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Emerging Concept (emerging + concept)
Selected AbstractsEmerging Concepts of Academic Leadership and their Implications for Intra-institutional Roles and Relationships in Higher EducationEUROPEAN JOURNAL OF EDUCATION, Issue 1 2002Mary Henkel [source] Emerging Concepts in the Pathophysiology of Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Prasanth N. Surampudi MD Abstract Type 2 diabetes mellitus is a multifactorial metabolic disorder. It is characterized by chronic hyperglycemia, insulin resistance, and a relative insulin secretion defect. The prevalence of type 2 diabetes mellitus has risen worldwide in large part because of an increase in obesity and sedentary lifestyles. The underlying pathophysiology and complications of type 2 diabetes mellitus are still being elucidated. Recent advances in diabetes research have helped us to gain a better understanding about insulin resistance and insulin secretion defects. The evolving understanding about the influence of the incretin effect, insulin signal transduction, adipose tissue, intra,islet cell communication, and inflammation is changing the way in which we view type 2 diabetes mellitus. This new understanding will eventually provide us with new treatment approaches to help patients who have type 2 diabetes mellitus. This article gives a review of the current and emerging concepts of the pathophysiology of type 2 diabetes mellitus. Mt Sinai J Med 76: 216,226, 2009. © 2009 Mount Sinai School of Medicine [source] Emerging concepts in cardiovascular disease risk assessment: Where do women fit in?JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 9 2009Adjunct Instructor, CRNP Cardiovascular Nurse Practitioner, Deborah Gleeson MSN Abstract Purpose: To highlight the current limitations in the assessment of cardiovascular disease (CVD) risk for women. This article will offer the reader information on the current process for assessing CVD risk in women, the pitfalls associated with this current strategy, and the role of novel risk factors. Data sources: Extensive review of the medical literature in the area of women's cardiovascular health. Conclusions: The assessment of CVD risk for women is currently an evolving science. Limitations in the ability of the Framingham score to accurately estimate risk in women from diverse populations are increasingly recognized. Vastly different treatment goals between the genders for similar levels of risk factors have led to a re-evaluation of this strategy in women. While the Framingham score is still useful for guiding cholesterol treatment goals, the current preventive guidelines for women emphasize assessing a woman's risk throughout her lifetime. The future development of tools for improved risk stratification that incorporate novel risk factors may in fact improve our ability to appropriately risk stratify women to evidence-based therapies. Implications for practice: Utilizing the Framingham Risk Assessment Tool and further CVD risk stratification using novel markers such as high sensitivity C-reactive protein, family history, and functional capacity may identify unique subsets of women at higher risk for CVD. Nurse practitioners can be instrumental in this assessment, education, and treatment of women at risk for CVD. [source] IPF: new insight on pathogenesis and treatmentALLERGY, Issue 5 2010S. Harari To cite this article: Harari S, Caminati A. IPF: new insight on pathogenesis and treatment. Allergy 2010; 65: 537,553. Abstract Recent years have seen a robust influx of exciting new observations regarding the mechanisms that regulate the initiation and progression of pulmonary fibrosis but the pathogenesis remains poorly understood. The search for an alternative hypothesis to unremitting, chronic inflammation as the primary explanation for the pathophysiology of idiopathic pulmonary fibrosis (IPF) derives, in part, from the lack of therapeutic efficacy of high-dose immunosuppressive therapy in patients with IPF. The inflammatory hypothesis of IPF has since been challenged by the epithelial injury hypothesis, in which fibrosis is believed to result from epithelial injury, activation, and/or apoptosis with abnormal wound healing. This hypothesis suggests that recurrent unknown injury to distal pulmonary parenchyma causes repeated epithelial injury and apoptosis. The resultant loss of alveolar epithelium exposes the underlying basement membrane to oxidative damage and degradation. Emerging concepts suggest that IPF is the result of epithelial,mesenchymal interaction. The initiation of this fibrotic response may depend upon genetic factors and environmental triggers; the role of Th1 or Th2 cell-derived cytokines may also be important. This process appears to be unique to usual interstitial pneumonia/IPF. It is clear that IPF is a heterogeneous disease with variations in pathology, high-resolution computed tomography findings, and patterns of progression. Idiopathic pulmonary fibrosis is a complex disorder, and