Long-term survivors of childhood and adolescent cancers continue to demonstrate significant excess mortality. However, overall mortality among 15+ year survivors without a relapse appears to be comparable to the general population. The leading cause of death among 15+ year survivors is second malignancy in this study, which represents a novel and important finding in terms of long-term follow-up.
The Malpighian tubules of insects are structurally simple but functionally important organs, and their integrity is important for the normal excretory process. They are functional analogs of human kidneys which are important physiological organs as they maintain water and electrolyte balance in the blood and simultaneously help the body to get rid of waste and toxic products after various metabolic activities. In addition, it receives early indications of insults to the body such as immune challenge and other toxic components and is essential for sustaining life. According to National Vital Statistics Reports 2016, renal dysfunction has been ranked as the ninth most abundant cause of death in the USA. This chapter provides detailed descriptions of Drosophila Malpighian tubule development, physiology, immune function and also presents evidences that Malpighian tubules can be used as a model organ system to address the fundamental questions in developmental and functional disorders of the kidney.
Malpighian tubules (MT) of Drosophila melanogaster are osmoregulatory organs that maintain the ionic balance and remove toxic substances from the body. Additionally they act as autonomous immune sensing organs, which secrete antimicrobial peptides in response to invading microbial pathogens. We show that the antimicrobial peptides (AMP) diptericin, cecropinA, drosocin and attacinA are constitutively expressed and are regulated in developmental stage specific manner. Their developmental expression begins from 3rd instar larval stage and an immune challenge increases the expression several folds. Spatial variatons in the level of expression along the MT tissue are observed. The mortality of 3rd instar larvae fed on bacterial food is much less than that of the earlier larval stages, coinciding with the onset of innate immunity response in MT. Ectopic expression of AMP imparts better resistance to infection while, loss of function of one of the AMP through directed RNAi reduces host survival after immune challenge. The AMP secreted from the MT exhibit bactericidal activity. Expression of the NF-κB transcription factor, Relish, also coincides with activation of immune responsive genes in MT, demonstrating that immune regulation in MT is under developmental control and is governed by the Imd pathway.
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