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Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression.

碱性成纤维细胞生长因子通过影响XRCC5 表达促进软骨肉瘤细胞对多柔比星的耐药性。

  • 影响因子:3.43
  • DOI:10.1002/mc.23153
  • 作者列表:"Hsieh MJ","Huang C","Lin CC","Tang CH","Lin CY","Lee IN","Huang HC","Chen JC
  • 发表时间:2020-03-01
Abstract

:Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.

摘要

: 软骨肉瘤是骨癌的第二常见形式,其特征在于其产生软骨细胞外基质的能力。高级别软骨肉瘤具有高度侵袭性,可转移至身体其他部位。软骨肉瘤对常规化疗和放疗均耐药; 因此,目前的主要治疗仍然是手术切除。与未治疗的软骨肉瘤相比,阿霉素 (Dox) 已被证明可显著改善患者生存率。但对于有转移的患者,单纯手术切除很难治疗。此外,耐药性是软骨肉瘤患者死亡的主要原因之一。分泌蛋白可以介导肿瘤微环境中的细胞-细胞相互作用,这可能与耐药性的发展有关。在本研究中,用Dox处理软骨肉瘤细胞,然后收集条件培养基,并使用抗体阵列分析分泌蛋白的变化。结果表明,Dox处理组碱性成纤维细胞生长因子 (bFGF) 的分泌最高,表明bFGF对软骨肉瘤Dox敏感性的影响。此外,慢病毒介导的敲除和外源性重组蛋白的处理被用来进一步研究bFGF对Dox耐药的影响。结果表明,bFGF能促进x射线修复交叉互补蛋白 5 (XRCC5) 的表达,导致Dox耐药。分泌的bFGF很可能在血清中检测到,除了作为预测Dox耐药的生物标志物,dox与bFGF/XRCC5 阻断剂联合应用可能是未来提高Dox疗效的新的治疗策略。

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影响因子:2.12
发表时间:2020-03-01
DOI:10.1259/bjr.20180883
作者列表:["Tran S","Puric E","Walser M","Poel R","Datta NR","Heuberger J","Pica A","Marder D","Lomax N","Bolsi A","Morach P","Bachtiary B","Seddon BM","Schneider R","Bodis S","Weber DC"]

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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.

翻译标题与摘要 下载文献
影响因子:2.83
发表时间:2020-01-01
DOI:10.1007/s00520-019-04843-9
作者列表:["Dohzono S","Sasaoka R","Takamatsu K","Hoshino M","Nakamura H"]

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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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