Biology subjects

Vares, G.

Publications and source records attributed to Vares, G..

3 recordsLinked to original sources

bioRxiv2026

Medical diagnostic radiation promotes murine Apc/Kras-driven colon carcinogenesis

Computed tomography (CT) is one of the most widely used diagnostic imaging modalities worldwide, yet the biological risks associated with such exposures remain incompletely understood. Here, we investigated the effects of clinically relevant low (25 mGy) and moderate (250 mGy) dose radiation exposures on colon carcinogenesis using in vivo KPC:APC transgenic mice and an ex vivo organoid system carrying inducible Apc and Kras driver mutations. While medical diagnostic radiation did not initiate carcinogenesis in wild-type and did not alter carcinogenesis in Apc-mutant tissues, it significantly promoted the progression of precancerous lesions in the presence of both mutations, especially when exposure occurred during early tumor initiation. Organoids derived from mice harboring both Apc and Kras mutations mirrored this susceptibility, exhibiting radiation-induced enlargement and activation of transcriptomic and proteomic programs associated with colorectal cancer, including cell-cycle dysregulation and mTORC1 pathway activation. These findings show that radiation doses within the range delivered by routine abdominal CT imaging can potentiate the carcinogenic processes in genetically predisposed cells, underscoring the need to consider individual susceptibility when evaluating the benefit-risk balance of medical diagnostic exposures.

Cancer Biology↗

bioRxiv2024

Post-transcriptional regulation by the CCR4-NOT deadenylase complex maintains redox homeostasis in insulin biosynthesis in mouse pancreatic β cells

Pancreatic {beta} cells synthesize insulin to maintain glucose homeostasis. In diabetes, elevated blood glucose and insulin resistance compel {beta} cells to produce insulin, and hence {beta} cells are vulnerable to oxidative stress by glucotoxicity. In insulin biosynthesis, the conversion of proinsulin to insulin is initiated by forming disulfide bonds in proinsulin for oxidative protein folding. Insulin content and insulin secretion in {beta} cells are decreased by deletion of CNOT7, a catalytic subunit of the CCR4-NOT complex, and accompanied by increased proinsulin, implying the impaired conversion of proinsulin to insulin. We found that PRDX4 essential for disulfide bond formation in proinsulin, is reduced in Cnot7-KO {beta} cells. Moreover, protein expression of CNOT8, a paralog of CNOT7, is increased in Cnot7-KO {beta} cells and binds to Prdx4 mRNA via MSI2. Here, we demonstrate the post-transcriptional regulation of Prdx4 mRNA by the CCR4-NOT complex to maintain oxidative-reductive homeostasis in insulin biosynthesis. HIGHLIGHTSO_LIInsulin content and secretion are decreased in Cnot7-KO pancreatic {beta} cells. C_LIO_LIPRDX4, needed for proinsulin folding, is decreased in Cnot7-KO pancreatic islets. C_LIO_LIThe conversion of proinsulin to insulin is impaired in Cnot7-KO {beta} cells. C_LIO_LICNOT8, but not CNOT7, interacts with MSI2 that binds to Prdx4 mRNA C_LI

physiology↗

bioRxiv2018

Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

Treatment resistance, relapse and metastasis remain critical issues in some challenging cancers, such as chondrosarcomas. Boron-neutron Capture Therapy (BNCT) is a targeted radiation therapy modality that relies on the ability of boron atoms to capture low energy neutrons, yielding high linear energy transfer alpha particles. We have developed an innovative boron-delivery system for BNCT, composed of multifunctional fluorescent mesoporous silica nanoparticles (B-MSNs), grafted with an activatable cell penetrating peptide (ACPP) for improved penetration in tumors and with Gadolinium for magnetic resonance imaging (MRI) in vivo. Chondrosarcoma cells were exposed in vitro to an epithermal neutron beam after B-MSNs administration. BNCT beam exposure successfully induced DNA damage and cell death, including in radio-resistant ALDH+ cancer stem cells (CSCs), suggesting that BNCT using this system might be a suitable treatment modality for chondrosarcoma or other hard-to-treat cancers.

cancer biology↗