CORE--MOUSE CORE

在其他组分中生产和筛选的合成肽（选择肽） 将基于其细胞毒性或细胞抑制性选择该NCDDG的 对6种标准化人细胞系（HL 60白血病，A375 黑色素瘤、MCF-7乳腺癌、SW 480结肠癌、A549肺癌和 NCap前列腺癌）。 这些细胞系以可重复的方式生长 当植入严重的合并症时， 免疫缺陷（SCID）小鼠。 植入这些细胞系的SCID小鼠 将用于评估具有体外活性的合成肽， 确定其药代动力学最大耐受剂量和疗效。 SCID 小鼠（每个处理组15只动物）将接种细胞类型 或在体外表现出敏感性的类型。 第一次出现时 在肿瘤中，将开始使用所选肽的每日治疗， 持续4周。 皮下肿瘤大小将与 未经处理的动物。 治疗的剂量和时间表将由 药理学和毒理学研究。 将结果反馈给其他人 项目将产生额外的肽，修改，以提高其 药理学或治疗特性。 预期的结果是 具有抗肿瘤活性的肽的鉴定 NCI和Selectide公司进行进一步开发。

Synthetic peptides (selectides) produced and screened in other components of this NCDDG will be selected based on their cytotoxic or cytostatic activity against 6 standardized human cell lines (HL60 leukemia, A375 melanoma, MCF-7 breast cancer, SW480 colon cancer, A549 lung cancer and NCap prostate cancer). These cell lines grow in a reproducible fashion with readily measured end points when implanted in the severe combined immune deficient (SCID) mouse. The SCID mouse implanted with these lines will be used to evaluate synthetic peptides with in vitro activity to determine their pharmacokinetics maximum tolerated dose and efficacy. SCID mice (15 animals per treatment group) will be inoculated with the cell type or types which showed sensitivity in vitro. On appearance of the first tumor, daily therapy with the selected peptide will be initiated and continued for 4 weeks. Subcutaneous tumor size will be compared to untreated animals. The dose and schedule of therapy will be determined by pharmacological and toxicological studies. Feedback of results to other projects will result in additional peptides, modified to improve their pharmacological or therapeutic profile. The anticipated outcome is the identification of peptides with antitumor activity to be submitted to the NCI and the Selectide Corporation for further development.