The Dose‐Related Effects of Doxorubicin Chemotherapy on Interstitial Amino Acid Concentrations in Skeletal Muscle
Bibliographic record
Abstract
Doxorubicin (DOX) is a frontline anticancer therapeutic which has proven effective in the treatment of various cancers. However, very little is known regarding the effect that DOX has on SM metabolism, specifically its influence on interstitial amino acid (AA) concentrations. In SM, the interstitial space represents an important active compartment located between the vasculature and the tissue and it has been shown to play a functional role in the regulation and integration of various metabolic substances. The purpose of the current study was to determine the effect of DOX on interstitial AA concentrations in SM. Rats received a 1.5 or 4.5 mg/kg dose of DOX i.p. and grouped into endpoints every 24 hrs up to 192 hrs. A control group was administered a sham i.p. injection of saline. Total amino acids (TAA), essential amino acids (EAA) and branched‐chain amino acids (BCAA) were quantified in the interstitial space. The administration of DOX resulted in a dose‐related difference in interstitial AA. The 1.5 mg/kg dose resulted in a transient increase (P<0.05) in TAA, EAA and BCAA from 24–96 hrs as compared to control. Contrarily, TAA, EAA and BCAA decreased (P<0.05) 24–192 hours following the administration of 4.5 mg/kg DOX as compared to control. This study by way of the microdialysis technique, represents the first time that amino acid concentrations have been quantified in the interstitial space following the administration of a chemotherapeutic drug. In addition, the possibility of a dose‐related effect of DOX on amino acid transport mechanisms from the skeletal muscle compartment into the interstitium/vasculature is of particular interest as this may represent a regulatory mechanism that has not previously been considered. Support or Funding Information Supported by NOSMFA This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".