Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA.
Endocrine. 2010 Jun;37(3):430-9. doi: 10.1007/s12020-010-9333-5. Epub 2010 Apr 20.
Women with ovarian cancer have a low survival rate and develop resistance to chemotherapy, so new approaches to treatment are needed. We unexpectedly found administration of a replication-deficient adenovirus containing human growth hormone sequences (AdXGH) was beneficial in a mouse model of human ovarian cancer. Intraperitoneal injections of AdXGH prolonged median survival from a mean of 31 ± 1.2 to 40 ± 1.4 days in immunodeficient SCID mice given SKOV3.ip1 human ovarian cancer cells in the peritoneal cavity. Adenovirus containing human prolactin or del32-71growth hormone sequences had no effect. Repeated injection of growth hormone or implantation of tablets with sustained growth hormone release did not increase survival. Control mice had overlapping tumors throughout the peritoneal cavity and liver and frequent lung metastases 24 days after tumor cell injection. Mice that received two injections of AdXGH had no lung metastases. Mice that received four injections had no lung or liver metastases and peritoneal fibrosis. They did not survive longer than mice that received two injections, but they had enlarged livers with hepatocellular changes, indicating that a limitation of increasing the dose is liver toxicity.
患有卵巢癌的女性存活率低，并对化疗产生耐药性，因此需要新的治疗方法。我们出人意料地发现，给予携带人生长激素序列的复制缺陷型腺病毒（AdXGH）在人卵巢癌的小鼠模型中是有益的。腹腔内注射 AdXGH 可延长免疫缺陷性 SCID 小鼠的中位生存期，从腹腔内给予 SKOV3.ip1 人卵巢癌细胞的平均 31 ± 1.2 天延长至 40 ± 1.4 天。含有人生长激素或 del32-71 生长激素序列的腺病毒没有效果。重复注射生长激素或植入具有持续生长激素释放的片剂均不能提高生存率。对照小鼠在腹腔和肝脏中具有重叠的肿瘤，并且在肿瘤细胞注射后 24 天经常发生肺转移。接受两次 AdXGH 注射的小鼠没有肺转移。接受四次注射的小鼠没有肺或肝转移和腹膜纤维化。它们的存活时间不比接受两次注射的小鼠长，但它们的肝脏增大，伴有肝细胞变化，这表明增加剂量的限制是肝毒性。
