急性白血病患者周期素D_1及其激酶抑制蛋白p15检测的意义

目的 :探讨细胞周期素 D1 及其激酶抑制蛋白 p15表达在急性白血病 (AL)中的临床意义。方法 :用间接免疫荧光标记流式细胞术研究 46例初治 AL 细胞治疗前后 D1 、p15、细胞周期及 DNA倍体与疗效间关系。结果 :2 8例急性髓系白血病 (AML)中 2 2例 p15阳性 ,6例阴性。 18例急性淋巴细胞白血病 (AL L)中 p15均阳性。AML与 AL L D1 均阳性。高 p15者 G1 期细胞百分率 (G1 % )增多 ,S期细胞百分率 (S% )减少。低 p15者 G1 %减少 ,S%增多。 DNA非整倍体者均高表达 p15和 D1 ,完全缓解率低 (30 % )。高 p15低 D1 者 2 0例中 18例 (80 % )完全缓解 (CR) ;低 p15高 D1 者 10例 ,8例 (80 % ) CR;高 p15高 D1 者 14例中 10例 (71.4% ) CR,低 p15低 D1 者 2例均 CR。结论 :p15和 D1 在 AL 中表达有异质性。高 p15者显示 G1 期阻滞 ,低 p15显示 G1 / S期转化 ,p15和 D1表达有助于指导治疗     

细胞周期蛋白依赖性激酶抑制蛋白与糖尿病和冠心病的相关性

近年来,随着糖尿病和冠心病的发病率逐渐增高,糖尿病患者的心血管疾病风险明显增加。冠心病的主要病变是动脉粥样硬化（AS）,AS进程的主要表现是血管内膜增生,其标志为动脉血管壁的炎症细胞浸润和血管平滑肌细胞（VSMCs）的异常增殖。由此推断,影响血管内皮细胞增殖过程和调节细胞周期的遗传因素可能会对AS过程产生影响,如目前的研究热点细胞周期蛋白依赖性激酶抑制蛋白（CDKIs）及其成员2A／2B（CDKN2A／2B）。     

正肝方对大鼠癌前病变肝组织细胞周期蛋白D1及依赖性激酶4的影响

[目的]观察正肝方对黄曲霉毒素B1（AFB1）诱发的大鼠癌前病变肝组织细胞周期蛋白D1（Cyclin D1）、细胞周期蛋白依赖性激酶4（CDK4）的影响。[方法]Wistar大鼠100只随机分为4组：模型、正肝方小剂量、正肝方大剂量组各30只、正常组10只。除正常组外,先后用AFB1和2-乙酰氨基芴（2-AAF）处理各组大鼠造模。正肝方大、小剂量组在造模期间,将正肝方水剂（0.6、0.3 g/ml）按10 ml/kg分别灌胃;模型组用无菌蒸馏水按10 ml/kg灌胃。8周后处死大鼠,肝组织取材。分别采用免疫组化法和RT-PCR法,检测大鼠肝组织中Cyclin D1、CDK4蛋白和mRNA表达。[结果]模型组Cyclin D1、CDK4染色阳性细胞百分率（LI）和表达强度（PU）最高,Cyclin D1、CDK4mRNA表达水平也最高（P〈0.01）。正肝方能降低大鼠癌前病变肝组织Cyclin D1、CDK4蛋白和mRNA的异常高表达（P〈0.01或〈0.05）,且呈现出一定的量效关系。[结论]正肝方能通过下调Cyclin D1、CDK4异常表达,改善细胞周期G1~S期调控点失控,从而减缓肝细胞异常增生。     

循环细胞周期蛋白依赖性激酶抑制因子1C mRNA对女性急性心肌梗死患者经皮冠状动脉介入术后心功能的预测价值

目的 分析细胞周期蛋白依赖性激酶抑制因子1C(CDKN1C)mRNA对女性急性心肌梗死（AMI）患者行经皮冠状动脉介入（PCI）术后心功能的预测价值。方法 选取2018年1月至2020年1月遂宁市中心医院急诊PCI的AMI患者198例,术后1 d检测N末端脑钠肽前体（NT-proBNP）和CDKN1C mRNA水平,术后4个月通过超声心动图检测心功能,根据左心室射血分数（LVEF）分为三组：A组（LVEF≥50%）112例;B组（40%≤LVEF <50%）54例;C组（LVEF <40%）32例。通过ROC曲线分析不同性别患者CDKN1C mRNA与NT-proBNP水平对心功能的预测价值。结果 A组CDKN1C mRNA水平高于B组和C组（F=6.831,P <0.05）,A组NT-proBNP水平低于B组和C组（F=3.421,P <0.05）。A组女性患者CDKN1C mRNA水平高于B组和C组女性患者（F=6.717,P <0.05）。CDKN1C mRNA的AUC为0.805(95%CI=0.732～0.864),预测价值优于NT-pro BN...     

