Expression of positive and negative regulators of cell cycle during wound healing

Ｗｏｕｎｄｈｅａｌｉｎｇｉｓｔｈｅｐｒｏｃｅｓｓｂｙｗｈｉｃｈｃｅｌｌｐｒｏｌｉｆｅｒａｔｉｏｎｉｓｓｔｒｉｎｇｅｎｔｌｙｃｏｎｔｒｏｌｌｅｄ ＰｒｏｇｒｅｓｓｉｏｎｔｈｒｏｕｇｈｔｈｅＧ1ｐｈａｓｅａｎｄｉｎｉｔｉａｔｉｏｎｏｆｔｈｅｃｅｌｌｃｙｃｌｅｉｎｍａｍｍａｌｉａｎｃｅｌｌｓｄｅｐｅｎｄｓｏｎｔｈｅｂａｌａｎｃｅｏｆｉｎｔｅｒａｃｔｉｏｎｂｅｔｗｅｅｎｃｅｌｌｃｙｃｌｅｐｏｓｉｔｉｖｅｒｅｇｕｌａｔｏｒｓｓｕｃｈａｓｃｙｃｌｉｎＤ1,ｃｙｃｌｉｎＥ ,ｃｙｃｌｉｎ ｄｅｐｅｎｄｅｎｔｋｉｎａ…     

Cotransfection of TrkA and p75~(NTR) in neuroblastoma cell line (IMR-32) promotes differentiation and apoptosis of tumor cells

Objective To assess the effects of both TrkA and p75NTR on nerve growth factor (NGF)-induced differentiation of neuroblastoma cells.Methods Retroviral vectors were constructed to express the high affinity NGF receptor (TrkA) and low affinity NGF receptor (p75NTR). Neuroblastoma cell line IMR-32 was transfected by the vectors expressing either TrkA or p75NTR or both by using lipofectmine?reagent separately or cotransfected at the same time. Southern blot, Northern blot, RT-PCR and flow cytometry were used to determine the success of the transfection. MTT technique was to monitor the cell proliferation. Colony formation in soft agar and tumor forming assay in nude mice were used to test the biological characteristics of the tumor cells. Terminal-deoxynucleotidytransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to test the apoptosis of the tumor cells.Results Stable transformant cell lines expressing TrkA, p75NTR or both genes were established. Studies on these transformant cell line     

Effects of endothelin B receptor antagonists, BQ788 and ET-1_(11-21) fragment on the bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

Ｅｎｄｏｔｈｅｌｉｎ (ＥＴ)ｗａｓｏｒｉｇｉｎａｌｌｙｉｄｅｎｔｉｆｉｅｄｉｎ 1988ａｓａｖａｓｏｃｏｎｓｔｒｉｃｔｏｒｃｏｍｐｏｕｎｄｉｎｔｈｅｃｕｌｔｕｒｅｓｕｐｅｒｎａｔａｎｔｏｆｐｏｒｃｉｎｅａｏｒｔｉｃｅｎｄｏｔｈｅｌｉａｌｃｅｌｌｓ 1　ＥＴｓ (ＥＴ 1,ＥＴ 2ａｎｄＥＴ 3)ａｒｅ 2 1ａｍｉｎｏａｃｉｄｐｅｐｔｉｄｅｓ 2 　ＮｕｍｅｒｏｕｓｃｅｌｌｓｓｙｎｔｈｅｓｉｚｅａｎｄｒｅｌｅａｓｅＥＴｓ ,ｉｎｃｌｕｄｉｎｇｍａｉｎｌｙＥＴｃｅｌｌｓ ,ｂｕｔａｌｓｏｈｕｍａｎｉｓｏｌａｔｅｄｂｒｏｎｃ…     

Neoadjuvant therapy for early human epidermal growth factor receptor 2 positive breast cancer in China: A multicenter real-world study (CSBrS-015)

Background: Pertuzumab has been approved for application in China by the National Medical Products Administration, and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab + pertuzumab plus chemotherapy regimens for patients with indications. The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epid...     

Pien Tze Huang (片仔癀)-induced apoptosis in human colon cancer HT-29 cells is associated with regulation of the Bcl-2 family and activation of caspase 3

Objective  

To investigate the cellular effects of Pien Tze Huang (片仔癀, PZH) in the HT-29 human colon carcinoma cell line.     

