Abstract 1454: Patient-derived xenograft model using peritoneal fluid of gastric cancer patients

Abstract

Abstract Peritoneal metastasis is the most frequent pattern of recurrence in patients with gastric cancer (GC). Patient derived xenograft (PDX) models using peritoneal fluid have been required to understand its biology and for the drug screening. So, we established the PDX model by peritoneal fluid in stage IV GC patients. First, we confirmed the preparation condition of peritoneal fluid cells for PDX model as approximately 1×107 cells in PBS. Then, we observed the engraftment rate of PDX which was 15.8% (3 of 19 patients, P2, P10 and P11). The time to 100 mm3 tumor size at F1 of 3 models was 47 ± 1, 26.7 ± 0.6 and 68 days respectively. Then, we checked the change of serial engraftment rate until F3. The more passage was progressed, the higher engraft rate was, 75% (3 of 4 mice) to 90% (9 of 10 mice) at P2, 60% (3 of 5 mice) to 85% (17 of 20 mice) at P10 and 33.3% (1 of 3 mice) to 86.7% (13 of 15 mice) at P11. In addition, time to 100mm3 tumor size of engrafted PDXs was faster at F3 than F1 in all 3 cases (41.1% in P2, 46.4% in P10 and 47.5% in P11). Also, tumor doubling time showed decreased in all engrafted PDXs according to passage (70.8% in P2, 11.5% in P10 and 71.5% in P12). Then, we checked the re-engraftment rate after thawing the frozen F3 tissue section of P2. F4 PDXs were re-engrafted 100% (3/ 3 mice) after thawing, and time to 100mm3 tumor size and tumor doubling times were not different between F3 and F4. It means that freezing and thawing of tumor fragment did not affect to engraft. After that, we compared the characterization of F0 peritoneal fluid of patient, F1∼F3 PDX tumor and the cell line established from F0. The morphologies of them were comparable by H&E staining. Also, molecule expressions ofF0 to F3 and cell lines were analogous. The genetic alterations according to passages in F0 to F3 are on-going. As a result, we observed PDX from peritoneal fluid of advanced gastric cancer is feasible but various according to each patient. The PDX model by peritoneal fluid of GC patients might be helpful the biological understanding and drug development for personalized therapies. Citation Format: Jeong Min Kim, Won Suk Lee, Woo Sun Kwon, Han Na Park, Hye Rin Lee, Hyun Myong Kim, Tae Soo Kim, Hyunki Kim, Jae Kyung Roh, Hyun Cheol Chung, Sun Young Rha. Patient-derived xenograft model using peritoneal fluid of gastric cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1454. doi:10.1158/1538-7445.AM2015-1454