no unifying hypothesis has been identified at present that explains all the abnormalities. [source] Osteopontin as a new player in mast cell biologyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008Silvia Bulfone-Paus Abstract The secreted glycoprotein osteopontin (OPN) sets into motion an astounding variety of activities that range from bone remodeling via immunomodulation to the inhibition of apoptosis. In the current issue of the European Journal of Immunology, OPN now also enters mast cell biology and the regulation of IgE-dependent immune responses since it is reported that connective tissue-type mast cells from fetal murine skin constitutively secrete biologically active OPN. Moreover, it is shown that, in vitro, OPN augments IgE-mediated mast cell degranulation and migration via ligand binding to cognate OPN receptors on the mast cell surface (CD44, ,v integrin) and that the magnitude of an IgE-mediated passive cutaneous anaphylaxis reaction is augmented by OPN in vivo. Here, we discuss why this newly discovered property of OPN fits well into the emerging concept that OPN may serve as a multi-purpose environmental damage-response protein. See accompanying article: http://dx.doi.org/10.1002/eji200737057 [source] Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Abstract Neutrophils are generally considered to contribute to host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated the role of neutrophils in defense against pulmonary Cryptococcus neoformans infection using neutrophil-depleted BALB/c mice generated by administering mAb RB6,8C5. Neutropenic mice with pulmonary infection survived significantly longer than control mice, but there was no difference between groups infected intravenously. On day,1 of infection, neutropenic mice had significantly smaller fungal burdens than control mice. On day,7, neutropenic mice had significantly higher lung concentrations of IL-10, TNF-,, IL-4, and IL-12 than control mice, but there was no difference in IFN-, and MCP-1 levels. Neutrophils influenced the outcome of cryptococcal infection in mice through mechanisms that did not involve a reduction in early fungal burden. The absence of neutrophils in lung tissue during the initial stages of infection appeared to alter the inflammatory response in a manner thatwas subsequently beneficial to the host. Higher levels of Th1- and Th2-associated cytokines in neutropenic mice could have simultaneously promoted a strong cellular response while reducing inflammatory damage to the lung. Our results support the emerging concept that neutrophils play an important function in modulating the development of the immune response. [source] Complete ascertainment of intragenic copy number mutations (CNMs) in the CFTR gene and its implications for CNM formation at other autosomal loci,HUMAN MUTATION, Issue 4 2010Sylvia Quemener Abstract Over the last 20 years since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, more than 1,600 different putatively pathological CFTR mutations have been identified. Until now, however, copy number mutations (CNMs) involving the CFTR gene have not been methodically analyzed, resulting almost certainly in the underascertainment of CFTR gene duplications compared with deletions. Here, high-resolution array comparative genomic hybridization (averaging one interrogating probe every 95,bp) was used to analyze the entire length of the CFTR gene (189,kb) in 233 cystic fibrosis chromosomes lacking conventional mutations. We succeeded in identifying five duplication CNMs that would otherwise have been refractory to analysis. Based upon findings from this and other studies, we propose that deletion and duplication CNMs in the human autosomal genome are likely to be generated in the proportion of approximately 2,3:1. We further postulate that intragenic gene duplication CNMs in other disease loci may have been routinely underascertained. Finally, our analysis of ±20,bp flanking each of the 40 CFTR breakpoints characterized at the DNA sequence level provide support for the emerging concept that non-B DNA conformations in combination with specific sequence motifs predispose to both recurring and nonrecurring genomic rearrangements. Hum Mutat 31:1,8, 2010. © 2010 Wiley-Liss, Inc. [source] Biological foundation for periodontitis as a potential risk factor for atherosclerosisJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2005Yong-Hee P. Chun Objectives:, Links between periodontal diseases and systemic diseases have been well documented by epidemiological studies. Recently, research has shifted to elucidating the biologic mechanism for a causal relationship. One focus of interest is atherosclerosis, the underlying event of cardiovascular diseases due to its serious health impact. However, it is still not clear whether periodontopathic pathogens are truly etiologic agents or ubiquitous bystanders. This article reviews the current understanding about the molecular biological interactions between periodontal disease and atherosclerosis