Effect of Buyang Huanwu Decoction (补阳还五汤) on Plasma Thromboxane B_2, 6-Keto-Prostaglandin F_(1α), Endothelin and Calcitonin Gene Related Peptide in Primary Nephrotic Syndrome Patients

ＴｈｅｆｕｎｃｔｉｏｎｏｆｔｈｒｏｍｂｏｘａｎｅＢ2 （ＴＸＢ2 ）,6 ｋｅｔｏ ｐｒｏｓｔａｇｌａｎｄｉｎＦ1α （ 6 Ｋ ＰＧＦ1α）,ｅｎ ｄｏｔｈｅｌｉｎ（ＥＴ）ａｎｄｃａｌｃｉｔｏｎｉｎｇｅｎｅｒｅｌａｔｅｄｐｅｐ ｔｉｄｅ（ＣＧＲＰ）ｉｎｇｌｏｍｅｒｕｌｏｐａｔｈｙｈａｖｅａｌｒｅａｄｙａｒｏｕｓｅｄｉｎｔｅｒｓｔｏｆｃｌｉｎｉｃｉａｎｓ．（1 - 3） Ｓｉｎｃｅ 1 995,ｗｅｕｓｅｄＢｕｙａｎｇＨｕａｎｗｕＤｅｃｏｃｔｉｏｎ（补阳还五汤,ＢＹＨＷＤ）ａｓａｎｔｉｃｏａｇｕｌａｎｔｉｎｔｒｅａｔｉｎｇ…     

Expressions of cyclin E, cyclin dependent kinase 2 and p57KIP2 in human astric cancer

Objective To investigate the expressions of cyclin E, cyclin dependent kinase 2（CDK-2）a nd cyclin-dependent kinase inhibitor p57 (KIP2) in human gastric cancer, and to evaluate the relationships between protein levels and clinicopathological pa rameters. Methods Western blot was used to measure the expressions of cyclin E, CDK-2 and p57 (KIP2) proteins in the surgically resected gastric carcinoma, adjacent normal mu cosa and metastatic lymph nodes from 36 patients. Results Cyclin E and CDK-2 protein levels were higher in gastric cancer tissues in comp arison with normal tissues ( P <0. 05).Overexpression of cyclin E was correl ated with lymph node involvement, poor histological grade and serosa invasion ( P <0. 05).Overexpression of CDK-2 was correlated with lymph nodes involvem ent ( P <0. 05).No statistically significant difference between cyclin E and CDK-2 expression was found when samples were stratified according to tumor siz e ( P >0. 05).Expression of cyclin E and CDK-2 showed a positive linear cor relation( r =0. 451,P =0. 01).Protein levels of p57 (KIP2) were lower in gastric cancer tissues than in the normal mucosa ( P <0. 05).Decreased expr ession of p57 (KIP2) was correlated with lymph node involvement ( P <0. 05) .No statistically significant difference in p57 (KIP2) expression was found when sample were stratified according to tumor size, histological grade or sero sa invasion ( P >0. 05).In metastatic lymph nodes, expression of cyclin E wa s increased and the expression of p57 (KIP2) decreased. Conclusion Overexpressions of cyclin E, CDK-2 and downregulated expression of p57KIP2 may play important roles in tumorigenesis and metastatic potential of gastric cancer.     

p57kip2和cyclin E在人宫颈癌中的表达及其与临床病理及预后的关系

目的:探讨抑癌基因p57kip2和细胞周期素E(cyclin E)在宫颈癌发生发展中的作用及其与临床病理及预后的意义. 方法: 采用免疫组化二步法检测p57kip2和cyclin E在48例宫颈癌、13例宫颈上皮内瘤变(CIN)和15例正常宫颈组织中的表达. 结果: p57kip2在宫颈癌中的阳性表达率为21%,低于正常组(93%)和CIN组(77%),差异有显著性意义(P＜0.01). cyclin E在宫颈癌中的阳性表达率为77%,明显高于正常组(13%),差异有显著性意义(P＜0.01). 在宫颈癌组织中p57kip2和cyclin E的表达呈负相关(r=-0.597, P＜0.01). p57kip2的表达与病理分化程度及肿瘤直径有关(P均＜0.05);cyclin E的表达与病理分化程度及淋巴结转移有关(P＜0.01,P＜0.05). Kaplan-Meier单因素分析宫颈癌患者生存时间与p57kip2,cyclin E阳性表达有关(P＜0.01,P＜0.01). 结论: p57kip2的低表达或缺失和/或cyclin E的高表达可能在宫颈癌发生发展中起重要作用,与不良预后有关,两者在宫颈癌细胞周期调控中可能存在着负反馈调节机制.     