Cyclin D1、P53和CDK4蛋白与胰腺癌的相关性

目的:研究细胞周期蛋白D1(Cyclin D1)、P53蛋白和细胞周期蛋白依赖性激酶4(CDK4)在胰腺癌中的表达差异,阐明其与胰腺癌的相关性.方法:兰州大学第一医院和定西地区医院1997-07/2004-01手术切除胰腺癌患者48例,术后标本均经病理证实.采用免疫组化SP法检测Cyclin D1、P53和CDK4在胰腺癌患者不同临床指标下的表达水平.结果:胰腺癌不同性别、年龄分组中CyclinD1、P53与CDK4的阳性表达率均无显著差异.在低分化、有淋巴结转移、临床分期Ⅲ,Ⅳ期的胰腺癌组织中Cyclin D1和CDK4的阳性表达率明显高于高分化、无淋巴结转移、临床分期Ⅰ,Ⅱ期的胰腺癌中的阳性表达率(Cyclin D1:χ2=10.540,14.225,5.043,P<0.01或0.05;CDK4:χ2=7.619,4.006,5.581,P<0.05).有淋巴转移的胰腺癌组织中P53的阳性表达率明显高于无淋巴转移的组中的阳性表达率(χ2=6.146,P<0.05);而不同分化程度和临床分期的胰腺癌组织中P53的表达无明显的差异性.结论:Cyclin D1可以作为早期诊断胰腺癌的生物学指标,而P53和CDK4在胰腺癌的发生、发展过程中起重要的协同作用.     

番茄红素上调细胞周期素依赖性激酶4和细胞周期素D1的表达促进人外周血内皮祖细胞周期进展

目的探讨番茄红素对人外周血内皮祖细胞活性、周期调控的作用及其分子机制。方法体外原代培养人外周血内皮祖细胞,采用噻唑蓝法、流式细胞仪、逆转录聚合酶链反应、实时聚合酶链反应和Western blot方法检测番茄红素对内皮祖细胞活性、细胞周期分布的影响及细胞周期相关蛋白细胞周期素依赖性激酶4和细胞周期素D1的表达情况。结果噻唑蓝比色实验显示,不同浓度(0.01、0.1、1μmol/L)番茄红素能显著增加内皮祖细胞的生长能力,且呈一定的量效与时效关系;流式细胞仪分析显示,番茄红素呈浓度依赖性使内皮祖细胞的G0/G1期细胞比例减少,S期细胞比例增多;逆转录聚合酶链反应、实时聚合酶链反应和Western blot分析表明,番茄红素呈浓度依赖性使内皮祖细胞中细胞周期素依赖性激酶4和细胞周期素D1表达上调。结论番茄红素对内皮祖细胞的促进生长作用,可能与上调细胞周期素依赖性激酶4、细胞周期素D1的表达,使G0/G1期细胞比例减少有关。     

急性白血病患者细胞周期蛋白E及依赖激酶抑制剂表达的意义

目的：探讨细胞周期蛋白E（cyclin E)、细胞周期蛋白依赖激酶抑制剂（p27KIP1)对成人初治急性白血病（AL）发展及预后的作用。方法：用流式细胞术检测60例AL及17例对照cyclin E、p27 KIP1、多药耐药基因蛋白p170表达及细胞周期分布;逆转录－聚合酶链反应检测46例成人AL患者及17例对照的骨髓cyclin E、p27KIP1、多药耐药蛋白的mRNA水平。结果：60例AL患者全周期及G2／M期cyclinE表达均高于对照组（＜0．01或0．05）;p27KIP1全周期表达亦均高于对照组,但G2／M期差异无显著性（P＞0．05）;cyclinE与p27KIP1的表达呈正相关;AL患者cyclin E高表达组缓解率（44．8％）低于正常表达组（77．4％）（P＜0．01）;复发率（92．3％）高于正常表达组（41．7％）（P＝0．003;p27KIP1表达对AL缓解率、复发率的影响无统计学意义（P＞0．05,P＝0．89）。结论：cyclinE在成人AL有异常高表达,并可能促使AL的发展,是AL缓解率、复发率的重要危险因素。     

