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32 results on '"Albers, J.J."'

2. Targeting OGG1 arrests cancer cell proliferation by inducing replication stress

Author

Visnes, T., Benítez-Buelga, C., Cázares-Körner, A., Sanjiv, K., Hanna, B.M.F., Mortusewicz, O., Rajagopal, V., Albers, J.J., Hagey, D.W., Bekkhus, T., Eshtad, S., Baquero, J.M., Masuyer, G., Wallner, O., Müller, S., Pham, T., Göktürk, C., Rasti, A., Suman, S., Torres-Ruiz, R., Sarno, A., Wiita, E., Homan, E.J., Karsten, S., Marimuthu, K., Michel, M., Koolmeister, T., Scobie, M., Loseva, O., Almlöf, I., Unterlass, J.E., Pettke, A., Boström, J., Pandey, M., Gad, H., Herr, P., Jemth, A.-S., El Andaloussi, S., Kalderén, C., Rodriguez-Perales, S., Benítez, J., Krokan, H.E., Altun, M., Stenmark, P., Berglund, U.W., and Helleday, T.

Subjects
DNA Replication, Guanine, DNA Repair, AcademicSubjects/SCI00010, Poly (ADP-Ribose) Polymerase-1, Mice, Nude, Antineoplastic Agents, Genome Integrity, Repair and Replication, DNA Glycosylases, Mice, Cell Line, Tumor, repair and replication, Animals, Humans, Molecular Targeted Therapy, Enzyme Inhibitors, RNA, Small Interfering, Cell Proliferation, DNA, Neoplasm, HCT116 Cells, Survival Analysis, Xenograft Model Antitumor Assays, Genome integrity, Tumor Burden, Gene Expression Regulation, Neoplastic, Oxidative Stress, Colonic Neoplasms, Reactive Oxygen Species, DNA Damage, Signal Transduction
Abstract

Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment. C The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Published
2020

16. Secondary prevention of heart disease amongst patients with lipid abnormalities: practice and trends in the United States

Author

Brown, B.G., Zhao, X.Q., Bardsley, J., and Albers, J.J.

Abstract

Patients with established coronary disease and abnormalities of lipid metabolism represent a particularly important subgroup, since their mortality risk is typically 10 times greater than that amongst subjects with comparable risk factors but no clinical history. Such patients are commonly treated initially with anti-anginal therapy; if ischaemic symptoms persist they often undergo revascularization (bypass or angioplasty). While invasive procedures restore blood flow and relieve ischemia, they do not, in most cases, reduce risk of subsequent MI or death, or alter the underlying atherogenic process(es). Despite this, there has been a progressive 54% decline in age-adjusted cardiac mortality over the period 1960-1995, which appears best attributable to US lifestyle changes. In particular, the past decade has provided compelling evidence for the merits of a fourth approach: comprehensive risk factor management. Clinical outcome studies have confirmed the substantial merit of aspirin prophyllaxis and of intensive lipid-lowering therapy in secondary prevention. Prospective angiographic trials and evidence from studies of vascular biology have provided insight into mechanisms of benefit. As a consequence, lipid therapy and aspirin use have increased greatly among middle aged and older US citizens, especially those with CAD. The growth of comprehensive medical management now rivals that of invasive revascularization in secondary prevention.

Published
1997
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