and the biological plausibility of periodontitis as a potential risk factor for cardiovascular disease. Materials and methods:, The current literature regarding periodontal diseases and atherosclerosis and coronary vascular disease was searched using the Medline and PubMed databases. Results:,In vitro experiments and animal models are appropriate tools to investigate the biological interactions between periodontal disease and atherosclerosis at the cell molecular level. The concepts linking both pathologies refer to inflammatory response, immune responses, and hemostasis. In particular, Porphyromonas gingivalis appears to have unique, versatile pathogenic properties. Whether or not these findings from isolated cells or animal models are applicable in humans with genetic and environmental variations is yet to be determined. Likewise, the benefit from periodontal therapy on the development of atherosclerosis is unclear. Approaches targeting inflammatory and immune responses of periodontitis and atherosclerosis simultaneously are very intriguing. Conclusion:, An emerging concept suggests that a pathogenic burden from different sources might overcome an individual threshold culminating in clinical sequela. P. gingivalis contributes directly and indirectly to atherosclerosis. [source] Global Climate Change and the Fragmentation of International LawLAW & POLICY, Issue 4 2008HARRO VAN ASSELT Born into the wider body of international law, the climate regime needs to be understood in light of preexisting regimes. By drawing on the current debate about fragmentation in international law, this article highlights challenges for international lawyers and policymakers in navigating the relationship between the climate regime and the biodiversity regime, and the relationship between the climate regime and the multilateral trading system. This article concludes that a narrow focus on conflicts misrepresents the multifaceted nature of climate change and precludes an adequate jurisprudential understanding of the relationship between the climate regime and other regimes. An improved understanding, particularly with respect to interactions with the biodiversity regime, requires a broadening of the debate that takes account of the institutional aspects of these relationships that may allow enhanced political cooperation and coordination. Further, international law, and in particular the emerging concept of systemic integration, has the potential to make a positive contribution to the climate-trade interplay. [source] Protease inhibitors in bacteria: an emerging concept for the regulation of bacterial protein complexes?MOLECULAR MICROBIOLOGY, Issue 6 2006Wolfgang H. Schwarz Summary Serine protease inhibitors (serpins), the antagonists of serine proteases, were unknown in the bacterial kingdom until recently. Kang et al. in this issue of Molecular Microbiology report the cloning and functional analysis of the three serpin genes from the thermophilic anaerobic bacterium Clostridium thermocellum. Two of the serpins contain a dockerin module for location in the extracellular hydrolytic multienzyme complex, the cellulosome. The susceptibility of cellulosome to proteolytic degradation and the presence of a serine protease in the same complex provoke speculation that protease inhibitor/protease pairs could play hitherto unrecognized roles in protein stability and regulation in bacteria. [source] Transplanted dopaminergic neurons develop PD pathologic changes: A second case report,MOVEMENT DISORDERS, Issue 16 2008Jeffrey H. Kordower PhD Abstract This report describes pathological changes within the grafted neurons of another patient with Parkinson's disease (PD) who died 14 years posttransplantation. Although numerous healthy appearing grafted neurons were present at this long-term time point, some displayed Lewy bodies as evidenced by alpha-synuclein, ubiquitin, and thioflavin-S staining. Additionally, there was a general loss of dopamine transporter-immunoreactivity in grafted neurons. Some grafted cell displayed a loss of tyrosine hydroxylase. These data support the emerging concept that PD-like pathology is seen in young grafted neurons when they survive long term. © 2008 Movement Disorder Society [source] Mild Parkinsonian signs: An overview of an emerging conceptMOVEMENT DISORDERS, Issue 12 2007Elan D. Louis MD Abstract Mild Parkinsonian signs (MPS) include gait and balance changes, rigidity, bradykinesia, and tremor. MPS can occur commonly during the clinical examination of older people who do not have known neurological disease, with prevalence estimates for MPS as a whole ranging from 15% to 95%. MPS are generally progressive and they are coupled with functional difficulties, impaired gait and balance, and increased risks of mild cognitive impairment, dementia, and mortality. The mechanistic basis for these signs is unclear, but is likely to be multifactorial, with possible factors including an age-associated decline in dopaminergic nigrostriatal activity, the