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Biomedical subjects

Laura D Wood

Publications and source records attributed to Laura D Wood.

3 recordsLinked to original sources

Pancreatic ductal adenocarcinoma: The Vision of Heracles.

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, as tumors evolve faster than therapies. Resistance is ecological, not merely KRAS driven, involving overlooked players like high-grade pancreatic intraepithelial neoplasias (PanINs), peripancreatic fat, stromal mechanics, myeloid-neural circuits, metabolic rewiring, and systemic host responses. We propose precision interception targeting PanIN/intraductal papillary mucinous neoplasm (IPMN) biology, spatial-functional-proteogenomic classification beyond transcriptomics, the Heracles Protocol (measure, prime, strike, and adapt), and integrated technologies from AI pathology to exosomal delivery and CRISPR-based synergy mapping, together making PDAC more tractable.

Humans

Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct patterns and potential markers of progression.

To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection. Some high-grade associated proteins are also detected in pancreatic cyst fluids, which allows us to link proteins and glycoproteins expressed in neoplastic cells to clinically accessible biospecimens. Altered glycosylation level of extracellular matrix (ECM) proteins is observed in IPMNs compared to normal ducts. Additionally, we identify a subset of IPMNs with PDAC-like features, including elevated expression of ECM proteins. These findings offer insight into progression-associated proteins and emphasize the diagnostic and therapeutic potential of these proteins in pancreatic tumors.

Humans