Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.
Systems biology describes a holistic and integrative approach to understand physiology and pathology. The "omic" disciplines include genomics, transcriptomics, proteomics, and metabolic profiling (metabonomics and metabolomics). By adopting a stance, which is opposing (yet complimentary) to conventional research techniques, systems biology offers an overview by assessing the "net" biological effect imposed by a disease or nondisease state. There are a number of different organizational levels to be understood, from DNA to protein, metabolites, cells, organs and organisms, even beyond this to an organism's context. Systems biology relies on the existence of "nodes" and "edges." Nodes are the constituent part of the system being studied (eg, proteins in the proteome), while the edges are the way these constituents interact. In future, it will be increasingly important to collaborate, collating data from multiple studies to improve data sets, making them freely available and undertaking integrative analyses.
The annual rate of ipsilateral stroke associated with asymptomatic carotid stenosis has fallen from 2-4% to <1% in the last 20 years due to improvements in medical therapy. The fundamental benefits of this are relevant to whether patients undergo revascularisation or not. We aimed to evaluate existing international guidelines for the management of carotid stenosis, identifying important similarities and differences. The websites of the American Heart Association, Society for Vascular Surgery, European Society for Cardiology, European Society for Vascular Surgery, British Cardiovascular Society and UK Vascular Society were searched for guidelines relating to primary prevention for asymptomatic atherosclerotic carotid disease in September 2011 and independently reviewed by 2 authors. The following guidelines were identified and compared: The Joint British Societies 2nd (JBS2) 2005 guideline, the 4th European Society for Cardiology (ESC) 2007 guideline, the joint American Heart Association/Society for Vascular Surgery (AHA/SVS) guideline 2011 and subsequent 2011 SVS update, the American Heart Association (AHA) prevention of stroke guideline 2010, the AHA secondary prevention for atherosclerotic coronary and vascular disease 2011 update, and the European Society for Vascular Surgery (ESVS) Section A carotid guideline. There was no UK guidance from its vascular society. Important differences were evident in methods of risk assessment, treatment targets for blood pressure and low density lipoprotein cholesterol, and the use of anti-platelet agents. These differences are highlighted in 2 case scenarios. There is now clear, evidence based guidance from British, European and US cardiovascular bodies regarding optimal targets for risk factor modification. These can be adopted as standard operating procedure for clinical practice and the medical arms of carotid interventional trials. In the future imaging biomarkers may help provide an understanding of the risk of an individual carotid lesion to help guide therapy.
We describe here the first dorsal metacarpal artery propeller perforator flap, used to cover a full thickness, radiopalmar defect of the index finger after tumour excision. By associating a propeller design to the dissection of the first metacarpal pedicle, this flap can be effective in coverage of proximal index and web space defects, with primary closure and pleasant aesthetic outcomes. Harvested together with a superficial sensory branch from the radial nerve, this flap can provide effective coverage and sensory recovery.
Differences between animal and human atherosclerosis have led to the requirement for clinical data, imaging information and biological material from large numbers of patients and healthy persons. Where such "biobanks" exist, they have been fruitful sources for genomewide association, diagnostic accuracy, ethnicity, and risk stratification cohort studies. In addition once established, they attract funding for future projects. Biobanks require a network of medical contributors, secure storage facilities, bioinformatics expertise, database managers, and ethical working practices to function optimally. There is the opportunity for collaboration between individual biobanks to further amplify the advantages afforded.
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