A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy

Single-stage reconstruction of third-degree perineal lacerations in horses under general anesthesia : Utrecht repair method

OBJECTIVE: To describe perioperative management, surgical procedure, and outcome in mares with third-degree perineal lacerations (TDPL) treated with a single-stage repair, the Utrecht repair method (URM). STUDY DESIGN: Retrospective study. ANIMALS: Twenty mares with TDPL. METHODS: Medical records of mares with TDPL reconstructed with a URM were reviewed for perioperative management; surgical outcome; and postoperative fertility, athletic performance, and complications. RESULTS: Mares ranged in age from 3.5 to 11 years. Long-term follow-up was available for 13 mares. Mean duration of follow-up was 9 years (median, 9.5; range, 2-215 months (17.9 years)). Standardized perioperative fasting and postoperative refeeding protocols were used. Only five mares received supportive gastric medication. Reconstruction of the rectovestibular shelf was successful in 18 of 20 mares. Two of 20 mares developed a small rectovestibular fistula after the initial repair, which was successfully repaired with a second surgery. Other postoperative complications were observed in 13 mares and consisted of mild postanesthetic myositis, facial nerve paralysis, esophageal obstruction, rectal obstipation, partial perineal dehiscence, and rectal or vestibular wind-sucking. Six of seven mares that were subsequently bred became pregnant. One mare was successfully used for embryo recovery, and five of six mares foaled without recurrence of a TDPL. Nine of 13 mares were used for riding at various levels. CONCLUSION: The alternative single-stage reconstruction for TDPL was successful in 18 of 20 mares after a single surgery. No major complications related directly to the technique were noted. CLINICAL SIGNIFICANCE: The URM is a valid alternative surgical technique for repairing TDPL in mares