Anti-tumor effects of adenovirus containing human growth hormone sequences in a mouse model of human ovarian cancer.
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.
Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA.
Yonglian
Y
Zhu
José B
JB
Fariña
Syrus
S
Meshack
Ana
A
Santoveña
Shilpa
S
Patel
Alexis
A
Oliva
Matias
M
Llabrés
Michael E
ME
Hodsdon
Carmen J
CJ
Booth
Priscilla S
PS
Dannies
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D016190:Carboplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000628:therapy*; D017239:Paclitaxel / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019382:Human Growth Hormone; D016190:Carboplatin; D017239:Paclitaxel