缺血性急性肾衰病程中cyclin E和CDK2的作用

目的：探讨cyclin E和周期素依赖性激酶2（CDK2）在缺血性急性肾衰大鼠肾组织中的表达及其与肾小管上皮细胞增殖之间的关系。方法：急性肾衰大鼠分别在第0、2、7、10、14天处死，取血测定肌酐值，免疫组化法观察肾细胞增殖程度以及cyclin E和CDK2的分布，蛋白印迹法检测肾组织中cyclin E和CDK2蛋白表达。结果：大鼠血清肌酐值在缺血再灌注第2天时显著增高，第7天时最高，第10天时开始降低，第14天时基本降至正常。对照组肾组织的细胞增殖指数（PI）为0.7%，肾缺血后第2、7、10和14天分别为14.8%、30.9%、23.6%和12.4%。Cyclin E和CDK2蛋白在肾组织内主要分布于肾小管，且第2天表达弱阳性，第7和10天表达分别为强阳性和阳性，第14天表达减弱；两种蛋白的水平与免疫组化结果一致。两种蛋白表达水平和PI之间均呈正相关。结论：缺血性急性肾衰大鼠肾小管上皮细胞增殖与肾组织cyclin E和CDK2表达上调密切相关。     

细胞周期蛋白E1基因表达上调与胃癌发生的关系

目的在基因和蛋白水平检测胃癌组织中细胞周期蛋白E1(CCNE1)的表达,研究其与临床病理参数的相关性,探讨其与胃癌发生发展之间的关系。方法通过Oncomine(肿瘤微阵列数据库)分析CCNE1在胃癌中的表达。采用SYBR Green实时荧光定量PCR技术检测34例配对样本中CCNE1的mRNA的表达水平。采用组织芯片/组织微阵列技术结合免疫组化方法检测CCNE1在34例配对样本中的蛋白表达情况。结果胃癌原发灶CCNE1 mRNA表达水平显著高于癌旁正常组织(P=0.001),在胃癌组织中CCNE1 mRNA表达水平在Ⅰ+Ⅱ期和Ⅲ+Ⅳ期均呈现显著上调(P=0.042,P=0.016)。在胃癌原发组织中CCNE1蛋白阳性表达率[41.2%(14/34)]显著高于癌旁正常组织[0(0/34)]及胃炎组织[0(0/34)],P0.01。CCNE1蛋白表达水平在不同分化程度、浸润深度及有无淋巴结转移肿瘤的表达不同,差异有统计学意义(P0.05)。结论 CCNE1表达上调可能与胃癌的发生、发展密切相关,提示CCNE1的检测可能为胃癌的诊断和预后提供参考。     

细胞周期相关蛋白cyclin E、cdk2和p27kip1在垂体腺瘤中的表达

目的 观察细胞周期相关蛋白cyclin E、cdk2和p27kip1在垂体腺瘤中的表达情况,探讨其与垂体腺瘤临床生物学行为的关系.方法 采用免疫组织化学SP法检测37例非侵袭性垂体腺瘤和21例侵袭性垂体腺瘤组织中cyclin E、cdk2和p27 kip1蛋白的表达情况.结果 在侵袭性垂体腺瘤中cyclin E和cdk2的表达明显高于非侵袭性垂体腺瘤(均P<0.01),p27kip1的表达明显低于非侵袭性垂体腺瘤(P<0.01);cyclin E与cdk2在垂体腺瘤中的表达呈正相关(r=1,P<0.01),两者与p27kip1的表达呈负相关(均r=-1,P<0.01);cyclin E和cdk2的表达与垂体腺瘤的侵袭性呈正相关(r=0.685,r=0.667,均P<0.01),而p27kip1的表达与垂体腺瘤的侵袭性呈负相关(r=0.659,P<0.01).结论 cyclin E、cdk2及p27kip1的表达情况可以作为判断垂体腺瘤的侵袭性和预后的指标.     

