Bcl-1 Rearrangement and Cyclin D1 Protein Expression in Multiple Myeloma Precursor Cells

The rearrangement of Bcl-1 gene (Bcl-1/IgH rearrangement) and expression of cyclin D1 in multiple myeloma (MM) precursor cells were studied and the role of cyclin D1 in the pathogenesis of MM was investigated. The BCL-1 rearrangement and cyclin D1 protein expression in 15 cases of MM were detected. By using hemi-nested polymerase chain reaction (PCR) the genomic DNA from fresh peripheral blood and bone marrow was amplified and the expression of cyclin D1 in the smears was detected by using immunohistochemical method. Ten volunteer with normal bone marrow served as control group. The results showed Bcl-1 rearrangement was detectable in 3/15 (20 %) MM patients and cyclin D, expression in 4/15 (27 % ) MM patients. BeLl-1 rearrangement and cyclin D1 protein expression were also detected in MM precursor cells. No overexpression of cyclin D1 or the rearrangement of the BeL-1 gene was found in the 10 volunteers. It was concluded that Bel-1 rearrangement and cyclin D1 protein overexpression were detected in MM precursor cells, speculating that overexpression of cyclin D1 protein may play an initial (critical) role in the pathogenesis of MM.

EXPRESSION OF p16,CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene have some value to the diagnosis at earlier stage of gastric cancer. Detection of expression of p16, cyclin D1 gene would be helpful to judge the prognosis of gastric cancer.

膀胱移行细胞癌p^(16)、cyclin D_1蛋白免疫组织化学研究

目的 : 探讨p16、cyclinD1蛋白表达与膀胱移行细胞癌 (TCC)生物学行为的关系。方法 用免疫组化SP法检测 48例膀胱TCC组织中p16、cyclinD1蛋白的表达。结果 膀胱TCC组织中p16蛋白阳性表达率为 45 .8% ,与癌组织病理分级、临床分期密切相关 ,高分化、浅表性癌组织中p16蛋白阳性表达明显高于低分化、浸润性癌组织 (P <0 .0 5 )。cyclinD1蛋白阳性表达率为 6 2 .5 % ,浸润性癌组织阳性率明显高于浅表性癌组织 (P <0 .0 5 ) ,与癌组织病理分级无关。p16和cyclinD1蛋白表达呈负相关 (P <0 .0 1)。

The expressions of Pin1, β-catenin and cyclin D1 in elderly lung carcinomas and their significance

Objective： To investigate the expressions and correlations of Pin1, β-catenin and cyclin D1 in elderly lung carcinomas. Methods： The expressions of Pin1, β-catenin and cyclin D1 were examined in the specimens of 92 elderly lung carcinomas and 10 normal lung tissues by immunohistochemistry and explored the relationship between the expression levels and clinicopathological factors. Results： （1） The overexpression of Pin1 and cyclin D1 in lung carcinomas was 46 （50%） cases and 60 （65.22%） cases respectively and 56 （60.82%） cases showed positive immunoreactivity for 13-catenin in the nuclear and （or） cytoplasmic fraction in tumor tissues. In normal tissue, the expressions of Pin1 and cyclin D1 were negative, the expression of β-catenin was lied in cell membrane. （2） In lung carcinomas the expressions of Pin1, β-catenin and cyclin D1 correlated with tumor differentiation （P 〈 0.05）. The pesitive expression rate and intensity of Pin1 correlated with tumor stage （P = 0.032） and lymph node positive disease （P = 0.041）. The expression of β-catenin correlated with lymph node positive disease （P = 0.012）. （3） High expression levels of Pin1 correlated with aberrant I]-catenin expression （P = 0.000） but did not show a correlation with cyclin D1 （P = 0.157）. Conclusion： In elderly lung carcinomas, the positive expression of Pin1 causes abnormal accumulation of β-catenin and actives its target gene, however, this target gene was not cyclin DI. The detection of Pin1 expression had some clinical significance in estimating prognosis of elderly patient with lung carcinomas.

