Journal of internal medicine
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Lung Cancer is the leading cause of cancer-related deaths worldwide. This is mainly due to late diagnosis and therefore advanced stage of the disease. Understanding the cell of origin of cancer and the processes that lead to its transformation will allow for earlier diagnosis and more accurate prediction of tumour type, ultimately leading to better treatments and lower patient morbidity. ⋯ We first elaborate on the different oncogenes that are associated with LUAD and other lung cancers. After, we lay out in detail what is known about AT2 biology, to further delve into AT2 cells as cell of origin for adenocarcinoma. Understanding the precursors of LUAD and identifying the molecular changes during its progression will allow for earlier detection and better molecular targeting of the disease in early stages.
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Type 1 diabetes (T1D) is an autoimmune disease affecting individuals in the early years of life. Although previous studies have identified genetic loci influencing T1D diagnosis age, these studies did not investigate the genome with high resolution. ⋯ Multiple genes on chr17q12 and PHF20L1 on chr8 were associated with T1D diagnosis age and only further studies may elucidate the role of these genes for immunity and T1D onset.
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Studies developing and applying organoid technology have greatly increased in volume and visibility over the past decade. Organoids are three-dimensional structures that are established from pluripotent stem cells (PSCs) or adult tissue stem cells (ASCs). They consist of organ-specific cell types that self-organize through cell sorting and spatially restricted lineage commitment to generate architectural and functional characteristics of the tissue of interest. ⋯ Starting from human cells (PSCs or ASCs), models of the two segments of the lung, the airways and the alveoli, can be built. Such organoids allow the study of development, physiology and disease and thus bridge the gap between animal models and clinical studies. This review discusses current developments in the pulmonary organoid field, highlighting the potential and limitations of current models.
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According to the cancer stem cell (CSC) hypothesis, CSCs are the only cancer cells that can give rise to and sustain all cells that constitute a cancer as they possess inherent or acquired self-renewal potential, and their elimination is required and potentially sufficient to achieve a cure. Whilst establishing CSC identity remains challenging in most cancers, studies of low-intermediate risk myelodysplastic syndromes (MDS), other chronic myeloid malignancies and clonal haematopoiesis of indeterminant potential (CHIP) strongly support that the primary target cell usually resides in the rare haematopoietic stem cell (HSC) compartment. This probably reflects the unique self-renewal potential of HSCs in normal human haematopoiesis, combined with the somatic initiating genomic driver lesion not conferring extensive self-renewal potential to downstream progenitor cells. ⋯ This implies that MDS stem cells might possess unique resistance mechanisms responsible for relapses following otherwise efficient treatments. Specific surveillance of MDS stem cells should be considered to assess the efficiency of therapies and as an early indicator of emerging relapses in patients in clinical remission. Moreover, further molecular characterization of purified MDS stem cells should facilitate identification and validation of improved and more stem cell-specific therapies for MDS.