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| http://dx.doi.org/10.1002/anie.201102459 | DOI Listing |
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Imaging phenotype reveals that disulfirams induce protein insolubility in the mitochondrial matrix.
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December 2024
Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Shizuoka, Japan.
The cell painting assay is useful for understanding cellular phenotypic changes and drug effects. To identify other aspects of well-known chemicals, we screened 258 compounds with the cell painting assay and focused on a mitochondrial punctate phenotype seen with disulfiram. To elucidate the reason for this punctate phenotype, we looked for clues by examining staining steps and gene knockdown as well as examining protein solubility and comparing cell lines.
View Article and Find Full Text PDFRole of immune-checkpoint LAG3 as a biomarker finding tool in patient-derived organoid cultures of breast cancer.
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IRCCS SYNLAB SDN, Naples, 80143, Italy.
LAG3 plays a regulatory role in immunity and emerged as an inhibitory immune checkpoint molecule comparable to PD-L1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. We generated 3D cancer cultures as a model to identify novel molecular biomarkers for the selection of patients suitable for α-LAG3 treatment and simultaneously the possibility to perform an early diagnosis due to its higher presence in breast cancer, also to achieve a theragnostic approach. Our data confirm the extreme dysregulation of LAG3 in breast cancer with significantly higher expression in tumor tissue specimens, compared to non-cancerous tissue controls.
View Article and Find Full Text PDFInvestigating the effects of stereotactic body radiation therapy on pancreatic tumor hypoxia and microvasculature in an orthotopic mouse model using intravital fluorescence microscopy.
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Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Despite decades of improvements in cytotoxic therapy, the current standard of care for locally advanced pancreatic cancer (LAPC) provides, on average, only a few months of survival benefit. Stereotactic Body Radiation Therapy (SBRT), a technique that accurately delivers high doses of radiation to tumors in fewer fractions, has emerged as a promising therapy to improve local control of LAPC; however, its effects on the tumor microenvironment and hypoxia remain poorly understood. To explore how SBRT affects pancreatic tumors, we combined an orthotopic mouse model of pancreatic cancer with an intravital microscopy platform to visualize changes to the in vivo tumor microenvironment in real-time.
View Article and Find Full Text PDFApical-out intestinal organoids as an alternative model for evaluating deoxynivalenol toxicity and Lactobacillus detoxification in bovine.
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Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Wanju, Republic of Korea.
Small intestinal organoids are similar to actual small intestines in structure and function and can be used in various fields, such as nutrition, disease, and toxicity research. However, the basal-out type is difficult to homogenize because of the diversity of cell sizes and types, and the Matrigel-based culture conditions. Contrastingly, the apical-out form of small intestinal organoids is relatively uniform and easy to manipulate without Matrigel.
View Article and Find Full Text PDFHypoxia-induced TPC2 transcription and glycosylation aggravates pulmonary arterial hypertension by blocking autophagy flux.
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December 2024
Department of Respiratory Medicine, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), No. 61 Jiefang Xi Road, Changsha, Hunan, 410219, China.
Pulmonary arterial hypertension (PAH) is a serious medical condition that causes a failure in the right heart. Two-pore channel 2 (TPC2) is upregulated in PAH, but its roles in PAH remain largely unknown. Our investigation aims at the mechanisms by which TPC2 regulates PAH development.
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