大肠癌p16、cyclin D_1表达及其临床病理意义

采用免疫组化中的 S- P法检测 6 7例大肠癌中 p16、cyclin D1 的表达。结果大肠癌 p16、cyclin D1 的阳性表达率分别为 47.8%和 44 .8% ,高分化癌 p16阳性率明显高于低分化癌 (P<0 .0 5 ) ,而低分化癌 cyclin D1 过表达率高于高分化癌 (P<0 .0 5 ) ;淋巴结转移阳性组的 p16阳性率低于淋巴结转移阴性组 ,而淋巴结转移阳性组 cyclin D1 过表达率高于淋巴结转移阴性组 (P<0 .0 5 )。相关分析表明 ,在大肠癌中 p16与 cyclin D1 呈负相关。提示 p16基因失表达和cyclin D1 过表达与大肠癌的分化程度和淋巴结转移有关 ,其在大肠癌中的反向表达支持两者之间可能存在相互抑制机制。

THE OVEREXPRESSION AND SIGNIFICANCE OF CYCLIN D1 AND P53 IN CERVICAL SQUAMOUS CELL CARCINOMAS

Objective To investigate the significance of overexpresson of cyclin D1 and P53 protein in cervical squamous cell carcinomas.Methods Fifty cases of invasive cervical squamous cell carcinomas and 10 cases of normal cervical squamous epithelia were investigated with immunihistochemical technique. Results The overexpression of cyclin D1 and P53 in invasive cervical carcinomas was 70% and 50%, respectively. There was no overexpression of them in the control group. The overexpression of cyclin D1 in grade Ⅱ and Ⅲ was much higher than that in gradeⅠ(P<0.05). The overexpresson of cyclin D1 in stage Ⅲ of cervical carcinoma was significantly higher than that in stage Ⅱ (P<0.05). The overexpression of P53 in grade Ⅱ and grade Ⅲ of cervical carcinoma was remarkably higher than that in grade Ⅰ (P<0.05).Conclusion The action point of both cyclin D1 and P53 may be at G1/S transition. The overexpression of them was associated with development and progression of cervical carcinoma probably in different mechanisms and different pathways.

BCL-1 Rearrangement in Acute Lymphocytic Leukemia and Its Clinical Significance

BCL 1 rearrangement (BCL 1/IgH gene rearrangement) in acute lymphocytic leukemia and its clinical significance was investigated. In 38 patients with acute lymphocytic leukemia (ALL), the genomic DNA of mononuclear cells isolated from peripheral blood and bone marrow was amplified by using hemi nested polymerase chain reaction (PCR) technique and the expression of cycline D1 protein of mononuclear cells was detected by using immunohistochemical method. Ten patients with acute granulocytic leukemia, 2 with chronic granulocytic leukemia and 10 with normal bone marrow served as control group. The results showed that BCL 1 rearrangement was detectable in 3 of 38 ALL patients (7.9 %) and cyclin D1 protein positive expression was detected in 4 ALL patients (10 5 %). Three ALL patients with BCL 1 rearrangement were all B cell leukemia (B ALL) and accompanied by cyclin D1 protein expression. No BCL 1/IgH rearrangement or cyclin D1 protein expression was detected in 12 patients with granulocytic leukemia and 10 cases of normal bone marrow. Leukocyte counts in peripheral blood of B ALL patients with BCL 1 rearrangement and(or) cyclin D1 protein expression were significantly increased and the patients had bad reaction to chemotherapy. It was concluded that: 1) BCL 1/IgH gene rearrangement were detected in acute B lymphocytic leukemia; 2) B ALL patients with BCL 1 rearrangement and(or) cyclin D1 protein expression had poor prognosis.

Effect of Combination Regimen of Low-dose Gossypol Acetic Acid with Steroid Hormones on Expression of Protein Kinase C alpha (PKC-α) and Cyclin D1 in Rat Testes

Objective To investigate the contraceptive mechanism of combination regimen of low- dose gossypol acetic acid （GA） with steroid hormones [desogestre/ethinylestradiol/ testosterone undeeanote（DSG/EE/TU）]. Methods Adult male rats were randomly divided into four groups. Group GH： rats were fed orally with gossypol acetic acid （GA, 12.5 mg/kg） and desogestrel （DSG, 0.125 mg/kg）/ ethinylestradiol （EE, 0.025 mg/kg）/testosterone undecanoate （TU, 100 mg/kg per day, qd X4 weeks or 10 weeks）; group G： a single dose of GA （12.5 mg/kg per day, qd X 4 weeks or I0 weeks）; group H： the same dosage of DSG/EE/TUas in group GH; group C： rats were treated with vehicle （1% methyl cellulose） as the control. Expression of protein kinase C alpha （PKC-a） and cyclin D1 in rat testes were tested mainly by immunohistochemistry （IHC） and Western blotting. Results IHC results showed that protein PKC- a was expressed mainly in interstitial tissue of testis among seminiferous tubule. The expression of PKC-oc in groups H and GH at week 10 was decreased greatly compared with that in group C. The protein cyclin D1 was expressed mainly in residual body of seminiferous tubule eavosurface and interstitial tissue among seminiferous tubule of testis. Western blotting results showed that the expression of PKC-a in groups H and GH at week 10 was decreased significantly compared with that in group C （P〈0.05）. The expression of cyclin D1 in groups G, H or GH at week 10 rose significantly compared with that in group C （P 〈0.05）.Conclusion The administration of low-dose gossypol acetic acid with steroid hormones for 10 weeks can decrease the expression of PKC-a greatly.

