Burke F, East N, Upton C, Patel K, Balkwill F R
Biological Therapy Laboratory, Imperial Cancer Research Fund, London, U.K.
Eur J Cancer. 1997 Jun;33(7):1114-21. doi: 10.1016/s0959-8049(97)88065-3.
Locoregional human IFN-gamma may have activity against refractory ovarian cancer. We investigated this further in an ovarian cancer xenograft model. Administered at clinically relevant doses, intraperitoneal IFN-gamma prolonged the survival of mice bearing multiple established peritoneal tumours, with optimal treatment giving a 3-6-fold increase in median survival time. Daily dosing, which was superior to intermittent treatment, decreased DNA synthesis and induced apoptosis in tumour cells with maximal effects after 7-21 days treatment. This was preceded by an increase in p53 protein at 48 h. The effect of IFN-gamma was not enhanced by sequential treatment with carboplatin. However, the matrix metalloprotease inhibitor, batimastat, further increased mouse survival when given after IFN-gamma. Thus IFN-gamma is cytotoxic to ovarian epithelial cells in vivo and intensive locoregional dosing over short periods is effective. Sequential administration of novel agents that perturb the host/tumour relationship may be of benefit.
局部区域使用的人γ干扰素可能对难治性卵巢癌具有活性。我们在卵巢癌异种移植模型中对此进行了进一步研究。以临床相关剂量腹腔注射γ干扰素可延长患有多个已形成腹膜肿瘤的小鼠的生存期，最佳治疗可使中位生存时间增加3至6倍。每日给药优于间歇治疗，可减少肿瘤细胞中的DNA合成并诱导细胞凋亡，在治疗7至21天后效果最为明显。在此之前，p53蛋白在48小时时增加。顺铂序贯治疗并未增强γ干扰素的效果。然而，基质金属蛋白酶抑制剂batimastat在γ干扰素给药后使用可进一步提高小鼠生存率。因此，γ干扰素在体内对卵巢上皮细胞具有细胞毒性，短期内进行强化局部区域给药是有效的。序贯给予扰乱宿主/肿瘤关系的新型药物可能有益。
