Tea polyphenol epigallocatechin-3-gallate inhibits cell proliferation in a patient-derived triple-negative breast cancer xenograft mouse model via inhibition of proline-dehydrogenase-induced effects

Triple-negative breast cancers (TNBCs) lack specific targeted therapy options and have evolved into highly chemo-resistant tumors that metastasize to multiple organs. The present study demonstrated that the proline dehydrogenase (PRODH) mRNA level in paired (tumor vs. normal) human breast tissue samples (n=234) was 6.6-fold greater than normal cells (*p=0.021). We established stable PRODH-overexpressing TNBC (HS578T) cells, and the malignant phenotypes were evaluated using soft agar colony formation and Transwell migration assays. The results demonstrated that PRODH induced epithelial-mesenchymal transition in cancer cells and increased cell proliferation. The present study found that the tea polyphenol epigallocatechin-3-gallate (EGCG) significantly inhibited PRODH and its regulated proteins, such as alpha-smooth muscle actin (alpha-SMA) expression in TNBC cells. These findings support the targeting of the PRODH signaling pathway as a potential therapeutic strategy in preventing cancer cell metastasis. The patient-derived xenograft (PDX) mouse model is highly relevant to real human tumor growth. We established a TNBC-PDX (F4, n=4 in each group)mouse model. The PDX mice were treated with EGCG (50 mg/kg), and the results indicated that EGCG significantly inhibited PDX tumor growth (*p = 0.013). These experiments provide additional evidence to evaluate the antitumor effects of EGCG-induced PRODH inhibition for clinical therapeutic application, especially in TNBC patients.     

PRR11在肝细胞癌组织中的表达以及对癌细胞生物学行为的影响

目的 研究富含脯氨酸蛋白11(PRR11)在肝细胞癌(HCC)组织中的表达及其对HCC细胞生物学行为的影响.方法 采用基因表达谱数据动态GEPIA分析PRR11在不同HCC组织和癌旁组织中表达并分析与患者预后的影响;构建PRR11沉默细胞系,通过实验验证PRR11对HCC细胞生物学行为.结果 GEPIA分析发现,HCC...     

High proline levels in the brains of mice as related to specific learning deficits

Hyperprolinemic PRO/Re mice have been studied as potential models for hyperprolinemia in man. In addition to high proline levels, some heretofore unreported amino acid abnormalities in the brains of PRO/Re mice are described. The T-maze and shuttlebox learning abilities of PRO/Re mice were compared with those of CD-1 mice having normal proline levels. PRO/Re mice had a significant deficit for T-maze learning, but a significantly greater aptitude for shuttlebox learning when compared to CD-1 mice. By studying the F3 progency of the PRO/Re X CD-1 cross, these strain-specific differences in learning ability for different tasks were shown to be unrelated to the differences in brain proline levels. F3 mice could be subdivided into two distinct groups: those with high proline (HP+) and low proline (HP-) titers. Other amino acids in brain tissues were essentially identical in both groups. A comparison of learning abilities of these HP+ mice with their HP- littermates showed no meaningful differences. However, the slightly slower rate at which HP+ mice acquired shuttlebox learning was sufficiently consistent over the 8 day training period so that it became significant. These results do not support the hypothesis that high levels of proline in brain tissues and blood are necessarily accompanied by impaired learning and memory, but are in agreement with those studies of hyperprolinemia in man that suggest no consistent learning deficits in hyperprolinemic subjects. The results seem to validate the suitability of the PRO/Re mouse as a model for hyperprolinemia in man. The data suggest also that the altered amino acid pattern in brains of PRO/Re mice has multiple etiologies.(ABSTRACT TRUNCATED AT 250 WORDS)     

