癌组织中表达，研究ｐ５３蛋白表达在大肠癌演变中的作用以及与临床病理关系。材料与方法一、临床资料本研究共收集２...     

泛素、Skp2、p27在大肠癌组织中的表达及意义

采用组织芯片技术制作80例大肠癌癌组织芯片。S-P免疫组织化学方法检测芯片中泛素、S期激酶相关蛋白2（Skp2）和p27表达。结果泛素表达阳性率为45．0％,Skp2阳性率为47．5％,p27阳性率为38．8％,不同组织学类型大肠癌中泛素、skp2、p27的表达未见明显差异（P〉0．05）;有淋巴结转移者Skp2阳性率显著高于无淋巴结转移者（P〈0．01）,p27阳性率显著低于无淋巴结转移者（P〈0．01）。提示Skp2高表达和p27低表达与大肠癌的进展相关,Skp2和p27的表达可以作为评估大肠癌预后的参考指标;泛素和Skp2在p27的表达调控中起重要作用;应用组织芯片大规模高效检测临床组织样本是可行的,具有快速、方便、经济、准确的特点。     

骨肉瘤组织中Skp2、p27蛋白的表达变化及意义

目的观察p27和Skp2蛋白在骨肉瘤组织中的表达变化,并探讨其意义。方法选取40例骨肉瘤组织标本作为骨肉瘤组,另选40例正常骨组织作为对照组。用免疫组化SP法检测两组中的p27和Skp2蛋白。结果骨肉瘤组中Skp2的阳性表达率明显高于、p27的阳性表达率明显低于正常骨组织(P均<0.05)。Skp2表达与骨肉瘤组织类型、分化程度及淋巴结转移有关(P均<0.05);p27蛋白表达与骨肉瘤组织类型、分化程度有关(P均<0.05)。Skp2、p27蛋白在骨肉瘤组织中的表达呈负相关(r=-0.34,P<0.05)。结论 p27蛋白在骨肉瘤组织中呈低表达,Skp2蛋白在骨肉瘤组织中呈高表达,二者呈负相关关系,且与骨肉瘤的发生和转移有关,有可能成为了解骨肉瘤生物学行为的参考指标。     

p27、Cyclin A在肝细胞癌中的表达及其意义

细胞周期调节因子p27及Cyclin A蛋白水平升高或基因改变与多种肿瘤的发生有关。用免疫组织化学SABC法，联合检测45例肝细胞癌(HCC)组织及30例癌旁肝组织中p27及Cyclin A的表达，以探讨其与HCC发生、发展及侵袭转移的关系。     

High expression of skp2 correlates with poor prognosis in endometrial endometrioid adenocarcinoma

Purpose: Skp2 interacts with the degradation of cyclin-dependent kinase inhibitor p27. This study aimed to investigate the correlation of skp2 expression with the expression of p27 and other cell cycle regulators, and clinicopathological parameters in endometrial endometrioid adenocarcinoma. Methods: Tissue samples of 136 endometrioid adenocarcinomas, in addition to 20 endometrial hyperplasias and 20 normal endometria, were immunohistochemically stained for skp2. The expression was represented as a labeling index (LI), which indicates the percentage of positive nuclei. Results: Skp2 staining was localized in the nuclei of the glandular cells of the proliferative phase endometrium, and endometrial hyperplasia and carcinoma cells. Skp2 expression was increased significantly in those of higher histological grade. The high level of skp2 expression was significantly correlated with the presence of lymph node metastasis and lymph-vascular space involvement. The LI of skp2 in endometrial carcinoma was significantly correlated with that of p27, Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p53 and PTEN. The high level of skp2 expression (LI≧20%) was significantly correlated with the patients’ poor survival. Conclusions: The skp2 level might have increased due to p27 accumulation and may be a good indicator of proliferative activity and poor prognosis.     

