| 1. |
- Chen, Yiqin, et al.
(författare)
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Persistent organic pollutants in infants and toddlers : Relationship between concentrations in matched plasma and faecal samples
- 2017
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 107, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Early-childhood biomonitoring of persistent organic pollutants (POPs) is challenging due to the logistic and ethical limitations associated with blood sampling. We investigated using faeces as a non-invasive matrix to estimate internal exposure to POPs. The concentrations of selected POPs were measured in matched plasma and faecal samples collected from 20 infants/toddlers (aged 13 +/- 4.8 months), including a repeat sample time point for 13 infants (similar to 5 months apart). We observed higher rates of POP quantification in faeces (2 g dry weight) than in plasma (0.5 mL). Among the five chemicals that had quantification frequencies over 50% in both matrices, except for HCB, log concentration in faeces (C-f) and blood (C-b) were correlated (r > 0.74, P < 0.05) for p.p'-dichlorodiphenyldichloroethylene (p,p'-DDE), 2,3', 4,4', 5-pentachlorobiphenyl (PCB118), 2,2', 3,4,4', 5'-pentachlorobiphenyl (PCB138) and 2,2', 4,4', 5,5'-pentachlorobiphenyl (PCB153). We determined faeces: plasma concentration ratios (K-fb), which can be used to estimate C-b from measurements of C-f for infants/toddlers. For a given chemical, the variation in K-fb across individuals was considerable (CV from 0.46 to 0.70). Between 5% and 50% of this variation was attributed to short-term intra-individual variability between successive faecal samples. This variability could be reduced by pooling faeces samples over several days. Some of the remaining variability was attributed to longer-term intra-individual variability, which was consistent with previously reported observations of a decrease in K-fb over the first year of life. The strong correlations between C-f and C-b demonstrate the promise of using faeces for biomonitoring of these compounds. Future research on the sources of variability in K-fb could improve the precision and utility of this technique.
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| 2. |
- Marsh, Timothy, et al.
(författare)
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Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression
- 2016
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Ingår i: Cancer Research. - 0008-5472. ; 76:10, s. 2932-2943
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs.
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