Expression and prognostic significance of NKD2 in ovarian cancer.
- 作者列表："Wei W","Zheng L","Gao Y","He M","Yang F
PURPOSE:Naked2 (NKD2) is a negative regulator of Wnt signaling pathway and associates with transforming growth factor secretion. The role of NKD2 in ovarian cancer is unknown. PATIENTS AND METHODS:Gene expression profiles were measured and compared in nine patients by RNA sequencing. NKD2 expressions in ovarian cancer were measured by reverse transcription polymerase chain reaction and western blot. Tissue slides of 79 patients were stained and scored for NKD2 expression. In vitro experiments were conducted to explore the role of NKD2 in ovarian cancer. The prognostic role of NKD2 was evaluated by survival analysis. RESULTS:NKD2 was upregulated in patients with better survival by mRNA and protein expression. Patients were classified as NKD2-high group (n = 30) and NKD2-low group (n = 49) according to immunohistochemical score. High NKD2 was correlated with lower recurrence rate (P = 0.002) and higher percentage of platinum-sensitive recurrence (P = 0.006). Median progression-free survival was significantly longer for NKD2-high patients than NKD2-low patients (49.1 vs.14.1 months, P < 0.001). Accordingly, there was a significantly difference in terms of overall survival time between two groups (hazard ratio: 3.04; 95% confidence interval: 1.58-5.85, P < 0.001). Multivariate regression suggested that NKD2 was independently prognostic factors in terms of progression-free survival (hazard ratio: 2.91; 95% confidence interval: 1.61-5.27, P < 0.001) and overall survival (hazard ratio: 3.6; 95% confidence interval: 1.80-7.21, P < 0.001). In vitro studies further demonstrated that NKD2 suppressed ovarian cancer cell proliferation, colony formation and cell migration. CONCLUSION:NKD2 is a novel prognostic marker and could suppress tumor progression in ovarian cancer.
目的: Naked2 (NKD2) 是Wnt信号通路的负调控因子，与转化生长因子分泌有关。NKD2在卵巢癌中的作用尚不清楚。 患者和方法: 通过RNA测序测量并比较9例患者的基因表达谱。采用逆转录聚合酶链反应和western blot检测NKD2在卵巢癌中的表达。对79名患者的组织载玻片进行染色并对NKD2表达进行评分。体外实验探讨NKD2在卵巢癌中的作用。通过生存分析评估NKD2的预后作用。 结果: NKD2通过mRNA和蛋白表达在存活较好的患者中上调。根据免疫组化评分将患者分为NKD2-high组 (n = 30) 和NKD2-low组 (n = 49)。高NKD2与较低的复发率 (P = 0.002) 和较高的铂敏感复发百分比 (P = 0.006) 相关。NKD2-high例患者的中位无进展生存期显著长于NKD2-low例患者 (49.1 vs.14.1个月，P <0.001)。因此，两组之间的总生存时间存在显著差异 (风险比: 3.04; 95% 置信区间: 1.58-5.85，P <0.001)。多变量回归提示NKD2是无进展生存期 (风险比: 2.91; 95% 置信区间: 1.61-5.27，P <0.001) 和总生存期 (风险比: 3.6; 95% 置信区间: 1.80-7.21，P <0.001) 的独立预后因素。体外研究进一步证明NKD2抑制卵巢癌细胞增殖、集落形成和细胞迁移。 结论: NKD2是一种新的卵巢癌预后标志物，可抑制卵巢癌的进展。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.