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医学临床研究 2006年第5期23卷 682-684页

作者：罗小中倪江东中南大学湘雅二医院骨科湖南长沙410011

【目的】研究骨肉瘤组织中基质金属蛋白酶-9(MMP-9)和增殖细胞核抗原(PCNA)的表达及两者的相关性及临床意义。【方法】对54例骨肉瘤组织和20例正常骨组织进行MMP-9和PCNA免疫组化染色。【结果】两者在骨肉瘤组织中的阳性表达明显高于正... 详细信息

【目的】研究骨肉瘤组织中基质金属蛋白酶-9(MMP-9)和增殖细胞核抗原(PCNA)的表达及两者的相关性及临床意义。【方法】对54例骨肉瘤组织和20例正常骨组织进行MMP-9和PCNA免疫组化染色。【结果】两者在骨肉瘤组织中的阳性表达明显高于正常组骨组织,且呈正相关(P<0.05);MMP-9在骨肉瘤组织中的表达与其临床分期无明显相关性;而与骨肉瘤侵袭软组织及预后有显著相关性。PCNA在骨肉瘤组织中的表达与其临床分期和预后有相关性。【结论】MMP-9和PCNA在骨肉瘤组织的表达明显上调;MMP-9与骨肉瘤的侵袭、转移有关,可作为预测转移潜能的指标。PCNA可作为骨肉瘤增殖的一个指标。

关键词：骨肉瘤/病理学金属蛋白酶类/分析增殖细胞核抗原/分析

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PCNA、MMP-2在小儿颈部囊状淋巴管瘤中的表达及意义

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临床小儿外科杂志 2005年第1期4卷 37-39页

作者：吴平辉吴江黄庆荣曹闯吴德庆吴绍文广东医学院附属医院小儿外科广东湛江524001 廉江市人民医院广东廉江524400

目的探讨小儿颈部囊状淋巴管瘤的发病机制及小儿颈部囊状淋巴管瘤的病理性质,为临床治疗方案提供一定的指导。方法在68例小儿颈部囊状淋巴管瘤组织中应用免疫组化法(S-P法)检测PCNA、MMP-2的阳性表达情况,并以20例大月份引产胎儿的胸导... 详细信息

目的探讨小儿颈部囊状淋巴管瘤的发病机制及小儿颈部囊状淋巴管瘤的病理性质,为临床治疗方案提供一定的指导。方法在68例小儿颈部囊状淋巴管瘤组织中应用免疫组化法(S-P法)检测PCNA、MMP-2的阳性表达情况,并以20例大月份引产胎儿的胸导管作为正常淋巴管组织对照。结果PCNA、MMP-2在小儿颈部囊状淋巴管瘤中阳性表达率分别为17.6%、8.8%,与正常淋巴管组织阳性表达差异无统计学意义(各组P值均>0.05)。结论小儿颈部囊状淋巴结瘤可能是一种淋巴管畸形而非真性肿瘤。

关键词：囊状淋巴管瘤/病理学头颈部肿瘤/病理学增殖细胞核抗原/分析金属蛋白酶类/分析

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增殖细胞核抗原及p53蛋白在颌面部肿瘤中的表达

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中国误诊学杂志 2004年第7期4卷 985-987页

作者：刘莹吕玉波刘玉胜刘宏伟王家耀山东省立医院病理科济南250021 山东省医学影像学研究所山东省济南市第四人民医院内科

目的 :探讨增殖细胞核抗原 (PCNA)和 p5 3蛋白在颌面部肿瘤中的表达及其相互联系。方法 :对 6 5例手术切除的颌面部肿瘤组织标本进行免疫组化染色。结果 :恶性肿瘤的 PCNA和 p5 3表达均高于良性肿瘤 ,其χ2 值分别为2 1.89,17.4 5 ,P<... 详细信息

目的 :探讨增殖细胞核抗原 (PCNA)和 p5 3蛋白在颌面部肿瘤中的表达及其相互联系。方法 :对 6 5例手术切除的颌面部肿瘤组织标本进行免疫组化染色。结果 :恶性肿瘤的 PCNA和 p5 3表达均高于良性肿瘤 ,其χ2 值分别为2 1.89,17.4 5 ,P<0 .0 5 ,且都随恶性程度的增高而增高 ,其χ2 值分别为 10 .16 ,13.73,P<0 .0 5 ,淋巴结转移与 PCNA和p5 3蛋白表达之间均有明显相关性 ,其χ2 值分别为 19.2 4 ,2 6 .4 1,P<0 .0 5。 PCNA与 p5 3蛋白表达之间有明显相关性 ,其χ2 值为 2 0 .82 ,P<0 .0 5。结论 :联合检测 PCNA及 p5 3蛋白对颌面部肿瘤的诊断及预后有重大意义。