CKS1和Cyclin D1在老年肝细胞癌中的表达

肝细胞癌(HCC)是最常见的肝脏原发恶性肿瘤,尽管手术切除和肝移植已经显著改善小肝癌及无转移肝癌患者的生存时间,但是晚期肝癌患者的预后仍然较差[1].细胞周期蛋白依赖性激酶调节亚基1(CKS1)是高度保守的细胞周期调节蛋白SUC1/CKS蛋白家族成员之一[2],在胃癌、乳腺癌和肝癌等多种肿瘤组织中高表达[3,4].细胞周期蛋白D1(Cyclin D1)在乳腺癌、结肠癌和肝癌组织中表达升高,其表达失调会导致细胞周期异常从而促进肿瘤发生[5].本研究分析CKS1和Cyclin D1蛋白在HCC及对应癌旁组织中的表达水平及其与临床病理特征之间的相关性.     

蛙皮素对人胰腺癌细胞系CFPAC-1细胞周期蛋白D1/细胞周期蛋白依赖性激酶4的影响

背景:胃肠激素蛙皮素作为一种强有力的有丝分裂原,能刺激多种正常和肿瘤组织生长。目的:探讨蛙皮素对人胰腺癌细胞系CFPAC-1的促生长作用及其对细胞周期调控因子细胞周期蛋白(cyelin)D_1和细胞周期蛋白依赖性激酶(CDK)4的调节作用,以及蛙皮素促生长作用的机制。方法:用四唑蓝(MTT)比色法作为增殖指标,研究蛙皮素对CFPAC-1细胞生长的影响。用流式细胞仪观察蛙皮素对CFPAC-1细胞cyclin D_1表达的影响。用Western印迹和增强化学发光法(ECL)自显影观察蛙皮素对CFPAC-1细胞CDK4蛋白表达的影响。结果:一定浓度的蛙皮素对CFPAC-1细胞的生长具有促进作用,以1×10~(-10)mol/L蛙皮素的促生长作用最为明显(MTT OD_(570nm):蛙皮素1×10~(-10)mol/L组和对照组分别为0.652±0.155和0.359±0.109,n=3,P=0.002)。流式细胞仪检测发现,1×10~(-10)mol/L蛙皮素作用30min对CFPAC-1细胞cyclin D_1的表达有促进作用,但无显著统计学差异(P>0.05)。Western印迹和ECL自显影结果表明,1×10~(-10)mol/L蛙皮素作用15min可使CFPAC-1细胞CDK4蛋白表达升高,而后逐渐下降。结论:蛙皮素对CFPAC-1细胞的促生长作用部分是通过蛙皮素介导的细胞周期调控因子cyclin D_1/CDK4蛋白表达升高,从而促进细胞周期进展而实现的。     

端粒酶和细胞周期蛋白依赖激酶抑制蛋白与肾上腺肿瘤

临床上肾上腺肿瘤的良、恶性难以鉴别,缺乏早期诊断依据,给临床治疗带来一定困难。端粒酶是由蛋白质和RNA构成的逆转录酶,与细胞周期、衰老、凋亡和永生化密切相关,恶性肿瘤中端粒酶激活而使细胞获得永生化。细胞周期蛋白依赖激酶抑制在蛋白细胞周期调控网络中发挥负调节作用,而细胞周期调控网络的异常与肿瘤的发生发展密切相关。目前研究提示二者在肾上腺肿瘤中的表达均有异常,可能联合参与肾上腺肿瘤的发生、发展,为肾上腺肿瘤的诊断和治疗提供依据。     

