RAS and K-RAS activity was measerd by GST-RBD Pull-down assay. Results: Knockdown of DJ-1 expression decreased IC-50 of erlotinib in BxPC-3 measured by CCK-8 assay (67 uM vs. 20 uM p < 0.05). Further study showed that both inhibition of proliferation and induction of apoptosis were contributed to this effect. In BxPC-3/NC treated with erlotinib 5 and 50 uM for 72 h, BrdU positive JQ1 cost cell percentage was decreased to 62.3 ± 1.9%, 18.5 ± 0.6% respectively of control. But in BxPC-3/DJ-1 cells, it was

decreased to 41.3 ± 1.3%, 8.3 ± 0.2% respectively of control (both p < 0.05 vs. BxPC-3/NC). Treatment with0, 5 or 50 uM erlotinib for 72 h increased BxPC-3/NC TUNEL positive cell form 3.0% to 7.3% PLX4032 mw and 13.1% respectively, but in BxPC-3/DJ-1 it was increased from 2.8% to 10.5% and 21.7% (both p < 0.05 vs. BxPC-3/NC). Knockdown DJ-1 also decreased

bothRAS and K-RAS activity to 71% and 40.5% in BxPC-3 (p < 0.05 , p < 0.05). Conclusion: Silence of DJ-1 decreased K-RAS activity, augment anti-proliferation and pro-apoptotic effects of erlotinib in pancreatic cancer. Key Word(s): 1. DJ-1; 2. anti-EGFR therapy; 3. pancreatic cancer; 4. K-RAS Presenting Author: SUSUMU HIJIOKA Additional Authors: NOBUMASA MIZUNO, KAZUO HARA, HIROSHI IMAOKA, KENJI YAMAO Corresponding Author: SUSUMU HIJIOKA Affiliations: Aichi Cancer Center Hospital, Aichi Cancer Center Hospital, Aichi Cancer Center Hospital, Aichi Cancer Center Hospital Objective: Background: Progesterone In 2010, World Health Organization classified pancreatic neuroendocrine neoplasm (pNEN) as follows: G1, G2, neuroendocrine carcinoma (WHO-NEC) according to the Ki67 activity index. However, the WHO-NEC may exert a heterogeneous behavior which still not fully studied. Therefore, we tried to characterize the clinicopathologic characteristics of the WHO-NEC and examine to which extent the WHO 2010 classification

system can define all pNENs clearly. Methods: We, retrospectively, evaluate the clinic pathologic characteristics, K-ras mutations, treatment and the prognoses of eleven patients diagnosed as NEC between 2001 and 2013 according to the WHO 2010 classification. Results: The median Ki67 was 47.7 (32-90) and median tumor size was 35 mm. 9 (82%) patients had liver metastasis. For more morphological characterization, we divided WHO-NEC to a well-differentiated (NET-G3; n = 4), and a poorly-differentiated (Pure-NEC; n = 7) lesions and a further morphological subgrouping of the pure-NEC into large-cell type (LCNEC; n = 3), and small cell type (SCNEC; n = 4). A clinicopathological comparison between the NET-G3 and Pure-NEC group was revealed: 1) the detection of vascularity by multi-detector CT scan was 50% (2/4) in NET-G3 and 0% (0/7) in Pure-NEC (P = 0.109); 2) the median Ki67 was 45.1 (40-53) in NET-G3 and 64.2% (32-90), in Pure-NEC (P = 0.201); 3) the K-ras mutation was 0% (0/3) in NET-G3 and 85.7% (6/7) in Pure-NEC (P = 0.