关键词：颌肿瘤/诊断增殖细胞核抗原/分析蛋白质p53/分析免疫组织化学

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人骨肉瘤中Bcl-2和PCNA的表达

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中国误诊学杂志 2004年第8期4卷 1179-1181页

作者：张广泉赵炬才郑稼李文辉罗建平刘正国河南省人民医院骨科研究所 450003 郑州大学一附院骨科 450052 河南省人民医院病理科 450003

目的 :研究骨肉瘤中 Bcl- 2和 PCNA表达的生物学意义。方法 :用免疫组织化学 S- P法 ,研究 30例骨肉瘤和 15例正常骨中 Bcl- 2和 PCNA表达情况。结果 :骨肉瘤组与正常骨组 ,骨肉瘤、级组与级组 ,骨肉瘤生存组与死亡组相比 ,PCNA指... 详细信息

目的 :研究骨肉瘤中 Bcl- 2和 PCNA表达的生物学意义。方法 :用免疫组织化学 S- P法 ,研究 30例骨肉瘤和 15例正常骨中 Bcl- 2和 PCNA表达情况。结果 :骨肉瘤组与正常骨组 ,骨肉瘤、级组与级组 ,骨肉瘤生存组与死亡组相比 ,PCNA指数差异有显著性 (P<0 .0 5 )。骨肉瘤组与正常骨组相比 ,Bcl- 2差异有显著性 (P<0 .0 5 )。骨肉瘤、级组与级组 ,骨肉瘤生存组与死亡组相比 ,Bcl- 2差异无显著性 (P>0 .0 5 )。骨肉瘤中 Bcl- 2和 PCNA表达呈显著相关性 (P<0 .0 5 )。结论 :细胞凋亡抑制和过度增殖协同作用导致骨肉瘤的发生。 PCNA指数可作为反映骨肉瘤分级和预后的指标。 Bcl- 2不能作为判断骨肉瘤分级和预后的指标。

关键词：骨肉瘤/病理学基因表达基因,bcl-2 增殖细胞核抗原/分析

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SKI-2053R对胃癌细胞作用的体外研究

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肿瘤防治杂志 2003年第11期10卷 1156-1158页

作者：薛兴奎陈晓萍左文述宋恕平宋现让王兴武山东省肿瘤医院基础研究中心山东济南250117 浙江省肿瘤医院内科浙江杭州310022 山东省肿瘤医院外一科山东济南250117 山东省肿瘤医院内三科山东济南250117

目的 :研究SKI 2 0 5 3R对胃癌细胞株SGC 790 1的作用及其机制。方法 :MTT法检测SKI 2 0 5 3R对SGC 790 1的增殖抑制作用 ,流式细胞术检测药物作用前后细胞周期的变化及增殖细胞核抗原(PCNA)的表达改变。结果 :SKI 2 0 5 3R可明显抑制SG... 详细信息

目的 :研究SKI 2 0 5 3R对胃癌细胞株SGC 790 1的作用及其机制。方法 :MTT法检测SKI 2 0 5 3R对SGC 790 1的增殖抑制作用 ,流式细胞术检测药物作用前后细胞周期的变化及增殖细胞核抗原(PCNA)的表达改变。结果 :SKI 2 0 5 3R可明显抑制SGC 790 1的增殖活性 ,改变SGC 790 1的细胞周期分布 ,降低PCNA的表达。结论 :SKI 2 0 5 3R对SGC 790 1有明显的杀伤和抑制增殖的作用 ,其机制可能与下调PCNA的表达有关。

关键词：抗肿瘤药/药理学胃肿瘤/药物疗法肿瘤细胞,培养的增殖细胞核抗原/分析细胞周期

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Proliferation and remodeling of the peritubular microcirculation after nephron reduction - Association with the progression of renal lesions

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AMERICAN JOURNAL OF PATHOLOGY 2001年第2期159卷 547-560页

