There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.
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http://dx.doi.org/10.3967/bes2018.062 | DOI Listing |
PLoS One
September 2024
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Int J Mol Sci
November 2022
Laboratoire d'Oncologie Moléculaire, Centre de Recherche CERMO-FC, Département de Chimie, Université du Québec à Montréal, Montréal, QC H3C 3P8, Canada.
Modulations in cell surface receptor ectodomain proteolytic shedding impact on receptor function and cancer biomarker expression. As such, heavily pursued therapeutic avenues have exploited LDL receptor-related protein-1 (LRP-1)-mediated capacity in internalizing Angiopep-2 (An2), a brain-penetrating peptide that allows An2-drug conjugates to cross the blood-brain tumor barrier (BBTB). Given that LRP-1 is proteolytically shed from the cell surface through matrix metalloproteinase (MMP) activity, the balance between MMP expression/function and LRP-1-mediated An2 internalization is unknown.
View Article and Find Full Text PDFFront Oncol
January 2022
Department of Genetics of Skin Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
The BRAF inhibitor vemurafenib, approved for treating patients with BRAF V600E-mutant and unresectable or metastatic melanomas, rapidly induces cutaneous adverse events, including hyperkeratotic skin lesions and cutaneous squamous cell carcinomas (cSCC). To determine, how vemurafenib would provoke these adverse events, we utilized long-term skin equivalents (SEs) comprising epidermal keratinocytes and dermal fibroblasts in their physiological environment. We inserted keratinocytes with different genetic background [normal keratinocytes: NHEK, HaCaT (p53/mut), and HrasA5 (p53/mut+Hras/mut)] to analyze effects depending on the stage of carcinogenesis.
View Article and Find Full Text PDFPLoS One
April 2021
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
Ilomastat, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), has drawn attentions for its function in alleviating radiation damage. However, the detailed mechanisms of Ilomastat's protection from animal model remain not fully clear. In this study, the C57BL/6 mice were pre-administrated with Ilomastat or vihicle for 2 h, and then total body of mice were exposed to 6 Gy of γ-rays.
View Article and Find Full Text PDFClin Exp Immunol
January 2021
Department of Computer Science, University of Verona, Verona, Italy.
Pseudomonas aeruginosa is the major respiratory pathogen in patients with cystic fibrosis (CF). P. aeruginosa-secreted proteases, in addition to host proteases, degrade lung tissue and interfere with immune processes.
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