Skip to content
Other Publications (38)
- International Journal of Radiation Oncology, Biology, Physics
- Bulletin Du Cancer
- Metabolic Engineering
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- International Journal of Radiation Oncology, Biology, Physics
- Technology in Cancer Research & Treatment
- Cancer
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- Archives of Medical Science : AMS
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- The Journal of Biological Chemistry
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- Radiation Oncology (London, England)
- Frontiers in Oncology
- Radiation Oncology (London, England)
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Chemical Communications (Cambridge, England)
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiation Oncology (London, England)
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- World Journal of Gastroenterology : WJG
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Technology in Cancer Research & Treatment
- Expert Review of Gastroenterology & Hepatology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Articles by Benedikt Engels in JoVE
-
Dynamisk lungtumör Tracking för Stereotactic Ablativ Body strålterapi
Charles A. Kunos1, Jeffrey M. Fabien1, John P. Shanahan1, Christine Collen2, Thierry Gevaert2, Kenneth Poels2, Robbe Van den Begin2, Benedikt Engels2, Mark De Ridder2
1Department of Radiation Oncology, Summa Cancer Institute, 2Department of Radiation Oncology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel
Other articles by Benedikt Engels on PubMed
-
-
Hypoxic Tumor Cell Radiosensitization: Role of the INOS/NO Pathway
Bulletin Du Cancer.
Mar, 2008 |
Pubmed ID: 18390408 Hypoxia is a common feature of the tumor microenvironment and a major cause of clinical radioresistance. During the last decades, several strategies to improve tumor oxygenation were developed such as breathing high oxygen content gas under hyperbaric conditions (3 atmosphere) and improving tumor perfusion by nicotinamide, in combination with carbogen breathing and accelerated radiotherapy to counteract tumor repopulation (ARCON). Other strategies to overcome hypoxia induced radioresistance are the use of hypoxic cell radiosensitizers, which mimic oxygen and enhance thereby radiation damage (e.g. the nitroimidazoles) and bioreductive drugs, which undergo intracellular reduction to form active cytotoxic species under low oxygen tension (e.g. mitomycin C and tirapazamine). A meta-analysis of all randomized trials in which some form of hypoxic modification was performed, showed an improved local control and survival, especially in cervix and head-and-neck cancer. Nevertheless, none of the discussed strategies are used in clinical routine because of feasibility and toxicity issues. We developed an alternative strategy that takes advantage of the microenvironment of solid tumors for tumor specific radiosensitization. The inducible isoform of nitric oxide synthase (iNOS) may be induced by bacterial LPS or its derivate lipid A, is expressed by a variety of solid tumors and generates NO at high rates inside tumor cells. This local production of NO results in efficient hypoxic tumor cell radiosensitization, at non-toxic extracellular concentrations of NO. In addition, iNOS is transcriptionally upregulated by hypoxia and proinflammatory cytokines such as interferon-gamma. Hence, we proposed the pro-inflammatory tumor infiltrate as a new target for radiosensitizing strategies and identified two mechanisms: First, tumor associated immune cells (macrophages, T/NK-cells) are a source of mediators that may induce the iNOS/NO pathway inside tumor cells. Second, tumor associated macrophages can produce high levels of NO that may radiosensitize bystander tumor cells. Our ongoing research is focused on combining immunostimulatory and radiosensitizing strategies.
-
Metabolic Engineering of Taxadiene Biosynthesis in Yeast As a First Step Towards Taxol (Paclitaxel) Production
Metabolic Engineering.
May-Jul, 2008 |
Pubmed ID: 18485776 Metabolic engineering in microbes could be used to produce large amounts of valuable metabolites that are difficult to extract from their natural sources and too expensive or complex to produce by chemical synthesis. As a step towards the production of Taxol in the yeast Saccharomyces cerevisiae, we introduced heterologous genes encoding biosynthetic enzymes from the early part of the taxoid biosynthetic pathway, isoprenoid pathway, as well as a regulatory factor to inhibit competitive pathways, and studied their impact on taxadiene synthesis. Expression of Taxus chinensis taxadiene synthase alone did not increase taxadiene levels because of insufficient levels of the universal diterpenoid precursor geranylgeranyl diphosphate. Coexpression of T. chinensis taxadiene synthase and geranylgeranyl diphosphate synthase failed to increase levels, probably due to steroid-based negative feedback, so we also expressed a truncated version of 3-hydroxyl-3-methylglutaryl-CoA reductase (HMG-CoA reductase) isoenzyme 1 that is not subject to feedback inhibition and a mutant regulatory protein, UPC2-1, to allow steroid uptake under aerobic conditions, resulting in a 50% increase in taxadiene. Finally, we replaced the T. chinensis geranylgeranyl diphosphate synthase with its counterpart from Sulfolobus acidocaldarius, which does not compete with steroid synthesis, and codon optimized the T. chinensis taxadiene synthase gene to ensure high-level expression, resulting in a 40-fold increase in taxadiene to 8.7+/-0.85mg/l as well as significant amounts of geranylgeraniol (33.1+/-5.6mg/l), suggesting taxadiene levels could be increased even further. This is the first demonstration of such enhanced taxadiene levels in yeast and offers the prospect for Taxol production in recombinant microbes.
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Get cutting-edge science videos from JoVE sent straight to your inbox every month.