作者： Pillebout, E Burtin, M Yuan, HT Briand, P Woolf, AS Friedlander, G Terzi, F Univ Paris INSERM U426 Fac Med Xavier Bichat F-75870 Paris 18 France Inst Cochin Genet Mol INSERM U380 F-75014 Paris France UCL Inst Child Hlth Nephrourol Unit London England

Little is known about the serial changes that might occur in renal capillaries after reduction of renal mass. In the current study, our aim was to document potential alterations in the morphology and proliferation of the renal cortical peritubular microcirculation at specific time points (7 and 60 days) after experimental 75% surgical nephron reduction using two strains of mice that we here demonstrate react differently to the same initial insult: one strain (C57BL6xDBA2/F1 mice) undergoes compensatory growth alone, whereas the other (FVB/N mice) additionally develops severe tabulo-interstitial lesions. Our data demonstrate that significant remodeling and proliferation occur in renal cortical peritubular capillaries after experimental nephron reduction, as assessed by microangiography using infusion of fluorescein isothiocyanate-labeled dextran, expression of the endothelial markers CD34 and Tie-2, and co-expression of CD34 and proliferating cell nuclear antigen, a surrogate marker of cell proliferation. This was accompanied by an increase of renal vascular endothelial growth factor protein levels and a change in distribution of this protein within the kidney itself. Moreover, most of these responses were accentuated in FVB/N mice in the presence of progressive renal disease and positively correlated with tubular epithelial cell proliferation. Hence, we have made three significant novel observations that illuminate the complex pathophysiology of chronic kidney damage after nephron reduction: 1) cortical peritubular capillaries grow by proliferation and remodeling, 2) vascular endothelial growth factor expression is altered, and 3) the development of tubulo-interstitial disease is genetically determined.

关键词：抗原 CD34/分析生物学标记/分析细胞分裂交叉遗传右旋糖酐类内皮生长因子/分析内皮血管/细胞学内皮血管/生理学荧光素-5-异硫氰酸盐/类似物和衍生物免疫组织化学肾小管/血液供给肾小管/细胞学淋巴因子/分析小鼠近交C57BL 小鼠近交DBA 小鼠近交系微循环/细胞学微循环/生理学新生血管化生理性/生理学肾切除术肾单位/生理学增殖细胞核抗原/分析受体蛋白质酪氨酸激酶类/分析受体 TIE-2 种特异性尿道上皮/细胞学尿道上皮/生理学血管内皮生长因子A 血管内皮生长因子类动物女(雌)性小鼠

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3-methylcholanthrene triggers the differentiation of alveolar tumor cells from canine bronchial basal cells and an altered p53 gene promotes their clonal expansion

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CARCINOGENESIS 2000年第8期21卷 1477-1484页

作者： TenHave-Opbroek, AAW Shi, XB Gumerlock, PH Leiden Univ Med Ctr Dept Pulm NL-2300 RC Leiden Netherlands Univ Calif Davis Med Ctr Dept Internal Med Sacramento CA 95817 USA Univ Calif Davis Med Ctr Dept Urol Sacramento CA 95817 USA

Alveolar type II cells arising in canine bronchial autografts following exposure to 3-methylcholanthrene (MCA) give rise to carcinomas of varying glandular and squamous growth patterns. To study the role of the tumor suppressor gene p53 in this process, sections from progressive lesions were immunostained for p53 protein;microdissected regions were screened for p53 mutations. Adjacent sections were examined for type II cell expression [cuboid cell shape, large roundish nucleus, cytoplasmic staining for surfactant protein A (SP-A)] and proliferating cell nuclear antigen expression. Evidence for an altered p53 function (nuclear staining, missense mutations) was found in most carcinomas of all histologic types and in all grades of bronchial dysplasia, but not in hyperplastic or normal bronchial epithelium. It was primarily associated with the hyperplastic type II cell populations present in the basal zone of the lesions. In addition, we found SP-A staining in hyperplastic (but not in normal) bronchial basal cells. These data suggest that MCA initiates type II cell differentiation through phenotypic selection (basal cells). Inactivation of the p53 gene promotes the clonal expansion of the type II cells into discernible populations of (squamous or glandular) alveolar tumor cells. This in vivo study is the first to show that p53 is involved in a specific pathway leading to bronchogenic carcinoma.

