title: Antiangiogenic Therapy with Human Apolipoprotein(a) Kringle V and Paclitaxel in a Human Ovarian Cancer Mouse Model.
abstract: BACKGROUND
  The present study compared the effect of combination therapy using human apolipoprotein(a) kringle V (rhLK8) to conventional chemotherapy with paclitaxel for human ovarian carcinoma producing high or low levels of vascular endothelial growth factor (VEGF).
  
  
  METHODS
  Human ovarian carcinoma cells producing high (SKOV3ip1) or low (HeyA8) levels of VEGF were implanted into the peritoneal cavity of female nude mice. Seven days later, mice were randomized into four groups: control (vehicle), paclitaxel [5 mg/kg, weekly intraperitoneal (i.p.) injection], rhLK8 (50 mg/kg, daily i.p. injection), or the combination of paclitaxel and rhLK8. Mice were treated for 4 weeks and examined by necropsy.
  
  
  RESULTS
  In mice implanted with SKOV3ip1 cells, rhLK8 treatment had no significant effect on tumor incidence or the volume of ascites but induced a significant decrease in tumor weight compared with control mice. Paclitaxel significantly reduced tumor weight and ascites volume, and combination treatment with paclitaxel and rhLK8 had an additive therapeutic effect. Similarly, in HeyA8 mice, the effect of combination treatment on tumor weight and tumor incidence was statistically significantly greater than that of paclitaxel or rhLK8 alone. Immunohistochemical analysis showed a significant decrease in microvessel density and a marked increase of apoptosis in tumor and tumor-associated endothelial cells in response to combination treatment with paclitaxel and rhLK8.
  
  
  CONCLUSIONS
  Collectively, these results suggest that antiangiogenic therapy with rhLK8 in combination with taxane-based conventional chemotherapy could be effective for the treatment of ovarian carcinomas, regardless of VEGF status.
authors.affiliation: Mogam Biotechnology Research Institute, Yongin, Republic of Korea ; Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Yu
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ho-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Obstetrics and Gynecology, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sun-Joo
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Langley
authors.affiliation: Mogam Biotechnology Research Institute, Yongin, Republic of Korea.
authors.forename: Yeup
authors.initials: Y
authors.lastname: Yoon
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Lee S H
authors.initials: LS
authors.lastname: Yi
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
authors.affiliation: Research Center for Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Jang-Seong
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sun Jin
authors.initials: SJ
authors.lastname: Kim