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To assess the level of activity and toxicity of gefitinib (ZD1839, Iressatrade mark) in a population of patients with locally recurrent and/or metastatic head and neck cancer. Patients were recruited into an expanded access programme through the multidisciplinary head and neck clinics at the Royal Marsden and St George's Hospitals. Patients were required to(More)
Primary human tumours can often be eradicated by surgery if detected early; however metastatic disease renders complete cure less likely and the development of resistance to therapy results in tumour escape and increased risk of death. Interactions of tumour cells with each other, surrounding normal cells and extracellular matrix or basement membrane(More)
Chimeric antigen receptor (CAR) engineered T-cells occupy an increasing niche in cancer immunotherapy. In this context, CAR-mediated CD3ζ signaling is sufficient to elicit cytotoxicity and interferon-γ production while the additional provision of CD28-mediated signal 2 promotes T-cell proliferation and interleukin (IL)-2 production. This(More)
Squamous cell carcinoma of the head and neck (SCCHN) is associated with high morbidity and mortality. Despite significant surgical advances and refinement in the delivery of chemotherapy and radiotherapy, prognosis has improved little in recent decades. Better local control has led to the late presentation of distant metastases and novel therapeutic agents(More)
Receptor tyrosine kinases (RTK) are key targets for novel cancer therapeutics since they activate multiple oncogenic signalling pathways. Also, they are inherently 'druggable' due to their small ATP-dependent kinase domains (inhibitable by small molecules) and cell surface location which renders them accessible to monoclonal antibody-based therapies. The(More)
Despite a continuing debate about the existence of cancer stem cells (CSCs), recent discoveries have provided further support for their existence and their roles in drug resistance, cancer recurrence and metastasis. CSC characteristics, such as self-renewal and tumour initiation, and supporting cellular processes, particularly the epithelial-to-mesenchymal(More)
Syk, a non-receptor tyrosine kinase, is an important component of immunoreceptor signaling in hematopoietic cells. It has been implicated in key regulatory pathways including phosphoinositide 3-kinase and phospholipase Cgamma (PLCgamma) activation in B cells and integrin signaling in platelets and bronchial epithelial cells. Recently, potential roles in(More)
Invasive capacity is the single most important trait that distinguishes benign from malignant lesions. Tumour cells, during intravasation and extravasation of blood and lymphatic channels and when establishing colonies at secondary sites, must move through tissue boundaries that normal adult cells (other than, for example activated leukocytes) do not cross.(More)
Motility and invasion are key hallmarks that distinguish benign from malignant tumors, enabling cells to cross tissue boundaries, disseminate in blood and lymph and establish metastases at distant sites. Similar properties are also utilized by activated endothelial cells during tumor-induced angiogenesis. It is now appreciated that these processes might(More)
Cell migration is a key hallmark of malignant cells that contributes to the progression of cancers from a primary, localized mass to an invasive and/or metastatic phenotype. Traditional methods for the evaluation of tumor cell migration in vitro generally employ two-dimensional (2D), homogeneous cultures that do not take into account tumor heterogeneity,(More)