关键词：支气管/病理学支气管/移植致癌物癌支气管原/化学诱导癌支气管原/遗传学癌支气管原/病理学细胞分化/药物作用细胞转化肿瘤/药物作用细胞转化肿瘤/遗传学细胞转化肿瘤/病理学克隆细胞基因 p53/遗传学肺肿瘤/化学诱导肺肿瘤/遗传学肺肿瘤/病理学甲基胆蒽小鼠裸突变误义点突变增殖细胞核抗原/分析增殖细胞核抗原/免疫学蛋白脂质类/分析蛋白脂质类/免疫学肺泡/药物作用肺泡/代谢肺泡/病理学肺表面活性物质相关蛋白质A 肺表面活性物质相关蛋白质类肺表面活性剂/分析肺表面活性剂/免疫学肿瘤抑制蛋白质p53/遗传学肿瘤抑制蛋白质p53/代谢动物狗小鼠

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c-myc antisense limits rat liver regeneration and indicates role for c-myc in regulating cytochrome P-450 3A activity

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第3期292卷 921-928页

作者： Arora, V Knapp, DC Smith, BL Statdfield, ML Stein, DA Reddy, MT Weller, DD Iversen, PL AVI Biopharma Corvallis OR 97333 USA Oregon State Univ Lab Anim Resources Corvallis OR 97331 USA

Expression of c-myc protein is associated with cell proliferation. The present study uses antisense oligomers to inhibit c-myc expression in the regenerating rat liver after 70% partial hepatectomy (PH). Antisense phosphorodiamidate morpholino oligomers (novel DNA analogs) were administered i.p. immediately after surgery to block expression of c-myc within the first 24 h after PH. A 20-mer PMO complimentary to the c-myc mRNA at the translation start site was an effective sequence (AVI-4126, 5'-ACGTTGAGGGGCATCGTCGC-3'). A single i.p. dose of 0.5 mg/kg AVI-4126 caused reduction of the regenerating liver c-myc protein in a sequence-specific and dose-dependent manner. Inhibition of c-myc expression resulted in reduction of proliferating cell nuclear antigen and arrested cells in the G(0)/G(1) phase of the cell cycle. The ratio of G(2):G(0) cell populations in the regenerating liver 24 h after PH dropped from 29.1 in saline vehicle-treated rats to 18.0 in rats treated with 2.5 mg/kg AVI-4126. The expression of cell cycle checkpoint protein p53 was inhibited with increasing doses of AVI-4126, but expression of p21(waf-1) was unaffected. The activity of cytochrome P-450 3A2 (CYP3A2) was evaluated by immunoblot analysis and erythromycin N-demethylation. AVI-4126 did not alter CYP3A activity in nonhepatectamized animals but showed a dose-dependent decrease in PH rats. We conclude that AVI-4126, antisense oligomer to c-myc, can reduce cell proliferation in the regenerating rat liver. Furthermore, inhibition of c-myc may indirectly influence the expression of CYP3A.

关键词：反义成分(遗传学)/药理学周期素依赖激酶抑制剂p21 细胞周期蛋白类/分析细胞色素P450酶系统/代谢剂量效应关系药物 G2期基因 myc/生理学肝切除术肝/酶学肝再生/药物作用增殖细胞核抗原/分析大鼠 Sprague-Dawley 甾类羟化酶类/代谢肿瘤抑制蛋白质p53/分析动物大鼠

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Immunoelectron microscopy of PCNA as an efficient marker for studying replication times and sites during pollen development

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CHROMOSOMA 2000年第6期109卷 397-409页

作者： González-Melendi, P Testillano, PS Ahmadian, P Reyes, J Risueño, MC CSIC Ctr Invest Biol Lab Nucl Org During Plant Dev E-28006 Madrid Spain Ctr Ingeneria Genet & Biotechnol La Habana Cuba John Innes Ctr Plant Sci Res Dept Cell Biol Norwich NR4 7UH Norfolk England