采用组织芯片技术探讨p16和cyclin D1在胆囊癌中的表达及临床意义

目的探讨多肿瘤抑制蛋白（p16）和细胞周期蛋白（cyclin D1）的表达在胆囊癌发生发展中的作用及其对预后的影响,研究应用组织芯片在大规模高效检测临床组织样本的可行性。方法取40例胆囊癌、24例胆囊良性病变和16例癌旁黏膜标本,采用组织芯片技术制作成组织芯片,同时用S-P免疫组织化学方法检测组织芯片中p16和cyclinD1的表达。结果p16和cyclin D1在胆囊癌中的阳性表达率分别为40.0（和57.5（,与胆囊良性病变（75.0（,29.2（）和癌旁黏膜（93.8（,12.5（）相比有显著性差异（P〈0.005）。p16的低表达和cyclin D1的高表达与胆囊癌的分化程度（P（0.025,P〈0.01）、浸润深度（P〈0.01,P〈0.025）、淋巴结转移（P〈0.01,P〈0.01）以及患者的5年生存率（P〈0.025,P〈0.05）密切相关。p16和cyclinD1在胆囊癌中的表达呈负相关（r=-0.54）。结论p16和cyclin D1的异常表达在胆囊癌的发生、发展过程中起重要作用。p16和cyclin D1的表达水平可以作为评估胆囊癌预后的参考指标。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。     

Cyclin B1、CDK1在食管鳞癌组织中的表达及临床意义

目的: 探讨食管鳞癌组织中细胞周期蛋白Cyclin B1和细胞周期蛋白依赖性激酶CDK1表达及其临床病理学意义.方法: 应用免疫组织化学SP法对52例食管鳞癌(组织学Ⅰ级8例, Ⅱ级20例, Ⅲ级24例;有淋巴结转移20例, 无淋巴结转移32例;原位癌16例, 侵袭性癌36例包括浸润至黏膜下层、肌层、全层)及其配对的癌旁正常组织进行Cyclin B1、CDK1的检测, 分析其阳性表达与食管鳞癌患者临床病理因素的关系.结果: 食管鳞癌组织中Cyclin B1、CDK1的阳性表达高于癌旁正常食管黏膜组织, 2组差异都有统计学意义(71.2% vs 2.0%, 65.4%vs 3.9%, 均P <0.05). 食管鳞癌组织中CyclinB1、CDK1的表达都与性别、年龄无关;与组织学分级、浸润深度及淋巴结转移有关(均P <0.05). Cyclin B1阳性表达强度与CDK1的阳性表达强度之间呈正相关(r = 0.697, P <0.05) .结论: Cyclin B1、CDK1的高表达会促进食管鳞癌的发生与发展. 而且食管鳞癌中CyclinB1与CDK1的表达密切相关, 可作为食管鳞癌生物学行为预测的参考指标.     

Ethanol reduces p38 kinase activation and cyclin D1 protein expression after partial hepatectomy in rats

BACKGROUND/AIMS: Chronic ethanol consumption inhibits liver regeneration. We examined the effects of chronic ethanol consumption on two mitogen-activated protein kinases in relation to induction of cell cycle proteins after partial hepatectomy (PH). METHODS: Male Wistar rats were ethanol-fed (EF) or pair-fed (PF) for 16 weeks before PH. Hepatic activation of extracellular signal regulated kinase (ERK)1/2, p38 kinase and expression of cyclinD1, cyclin-dependent kinase-4 (cdk4) and proliferating cell nuclear antigen (PCNA) were studied. RESULTS: In PF rats, PH-induced p38 activation was evident at 2h and was maximal at 12h. There was a close temporal relationship between p38 activation, cyclin D1 and PCNA expression. Alcohol exposure reduced p38 activation, cyclin D1 and PCNA, each by approximately 50%. ERK1/2 activation occurred during the first 2h post-PH in both EF and PF rats, and there was no later increase in PF rats. In vivo inhibition of p38 suppressed PCNA expression whereas the effect of ERK1/2 inhibition was inconsistent. CONCLUSIONS: p38 kinase activation is linked temporally with cyclin D1 expression after PH and appears to exert cell cycle control in the adult liver. p38 signaling also appears to be a target for the inhibitory effect of chronic alcohol on liver regeneration.     

Cyclin D1 expression in acute leukemia

Background: Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the involvement of cyclin D1 in acute leukemia.

Patients and methods: In this study, we analyzed the expression of cyclin D1 at protein level in, 40 newly diagnosed patients with acute myeloid leukemia (AML), 10 patients with acute lymphoblastic leukemia (ALL), and 11 normal controls using flow cytometry.