Antitumor bioactivity of adenovirus-mediated p27mt in colorectal cancer cell line SW480

AIM： To explore the antitumor bioactivity of adenovirusmediated mutant type p27^kip1 gene in a colorectal cancer cell line SW480. METHODS： We constructed recombinant adenovirus vector expressing a mutant type p27^kip1 gene （ad- p27mt）, with mutation of Thr-187/Pro-188 （ACGCCC） to Met-187/Ile-188 （ATGATC）, and transduced into SW480 cells. Then we detected expression of p27, Bcl-2 and Bax protein in the transductants by Western blotting, cell cycle of transductants by a digital flow cytometric system, migrating potential with Boyden Chamber and SW480 tumor cell growth inhibition in vitro and in vivo. RESULTS： We found that a recombinant adenovirus vector of expressing ad-p27mt, with mutation of Thr-187/Pro-188 （ACGCCC） to Met-187/Ile-188 （ATGATC） has potent inhibition of SW480 tumor cell growth in vitro and in vivo. Furthermore, ad-p27mt induced cell apoptosis via regulating bax and bcl-2 expressions, and G1/S arrest in SW480 cells and inhibited cell migration. CONCLUSION： ad-p27mt has a strong anti-tumor bioactivity and has the potential to develop into new therapeutic agents for colorectal cancer.     

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathoiogic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages Ⅲ-Ⅳand with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages Ⅰ-Ⅱ and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2-positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.     

波动性高糖对胰岛β细胞增殖及Skp2-p27表达的影响

目的 探讨波动性高糖对INS-1细胞增殖、凋亡及对细胞周期进程的影响,并研究其可能的分子机制.方法 采用细胞计数试剂盒(cell counting kit-8)检测细胞增殖活性,流式细胞仪测定细胞周期及细胞ROS水平,Annexin-V/PI双标流式细胞术检测细胞凋亡.应用Western印迹检测细胞周期调控蛋白p27及Skp2的表达水平.结果 (1)波动性高糖及持续性高糖均明显抑制INS-1细胞的生长,且波动性高糖对细胞增殖的抑制作用更为显著.(2)波动性高糖及持续性高糖均明显增加INS-1细胞的凋亡,且波动性高糖作用更为显著.(3)波动性高糖及持续性高糖能明显抑制细胞周期进程,使INS-1细胞周期更多滞留在G0/G1期,G2/M期与S期细胞比例下降,波动性高糖作用更显著.(4)波动性高糖及持续性高糖均能显著增强细胞周期调控蛋白p27的表达,同时减弱Skp2蛋白的表达水平.结论 波动性高糖较持续性高糖更能够抑制INS-1细胞的增殖和诱导凋亡,可能是通过减弱Skp2蛋白的表达水平,增加p27蛋白的活性,使细胞阻滞在G0/G1期,抑制细胞周期进程,从而减弱细胞的增殖活性.

Abstract：

Objective To investigate the effect of intermittent high glucose on proliferation, apoptosis, and cell cycle progression of INS-1 cells, and the possible intracellular pathways activated by intermittent high glucose. Methods Cell viability was evaluated by cell counting kit, the cell cycle was determined by flow cytometry,Annexin-V/PI double-labeled cell apoptosis detection kit was used to monitor cell apoptosis. Cell cycle related protein Skp2 and p27 expressions were detected by Western blot. Results ( 1 ) Both intermittent and constant high glucose significantly inhibited the growth of INS-1 cells, and the former effect was more significant. ( 2 ) Intermittent and constant high glucose levels significantly increased apoptosis in INS-1 cells, and the former effect was more significant. (3) Intermittent and constant high glucose levels significantly inhibited the cell process, the G0/G1 cell cycle arrest also was induced by intermittent high glucose, resulting in lowered proportion of the G2/M phase and S phase of INS-1 cells. (4) Intermittent and constant high glucose significantly decreased the level of protein Skp2 and increased the level of cell cycle related protein p27. Conclusion Intermittent high glucose levels affect INS-1 cell growth and proliferation, as well as induce cell apoptosis, probably by decreasing the level of protein Skp2 and increasing the level of p27 in the cells, resulting in arrest of progression through the G1 phase to the S phase of INS1 cells, and thus impairment of cell proliferation.     

