Topic
Transplantation
About: Transplantation is a research topic. Over the lifetime, 276584 publications have been published within this topic receiving 7961661 citations.
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TL;DR: Oxidative stress limits distant metastasis by melanoma cells in vivo, particularly among inefficiently metastasizing melanomas, which underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress.
Abstract: Solid cancer cells commonly enter the blood and disseminate systemically, but are highly inefficient at forming distant metastases for poorly understood reasons. Here we studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NOD-SCID-Il2rg(-/-) (NSG) mice. We show that melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficiently metastasizing melanomas. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence on NADPH-generating enzymes in the folate pathway. Antioxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumours in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo.
910 citations
TL;DR: The new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival and will be useful for clinical trials and patient counseling before HCT.
907 citations
TL;DR: Risk factor analyses verify previously recognized risk factors (GVHD, receipt of corticosteroids, and neutropenia) and uncover the roles of lymphopenia and viral infections in increasing the incidence of postengraftment IA in the 1990s.
906 citations
TL;DR: This work comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state.
905 citations
TL;DR: Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications and further studies are needed to establish the optimum doses for the combined regimen.
905 citations