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Interaction of arsenic trioxide and etoposide in Ewing sarcoma cell lines.

三氧化二砷和依托泊苷在尤文肉瘤细胞系中的相互作用。

  • 影响因子:3.07
  • DOI:10.3892/or.2019.7409
  • 作者列表:"Lenz JE","Riester R","Schleicher SB","Handgretinger R","Boehme KA","Traub F
  • 发表时间:2020-01-01
Abstract

:Ewing sarcomas (ES) are highly malignant mesenchymal tumors, which most often occur in children and adolescents. The current treatment of choice comprises wide resection in combination with multimodal chemotherapy including etoposide (Eto). Due to the serious side effects associated with common chemotherapeutics and prevalent multidrug resistance in recurrent and metastatic ES, there is a growing demand for alternative strategies and add‑on drugs. Previous research has demonstrated efficient cell death induction by Eto in combination with arsenic trioxide (ATO) in ES cell lines. The aim of the present study was to investigate the effect of different temporal sequences of ATO and Eto administration on apoptosis induction and to explore the effect of both drugs on inhibitory glycogen synthase kinase‑3β (GSK3‑β) phosphorylation as well as multidrug transporter gene expression. The intensity of caspase activation was mainly determined by the Eto doses in A673 and TC‑71 cells, whereas in RD‑ES cells ATO application actively suppressed Eto‑induced apoptosis. This coincided with an increase in inhibitory GSK‑3β phosphorylation in ATO‑treated RD‑ES cells. Inherent mRNA expression of multidrug resistance‑associated protein 1 (MRP1) was low in the ES cell lines compared to that observed in the mesenchymal stem cells (MSC), whereas multidrug resistance protein 1 (MDR1) gene expression was considerably increased in the ES cell lines. ATO treatment reduced MRP1 mRNA expression in the A673 and TC‑71 cells, while expression was induced in the MSC and RD‑ES cells. In contrast, MDR1 mRNA expression was specifically induced by ATO in the A673 and TC‑71 cells, reinforcing the expression differences between MSC and the ES cell lines. Although a reliable cell death induction by the combination of ATO and Eto has been previously shown in ES cell lines, the present study showed marked heterogeneity of the ES cell response to ATO and Eto treatment, illustrating the difficulty of prediction of individual treatment outcome in ES.

摘要

: 尤因肉瘤 (Ewing sarcomas,ES) 是高度恶性的间叶性肿瘤,最常发生在儿童和青少年。目前的治疗选择包括广泛切除联合包括依托泊苷 (Eto) 在内的多模式化疗。由于常见化疗药物相关的严重副作用以及复发和转移性ES中普遍存在的多药耐药,对替代策略和添加药物的需求日益增长。以前的研究已经证明Eto与三氧化二砷 (ATO) 联合在ES细胞系中诱导细胞死亡是有效的。本研究的目的是研究ATO和Eto给药的不同时间序列对凋亡诱导的影响,并探讨两种药物对抑制性糖原合成酶激酶 ‑ 3 β (GSK3 ‑ β) 的影响。) 磷酸化以及多药转运蛋白基因表达。Caspase激活的强度主要由A673 和tc ‑ 71 细胞中的Eto剂量决定,而在rd‑ es细胞中ATO应用积极抑制Eto ‑ 诱导的凋亡。这与at ‑ 处理的rd‑ es细胞中抑制性gsk ‑ 3 β 磷酸化的增加相一致。与间充质干细胞 (MSC) 中观察到的相比,ES细胞系中多药耐药相关蛋白 1 (MRP1) 的固有mRNA表达较低,而多药耐药蛋白 1 (MDR1) ES细胞系的基因表达显著增加。ATO处理降低了A673 和tc ‑ 71 细胞中MRP1 mRNA的表达,而在MSC和rd ‑ es细胞中诱导了表达。相反,ATO在A673 和tc ‑ 71 细胞中特异性诱导MDR1 mRNA表达,加强了MSC和ES细胞系之间的表达差异。虽然以前在ES细胞系中已经证明了ATO和Eto组合诱导的可靠的细胞死亡,但是本研究显示ES细胞对ATO和Eto处理的反应存在明显的异质性,说明ES中个体治疗结果的预测难度。

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影响因子:1.41
发表时间:2020-03-01
DOI:10.1177/1078155219842277
作者列表:["Gyori DJ","Bullington SM","Crawford BS","Vernon VP"]

METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.

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影响因子:2.83
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DOI:10.1007/s00520-019-04843-9
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骨肿瘤方向

骨肿瘤是发生于骨骼或其附属组织的肿瘤。有良性,恶性之分,良性骨肿瘤易根治,预后良好,恶性骨肿瘤发展迅速,预后不佳,死亡率高。

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