A hallmark of pancreatic ductal adenocarcinoma cancer (PDAC) cells is metabolic reprogramming that facilitates tumor progression. In a recent paper published in Molecular Cell, Nagarajan et al. discover that paraoxonase (PON)2 stimulates glucose transporter (GLUT)1-mediated glucose uptake, prevents AMP-activated protein kinase (AMPK)-mediated anoikis, and consequently promotes PDAC development and metastasis.
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Effect of tumor microenvironment in pancreatic cancer on the loss of β-cell mass: implications for type 3c diabetes.
J Gastroenterol
January 2025
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
Background: To explore the complex interactions between the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) and the loss of β-cell mass, further elucidating the mechanisms of type 3c diabetes mellitus (T3cDM) onset.
Methods: Single-cell RNA sequencing was employed to analyze the PDAC TME, identifying cell interactions and gene expression changes of endocrine cells. Pathological changes and paraneoplastic islets were assessed in the proximal paratumor (PP) and distal paratumor (DP).
Arginine demethylation of Serine/Arginine-rich splicing factor 1 enhances miRNA enrichment in small extracellular vesicles derived from pancreatic ductal adenocarcinoma cells.
FASEB J
January 2025
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Small extracellular vesicles (sEVs) are enriched in certain miRNAs, impacting the progression of pancreatic ductal adenocarcinoma (PDAC). The mechanisms involved in the selective sEV miRNA enrichment remain to be elucidated. We recently reported that Serine/Arginine-rich splicing factor 1 (SRSF1) regulates selective sEV miRNA enrichment in PDAC cells.
View Article and Find Full Text PDFAim: Lymph node metastasis is an adverse prognostic factor in pancreatic ductal adenocarcinoma. However, it remains a challenge to predict lymph node metastasis using preoperative imaging alone. We used machine learning (combining preoperative imaging findings, tumor markers, and clinical information) to create a novel prediction model for lymph node metastasis in resectable pancreatic ductal adenocarcinoma.
View Article and Find Full Text PDFCost-effectiveness analysis of first-line combination chemotherapy regimens for metastatic pancreatic cancer and evidence-based pricing strategy of liposomal irinotecan in China.
Front Pharmacol
December 2024
Department of Pharmacy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, China.
Background: The phase III NAPOLI-3 trial, which upgraded FOLFIRINOX (leucovorin, fluorouracil, irinotecan and oxaliplatin) to NALIRIFOX (liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil), demonstrated the superiority of NALIRIFOX over GEMNABP (gemcitabine and nab-paclitaxel) as the first-line treatment for metastatic pancreatic ductal adenocarcinoma. The purpose of this study was to assess the cost-effectiveness of NALIRIFOX, FOLFIRINOX, and GEMNABP, and to simulate the price of liposomal irinotecan at which NALIRIFOX could achieve cost-effectiveness.
Methods: A partitioned survival model was performed to evaluate the cost-effectiveness of NALIRIFOX, FOLFIRINOX and GEMNABP from the perspective of the Chinese healthcare system.
Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer.
Front Oncol
December 2024
Research Institute of Internal Medicine and Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.
Background/aims: It was recently reported that a higher concentration of the bacterially produced metabolite indole 3-acetate (3-IAA) in blood was linked to a better response to chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to extend these observations to patients diagnosed with non-metastatic PDAC.
Method: We measured circulating 3-IAA in samples from a prospective population-based cohort of 124 patients with borderline resectable or locally advanced PDAC, collected before initiating neoadjuvant chemotherapy.
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