Adv Exp Med Biol
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Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1). ⋯ It has, however, been possible to backtrack this process through molecular analysis of appropriate clinical samples: (i) leukaemic clones in monozygotic twins that are either concordant or discordant for ALL; (ii) archived neonatal blood spots or Guthrie cards from individuals who later developed leukaemia; and (iii) stored, viable cord blood cells. Here, we outline our studies on the aetiology and pathology of childhood ALL that provide molecular evidence for a monoclonal, prenatal origin of ETV6-RUNX1+ leukaemia in monozygotic identical twins. We provide mechanistic support for the concept that altered patterns of infection during early childhood can deliver the necessary promotional drive for the progression of ETV6-RUNX1+ pre-leukaemic cells into a postnatal overt leukaemia.
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The review focuses on the current knowledge and the most pertinent hypotheses regarding the local host immune response as the key factor for the pathogenesis of implant-associated infections. Although bacterial biofilms have long been recognized as causative agents, the link between the infection and the devastating inflammatory response, particularly the localized tissue destruction and bone degradation is less well understood. Understanding these consequences of infection, however, is of utmost importance, because suppressing inflammation and preventing bone destruction could be a novel, alternative therapeutic option in cases when eradicating the infections fails.
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Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. ⋯ This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ). This is followed by a discussion of regulatory mechanisms underlying CDI and NDI , with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R ) and the water channel molecule, aquaporin 2 (AQP2 ). The clinical manifestation, diagnosis and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.
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Ultrasound (US) allows the non-invasive evaluation of morphological changes of kidney structure (by means of B-Mode) and patterns of renal and extrarenal vascularization (by means of color-Doppler and contrast-enhanced US). In hypertensive subjects it offers a relevant contribution to the diagnosis of early renal damage, acute or chronic nephropathies and nephrovascular disease. However, morphological changes are often detected late and non-specific and in recent years evidence has increased regarding the clinical relevance of renal resistive index (RRI) for the study of vascular and renal parenchymal renal abnormalities. ⋯ The recent claim that systemic (pulse pressure) rather than renal hemodynamic determinants sustain this predictive role of RRI, does not significantly reduce this predictive role of RRI. (c) Doppler ultrasound allows diagnosis and grading of renal stenosis in both fibromuscolar dysplastic and atherosclerotic diseases. Moreover, by RRI assay Doppler ultrasound can indirectly measure the hemodynamic impact of renal artery stenosis on the homolateral kidney, by virtue of the stenosis-related decrease in pulse pressure. However, in elderly subjects with atherosclerotic renal artery stenosis coexisting renal diseases can independently increase RRI by the augmentation in renal vascular stiffness and tubulo-interstitial pressure and hidden changes due to renal artery stenosis.
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Review
The Mechanistic Role of the Calcium-Activated Chloride Channel ANO1 in Tumor Growth and Signaling.
Multiple studies have described the high expression and amplification of Anoctamin 1 (ANO1) in various cancers, including, but not limited to breast cancer, head and neck cancer, gastrointestinal stromal tumors and glioblastoma. ANO1 has been demonstrated to be critical for tumor growth in breast and head and neck cancers through its regulation of EGFR signaling and pathway modulators like MAPK and protein kinase B. However, the discovery of ANO1 as a calcium activated chloride channel came as a surprise to the field and has given rise to many questions. How does a chloride channel promote oncogenesis? Is the chloride channel function of ANO1 important for its role in cancer? Does ANO1 exhibits chloride-independent functions in cancer cells? This review summarizes the current understanding of ANO1's function in cancer, provides a synopsis of the findings addressing the open questions in the field and gives an outlook on the promising future of ANO1 as a potential therapeutic target for the treatment of various cancers.