Results: The expression of cyclin D1 was not significantly different in AML group as compared to normal controls. On the other hand, over expression of cyclin D1 was evident in ALL group (4/10) as compared to that in healthy control. The ALL cases with cyclin D1 over expression were significantly correlated to blast cell counts in the peripheral blood and bone marrow (BM) but not with hemoglobin level, WBC, and platelets count. The ALL group with lymphadenopathy and organomegaly express significantly higher cyclin D1 over expression as compared to those without.

Conclusion: The biological value of cyclin D1 over expression might be different in AML and ALL.     

Cyclin D1 expression in acute leukemia

BACKGROUND: Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the involvement of cyclin D1 in acute leukemia. PATIENTS AND METHODS: In this study, we analyzed the expression of cyclin D1 at protein level in, 40 newly diagnosed patients with acute myeloid leukemia (AML), 10 patients with acute lymphoblastic leukemia (ALL), and 11 normal controls using flow cytometry. RESULTS: The expression of cyclin D1 was not significantly different in AML group as compared to normal controls. On the other hand, over expression of cyclin D1 was evident in ALL group (4/10) as compared to that in healthy control. The ALL cases with cyclin D1 over expression were significantly correlated to blast cell counts in the peripheral blood and bone marrow (BM) but not with hemoglobin level, WBC, and platelets count. The ALL group with lymphadenopathy and organomegaly express significantly higher cyclin D1 over expression as compared to those without. CONCLUSION: The biological value of cyclin D1 over expression might be different in AML and ALL.     

Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance

AIM: To detect the genetic alteration and abnormal expression of cyclin D1 in gastric carcinoma and investigate its clinicopathologic significance in advanced gastric carcinoma. METHODS: Proteins of cyclin D1 were detected by immunohistochemistry in 42 cases of advanced gastric carcinoma with their follow-up data available, 27 cases of early stage carcinoma, 21 cases of gastric adenoma, 22 cases of hyperplastic polyp and 20 cases of normal mucosa adjacent to adenocarcinomas. Genetic alteration of cyclin D1 was detected by Southern blot and expression of cyclin D1 mRNA was detected by PT-PCR in 42 cases of advanced gastric carcinoma. RESULTS: Cyclin D1 protein was not expressed in normal mucosa, hyperplastic polyp and gastric adenoma, while it was only positively expressed in gastric carcinoma. The expression rate of cyclin D1 protein in early stage gastric carcinoma, advanced gastric carcinoma and lymph node metastasis was 48.1%, 47.4% and 50.0%, respectively. The amplification of cyclin D1 gene was detected in 16.6% of advanced gastric carcinomas. The overexpression of cyclin D1 mRNA was detected in 40.5% of the samples. There was no significant correlation between cyclin D1 protein expression and age, lymph-node metastasis and histological grading in patients with advanced gastric carcinoma (chi2 = 0.038, 0.059, 0.241, P>0.05). Significant correlation was observed between the expression of cyclin D1 protein and the 5-year survival rate (chi2 = 3.92, P<0.05). CONCLUSION: Detection of cyclin D1 protein by immunohistochemistry may be useful in the diagnosis of early gastric carcinomas. Patients with positive expression of cyclin D1 protein tend to have a worse prognosis.     

Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus

OBJECTIVE: The roles of cyclins and cyclin dependent kinase (CDK) inhibitors of lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE) are unclear. We measured the expression of cyclin B1 and CDK inhibitor p21 in peripheral blood lymphocytes (PBL) from patients with SLE and controls. METHODS: PBL from 40 SLE patients with renal disease (RSLE), 40 SLE patients without renal disease (SLE), and 28 healthy control subjects were cultured with phytohemagglutinin (PHA). Bivariate distribution of cyclin B1 or p21 expression versus cellular DNA content was assessed by flow cytometry. RESULTS: Expression of p21 in lymphocytes was significantly lower in patients with RSLE and with SLE than controls (RSLE vs controls and SLE vs controls, both p < 0.001). Expression of cyclin B1 was similar in all groups. The percentages of RSLE lymphocytes in G0/G1 and S phase were significantly reduced and elevated, respectively, compared with controls. CONCLUSION: Downregulated p21 in PHA stimulated PBL from patients with SLE may be closely related to aberration of cell division in SLE lymphocytes.