Direct intra-tumour delivery of zoledronate is superior to systemic administration for mitigating metastasis- induced bone destruction
Notice bibliographique
Résumé
Background: Bone metastases are the most common cause of cancer-related pain and often lead to other complications. Bisphosphonates (BPs) are a class of potent anti-resorptive agents have been found recently to have direct anti-tumour properties. Currently, the use of BPs for cancer therapy is generally restricted to high dose systemic delivery. Questions/ purpose: (1) whether local delivery of BPs can inhibit tumour-induced osteolysis and tumour growth in an animal model of bone metastases; and (2) whether the efficacy in impairing cancer-induced osteolysis that is achieved by local delivery of BPs is comparable to that of systemic BPs treatment. Methods: Seven days following intra-tibial inoculation of MDA-MB-231 human breast cancer cells (N = 105) in athymic nude mice, the experimental group (N = 11) was treated by local administration of 2µg of zoledronate into the tibial lesion (three times/week for three weeks) and compared to vehicle-treated mice (N = 5). The formation of bone metastases and growth of the lesions were followed up by weekly bioluminescence imaging. In a subsequent experiment, a comparison of the effects of local versus systemic delivery of zoledronate on the formation of osteolytic bone metastases was carried in athymic mice (N = 19). The systemic group (N = 5) was treated with zoledronate (0.025mg/kg) once per week for 4 weeks and compared to systemic delivery of vehicle (N = 4). The local group (N=6) was treated by direct infusion of zoledronate (0.025mg/kg) once per week for 4 weeks and compared to local delivery of vehicle (N = 4). The effect of treatment on bone was determined using micro-computed tomography (μ-CT), and on tumour cells proliferation and apoptosis by immunohistochemistry using antibodies for Ki-67 and caspase-3. Results: The first experiment showed a statistically significant increase in mean bone volume/tissue volume % (BV/TV) in the treated group (12.30±2.80%) as compared to the control group (7.13±1.22%) (P<0.001, 95%CI=3.10-7.30). This corresponded to a net increase of 72.51% in response to zoledronate treatment. Bioluminescence imaging showed insignificant inhibition of the tumour growth in the treated group. Additionally, the treated group had an insignificant decrease in Ki-67-positive cells and this was mirrored with an insignificant increase in the number of caspase-3-positive cells. Comparison between the local and systemic effects of zoledronate also revealed a significant increase in the BV/TV in the locally treated group (10.90±1.25%) when compared to the cohort administered systemic bisphosphonate treatment (7.53±0.75%) (P<0.001, 95%CI=2.10-4.81), corresponding to a net increase of 44.8%. Conclusion: These preliminary results suggest that high dose sustained release of BPs can lead to a significant inhibition of tumour-induced osteolysis. Moreover, comparison between local and systemic delivery revealed that the effect of local BPs administration exceeds the benefits of systemic delivery in terms of osteolysis inhibition. Lastly, the noted effect of BPs local delivery triggers the need for further assessment of its anti-tumour activity.
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) | 0,001 | 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 | 0,001 |
| 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 ».