Glycinamide ribonucleotide formyl transferase is frequently overexpressed in glioma and critically regulates the proliferation of glioma cells

Aims

Current treatments for the most common form of brain tumor, glioma, are disappointing in their effectiveness. Low expression levels of GART, an enzyme in the core nucleotide metabolism, significantly correlate with chemosensitivity, conferring a survival advantage to tumor cells. Our study aimed to explore the expression and function of GART in glioma.

Methods

Immunohistochemical and Western blot analysis were performed in 70 cases of human gliomas and normal brain tissues. We mainly used cell growth assay and multicellular tumor spheroid formation assay to evaluate the proliferation and chemosensitivity of glioma cells.

Results

High GART expression (most cancer cells cytoplasm stained) was observed in 70 specimens and was related to the grade of malignancy. We also reviewed each grade of tumors separately and investigated whether GART expression predicted patient survival within each subgroup. In brief, GART overexpression was significantly associated with overall survival (P = 0.03). Interestingly, transfecting cells with GART-siRNA suppressed proliferation and enhanced temozolomide (TMZ)-induced apoptosis in glioma cells.

Conclusion

The current results showed that GART expression was associated with glioma grade and that high GART protein expression might be related to poor outcome.     

Quercetin induces morphological and proliferative changes of rat’s uteri under estrogen and progesterone influences

This study investigated the effect of 10 or 100 mg/kg/day quercetin on the uterus of ovariectomized adult female rats receiving sex-steroid replacement regime mimicking changes in hormonal profiles during the reproductive cycle. Following seven days of treatment with estrogen and progesterone with or without quercetin, uteri were harvested for histological and proliferative cell nuclear antigen (PCNA) protein and mRNA expression and PCNA protein distribution analyses. Our findings indicated that co-administration of 10 mg/kg/day quercetin with estrogen and progesterone caused a significant decrease in the size of uterine lumen and epithelial heights with lower PCNA protein and mRNA expression as compared to estrogen plus progesterone-only treatment (P < 0.05). Concomitant treatment with estrogen and progesterone with 100 mg/kg/day quercetin resulted in a marked increase in the number of glands with increased PCNA protein and mRNA expression. Significantly higher PCNA distribution was observed in the stroma and glands as compared to estrogen plus progesterone-only treatment (P < 0.05). In conclusion, at 10 mg/kg/day, quercetin affects uterine morphology but not proliferation, however at 100 mg/kg/day, quercetin induced significant stromal and glandular proliferation which could predispose the uterus towards neoplastic development.     

Temporal and histologic relationships of proliferating cell nuclear antigen and human papillomavirus type 11 in the mouse xenograft system

Proliferating cell nuclear antigen (PCNA) is an accessory protein of DNA polymerase delta. This protein is associated with cell cycle progression and can be detected in the replicating cells of normal tissues. Condylomata acuminata are benign epithelial tumors caused by infection with human papillomaviruses and are characterized by abnormal cell proliferation. The athymic mouse xenograft model of HPV 11 infection was used to test the hypothesis that PCNA is induced early in the course of HPV 11 infection and to study the temporal and histologic relationships between detection of PCNA and HPV DNA. Human foreskin tissue was infected with HPV 11 and implanted under the renal capsules of 10 athymic mice. Pairs of mice were sacrificed every week beginning four weeks after implantation. HPV DNA was detected in sections of foreskin implants by in situ hybridization. PCNA was as or more abundant in implants removed at earlier time points than at later time points, whereas HPV DNA became increasingly more abundant with time. PCNA was detected only in basal cells in areas of histologically normal epithelium that were also negative for HPV DNA. In contrast, PCNA was present throughout the epithelium in regions that were HPV DNA-positive. HPV DNA was detected only in differentiated epithelial cells in implants removed at all five time points, but in HPV DNA-positive regions, PCNA was detected with equal intensity in differentiated and undifferentiated cells. The foci of PCNA-positive cells were well demarcated and were larger than, but included, the foci of HPV DNA-positive cells. PCNA may be induced maximally in differentiated epithelium by HPV 11 prior to significant HPV DNA replication. © 1996 Wiley-Liss, Inc.     

柔红霉素诱导Jurkat细胞凋亡、抑制增殖与bcl-2、PCNA表达变化的关系

目的探讨柔红霉素（DNR）在体外诱导Jurkat细胞凋亡的情况并探讨其与细胞表达凋亡相关蛋白改变的关系。方法Annexin V／PI双标流式细胞仪（FCM）检测DNR诱导Jurkat细胞的凋亡作用,用免疫细胞化学观察相关蛋白表达水平的变化。结果当DNR为0．1～2．0μmol／L浓度范围时,作用一定时间后Jurkat细胞发生的凋亡率随药物浓度的增加与作用时间的延长而升高。但药物浓度超过2．0μmol／L,或2．0μmol／L作用48h后Jurkat细胞出现凋亡率下降,细胞大部分死亡。0．5μmol／L DNR作用于Jurkat细胞24h后,细胞中bcl-2、PCNA蛋白表达水平降低。结论一定浓度的DNR在体外可诱导Jurkat细胞凋亡,药物浓度达5．0μmol／L时细胞大部分死亡。本实验条件下DNR体外诱导Jurkat发生凋亡的机制可能是通过抑制bcl-2、PCNA蛋白的表达实现。     

PCNA和MMP9在宫颈癌组织中的表达与意义

目的: 探讨PCNA,MMP9在宫颈癌组织中的表达及临床意义. 方法: 用免疫组织化学SP法检测46例宫颈癌及10例正常宫颈中PCNA和MMP9的表达,分析不同组织中PCNA和MMP9表达的差异及两者的相关性. 结果: 宫颈癌组织PCNA的表达明显高于正常宫颈组织(P=0.000);38例宫颈癌的MMP9阳性表达(82.61%)明显高于10例正常宫颈组织的表达(30%, P﹤0.05);PCNA的表达与MMP9的表达呈正相关(rs=0.433, P=0.003),且PCNA和MMP9均与临床分期有关(P﹤0.05),而与年龄、病例分级及生长方式无关(P﹥0.05). 结论: MMP9在宫颈癌组织中表达异常增高,与细胞增殖关系密切,提示其对宫颈癌的发展起重要作用.     