胆管癌组织紧密连结蛋白18、丝氨酸蛋白酶抑制剂和p53蛋白表达及其临床意义

目的 探讨胆管癌组织紧密连结蛋白18（claudin-18）、丝氨酸蛋白酶抑制剂（maspin）和p53蛋白表达的临床意义。方法 采用免疫组化和Western blot法检测46例胆管癌和32例正常胆管组织claudin-18、maspin和p53蛋白的表达,采用Spearman等级相关分析。结果 胆管癌组织claudin-18和p53蛋白阳性率分别为52.17%和56.52%,显著高于正常胆管组织（0.0%和0.0%,P<0.01）;胆管癌组织maspin阳性率为86.96%,显著低于正常胆管组织（100.0%,P<0.01）;胆管癌组织claudin-18、maspin和p53蛋白表达量分别为2.83±0.52、2.45±1.24和1.73±1.26,均显著高于正常胆管组织（0.48±0.75、0.46±0.32和0.0±0.0,P<0.05）;胆管癌组织maspin与p53表达呈负相关（r=-8.546,P=0.001）。结论 胆管癌组织maspin、claudin-18和p53蛋白表达的意义还有待于进一步研究。     

Impact of p27mt gene on transplantation model of human colorectal cancer in nude mice

AIM： To investigate the inhibitory and anti-metastatic effect of mutant p27 gene （p27mt） on the growth of colorectal cancer xenografts in nude mice and its underlying mechanism. METHODS： Inhibitory effect of p27mt gene on the growth of colorectal cancer xenografts was determined by measurement of tumor size before and after direct intra-tumoral injection of Ad-p27mt in a pre-established transplantation model of human colorectal cancer in nude mice. Cell cycle and apoptosis were detected by flow cytometry performed on single-cell suspension from an isolated tumor. Expression of MMP-9 in tumor tissue was detected by immunohistochemistry. RESULTS： The average sizes of transplantation tumors were 1.94 ± 0.67 cm^3, 2.75 ± 0.83 cm^3 and 3.01 ± 0.76 cm^3 in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.05）. The average proliferation rates were 37.34% ± 1.45%, 53.16% ± 3.27% and 54.48% ± 2.43%, in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.05）. The average apoptosis rates were 19.79% ± 3.32%, 6.38% ± 4.91% and 7.25% ± 5.20% in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.01）. The average MMP-9 expression rates were 20%, 75% and 66.7% in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.01）. CONCLUSION： p27mt inhibits the growth of transplanted tumor by blocking the proliferation of cancer xenografts and by promoting apoptosis of transplantated tumor cells, as well as decrease transplanted tumor metastasis.     

p27kip1和p57kip2与CyclinD1在急性白血病的表达及其临床意义

目的:探讨p27kip1和p57kip2与CyclinD1在急性白血病中的表达情况及其临床意义.方法:采用免疫组化S-P法检测39例急性白血病及10例正常对照者骨髓中p27kip1和p57kip2与CyclinD1蛋白的表达情况,并结合临床病理资料进行分析.结果:p27kip1和p57kip2与CyclinD1蛋白在急性白血病患者的阳性表达率分别为31%、33%、54%,在对照组表达率为70%、40%、0.p27kip1与cyclinD1在白血病与对照组中的表达差异有统计学意义.在37例接受化疗的急性白血病中,p27kip1和p57kip2阳性表达组化疗后的缓解率(66%、69%)明显高于p27kip1和p57kip2表达阴性组的缓解率(32%、29%),其差异有统计学意义(P＜0.05).p57kip2与CyclinD1在白血病中的表达具有正相关性.结论:p27kip1和p57kip2与CyclinD1在急性白血病患者中存在异常表达其蛋白的表达水平可能会影响化疗疗效.     

结直肠癌中SCC-S2的表达及意义

目的SCC-S2是近期发现的一种在多种癌症中过表达,并且与癌细胞的恶性生物学行为关系密切的物质。但是在结直肠癌中,SCC-S2的表达和生物学作用未见报道。本研究目的是探索SCC-S2在结直肠癌及其癌旁正常组织中的表达水平,探讨SCC-S2与结直肠癌患者临床病理特征的关系。 方法本研究应用免疫组化分析了SCC-S2在136例结直肠癌组织中的表达情况,使用SPSS 18.0软件进行统计分析。 结果67例(49.26%)结直肠癌标本SCC-S2过表达。SCC-S2的过表达与结直肠癌的TNM分期显著相关(P<0.01);与淋巴结转移显著相关(P<0.05);与细胞增殖指数显著相关(P>0.01)。 结论SCC-S2在结直肠癌中表达升高,并与结直肠癌侵袭和淋巴结转移密切相关。SCC-S2在结直肠癌的发生发展中可能发挥着重要作用。