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BACKGROUND The inhibition of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) is a potential synthetic lethal therapeutic strategy for the treatment of cancers with specific DNA-repair defects, including those arising in carriers of a BRCA1 or BRCA2 mutation. We conducted a clinical evaluation in humans of olaparib (AZD2281), a novel, potent,(More)
PURPOSE To evaluate tumor response, pharmacodynamic effects, and safety of a combination of lomeguatrib (LM), an O6-methylguanine DNA-methyltransferase (MGMT) inactivator, and temozolomide (TMZ), TMZ alone, and LM/TMZ after disease progression on TMZ alone in patients with advanced melanoma. PATIENTS AND METHODS Patients with unresectable stage III or IV(More)
Lymphatic vessels are essential for the removal of interstitial fluid and prevention of tissue edema. Lymphatic capillaries lack associated mural cells, and collecting lymphatic vessels have valves, which prevent lymph backflow. In lymphedema-distichiasis (LD), lymphatic vessel function fails because of mutations affecting the forkhead transcription factor(More)
BACKGROUND Radiation-induced arm lymphoedema is a common and distressing complication of curative treatment for early breast cancer. Hyperbaric oxygen (HBO(2)) therapy promotes healing in bone rendered ischaemic by radiotherapy, and may help some soft-tissue injuries too, but is untested in arm lymphoedema. METHODS Twenty-one eligible research volunteers(More)
BACKGROUND All edemas result from an imbalance between capillary filtration and tissue (lymph) drainage. This basic approach was adopted to investigate mechanisms for chronic arm edema following breast carcinoma treatment. METHODS A review of causes of lymphedema is presented plus the traditional pathophysiology of breast carcinoma related lymphedema(More)
This paper describes a randomized controlled crossover study examining the effects of manual lymphatic drainage (MLD) in 31 women with breast cancer-related lymphoedema. MLD is a type of massage used in combination with skin care, support/compression therapy and exercise in the management of lymphoedema. A modified version of MLD, referred to as simple(More)
RATIONALE Mutations in vascular endothelial growth factor (VEGF) receptor-3 (VEGFR3 or FLT4) cause Milroy disease, an autosomal dominant condition that presents with congenital lymphedema. Mutations in VEGFR3 are identified in only 70% of patients with classic Milroy disease, suggesting genetic heterogeneity. OBJECTIVE To investigate the underlying cause(More)