The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers.

Disease progression and recurrence are major barriers to survival for breast cancer patients. Understanding the etiology of recurrent or metastatic breast cancer and underlying mechanisms is critical for the development of new treatments and improved survival. Here, we report that two commonly overexpressed breast cancer oncogenes, Ron (Recepteur d'Origine Nantaise) and DEK, cooperate to promote advanced disease through multipronged effects on ß-catenin signaling. The Ron receptor is commonly activated in breast cancers, and Ron overexpression in human disease stimulates ß-catenin nuclear translocation and is an independent predictor of metastatic dissemination. Dek is a chromatin-associated oncogene whose expression has been linked to cancer through multiple mechanisms, including ß-catenin activity. We demonstrate here that Dek is a downstream target of Ron receptor activation in murine and human models. The absence of Dek in the MMTV-Ron mouse model led to a significant delay in tumor development, characterized by decreased cell proliferation, diminished metastasis and fewer cells expressing mammary cancer stem cell markers. Dek complementation of cell lines established from this model was sufficient to promote cellular growth and invasion. Mechanistically, Dek expression stimulated the production and secretion of Wnt ligands to sustain an autocrine/paracrine canonical ß-catenin signaling loop. Finally, we show that Dek overexpression promotes tumorigenic phenotypes in immortalized human mammary epithelial MCF10A cells and, in the context of Ron receptor activation, correlates with disease recurrence and metastasis in patients. Overall, our studies demonstrate that DEK overexpression, due in part to Ron receptor activation, drives breast cancer progression through the induction of Wnt/ß-catenin signaling.

What do patients with brain metastases from non-small cell lung cancer want from their treatment?

Brain metastases are a common complication of non-small cell lung cancer (NSCLC). Prognosis is poor and the effectiveness of whole brain radiotherapy (WBRT) is uncertain for patients with moderate performance status. Studies on WBRT effectiveness have thus far used outcome measures, such as survival, performance status and cognitive function. The aim of this study was to study what patients with recently diagnosed brain metastases from NSCLC want from their treatment. We carried out semistructured interviews with nine patients with brain metastases from NSCLC, for whom the benefit of WBRT is uncertain. Interpretative phenomenological analysis was used. Themes identified included quality versus quantity of life, factors contributing to quality of life (including family, mobility and normality), 'Go for it!' - the desire to try anything, the desire for a cure or 'magic wand', fear and other factors (including family in decision making, information or lack of information, relationship with professionals, experience of steroids and radiotherapy including adverse effects). Quality of life is important to patients, but many are keen to try any treatment which might prolong their life. Understanding patients' values regarding treatment and goals of treatment can help clinicians discuss these issues with patients and provide appropriate information and can aid selection of appropriate outcome measures.

Death during transfer of a palliative care patient.

This short report illustrates the potential confusion that exists when terminally ill patients die during transfer between places of care. The report documents the legal requirements necessary if a terminally ill patient dies during transfer and raises the debate regarding what policies and practice currently exist, within the UK, for transfer of terminally ill patients.

Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review.

BACKGROUND: Brain metastases are the most common intracranial tumour in adults, estimated to occur in up to 40% of patients with cancer. Despite being used in clinical practice for 50 years, the effectiveness of whole brain radiotherapy for the treatment of brain metastases remains uncertain. OBJECTIVES: To assess the effectiveness of whole brain radiotherapy (WBRT) on survival and quality of life. To identify whether patient performance status, number of brain metastases, extent of extracranial disease and primary site of cancer are important effect modifiers. DESIGN: Systematic literature review. METHODS: Electronic searches of four databases, augmented by hand searches of the most frequently encountered journal and assessment of the reference lists of consensus statements and all retrieved papers. Included papers underwent structured data extraction, assessment and qualitative synthesis. RESULTS: Thirty-two primary studies were included, with a range of study designs, methodological quality, pre-treatment variables, interventions and outcome measures. From the limited evidence available, survival appeared to increase when patients were selected by performance status (survival increasing from approximately three to seven months in high performance status groups, as defined by Karnofsky performance status or Recursive Partitioning Analysis classification). The evidence suggests no survival benefit when patients with poor performance status were treated with whole brain radiotherapy. No studies undertook direct measurement of patients' quality of life. Surrogate measures of patients' quality of life, such as improvement in neurological function or improvement/maintenance of KPS > or =70, produced response rates ranging from 7 to 90%. CONCLUSION: The heterogeneity of study designs, quality and outcomes necessitates caution in interpreting the review findings. WBRT appears to be of benefit in higher performance status patients but not in low performance status patients. This suggests a basis for current practice, however further robust trial evidence is required.