L－脯氨酸产生菌的选育

以嗜乙酰乙酸棒杆菌ＡＴＣＣｌ３８７０为出发菌株，经硫酸二乙酯（ＤＥＳ）和亚硝基胍（ＮＴＧ）逐级诱变处理，结构类似物定向选育，获得一株Ｌ－脯氨酸高产菌ＺＱ－３（ＳＧｒ、Ｓｕｃｇ、ＤＨＰｒ）。在含１６％葡萄糖的培养基中，摇瓶发酵７２ｈ，产酸率为５．３％～５．５％。     

Glutamate kinase as a potential biomarker of heavy metal stress in plants

Changes of glutamate kinase activity (GKA) in plants under cadmium and zinc chronic stress reported here reveal a regulatory role of this enzyme in plant heavy metal stress adaptation and indicate its potential use as a stress biomarker. Results of the first experimental series confirmed the toxic effects of cadmium and zinc at tested levels (30, 60, 90 mg Cd kg⁻¹ and 250, 500, 750 mg Zn kg⁻¹ soil) for spinach. A significant decrease of GKA in plants grown on contaminated treatments was found. Changes of GKA of plants grown on the highest contaminated treatments in the second series of experiments showed a similar course as a curve of plant stress response indicating the process of plant adaptation to chronic stresses—the decline of GKA in period of damage of cell activities, increase of its activity in period of maximum resistance and its following decrease in period of the plant metabolism depletion.     

POX与肿瘤抑制的研究进展

脯氨酸氧化酶(POX)是p53下游的靶基因,在多种肿瘤中都呈低表达状态。研究发现POX不但能通过活性氧簇的生成促进胞内、外途径介导的肿瘤细胞凋亡,也能通过促进缺氧诱导因子1的降解与增强细胞的自噬能力使肿瘤细胞凋亡。POX作为控制癌细胞增殖代谢途径中重要的组成部分,成为值得研究的抗肿瘤分子靶点。现就POX与肿瘤抑制的研究进展予以综述。     

Pyk2在胃癌组织中的表达及其意义

目的:研究Pyk2(proline-rich tyrosine kinase-2)在正常胃黏膜组织与胃癌组织中表达的差异,探讨其意义.方法:应用免疫组织化学的方法检测59例正常胃黏膜组织标本和52例胃癌组织标本中Pyk2的表达情况.结果:免疫组织化学结果显示,Pyk2在正常胃黏膜组织中的表达阳性率为86.44%(51/59),在胃癌组织中表达阳性率为19.23%(10/52),两者差异具有统计学意义(P＜0.05);在高分化胃癌中表达阳性率为47.37%(9/19),而在中、低分化胃癌中表达阳性率为3.03%(1/33),两者差异具有统计学意义(P＜0.05).Pyk2表达阳性率在不同TNM分期胃癌中分别为:Ⅰ期66.67%(6/9),Ⅱ期30%(3/10),Ⅲ期3.45%(1/29),Ⅳ期0%(0/4),差异具有统计学意义[(Ⅱ Ⅲ Ⅳ)vI,x2=15.767,P＜0.05)].结论:本研究观察到Pyk2在正常胃黏膜组织中有表达,在胃癌组织中低表达或几乎无表达,并且其表达随着胃癌恶性度和TNM分期的增加而逐渐降低.提示Pyk2可能在胃癌的发生、发展过程中起重要作用.     

Hyperprolinaemia type I and white matter disease: Coincidence or causal relationship

We describe a 10-year-old boy with hyperprolinaemia type I and severe neurological abnormalities (mental retardation, cerebral palsy, epilepsy, nystagmus). Magnetic resonance imaging showed diffuse white matter involvement and electroretinography confirmed tapetoretinal degeneration. In view of reports in the literature, hyperprolinaemia type I may not be a benign condition, as usually assumed, but may lead to marked neurological abnormalities, particularly in affected males.Presented in abstract form at the Meeting of the Swiss Paediatric Society, Zug., 16–18 June, 1988     

Association between sigma-1 receptor gene polymorphism and prefrontal hemodynamic response induced by cognitive activation in schizophrenia