Here we report for the first time the ultrastructural localization of DNA replication sites in the nucleus of plant cells and the timing of replication through the pollen developmental programme by proliferating cell nuclear antigen (PCNA) immunogold labelling. Replication sites were identified by labelling with anti-PCNA antibodies in fibrils of the interchromatin region close to the condensed chromatin, defining a perichromatin sub-domain in the interchromatin space where DNA replication takes place. The same nuclear structures are decorated by anti-BrdU (5-bromo-2'-deoxyuridine) immunogold after short pulses of BrdU labelling. Double immunogold labelling for PCNA and DNA show colocalization on these perichromatin structures. PCNA immunoelectron microscopy also allows correlation of replicative activity with the dynamics of chromatin condensation. DNA replication was also monitored at different phases during pollen development by PCNA immunoelectron microscopy, revealing two peaks of DNA synthesis, at the beginning (early tetrad), and the end (late vacuolate), of microspore interphase. High-resolution autoradiography after [H-3]thymidine incorporation also showed high replicative activity at the same two periods of microspore interphase. In the bicellular pollen grain, PCNA immunogold labelling revealed that DNA replication in the generative cell starts at an intermediate stage of pollen maturation, whereas the vegetative nucleus does not replicate and is arrested in G1. The use of anti-PCNA antibodies at the ultrastructural level is an easier, faster and more feasible method than the detection of in vivo-incorporated nucleotides, especially in plant systems with long cell cycles. PCNA immunogold labelling is, there fore, proposed as an efficient marker for mapping the sites and timing of replication at the electron microscopy level.

关键词：放射自显影术/方法溴脱氧尿苷/代谢染色质/代谢染色质/超微结构 DNA复制/生理学免疫印迹法分裂间期显微镜检查免疫电子/方法有丝分裂洋葱/遗传学花粉/遗传学花粉/生长和发育增殖细胞核抗原/分析增殖细胞核抗原/免疫学增殖细胞核抗原/代谢胸苷/代谢

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Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis

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CARCINOGENESIS 2000年第2期21卷 331-335页

作者： Chuang, SE Kuo, ML Hsu, CH Chen, CR Lin, JK Lai, GM Hsieh, CY Cheng, AL Natl Hlth Res Inst Div Canc Res Taipei Taiwan Natl Taiwan Univ Coll Med Dept Toxicol Taipei 10764 Taiwan Natl Taiwan Univ Coll Med Dept Biochem Taipei 10764 Taiwan Natl Taiwan Univ Coll Med Canc Res Ctr Taipei 10764 Taiwan Natl Taiwan Univ Hosp Dept Oncol Taipei Taiwan Natl Taiwan Univ Hosp Dept Pathol Taipei Taiwan Natl Taiwan Univ Hosp Dept Internal Med Taipei 10016 Taiwan

Curcumin has been widely used as a spice and coloring agent in foods. Recently, curcumin was found to possess chemopreventive effects against skin cancer, forestomach cancer, colon cancer and oral cancer in mice, Clinical trials of curcumin for prevention of human cancers are currently ongoing. In this study, we examine the chemopreventive effect of curcumin on murine hepatocarcinogenesis. C3H/HeN mice were injected i.p. with N-diethylnitrosamine (DEN) at the age of 5 weeks, The curcumin group started eating 0.2% curcumin-containing diet 4 days before DEN injection until death. The mice were then serially killed at the scheduled times to examine the development of hepatocellular carcinoma (HCC) and changes in intermediate biological markers. At the age of 42 weeks, the curcumin group, as compared with the control group (DEN alone), had an 81% reduction in multiplicity (0.5 versus 2.57) and a 62% reduction in incidence (38 versus 100%) of development of HCC, A series of intermediate biological markers were examined by western blot. While hepatic tissues obtained from the DEN-treated mice showed a remarkable increase in the levels of p21(ras), PCNA and CDC2 proteins, eating a curcumin-containing diet reversed the levels to normal values. These results indicate that curcumin effectively inhibits DEN-induced hepatocarcinogenesis in the mouse. The underlying mechanisms of the phenomenon and the feasibility of using curcumin in the chemoprevention of human HCC should be further explored.

关键词：消炎药非甾类/药理学消炎药非甾类/治疗应用抗致癌药/治疗应用生物学标记 CDC2蛋白激酶/分析致癌物/毒性姜黄素/药理学姜黄素/治疗应用膳食二乙基亚硝胺/毒性肝炎中毒性/预防和控制肝/化学肝/药物作用肝肿瘤实验性/化学诱导肝肿瘤实验性/预防和控制小鼠近交C3H 肿瘤蛋白质类/分析增殖细胞核抗原/分析原癌基因蛋白质p21(ras)/分析香料调味品动物男(雄)性小鼠

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