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Dearden C.,The Institute of Cancer Research
British Journal of Haematology | Year: 2011

The WHO classification recognises three distinct disorders of large granular lymphocytes: T-cell large granular lymphocytic leukaemia (T-LGL), chronic lymphoproliferative disorders of NK-cells (CLPD-NK) and agressive NK-cell leukaemia. Despite the different cell of origin, there is considerable overlap between T-LGL and CLPD-NK in terms of clinical presentation and therapy. Many patients are asymptomatic and do not require treatment. Therapy, with immunosuppressant agents such as low dose methotrexate or ciclosporin, is usually indicated to correct cytopenias. In contrast, aggressive NK-cell leukaemia and the rare CD56 + aggressive T-LGL leukaemia follow a fulminant clinical course, affect younger individuals and require more intensive combination chemotherapy followed by allogeneic stem cell transplant in eligible patients. The relative rarity of these disorders means that there have been few clinical trials to inform management. However, there is now considerable interest in the pathogenesis of the chronic LGL leukaemias and this has stimulated early trials to evaluate novel agents which target the dysregulated apoptotic pathways characteristic of this disease. © 2010 Blackwell Publishing Ltd. Source

Greaves M.,The Institute of Cancer Research
Seminars in Cancer Biology | Year: 2010

Current models of cancer propagation or 'stem' cells pay scant attention to the evolutionary dynamics of cancer or to the underlying genetic, mutational drivers. Recent genetic studies on acute lymphoblastic leukaemia at the single cell level reveal a complex non-linear, branching clonal architecture-with sub-clones having distinctive genetic signatures. Most cancers appropriately interrogated are found to have intra-clonal genetic heterogeneity indicative of divergent clonal evolution. These data further suggest that clonal architecture might be driven by genetic heterogeneity of propagating or 'stem' cells. When assayed for leukaemic regeneration in NOD/SCID/γ mice, genetically diverse 'stem' cells read-out, broadly reflecting the clonal architecture. This has suggested a 'back to Darwin' model for cancer propagation. In this, cells with self-renewal potency or 'stem-ness' provide genetically diverse units of evolutionary selection in cancer progression. The model has significant implications for targeted cancer therapy. © 2010 Elsevier Ltd. Source

The Institute Of Cancer Research | Date: 2010-06-23

A radiotherapy system is disclosed, comprising a support for supporting a patient undergoing radiotherapy treatment, a gantry that is rotatable about an axis, a source of radiation mounted on the gantry and producing a beam of radiation directed towards a target region of the patient, a collimator coupled to said radiation source for collimating said radiation beam, the collimator comprising a plurality of beam-limiting elements, each movable to collectively define a shaped aperture through which the radiation beam passes, a portal imager mounted on the gantry opposite the radiation source for detecting the radiation after it has passed through the patient and generating corresponding images, and associated circuitry for controlling at least the gantry, the source, the collimator, and the portal imager, collating detected data comprising a plurality of images acquired from the imager including images at a plurality of angles of rotation of said gantry and images at a plurality of collimator shapes, and generating a three-dimensional image of the target region based thereon.

Vernalis, Cancer Research Technology Ltd. and The Institute Of Cancer Research | Date: 2010-01-21

Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, cancer: wherein R

Vernalis, The Institute Of Cancer Research and Cancer Research Technology Ltd | Date: 2013-06-27

Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: wherein R

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