The molecular biological role of the sigma-1 receptor (Sig-1R) has attracted much attention. Evidence suggests that the Sig-1R engaged in modulating NMDA and dopamine receptors is involved in the pathophysiology of schizophrenia and the mechanism of psychotropic drug efficacy. However, whether the Sig-1R genotype affects brain function in schizophrenia in vivo remains unknown. We investigated the association between Sig-1R functional polymorphism (Gln2Pro) and brain function in schizophrenia. The subjects were 40 patients with schizophrenia and 60 healthy controls, all right-handed, who gave written informed consent to participate. Signals, detected from prefrontal regions by 52-channel near-infrared spectroscopy (NIRS) during cognitive activation, were compared between two Sig1-R genotype subgroups (Gln/Gln individuals and Pro carriers) matched for age, gender, premorbid IQ and task performance. The prefrontal hemodynamic response of healthy controls during the verbal fluency task was higher than that of patients with schizophrenia. For the patients with schizophrenia, even after controlling the effect of medication, the [oxy-Hb] increase in the prefrontal cortex of the Gln/Gln genotype group was significantly greater than that of the Pro carriers (false discovery rate corrected p < 0.05). Clinical symptoms were not significantly different between the two Sig-1R genotype subgroups. These differences were not significant in the healthy controls. This is the first functional imaging genetics study that implicated the association between Sig-1R genotype and prefrontal cortical function in schizophrenia in vivo. Our findings also suggest that the prefrontal hemodynamic response assessed by noninvasive and less demanding NIRS is a useful intermediate phenotype for translational research in schizophrenia.     

肺组织NF-κB和PUMA与SAP-ALI的关系及PDTC的干扰作用

目的探讨NF-κB(核因子-κB)和PUMA(p53正向凋亡调节因子)在大鼠重症急性胰腺炎致急性肺损伤(SAP-ALI)发病中的作用及脯氨酸二硫代氨基甲酸酯(PDTC)对此过程的影响。方法 SD大鼠随机分为假手术组(A组),SAP-ALI组(B组),SAP+PDTC干预组(C组),每组24只。各组再按6,12,24 h时点分为3个亚组,每亚组8只。A组开腹后翻动胰腺数次;B组采用胰胆管逆行注入5%牛磺胆酸钠(1 mL/kg)诱导SAP-ALI模型;C组在B组的基础上于术前1 h给予PDTC(15 mg/kg),各组按各时点处死大鼠。观察胰腺和肺脏病理变化。检测不同组肺脏组织中NF-κBp65,PUMA和Caspase-3的表达及Caspase-3活性;检测组织TNF-α,MIP-2和ICAM-1 mRNA的表达、髓过氧化物酶(MPO)的活性和肺泡上皮细胞凋亡指数。结果成功建立大鼠SAP-ALI模型。Western-blotting和RT-PCR结果显示,B组肺上皮细胞NF-κB p65,PUMA和Caspase-3蛋白表达在12 h后显著增加(P0.05),NF-κB p65与PUMA呈高度正相关(r=0.987,P0.01)。TNF-α,MIP-2,ICAM-1mRNA表达及MPO和Caspase-3活性明显增加(P0.01)。C组肺损伤病理组织学评分在术后各时点较B组显著下降(P0.05),C组12 h后的肺组织NF-κB p65,PUMA和Caspase-3蛋白表达及MPO和Caspase-3活性明显降低(P0.05);TNF-α,MIP-2,ICAM-1 mRNA表达明显下降(P0.05),C组细胞凋亡指数较B组明显降低(P0.01)。结论大鼠SAP-ALI既与NF-κB活化引起的炎症因子释放有关又与NF-κB活化引起的PUMA上调促进细胞凋亡有关。PDTC通过抑制NF-κB活化,下调炎症因子释放及NF-κB活化引起的PUMA表达可抑制肺组织的细胞凋亡,从而减轻SAP-ALI的程度。