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D.M. Rassl



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    P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.02-013 - SDHB is overexpressed and may be a candidate target for therapeutic intervention in Malignant Pleural Mesothelioma (ID 3287)

      09:30 - 09:30  |  Author(s): D.M. Rassl

      • Abstract

      Background
      Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. The Succinate Dehydrogenase Complex, Subunit B, IronSulfur Protein (SDHB), is a subunit of the Succinate dehydrogenase or succinate-coenzyme Q reductase (SQR) or respiratory Complex II, and has recently been identified by us as an important element in MPM.

      Methods
      A panel of MPM cell lines inluding the normal pleural cells LP9 & Met5A were screened for expression of SDHB by RT-PCR. Levels were subsequently examined in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic, and sarcomatoid histologies by RT-PCR and western blot. Finally the expression of SDHB in a large cohort of MPM specimens with clinical data was asessed by IHC.

      Results
      Expression of SDHB occurs in all cell lines. Significantly higher expression of SDHB is observed in the malignant tumour material versus benign pleura. There was a trend towards better survival for patients expressing higher levels of SDHB, but this was not statistically significant.

      Conclusion
      SDHB, a key member of oxidative energy metabolism is significantly altered in MPM. This may have important future implications for the management of MPM.

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    P2.14 - Poster Session 2 - Mesothelioma (ID 196)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P2.14-011 - MesobanK: A UK based bioresource for malignant pleural mesothelioma (ID 1314)

      09:30 - 09:30  |  Author(s): D.M. Rassl

      • Abstract

      Background
      Availability of quality assured, fully annotated mesothelioma tissue collected to rigorous standard operating procedures will facilitate better understanding of mesothelioma biology. Currently, few bioresources of mesothelioma tissue exist, the largest being the National Mesothelioma Virtual Bank hosted by the University of Pittsburgh (http://www.mesotissue.org/). A few other clinical/research groups hold fresh tissue from small numbers of mesothelioma patients but these collections are not formally linked and often do not involve collection of tissue and data to Standard Operating Procedures. The British Lung Foundation/Mick Knighton Mesothelioma Research Fund has recently funded MesobanK, a UK based bioresource of malignant mesothelioma tissue samples.

      Methods
      Tissue Microarray: MesobanK will construct a tissue microarray (circa 1000 cases) using historical formalin fixed paraffin embedded blocks of tissue taken at thoracoscopy/surgical resection. Inclusion criteria requires sufficient tissue to permit multiple 0.5 mm cores (to allow for tumour heterogeneity) and a clinical minimum data set. Fresh tissue: Fresh frozen mesothelioma tissue (300 cases over 3 years) will be collected prospectively from multiple centres across the UK together with parallel pleural fluid, whole blood, serum and plasma. Each case will have a detailed anonymised linked clinical data set with follow up data. Cell lines: MesobanK plans to create 20 new fully annotated mesothelioma primary cell lines. The bioresource will be supported by a web-based IT infrastructure for annotating and searching the collection. Clinical data will be collected on each case and supplemented by laboratory and pathology results, Hospital Episode Statistics data and UK Cancer Registry data in order to achieve as complete a data set as possible. MesobanK will follow the Guiding Principles laid out by the NCRI Confederation of Cancer Biobanks and the UK Medical Research Council Operational and Ethical Guidelines on Human Tissue and Biological Materials for Use in Research. It will also be managed within the scope of all relevant regulatory frameworks and quality management/quality assurance systems. In addition, we share the aim of the US National Cancer Institute (NCI) National Biospecimen Network Blueprint: to create a comprehensive framework for sharing and comparing research results through a robust, flexible, scalable and secure bioinformatics system that supports the collection, processing, storage, annotation and distribution of biospecimens and data using standard operating procedures based on best practices. A steering committee will have overall control of MesobanK. An independent scientific advisory board will review applications for samples and advise the steering committee. Prioritisation for access to samples will be based solely on scientific merit. All researchers, whether in the UK National Health Service, universities, charities, government agencies or commercial companies, and whether based in the UK or abroad will be subject to the same application process and approval criteria.

      Results
      Not applicable

      Conclusion
      It is anticipated that initial tissue (TMA and cell lines) will be available in 2014.