P5-12-03: An Innovative Quantification Method for Tamoxifen and Three Metabolites in Formalin-Fixed Paraffin-Embedded Tissues by Liquid Chromatography and Tandem Mass Spectrometry.
Notice bibliographique
Résumé
Abstract Background Tamoxifen (TAM) has been commonly used as a selective estrogen receptor modulator for the treatment and prevention of breast cancer. Although this drug is effective in many patients, some develop resistant and eventually relapse. Recent studies suggest that the cancer recurrence could possibly be due to changes in drug metabolism. TAM is metabolized by the cytochrome P450 enzyme pathway into several metabolites including 4-hydroxy-tamoxifen (4-OH), N-desmethyl-tamoxifen (DMT) and N-desmethyl-4-hydroxy-tamoxifen (endoxifen). These metabolites have variable potencies in suppressing estrogen-dependent breast cancer. Differences in metabolism may contribute to the clinical inter-individual variability in TAM response. The aim of our study was to provide a comprehensive evaluation of TAM and its metabolites through quantitative measurement in breast cancer patients to help better understand the pharmacological effects of TAM therapy. In the past, most methods used to measure the levels of TAM and its metabolites were in plasma or fresh/frozen tissue samples. These samples are typically not available retrospectively, and their long-term storage is expensive and laborious. Methods: We therefore explored the possibility to utilize formalin-fixed and paraffin-embedded (FFPE) tissues archived post breast surgery for quantification of TAM and its metabolites. Our laboratory has developed a rapid, sensitive and specific analytical method using liquid chromatography and tandem mass spectrometry (LC-MS/MS) for the measurement of TAM and its metabolites in FFPE tissues. The FFPE tissues were thin sectioned and deparaffinized by incubating twice with xylene for 10 min at room temperature. Sample clean-up was carried out subsequently using C2 solid-phase extraction, and detection was performed in the multiple-reaction monitoring mode with a triple quadrupole mass spectrometer. This method allows simultaneous quantification of TAM and three metabolites in FFPE tissues with a run time of 12 min. Results: The assay had good inter- and intra-assay precisions (2-6 %CV), and was linear over the range of 0.01-5 ng/g for 4-OH and endoxifen, and 0.1-50 ng/g for TAM and DMT. The extraction recoveries were between 83–88%. The validated method was successfully applied to analyze the FFPE tissues obtained from two groups of breast cancer patients. Patients were categorized into those with tumor recurrence (R) and those without recurrence (NR) after at least 2 months of 20 mg/d TAM treatment. Levels of TAM, 4-OH, DMT and endoxifen in FFPE tissues were compared between the two groups. Our preliminary data show that the ratio of DMT/TAM was significantly higher in the R (6.7, n = 13) than the NR patients (14.2, n = 9) (p<0.05). Discussion: The assay described here not only allows accurate quantification of TAM and metabolites in FFPE tissues, but also opens up an incredible opportunity and new challenges for researchers to excavate precious information from FFPE tissues, especially when these archival samples represent the only source of biomaterial available. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-12-03.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,003 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».