ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Cisplatin-induced downregulation of OCTN2 affects carnitine wasting.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma.PloS one · 2020Trial
- L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)--a randomized multicentre trial.Nutrition journal · 2012Trial
- Reversible Secondary Carnitine Deficiency Associated With ChronicClinical medicine insights. Case reports · 2026Article
- L-carnitine in metabolic dysfunction-associated steatotic liver disease: mechanisms and therapeutic potential.Frontiers in nutrition · 2026Review
- Recent advances in mass spectrometry-based bioanalytical methods for endogenous biomarkers analysis in transporter-mediated drug-drug interactions.Journal of pharmaceutical analysis · 2025Review
- Carnitine Deficiency in Chronic Kidney Disease: Pathophysiology, Clinical Implications, and Therapeutic Perspectives.Nutrients · 2025Review
- Dysfunction of the carnitine cycle in tumor progression.Heliyon · 2024Review
- Roles of clinical application of lenvatinib and its resistance mechanism in advanced hepatocellular carcinoma (Review).American journal of cancer research · 2024Review
- Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock.The Journal of clinical investigation · 2023Article
- Metabolomic profiling of triple negative breast cancer cells suggests that valproic acid can enhance the anticancer effect of cisplatin.Frontiers in cell and developmental biology · 2022Article
- Article
- Limited Impact of Pivalate-Induced Secondary Carnitine Deficiency on Hepatic Transcriptome and Hepatic and Plasma Metabolome in Nursery Pigs.Metabolites · 2021Article
- Changes in carnitine levels through induction chemotherapy in head and neck cancer patients as a potential cause of therapy-related malaise.BMC cancer · 2021Article
- Influence of YES1 Kinase and Tyrosine Phosphorylation on the Activity of OCT1.Frontiers in pharmacology · 2021Article
- Review
- SLC22A5 (OCTN2) Carnitine Transporter-Indispensable for Cell Metabolism, a Jekyll and Hyde of Human Cancer.Molecules (Basel, Switzerland) · 2019Review
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Carnitine and Adiponectin Levels in Breast Cancer after Radiotherapy.Open medicine (Warsaw, Poland) · 2017Article
- Cisplatin-induced renal injury is independently mediated by OCT2 and p53.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Uptake carriers and oncology drug safety.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeCarnitine is an essential cofactor for mitochondrial fatty acid oxidation that is actively reabsorbed by the luminal transporter Octn2 (Slc22a5). Because the nephrotoxic agent cisplatin causes urinary loss of carnitine in humans, we hypothesized that cisplatin may affect Octn2 function. EXPERIMENTAL
designExcretion of carnitine and acetylcarnitine was measured in urine collected from mice with or without cisplatin administration. The transport of carnitine was assessed in cells that were transfected with OCT1 or OCT2. The effect of cisplatin treatment on gene expression was analyzed using a mouse GeneChip array and validated using quantitative reverse transcriptase-PCR.
resultsIn wild-type mice, urinary carnitine excretion at baseline was ∼3-fold higher than in mice lacking the basolateral cisplatin transporters Oct1 and Oct2 [Oct1/2(-/-) mice], indicating that carnitine itself undergoes basolateral uptake into the kidney. Transport of carnitine by OCT2, but not OCT1, was confirmed in transfected cells. We also found that cisplatin caused an increase in the urinary excretion of carnitine and acetylcarnitine in wild-type mice but not in Oct1/2(-/-) mice, suggesting that tubular transport of cisplatin is a prerequisite for this phenomenon. Cisplatin did not directly inhibit the transport of carnitine by Octn2 but downregulated multiple target genes of the transcription factor peroxisome proliferator activated receptor α, including Slc22a5, in the kidney of wild-type mice that were absent in Oct1/2(-/-) mice.
conclusionOur study shows a pivotal role of Oct1 and Oct2 in cisplatin-related disturbances in carnitine homeostasis. We postulate that this phenomenon is triggered by deactivation of peroxisome proliferator activated receptor α and leads to deregulation of carnitine-shuttle genes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.