The Journal of pathology
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The Journal of pathology · Jun 2009
ReviewHuman testicular (non)seminomatous germ cell tumours: the clinical implications of recent pathobiological insights.
Human germ cell tumours (GCTs) comprise several types of neoplasias with different pathogeneses and clinical behaviours. A classification into five subtypes has been proposed. Here, the so-called type II testicular GCTs (TGCTs), ie the seminomas and non-seminomas, will be reviewed with emphasis on pathogenesis and clinical implications. ⋯ The different non-seminomatous histological elements can be recognized using various markers, such as AFP and hCG, while others need confirmation. The value of micro-satellite instability as well as BRAF mutations in predicting treatment resistance needs validation in prospective trials. The availability of representative cell lines, both for seminoma and for embryonal carcinoma, allows mechanistic studies into the initiation and progression of this disease.
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The function of the kidney, as well as its morphology, changes markedly with age. The glomerular filtration rate falls progressively, independent of overt pathology. ⋯ Declining renal function with age has important implications, not only for individual homeostasis but also for the use of drug therapy and for the receipt and donation of organs for transplantation. Molecular mechanisms and cellular changes underlying some of the functional and structural changes associated with ageing are becoming clearer, as are some of the ways in which genetic background, age and disease can combine to produce functional damage.
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Complex changes occur within the endocrine system of ageing individuals. This article explores the changes that occur in the metabolism and production of various hormones and discusses the resulting clinical consequences. As individuals age there is a decline in the peripheral levels of oestrogen and testosterone, with an increase in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin. ⋯ The clinical significance of these deficiencies with age are variable and include reduced protein synthesis, decrease in lean body mass and bone mass, increased fat mass, insulin resistance, higher cardiovascular disease risk, increase in vasomotor symptoms, fatigue, depression, anaemia, poor libido, erectile deficiency and a decline in immune function. For each endocrine system, studies have been carried out in an attempt to reverse the effects of ageing by altering the serum hormonal levels of older individuals. However, the real benefits of hormonal treatment in older individuals are still being evaluated.
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The Journal of pathology · Mar 2006
ReviewRole of the ephrin and Eph receptor tyrosine kinase families in angiogenesis and development of the cardiovascular system.
Angiogenesis is a highly complex orchestrated process that plays a critical role in normal development and in the pathophysiology of multiple disease processes, including tumour neovascularization, ischaemic recovery, and wound healing. In recent years there has been a resurgence of interest in Eph receptors and their ligands, ephrins, as their participation in vasculogenesis and angiogenesis has become apparent. The Eph receptor family is the largest family of receptor tyrosine kinases identified to date. ⋯ These include vascular development, tissue-border formation, cell migration, axon guidance, and synaptic plasticity. The role of Eph receptors and ephrins in the processes of development of the cardiovascular system, angiogenesis, and vascular remodelling has been the subject of intense investigation since they were first identified in 1987. This review addresses the role of this new growth factor receptor tyrosine kinase family in those processes and provides new insights into the way in which Eph receptors and ephrin ligands modulate the angiogenic response and participate in vascular remodelling and vascular boundary formation during development of the cardiovascular system and vascularization of cancer.
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The Journal of pathology · Jan 2006
ReviewViral gene therapy strategies: from basic science to clinical application.
A major impediment to the successful application of gene therapy for the treatment of a range of diseases is not a paucity of therapeutic genes, but the lack of an efficient non-toxic gene delivery system. Having evolved to deliver their genes to target cells, viruses are currently the most effective means of gene delivery and can be manipulated to express therapeutic genes or to replicate specifically in certain cells. Gene therapy is being developed for a range of diseases including inherited monogenic disorders and cardiovascular disease, but it is in the treatment of cancer that this approach has been most evident, resulting in the recent licensing of a gene therapy for the routine treatment of head and neck cancer in China. ⋯ Paramount is the safety of these virus vectors and a greater understanding of the virus-host interaction is key to optimizing the use of these vectors for routine clinical use. Recent developments in the modification of the virus coat allow more targeted approaches and herald the advent of systemic delivery of therapeutic viruses. In the context of cancer, the ability of attenuated viruses to replicate specifically in tumour cells has already yielded some impressive results in clinical trials and bodes well for the future of this approach, particularly when combined with more traditional anti-cancer therapies.