脑胶质瘤中增殖细胞核抗原的表达及其临床意义

目的:研究增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在脑胶质瘤中的表达与肿瘤病理分级的关系,探讨其在脑胶质瘤预后判断上的价值。方法:应用免疫组化SP法检测47例脑胶质瘤和12例正常脑组织中PCNA的表达。结果:PCNA在胶质瘤中绝大部分阳性表达,在正常脑组织中全部阴性表达,PCNA在胶质瘤的表达明显升高(P<0.01),高级别组表达高于低级别组(P<0.05)。结论:PCNA较准确地反映脑胶质瘤的增殖行为和恶性程度。可能在该肿瘤的预后判断上有重要意义。     

Bmi-1和PCNA在皮肤鳞状细胞癌组织中的表达及意义

目的检测Bmi-1和PCNA在皮肤鳞状细胞癌组织中的表达,并探讨Bmi-1表达与皮肤鳞状细胞癌临床病理特征的关系。方法采用免疫组化SP法检测Bmi-1和PCNA在30例皮肤鳞状细胞癌组织和30例脂溢性角化症皮损中的表达,并分析Bmi-1的表达与皮肤鳞状细胞癌临床病理特征的相关性。结果 Bmi-1在皮肤鳞状细胞癌和脂溢性角化症中的阳性表达率分别是70.00%和16.67%,前者显著高于后者(P<0.001),而且Bmi-1的表达与病理分级、病理分期和淋巴结转移相关(P<0.05)。PCNA的阳性表达率分别是96.67%和66.67%,前者也显著高于后者(P<0.01)。但Bmi-1蛋白在皮肤鳞状细胞癌中的表达和PCNA的表达无相关关系(P>0.05)。结论 Bmi-1和PCNA在皮肤鳞状细胞癌组织中高表达,而且Bmi-1与皮肤鳞状细胞癌的分化、浸润和转移可能相关。     

肌腱生长蛋白在人脑胶质瘤中的表达与增殖性细胞核抗原的相关性研究

目的 探讨肌腱生长蛋白（Tenascin,TN)和增殖性细胞核抗原（Proliferation cell nuclear antigen,PCNA)在不同级别人脑胶质瘤中的表达情况。分析它与胶质瘤的侵袭相关性。方法 采用免疫组织化学方法，检测54例不同级别人脑胶质瘤组织中Tenascin和PCNA的表达。结果 Tenascin表达于胶质瘤新生血管，瘤细胞周围基质以及胶质瘤细胞；PCNA表达于细胞核，随着胶质瘤病理级别的升高，肿瘤新生血管和瘤细胞周围基质中的Tenascin表达增强，瘤细胞中PCNA表达亦增强，Tenascin与PCNA的表达呈正相关。结论 Tenascin在胶质瘤血管形成，瘤细胞增殖转移过程中发挥了重要作用，Tenascin和PCNA可作为评价胶质瘤生物学行为的有用指标。     

细胞凋亡及PCNA与胃癌生物学行为的关系

目的:探讨胃癌组织中细胞凋亡、增殖细胞核抗原(PCNA)与胃癌生物学行为的关系。方法:采用原位末端标记法(TUNEL)和SP免疫组化方法分别检测72例胃癌组织中细胞凋亡及PC-NA。结果:粘液癌及低分化胃癌组PCNA明显高于高分化组,而凋亡指数明显低于高分化组。胃癌组织浸润超过肌层PCNA较高,而凋亡指数较低。胃癌淋巴结转移组PCNA较高、凋亡指数较低。结论:检测胃癌组织中细胞凋亡及PCNA有助于评估病人的预后。     

NiTi放射性支架置入兔腹主动脉后对平滑肌细胞增殖和凋亡的影响

目的　观察NiTi放射性支架对平滑肌细胞增殖和凋亡的影响。方法　在 76只家兔腹主动脉中分别置入放射与非放射性支架。用免疫组化法和TUNEL法观察放射性支架对平滑肌细胞增殖和凋亡的影响。结果　 (1) 2周时放射与非放射性组新生内膜面积无显著差异 (P >0 0 5 ) ,1个月和 3个月时放射支架组新生内膜面积小于非放射性组 (P <0 0 1) ;(2 )PCNA法测定平滑肌细胞增殖显示放射性组在各时间点PCNA表达低于非放射性组 (P <0 0 5 ) ;(3)TUNEL法测定放射性组平滑肌细胞凋亡与对照组相比在 2周和 1个月时有显著差异 (P<0 0 5 ) ,在 3个月时两组平滑肌细胞凋亡无显著差异 (P >0 0 5 )。结论　 (1)放射性支架可减少支架置入术后支架内新生内膜面积。 (2 )放射性支架可抑制血管平滑肌细胞增殖。 (3)放射性支架促进血管平滑肌细胞凋亡