early development of neurodegenerative (Lewy body or Alzheimer's type) pathologies in the basal ganglia, or the accumulation of vascular pathology in the brain. It would be valuable to identify those individuals with MPS who are at increased risk for the development of future Alzheimer's disease, full-blown Parkinson's disease, or strokes, and to develop therapeutic strategies to intervene to lessen the likelihood of MPS-related morbidity and mortality. © 2007 Movement Disorder Society [source] Coupling surfactants/cosolvents with oxidants for enhanced DNAPL removal: A reviewREMEDIATION, Issue 3 2010Pamela J. Dugan Surfactants and cosolvents are useful for enhancing the apparent solubility of dense nonaqueous-phase liquid (DNAPL) compounds during surfactant-enhanced aquifer remediation (SEAR). In situ chemical oxidation (ISCO) with permanganate, persulfate, and catalyzed hydrogen peroxide has proven to be a cost-effective and viable remediation technology for the treatment of a wide range of organic contaminants. Coupling compatible remedial technologies either concurrently or sequentially in a treatment train is an emerging concept for more effective cleanup of DNAPL-contaminated sites. Surfactants are effective for DNAPL mass removal but not useful for dissolved plume treatment. ISCO is effective for plume control and treatment but can be less effective in areas where large masses of DNAPL are present. Therefore, coupling SEAR with ISCO is a logical next step for source-zone treatment. This article provides a critical review of peer-reviewed scientific literature, nonreviewed professional journals, and conference proceedings where surfactants/cosolvents and oxidants have been utilized, either concurrently or sequentially, for DNAPL mass removal. © 2010 Wiley Periodicals, Inc. [source] REVIEW ARTICLE: Clinical Relevance of Oxidative Stress in Male Factor Infertility: An UpdateAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2008Ashok Agarwal Male factor has been considered a major contributory factor to infertility. Along with the conventional causes for male infertility such as varicocele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumors, a new, yet important cause has been identified: oxidative stress. Oxidative stress (OS) is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body, which can lead to sperm damage, deformity and eventually male infertility. This involves peroxidative damage to sperm membrane and DNA fragmentation at both nuclear and mitochondrial levels. OS has been implicated as the major etiological factor leading to sperm DNA damage. OS-induced DNA damage can lead to abnormalities in the offspring including childhood cancer and achondroplasia. In this article, we discuss the need of ROS in normal sperm physiology, the mechanism of production of ROS and its pathophysiology in relation to male reproductive system. The benefits of incorporating antioxidants in clinical and experimental settings have been enumerated. We also highlight the emerging concept of utilizing OS as a method of contraception and the potential problems associated with it. [source] The "Thin Dividing Line": Prime Ministers and the Problem of Australian Nationalism, 1972,1996AUSTRALIAN JOURNAL OF POLITICS AND HISTORY, Issue 4 2002James Curran This paper is concerned with the way in which Australian prime ministers gave expression to an idea of "national community" in the post,1972 era. With the declining relevance of the British connection, the departure of "great and powerful" friends from the region, the imperative of engagement with Asia and the emerging concept of Australia as a "multicultural" society, one of the central challenges for these leaders has been whether or not they could offer an alternative myth of community which would preserve social cohesion in the new times. This raises an important historical question concerning Australian political culture at this time , what happened to the need for nationalism? By examining the speeches of Prime Ministers Whitlam, Fraser, Hawke and Keating, it can be seen that far from asserting an old,style, exclusive Australian nationalism, in most cases these leaders expressed great caution and hesitation towards the idea of nationalism itself. [source] Central and peripheral autoantigen presentation in immune toleranceIMMUNOLOGY, Issue 2 2004Alberto Pugliese Summary Recent studies in both humans and experimental rodent models provide new insight into key mechanisms regulating tolerance to self-molecules. These recent advances are bringing about a paradigm shift in our views about tolerance to self-molecules with tissue-restricted expression. There is, indeed, mounting evidence that selected antigen-presenting cells (APCs) have the ability to synthesize and express self-molecules, and that such expression is critical for self-tolerance. Insulin is a key hormone produced exclusively by pancreatic ,-cells and a critical autoantigen in type 1 diabetes. It provides an excellent example of a molecule with