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Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
Translational Oncology ( IF 5 ) Pub Date : 2021-08-17 , DOI: 10.1016/j.tranon.2021.101203
Mark W Nachtigal 1 , Paris Musaphir 2 , Shiv Dhiman 3 , Alon D Altman 4 , Frank Schweizer 3 , Gilbert Arthur 2
Affiliation  

Chemotherapy resistant high grade serous ovarian cancer remains a clinically intractable disease with a high rate of mortality. We tested a novel glycosylated antitumor ether lipid called l-Rham to assess the in vitro and in vivo efficacy on high grade serous ovarian cancer cell lines and patient samples. l-Rham effectively kills high grade serous ovarian cancer cells grown as 2D or 3D cultures in a dose and time dependent manner. l-Rham efficacy was tested in vivo in a chicken allantoic membrane/COV362 xenograft model, where l-Rham activity was as effective as paclitaxel in reducing tumor weight and metastasis. The efficacy of l-Rham to reduce OVCAR3 tumor xenografts in NRG mice was assessed in low and high tumor burden models. l-Rham effectively reduced tumor formation in the low tumor burden group, and blocked ascites formation in low and high tumor burden animals. l-Rham demonstrates efficacy against OVCAR3 tumor and ascites formation in vivo in NRG mice, laying the foundation for further development of this drug class for the treatment of high grade serous ovarian cancer patients.



中文翻译:

一种新型糖基化抗肿瘤醚脂质在体外和体内对化疗耐药的高级别浆液性卵巢癌的细胞毒性能力

化疗耐药的高级别浆液性卵巢癌仍然是一种临床难治性疾病,死亡率很高。我们测试了一种称为l- Rham的新型糖基化抗肿瘤醚脂质,以评估对高级别浆液性卵巢癌细胞系和患者样本的体外体内功效。l -Rham 以剂量和时间依赖性方式有效杀死作为 2D 或 3D 培养物生长的高级浆液性卵巢癌细胞。在鸡尿囊膜/COV362 异种移植模型中体内测试l -Rham 功效,其中l -Rham 活性在减少肿瘤重量和转移方面与紫杉醇一样有效。l功效-Rham 减少 NRG 小鼠 OVCAR3 肿瘤异种移植物在低和高肿瘤负荷模型中进行了评估。l -Rham 有效地减少了低肿瘤负荷组的肿瘤形成,并阻止了低和高肿瘤负荷动物的腹水形成。l -Rham在 NRG 小鼠体内显示出对抗 OVCAR3 肿瘤和腹水形成的功效,为进一步开发该类药物用于治疗高级别浆液性卵巢癌患者奠定了基础。

更新日期:2021-08-17
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