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实验性卵巢癌腹水的代谢组学特征分析

Metabolomic characterization of experimental ovarian cancer ascitic fluid.

作者信息

Bharti Santosh K, Wildes Flonné, Hung Chien-Fu, Wu T C, Bhujwalla Zaver M, Penet Marie-France

机构信息

Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD.

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD.

出版信息

Metabolomics. 2017 Oct;13. doi: 10.1007/s11306-017-1254-3. Epub 2017 Aug 24.

Abstract

INTRODUCTION

Malignant ascites (MA) is a major cause of morbidity that occurs in 37% of ovarian cancer patients. The accumulation of MA in the peritoneal cavity due to cancer results in debilitating symptoms and extremely poor quality of life. There is an urgent unmet need to expand the understanding of MA to design effective treatment strategies, and to improve MA diagnosis.

OBJECTIVE

Our purpose here is to contribute to a better characterization of MA metabolic composition in ovarian cancer.

METHOD

We determined the metabolic composition of ascitic fluids resulting from orthotopic growth of two ovarian cancer cell lines, the mouse ID8-vascular endothelial growth factor (VEGF)-Defb29 cell line and the human OVCAR3 cell line using high-resolution H MRS. ID8-VEGF-Defb29 tumors induce large volumes of ascites, while OVCAR3 tumors induce ascites less frequently and at smaller volumes. To better understand the factors driving the metabolic composition of the fluid, we characterized the metabolism of these ovarian cancer cells in culture by analyzing cell lysates and conditioned culture media with H NMR.

RESULTS

Distinct metabolite patterns were detected in ascitic fluid collected from OVCAR3 and ID8-VEGF-Defb29 tumor bearing mice that were not reflected in the corresponding cell culture or conditioned medium.

CONCLUSION

High-resolution H NMR metabolic markers of MA can be used to improve characterization and diagnosis of MA. Metabolic characterization of MA can provide new insights into how MA fluid supports cancer cell growth and resistance to treatment, and has the potential to identify metabolic targeting strategies to reduce or eliminate the formation of MA.

摘要

引言

恶性腹水(MA)是导致发病的主要原因,在37%的卵巢癌患者中出现。癌症导致腹腔内MA积聚,引发使人虚弱的症状,严重影响生活质量。迫切需要加深对MA的了解,以设计有效的治疗策略并改善MA的诊断。

目的

我们的目的是更好地描述卵巢癌中MA的代谢成分。

方法

我们使用高分辨率氢磁共振波谱(H MRS)测定了两种卵巢癌细胞系原位生长产生的腹水代谢成分,这两种细胞系分别是小鼠ID8-血管内皮生长因子(VEGF)-Defb29细胞系和人OVCAR3细胞系。ID8-VEGF-Defb29肿瘤会诱导大量腹水产生,而OVCAR3肿瘤诱导腹水产生的频率较低且量较少。为了更好地理解驱动腹水代谢成分的因素,我们通过用氢核磁共振(H NMR)分析细胞裂解物和条件培养基,对培养中的这些卵巢癌细胞代谢进行了表征。

结果

在从携带OVCAR3和ID8-VEGF-Defb29肿瘤的小鼠收集的腹水中检测到了独特的代谢物模式,这些模式在相应的细胞培养物或条件培养基中未得到体现。

结论

MA的高分辨率H NMR代谢标志物可用于改善MA的表征和诊断。MA的代谢表征可为MA液体如何支持癌细胞生长和抗治疗能力提供新见解,并有潜力识别减少或消除MA形成的代谢靶向策略。

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