tissue-restricted expression that is expressed ectopically by APCs. The fact that APCs expressing insulin have been demonstrated in both thymus and peripheral lymphoid tissues suggests that they may play a role in insulin presentation in both the central and peripheral immune system. Experimental mice, in which insulin expression was altered, provide functional data that help to dissect the role of insulin presentation by APCs of the immune system. This review addresses recent literature and emerging concepts about the expression of self-molecules in the thymus and peripheral lymphoid tissues and its relation to self-tolerance. [source] Cutaneous lymphomas: emerging conceptsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2009Katalin Ferenczi No abstract is available for this article. [source] Antibacterial peptides: basic facts and emerging conceptsJOURNAL OF INTERNAL MEDICINE, Issue 3 2003H. G. Boman Abstract., Boman HG (Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden). Antibacterial peptides: basic facts and emerging concepts (Review). J Intern Med 2003; 254: 197,215. Antibacterial peptides are the effector molecules of innate immunity. Generally they contain 15,45 amino acid residues and the net charge is positive. The cecropin type of linear peptides without cysteine were found first in insects, whilst the defensin type with three disulphide bridges were found in rabbit granulocytes. Now a database stores more than 800 sequences of antibacterial peptides and proteins from the animal and plant kingdoms. Generally, each species has 15,40 peptides made from genes, which code for only one precursor. The dominating targets are bacterial membranes and the killing reaction must be faster than the growth rate of the bacteria. Some antibacterial peptides are clearly multifunctional and an attempt to predict this property from the hydrophobicity of all amino acid side chains are given. Gene structures and biosynthesis are known both in the fruit fly Drosophila and several mammals. Humans need two classes of defensins and the cathelicidin-derived linear peptide LL-37. Clinical cases show that deficiencies in these peptides give severe symptoms. Examples given are morbus Kostmann and atopic allergy. Several antibacterial peptides are being developed as drugs. [source] Acquisition of Literacy in Bilingual Children: A Framework for ResearchLANGUAGE LEARNING, Issue 2007Ellen Bialystok Much of the research that contributes to understanding how bilingual children become literate is not able to isolate the contribution of bilingualism to the discussion of literacy acquisition for these children. This article begins by identifying three areas of research that are relevant to examining literacy acquisition in bilinguals, explaining the contribution of each, and associating each type of research with a skill required by monolingual children in becoming literate. Three prerequisite skills for the acquisition of literacy are competence with the oral language, understanding of symbolic concepts of print, and establishment of metalinguistic awareness. A review of the literature explores the extent to which these skills that influence literacy acquisition in monolinguals develop differently for bilingual children. The conclusion is that the relation between bilingualism and the development of each of the three skills is different, sometimes indicating an advantage (concepts of print), sometimes a disadvantage (oral language competence), and sometimes little difference (metalinguistic concepts) for bilingual children. Therefore, bilingualism is clearly a factor in children's development of literacy, but the effect of that factor is neither simple nor unitary. Since the publication of this article, our research has continued to explore the themes set out in this framework and provided more detail for the description of how bilingualism affects the acquisition of literacy. Two important advances in this research are the finding that some aspects of reading ability, notably phonological awareness, are rooted in general cognitive mechanisms and transfer easily across languages, whereas others, such as decoding, are more language dependent and language-specific and need to be relearned with each new writing system (Bialystok, Luk, & Kwan, 2005). Second, writing systems and the differences between them have a greater impact on children's acquisition of literacy than previously believed. Not surprisingly, this relation has been found for emerging ability with phonological awareness (Bialystok, McBride-Chang, & Luk, 2005) but, more surprisingly, has recently been shown to have a subtle influence on children's emerging concepts of print (Bialystok & Luk, in press). The interpretation that bilingualism must be considered in terms of both advantages and disadvantages has also been pursued in studies of cognitive and linguistic processing in adults. Recent research has shown that adult bilinguals display disadvantages on tasks measuring lexical retrieval and fluency (Michael & Gollan, 2005) but advantages on tasks assessing cognitive control of attention (Bialystok, Craik, Klein, & Viswanathan, 2004). This approach leads to a more detailed and, ultimately, more accurate description of how bilingualism affects cognitive performance. [source] New Expression Profiles of Voltage-gated Ion Channels in Arteries Exposed to High Blood PressureMICROCIRCULATION, Issue 4 2002Robert H. Cox The diameters of small arteries and arterioles are tightly regulated by the dynamic interaction between Ca2+ and K+ channels in the vascular smooth muscle cells. Calcium influx through voltage-gated Ca2+ channels induces vasoconstriction, whereas the opening of K+ channels mediates hyperpolarization, inactivation of voltage-gated Ca2+ channels, and vasodilation. Three types of voltage-sensitive ion channels have been highly implicated in the regulation of resting vascular tone. These include the L-type Ca2+ (CaL) channels, voltage-gated K+ (KV) channels, and high-conductance voltage- and Ca2+ -sensitive K+ (BKCa) channels. Recently, abnormal expression profiles of these ion channels have been identified as part of the pathogenesis of arterial hypertension and other vasospastic diseases. An increasing number of studies suggest that high blood pressure may trigger cellular signaling cascades that dynamically alter the expression profile of arterial ion channels to further modify vascular tone. This article will briefly review the properties of CaL, KV, and BKCa channels, present evidence that their expression profile is altered during systemic hypertension, and suggest potential mechanisms by which the signal of elevated blood pressure may result in altered ion channel expression. A final section will discuss emerging concepts and opportunities for the development of new vasoactive drugs, which may rely on targeting disease-specific changes in ion channel expression as a mechanism to lower vascular tone during hypertensive diseases. [source] Emerging Concepts in the Pathophysiology of Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Prasanth N. Surampudi MD Abstract Type 2 diabetes mellitus is a multifactorial metabolic disorder. It is characterized by chronic hyperglycemia, insulin resistance, and a relative insulin secretion defect. The prevalence of type 2 diabetes mellitus has risen worldwide in large part because of an increase in obesity and sedentary lifestyles. The underlying pathophysiology and complications of type 2 diabetes mellitus are still being elucidated. Recent advances in diabetes research have helped us to gain a better understanding about insulin resistance and insulin secretion defects. The evolving understanding about the influence of the incretin effect, insulin signal transduction, adipose tissue, intra,islet cell communication, and inflammation is changing the way in which we view type 2 diabetes mellitus. This new understanding will eventually provide us with new treatment approaches to help patients who have type 2 diabetes mellitus. This article gives a review of the current and emerging concepts of the pathophysiology of type 2 diabetes mellitus. Mt Sinai J Med 76: 216,226, 2009. © 2009 Mount Sinai School of Medicine [source] Current and emerging concepts in tumour metastasis,THE JOURNAL OF PATHOLOGY, Issue 1 2010Caroline Coghlin Abstract Disseminated cancer accounts for most deaths due to malignancy. Despite this, research has focused predominantly on tumour development and progression at the primary site. Recently, attention has shifted towards the field of tumour metastasis. Several new and exciting concepts that have emerged in the past few years may shed light on this complex area. The established canonical theory of tumour metastasis, as a process emerging from a stepwise accumulation of genetic events fuelled by clonal evolution, has been challenged. New evidence suggests that malignant cells can disseminate at a much earlier stage than previously recognized in tumourigenesis. These findings have direct relevance to clinical practice and shed new light on tumour biology. Gene-profiling studies support this theory, suggesting that metastatic ability may be an innate property shared by the bulk of cells present early in a developing tumour mass. There is a growing recognition of the importance of host factors outside the primary site in the development of metastatic disease. The role of the ,pre-metastatic niche' is being defined and with this comes a new understanding of the function of bone marrow-derived progenitor cells in directing the dissemination of malignant cells to distant sites. Current research has highlighted the crucial roles played by non-neoplastic host cells within the tumour microenvironment in regulating metastasis. These new concepts have wide-ranging implications for our overall understanding of tumour metastasis and for the development of cancer therapeutics. Copyright © 2010 Pathological Society of Great Britain and Ireland. 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