p57kip2和cyclin D2在人脑胶质瘤中的表达和临床意义

目的:探讨p57kip2蛋白和Cyclin D2蛋白在人脑胶质瘤中的表达情况及其临床意义.方法:采用免疫组织化学SP法检测p57kip2,Cyclin D2在55例人脑胶质瘤和10例正常脑组织中的表达.结果:在55例胶质瘤中,p57kip2蛋白阳性率为38.2%(21/55),低于正常脑组织(80%,P＜0.05).低度恶性(Ⅰ～Ⅱ级)与高度恶性(Ⅲ～Ⅳ级)间及不同生存时间组间阳性率差异有统计学意义(P＜0.05).Cyclin D2蛋白阳性率为52.7%(29/55),高于正常脑组织(0%,P＜0.01).脑胶质瘤不同恶性程度组间阳性率差异有统计学意义(P＜0.05),不同生存时间组间差异无统计学意义(P＞0.05).p57kip2蛋白的表达与Cyclin D2蛋白的表达无相关(P＞0.05).结论:p57kip2蛋白和Cyclin D2蛋白在脑胶质瘤的发生、发展中起重要作用.且与肿瘤的分化程度,预后相关.     

周期蛋白A、E在胃低分化腺癌中表达的研究

目的探讨胃低分化腺癌组织中细胞周期蛋白A(cyclin A)、周期蛋白E(cyclin E)的表达及其与胃癌临床病理因素的关系.方法用免疫组织化学方法检测了40例胃癌组织中cyclin A、cyclin E的表达.结果 40例胃低分化腺癌组织中cyclin A、cyclin E表达阳性率分别为37.5%(15/40)、45%(18/40);cyclin A的表达与肿瘤浸润深度相关;cyclin E的表达与肿瘤浸润深度、淋巴结转移及Roukos分型相关.cyclin A与cyclin E具有正性相关性.两种周期蛋白协同表达与淋巴结转移密切相关.结论cyclin A与cyclin E具有协同作用.cyclin E与胃低分化腺癌的预后密切相关.两种周期蛋白的共同表达更促进低分化腺癌淋巴道转移.     

Cyclin E,CDK2,Ki-67在白血病中的表达及其临床意义

目的:探讨白血病细胞周期素E(cyclin E)、细胞周期蛋白依赖性激酶2(CDK2)、细胞增殖相关抗原(Ki-67)在白血病中的表达及其临床意义.方法:应用免疫组织化学S-P法检测50例白血病病人骨髓(急性40例,慢性10例)cyclin E、CDK2和Ki-67的表达情况.结果:cyclin E阳性表达率38.0%,CDK2阳性表达率64.0%,均明显高于正常对照组(P＜0.05);Ki-67阳性表达率16.0%,与正常对照组比较无显著差异(P＞0.05).cyclin E表达与CDK2表达呈密切正相关(P＜0.05);CDK2表达与Ki-67表达密切正相关(P＜0.05).cyclin E和CDK2共同阳性表达者复发率明显增高.结论:cyciin E和CDK2的异常表达在白血病发生发展和复发过程中起重要作用,其表达水平对判断疾病的预后和疗效有一定价值.     

透明质酸结合蛋白对肿瘤细胞表达 cyclin E及p27kip1的影响

目的：研究透明质酸结合蛋白（HABP）对人乳腺癌、前列腺癌细胞和牛血管内皮细胞cyclinE及p27^kip1表达的影响。方法：将人脑透明质酸结合蛋白（hbHABP）全长cDNA转染到人乳腺癌细胞（MDA435）和前列腺癌细胞（TSU）中，研究细胞周期蛋白cyclinE及细胞周期蛋白依赖性激酶抑制物p27^kip1表达的变化。再将这些转基因细胞的培养上清液（CM）加入牛主动脉血管内皮细胞（ABAE）的培养上清液中，观察CM对ABAE的p27^kip1表达的影响。结果：MDA435和TSU细胞转染hbHABP基因后，cyclinE的表达水平均明显低于对照组细胞，而p27^kip1的表达水平均升高。ABAE细胞受CM作用后，p27^kip1的表达水平也高于对照组细胞。结论：hbHABP可能具有下调肿瘤细胞周期蛋白cyclinE和上调细胞周期蛋白依赖性激酶 抑制物p27^kip1的作用，从而抑制肿瘤细胞的生长；同时，hbHABP促进血管内皮细胞p27^kip1的表达，可以抑制肿瘤新生血管的形成。