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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
In addition to the original and revised hallmarks described by Hanahan and Weinberg [29, 30], Luo and Elledge outlined the stress phenotypes of cancer, i.e., DNA damage/replication stress, proteotoxic stress, mitotic stress, metabolic stress, and oxidative stress [36]. For example, production of reactive oxygen species (ROS) is the defining characteristic of oxidative stress in cancer. ROS have been regarded as very sensitive stimuli while designing activatable nanotheranostic platforms [218, 219]. Moreover, ROS are highly linked to endogenous DNA damage events in cancer cells. Aerobic glycolysis, which is used for extensive proliferation, enables tumor cells to acidify their microenvironment (metabolic stress), leading to the escape from immune surveillance [164–168, 171]. Therefore, the acidic microenvironment of cancer cells provides excellent opportunities to optimally design multifunctional nanoplatforms for theranostic applications.
Recombinant expression and characterization of yeast Mrc1, a DNA replication checkpoint mediator
Published in Preparative Biochemistry & Biotechnology, 2020
Mrc1, a mediator of replication checkpoint, is a component of DNA replisome that moves along the chromosome with the replication fork during DNA synthesis.[12,13] At the same time, Mrc1 is also involved in the response of S. cerevisiae cells to hydroxyurea [HU]. When DNA replication is blocked by HU, Mrc1 undergoes Mec1-dependent phosphorylation, which acts as an intermediary and participates in the process of transmitting the replication stress signal from Mec1 to the Rad53 effector kinase.[14–16] In this process, Rad17-RFC (Rad24-RFC in yeast) also plays an important role in regulating the phosphorylation of Claspin (Mrc1 in yeast).[17]
Evaluation of potential toxicity of smoke from controlled burns of furnished rooms – effect of flame retardancy
Published in Journal of Toxicology and Environmental Health, Part A, 2022
Thomas G. Osimitz, Wiebke Droege, Giel Hendriks, Matthew S. Blais
ToxTracker® is a mouse embryonic stem (mES) cell-based assay that monitors activation of specific cellular signaling pathways for detection of the biological reactivity of compounds (Hendriks et al. 2016). In contrast to the cancer-derived cell lines commonly used for in vitro genotoxicity testing, stem cells are genetically stable and proficient in all cellular pathways required for accurate detection of potentially carcinogenic properties of compounds. Extensive whole-genome transcription profiling led to identification of a panel of biomarker genes that are preferentially activated upon exposure to different classes of carcinogens and toxicants. Green fluorescent protein (GFP) mES reporter cell lines were developed to enable assessment of the activation status of these biomarker genes. The mES reporter cell lines discriminate between induction of DNA damage, oxidative stress, protein damage, and general cellular stress. Specifically: DNA damage – genotoxicity – Detected by the Bscl2-GFP reporter activated by promutagenic DNA lesions and DNA replication stress and the Rtkn-GFP reporter associated with DNA double-strand breaks.Oxidative stress – The Srxn1-GFP and Blvrb-GFP reporters indicate activation of the Nrf2 and Hmox1 antioxidant responses.DNA damage and oxidative stress – The Btg2-GFP reporter is activated as part of a p53-mediated response.Unfolded Protein Response (UPR) – The DDIT3-GFP reporter is directly associated with the unfolded protein response.