H, hexose F, fucose N, N-acetylglucosamine. ( E) Distribution of top N-glycans in PXO. Inviting his subjects to his Californian backyard with a week’s worth of their trash in tow, Gregg Segal’s confronting portraits draw attention to our careless relationship to waste. Red, high mannose green, pauci-mannose blue, hybrid purple, complex. Discover all 38 winners, jurors’ picks, and finalists of the LensCulture 2021 Street Photography Awards. Colored dots indicate abundance of glycans in each class. ( D) Relative abundance of the 57 common N-glycans in PDX or PXO samples. ( C) Numbers on y axis refer to numbers of the subgroups corresponding to varying degrees of sialylation or fucosylation, and x axis shows percentage of glycans with different distribution patterns. ( B) Average relative abundance of 3 major N-glycan classes in PDX and PXO models mean values and 95% confidence interval are indicated. Paired, glycans identified in both matched PDX and PXO models discordant, glycans identified in PDX and PXO from different tumors PDX only, glycans identified only in PDX tumors PXO only, glycans identified only in PXO. The y axis identifies the different classes of glycans, the numbers represent numbers of N-glycan in each class, and the x axis shows percentage of glycans with different distribution patterns. ( A) Major N-glycan classes and their occurrence in all PXO and matched PDX models analyzed. Thus, we demonstrate the utility of organoid cultures to not only model in vivo drug responses but also serve as a powerful platform for discovering clinically actionable serologic biomarkers. We validated our findings using plasma samples from patients with PDAC, benign gastrointestinal diseases, and chronic pancreatitis and discovered that 4 EV proteins are potential circulating biomarkers for PDAC. Last, we developed a secreted biomarker discovery pipeline using media supernatant of organoid cultures and identified potentially new extracellular vesicle (EV) protein markers. In addition, we identify a core set of 57 N-glycans detected in all 10 models that represent 50%-94% of the relative abundance of all N-glycans detected in each of the models. In addition, we analyzed the glycome of PDX and PXO models and demonstrate that PXOs recapitulate the in vivo glycan landscape.
We report a specific relationship between area under the curve value of organoid drug dose response and in vivo tumor growth, irrespective of the drug treatment. Here we conduct a methodical analysis of pancreatic ductal adenocarcinoma (PDAC) tumor organoid drug response in paired patient-derived xenograft (PDX) and PDX-derived organoid (PXO) models grown under WNT-free culture conditions. Patient-derived organoid models are proving to be a powerful platform for both basic and translational studies.
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