title: Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer.
abstract: OBJECTIVE
  Despite an 80% response rate to chemotherapy, epithelial ovarian cancer has the highest case fatality rate of all gynecologic malignancies. Several studies have shown the efficiency of anticancer peptides PNC-27 and PNC-28 in killing a variety of cancer cells selectively in vitro and in vivo. The purpose of this study was to evaluate the efficacy of PNC-27 against human primary epithelial ovarian cancer.
  
  
  METHODS
  We established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas. Two cell lines were obtained, one from mucinous cystadenocarcinoma, and the other from high-grade papillary serous carcinoma. The cancerous properties of these cells were characterized in vitro morphologically, by their growth requirements and serum independence. Treatment effects with PNC-27 were followed qualitatively by light microscopy, and quantitatively by measuring inhibition of cell growth using the MTT cell proliferation assay and direct cytotoxicity by measuring lactate dehydrogenase (LDH).
  
  
  RESULTS
  PNC-27 inhibits in a dose-dependent manner the growth of and is cytotoxic to human primary cancer cells that had been freshly isolated from two ovarian epithelial cancers. The results further show that the control peptide PNC-29 has no effect on the primary cancer cells. Our results also show that PNC-27 is cytotoxic to cells from long-established and chemotherapy-resistant human ovarian cancer cell lines.
  
  
  CONCLUSIONS
  These findings show, for the first time, the efficacy of PNC-27 on freshly isolated, primary human cancer cells. Our results indicate the potential of PNC-27 peptide as an efficient alternative treatment of previously untreated ovarian cancer as well as for ovarian cancers that have become resistant to present chemotherapies.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY, USA Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA ehsun.yazdi@downstate.edu jmichl@downstate.edu.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Sarafraz-Yazdi
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY, USA Division of Gynecologic Oncology, Methodist Hospital, Brooklyn, NY, USA.
authors.forename: Constantine
authors.initials: C
authors.lastname: Gorelick
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY, USA Department of Obstetrics and Gynecology, The Cancer Institute of New Jersey, UMDNJ, NJ, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Wagreich
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Ghadir
authors.initials: G
authors.lastname: Salame
authors.affiliation: Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Mallorie
authors.initials: M
authors.lastname: Angert
authors.affiliation: Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Gartman
authors.affiliation: Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Vinita
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Surgery, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Wilbur B
authors.initials: WB
authors.lastname: Bowne
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Ovadia
authors.initials: O
authors.lastname: Abulafia
authors.affiliation: Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA Department of Pathology, New York Harbor VA Medical Center, Brooklyn, NY, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Pincus
authors.affiliation: Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Josef
authors.initials: J
authors.lastname: Michl
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C549751:PNC-27; D016159:Tumor Suppressor Protein p53