Immunohistochemical Detection of Autophagy‐Related Proteins in Canine Appendicular Osteosarcoma
Notice bibliographique
Résumé
Dogs diagnosed with appendicular osteosarcoma commonly succumb to metastatic disease despite undergoing the standard of care treatment for curative intent: amputation of the affected limb, followed by adjuvant chemotherapy. Post‐surgical chemotherapy improves one‐ and two‐year survival rates, but prognosis is still poor. In response to adverse environmental conditions normal cells are capable of undergoing autophagy, a survival mechanism involving self‐degradation and recycling of cellular components. Neoplastic cells take advantage of this mechanism to enhance their survival during chemotherapy. Autophagy's role in osteosarcoma has been investigated in humans however similar studies in dogs are rare. Our objective was to examine the expression patterns of a select group of autophagy‐related proteins in canine osteosarcoma amputation samples and to identify potential correlations with survival. Immunohistochemistry for beclin‐1, LC3, phospho‐mTOR, phospho‐AKT1, phospho‐S6 ribosomal protein, and p62 was performed on a tissue microarray containing naïve canine appendicular osteosarcoma cores from dogs who began the standard of care treatment (≥1 dose of chemotherapy). For survival analyses, Kaplan‐Meier survival curves for different expression patterns were compared using the log‐rank test and interactions were considered significant if p < 0.05. The median survival time from the date of diagnosis was 250 days and survival time ranged from 67–897 days (n=20, 95% CI: 122–381). Intense phospho‐S6 ribosomal protein labeling was identified most consistently adjacent to osteoid matrix. Phospho‐mTOR labeling was most evident in the nuclear compartment, however cells undergoing mitosis displayed strong cytoplasmic labeling. Canine osteosarcoma cells exhibited a mixture of diffuse and punctate LC3 cytoplasmic labeling, potentially distinguishing between free cytoplasmic LC3‐I and autophagosome anchored LC3‐II, respectively. Western blot analysis of the beclin‐1 antibody produced a 58 kDa band as predicted. Three distinct intensities of cytoplasmic labeling were observed for beclin‐1 in canine osteosarcoma cells. Strong cytoplasmic beclin‐1 labeling in the majority of neoplastic cells was not observed in any cases with greater than one‐year survival (0/6); this pattern was observed only in cases with less than one‐year survival (5/14). Dogs with tumours having light (n=4), moderate (n=9), and strong (n=5) cytoplasmic labeling had median survival times of 294, 301, and 122 days, respectively. Strong cytoplasmic labeling was a significantly correlated with decreased survival time (Chisq=6.9, 2 df, p < 0.05). This preliminary study provides evidence that canine osteosarcoma cells undergo autophagy in vivo , with a similar LC3 labeling pattern to that described in other tumour types in various species. Additionally, it identifies beclin‐1 as a promising candidate biomarker of chemoresponsiveness in canine appendicular osteosarcoma. Support or Funding Information Funded by Pet Trust
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».