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- Silvestri, M, et al.
(författare)
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Detection of Genomically Aberrant Cells within Circulating Tumor Microemboli (CTMs) Isolated from Early-Stage Breast Cancer Patients
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Circulating tumor microemboli (CTMs) are clusters of cancer cells detached from solid tumors, whose study can reveal mechanisms underlying metastatization. As they frequently comprise unknown fractions of leukocytes, the analysis of copy number alterations (CNAs) is challenging. To address this, we titrated known numbers of leukocytes into cancer cells (MDA-MB-453 and MDA-MB-36, displaying high and low DNA content, respectively) generating tumor fractions from 0–100%. After low-pass sequencing, ichorCNA was identified as the best algorithm to build a linear mixed regression model for tumor fraction (TF) prediction. We then isolated 53 CTMs from blood samples of six early-stage breast cancer patients and predicted the TF of all clusters. We found that all clusters harbor cancer cells between 8 and 48%. Furthermore, by comparing the identified CNAs of CTMs with their matched primary tumors, we noted that only 31–71% of aberrations were shared. Surprisingly, CTM-private alterations were abundant (30–63%), whereas primary tumor-private alterations were rare (4–12%). This either indicates that CTMs are disseminated from further progressed regions of the primary tumor or stem from cancer cells already colonizing distant sites. In both cases, CTM-private mutations may inform us about specific metastasis-associated functions of involved genes that should be explored in follow-up and mechanistic studies.
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| 2. |
- Heredia-Martinez, A., et al.
(författare)
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Plasma Nitrate and Nitrite Kinetics after Single Intake of Beetroot Juice in Adult Patients on Chronic Hemodialysis and in Healthy Volunteers : A Randomized, Single-Blind, Placebo-Controlled, Crossover Study
- 2022
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. NO is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate–nitrite–NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL 400 mg nitrate) and placebo BJ (70 mL 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity. © 2022 by the authors.
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