Cyclin D1在不同分子亚型乳腺癌中的表达及其对预后的影响

目的检测cyclin D1在不同分子亚型乳腺癌中的表达,分析其表达与临床病理特征和预后的关系。方法采用免疫组织化学法检测175例乳腺癌组织标本中cyclin D1的表达情况,应用卡方检验分析cyclin D1在不同分子亚型乳腺癌中的表达,采用Spearman秩相关方法分析cyclin D1表达与临床病理特征的相关性,运用Kaplan-Meier生存曲线分析cyclin D1不同表达对预后的影响。结果①Cyclin D1阳性表达在Luminal A型所占比例最高(P<0.05),而cyclin D1阴性表达在Luminal B型所占比例最高(P<0.05)。②Cyclin D1阳性表达与临床分期、组织学分级及PR无关(P>0.05),与淋巴结转移数目(rs=0.197,P<0.01)、ER呈正相关(rs=0.139,P<0.05);cyclin D1阳性表达与Her-2呈负相关(rs=-0.131,P<0.05)。③Cyclin D1阳性表达越强,无瘤生存时间越长(P<0.05)。结论 Cyclin D1阳性表达与ER、Her-2及淋巴结转移数目有明显相关性,且其阳性表达提示相对良好的预后,可作为乳腺癌预后评估的参考指标。

喉鳞癌端粒酶活性与细胞周期蛋白D_1的表达及其意义

目的 :了解喉鳞癌端粒酶活性的表达情况及其与细胞周期蛋白D1(cyclinD1)过度表达的关系。方法 :分别应用TRAP法和免疫组化法对 38例喉鳞癌组织及相关喉粘膜组织的端粒酶活性和cyclinD1的表达情况进行检测。结果 :喉鳞癌病例中 82 % (31/ 38)有端粒酶活性表达 ,5 0 % (19/ 38)有cyclinD1过度表达 ;两者表达均与患者的年龄、肿瘤部位、T分期、病理学分级无关 (P >0 .0 5 ) ,而端粒酶表达与肿瘤的临床分期有关 (P <0 .0 5 ) ,cyclinD1表达与肿瘤的临床分期无关 (P >0 .0 5 ) ,喉正常粘膜中两者均无表达 ;喉鳞癌组织中两者均表达 18例 ,两者密切相关 (P <0 .0 5 )。结论 :端粒酶的激活在喉鳞癌组织中普遍存在 ,cyclinD1过度表达可能是喉鳞癌端粒酶激活的重要机制之一。

急性髓系白血病患者hDMP1表达特点及临床意义

目的探讨人类细胞周期调节蛋白依赖性Myb样蛋白1(hDMP1)在急性髓系白血病(AML)中的表达及其临床意义。方法 93例初诊AML患者及19例健康志愿者(对照组)骨髓标本,以β胆色原脱氢酶(GAPDH)表达水平为内参,应用实时定量RT-PCR方法检测hDMP1及肾母细胞瘤基因(WT1)的表达水平。分析hDMP1表达水平与患者临床资料、染色体核型的关系。结果AML患者骨髓细胞中hDMP1在表达水平较对照组显著降低(476.6vs.2103.0)(P<0.01),WT1基因表达水平较对照组显著升高(202.6vs.1.2)(P<0.01)。hDMP1和WT1基因表达水平与患者性别、年龄、有无肝脾淋巴结肿大、起病时外周血WBC计数、骨髓中原始细胞比例、AML亚型、染色体核型分组无关。结论 AML患者hDMP1的低表达伴随WT1基因高表达,两者均参与AML发病。