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Personalized Medicine in Lung Cancer
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
Daniela Morales-Espinosa, Silvia Garcá-Román, Rafael Rosell
Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. It was the first member of a class of platinum-containing anti-cancer drugs, which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death); cells able to remove these adducts are resistant to the compound. Many proteins involved in DNA damage-response (DDR) machinery have a role in repairing cross-links by platinum.16 Specifically, cisplatin has been used to treat late stage NSCLC as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been made to identify biomarkers that can be used to predict cisplatin sensitivity.17
p300 Acetylates JHDM1A to inhibit osteosarcoma carcinogenesis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Yongkun Wang, Baozhen Sun, Qiao Zhang, Hang Dong, Jingzhe Zhang
CoIP and ChIP were down as previously described [19]. Briefly, cells were mixed with 1% formaldehyde for 10 min and 0.125 M glycine solution was added to end this reaction. Then, cells were rinsed using washing buffer and re-suspended in sonication buffer. Followed by sonication, the samples were mixed with immunoprecipitation buffer and incubated with relevant antibodies. For ChIP, the immune-precipitates were rinsed using washing buffer. Followed by reverse-crosslinking, the DNA samples were isolated and analyzed by real-time quantitative PCR. The primer sequences for p21 promoter were: 5′-GTGCGTCTGATTGCGTTTCTG-3′ (forward) and 5′-CTGAAAACGAGCAGCGGAAG-3′ (reverse). The primer sequences for puma promoter were: 5′-GCGGAACTGTGCGCTTGTGT-3′ (forward) and 5′-CGCTCAGGGCTCACAAAGT-3′ (reverse).
Novel targeted strategies to overcome resistance in small-cell lung cancer: focus on PARP inhibitors and rovalpituzumab tesirine
Published in Expert Review of Anticancer Therapy, 2019
Robin Van Den Borg, Alessandro Leonetti, Marcello Tiseo, Elisa Giovannetti, Godefridus J. Peters
Cisplatin and carboplatin are chemotherapeutic agents that act by causing crosslinking of DNA which interferes with cellular DNA replication and/or repair, lastly resulting in the kill of rapid proliferating cells (Figure 1). In order to generate a cytotoxic response, platinum salts first need to be activated by the replacement of their cis-chloro ligands with water molecules [22]. Besides the similar mechanism of action, that relies on the same adduct structure, cisplatin and carboplatin differ for their leaving group [23]. Once activated, they can interact with N7 position of guanine, leading to DNA adduct formation, after which interstrand and intrastrand crosslinks are established [24]. Intrastrand adducts are responsible for most of the cytotoxic effect of cisplatin [25], accounting for 85–90% of total lesions [26]. Following the DNA damage induced by platinum salts, several downstream effects are documented.
The relationship between histone posttranslational modification and DNA damage signaling and repair
Published in International Journal of Radiation Biology, 2019
Ajit K Sharma, Michael J. Hendzel
Preserving the integrity of genetic information and encoded functions is essential for normal cellular homeostasis and for preventing genetic errors that can lead to diseases like cancer. The stability of the genome is frequently challenged by exogenous sources, such as exposure to ionizing radiation (IR), ultraviolet radiation (UV), and environmental toxins, or from endogenous sources, such as reactive oxygen species or DNA replication errors. Depending on the type of genotoxic agent, this can result in diverse types of DNA lesions including DNA base damage, single-stranded DNA (ssDNA) breaks, inter-strand crosslinking of DNA and DNA double-strand breaks (DSBs) (Jackson and Bartek 2009). In order to respond to these DNA lesions, cells have evolved multiple highly effective DNA repair pathways.