Hijioka, S. | Search bioRxiv

bioRxiv2025

Platform of single-molecule enzyme activity-based liquid biopsy for detection of pancreatic adenocarcinoma at early stages

Liquid biopsy analyzes biomolecules in biofluids to provide critical information for the early detection of diseases and the development of more effective treatment strategies. Among these biomolecules, the functional states of proteins offer particularly valuable insights due to their direct correlation with phenotypic changes. However, current approaches for assessing protein function in liquid biopsies are often limited by low detection sensitivity. Here, we present a liquid biopsy platform that analyzes single-molecule protease/peptidase activity to detect pathological alterations in enzyme function in blood samples. The platform demonstrates potential for identifying patients with early-stage (stage I-II) pancreatic ductal adenocarcinoma (PDAC).

biochemistry↗

bioRxiv2022

Metabolic intervention that reduces glucose-insulin signaling suppresses the onset and progression of neuroendocrine tumors

Insulin signaling often plays a role in the regulation of cancer including tumor initiation, progression, and response to treatment. In addition, the insulin-regulated PI3K-Akt-mTOR pathway plays an important role in the regulation of islet cell proliferation and this pathway is hyperactivated in human non-functional pancreatic neuroendocrine tumors (PanNETs). We therefore investigated the effect of a very low carbohydrate diet (ketogenic diet) on a mouse model that develops non-functional PanNETs to ask how reduced PI3K-Akt-mTOR signaling might affect the development and progression of non-functional PanNET. We found that this dietary intervention resulted in lower PI3K-Akt-mTOR signaling in islet cells and a significant reduction in PanNET formation and progression. We also found that this treatment had a significant effect on the suppression of pituitary NET development. Furthermore, we found that non-functional PanNET patients with lower blood glucose levels tend to have a better prognosis than patients with higher blood glucose levels. This preclinical study shows that a dietary intervention that results in lower serum insulin levels leads to lower insulin signal within the neuroendocrine cells and has a striking suppressive effect on the development and progression of both pancreatic and pituitary NETs.

cancer biology↗