PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy. Surgical relevance The immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4. This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.
Radiological features of intraventricular and extraventricular PAs were similar to typical ones, including enhanced nodules within cysts. Radiological findings can usually diagnose PAs correctly.
284 Background: Wild toad venom has been used for over 1,000 years as a traditional Chinese medicine; H, the extract of dried toad skin glands, is a potent cardiac glycoside without significant toxicity. H has demonstrated preliminary evidence of antitumor activity in phase I clinical trial evaluation (Cancer 2009, 115:5309-18). Methods: We conducted a randomized, single-blind, phase II clinical trial of G + H versus G + placebo in patients with LAPC or MPC. Plasma bufalin levels were performed in H-treated subjects. 80 evaluable subjects accrued from October 2007 to May 2010 and were treated with G 1,000mg/m2 (iv on days 1, 8, 15, q 28d) plus either H (20 mL/m2 iv daily for 21 days followed by 7 days off, q 28d) or placebo. Demographic data is demonstrated in the table below. Results: Grade 3/4 adverse events, objective radiographic response rates (ORR), time to progression (TTP), quality of life (QOL), and overall survival (OS) were similar in the two groups (Table). There was not a statistically significant difference in the average plasma bufalin levels in patients with a radiographic partial response (PR) or stable disease versus those with progressive disease (PD) (0.098 ± 0.093 ng/mL vs. 0.071 ± 0.048 ng/mL, p=0.679). Conclusions: H when added to G was well tolerated but did not improve OS, TTP, QOL, or ORR. Further investigation of a more potent oral formulation of H is planned. H provided by Shenzhen 999 Traditional Chinese Medicine & Development Co., Ltd. Supported by NIH U19CA121503-01. [Table: see text] No significant financial relationships to disclose.
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