Abstract 5247: Use of two markers of hypoxia to study migration, re-oxygenation and repopulation of originally hypoxic cells in MCF-7 tumor xenografts following chemotherapy
Notice bibliographique
Résumé
Abstract Background: Hypoxia occurs in solid tumors: chronic diffusion-limited hypoxia occurs distal from functional blood vessels, while acute hypoxia may occur because of interruptions in blood flow. Well-nourished tumor cells close to blood vessels tend to be rapidly proliferating but hypoxic cells located farther away are slowly-proliferating. Chemotherapy may spare hypoxic cells because of poor drug distribution to them and because most drugs are selectively toxic to proliferating cells. Intervals between administration of chemotherapy allow for recovery of normal tissues (e.g. repopulation of bone marrow) but might allow re-oxygenation and resumed proliferation of formerly hypoxic cells due to better supply of nutrients to them, as is observed during radiotherapy. Therefore, it is important to establish a technique whereby hypoxia can be studied allowing for the assessment of different hypoxia-modulating therapies that can be used to prevent tumor relapse. Methods: Two specific markers of hypoxic cells (pimonidazole [pimo] and EF5) were injected into mice bearing MCF7 tumor xenografts, and tumor cells labeled with one or both markers were recognized in tumor sections (in relation to DioC7+ve functional tumor blood vessels) using appropriate fluorescence-labeled antibodies and imunohistochemistry. Proliferating cells were identified by an antibody to Ki67. Mice were treated with pimo and then either doxorubicin or saline one hour later; EF5 was given after a variable interval of 24, 48, 72, 96 or 120 hours; mice were killed two hours after the second injection. Changes in the location, proliferation and oxygen status of formerly hypoxic (pimo+ve) cells were quantified by their distance from blood vessels, Ki67 status and uptake of EF5 as a function of time. Results: Following treatment with doxorubicin, the proportion of hypoxic cells in the entire tumor decreased from1.5% (pimo+ve) prior to injection to 0.7% (EF5+ve) at 24 hours. The proportion of pimo+ve formerly hypoxic cells that are no longer hypoxic (i.e. EF5 - ve) at 24 hours was 75% after treatment compared to 18% in controls indicating rescue of previous hypoxic cells that would have died in the absence of treatment. The proportion of these pimo+ve cells that were cycling (Ki67+ve) increased from 4.7% to 15.0% at 24 Hours and then slowly decreased. Conclusions: There is a decrease in the proportion of hypoxic cells in MCF7 xenografts following treatment with doxorubicin. Originally hypoxic cells (that may have died in the absence of treatment) can move closer to blood vessels, re-oxygenate, and repopulate the tumor. Treatment directed to killing hypoxic cells (e.g. with hypoxia activated pro-drugs) has the potential to improve the outcome of chemotherapy by inhibiting tumor cell repopulation. Supported by are search grant from the Canadian Institutes for Health Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5247. doi:1538-7445.AM2012-5247
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
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 ».