Abstract 1695: Vascularization of colorectal cancer liver metastasis: correlation with growth patterns
Notice bibliographique
Résumé
Abstract Colorectal cancer (CRC) is the third leading cause of cancer-related death in North America. Approximately 50% of patients will be diagnosed with CRC liver metastasis (CRLM) during the course of their disease. Untreated, patients will survive for only a few months, but with chemotherapy, a median survival of 20 months can be achieved. At present, no reliable indicators exist to predict outcome or prognosis in treatable patients. Moreover, no biological parameters are currently being considered for patient stratification into different treatment groups. We examined CRCLM resected from patients and have identified two major histologic growth patterns (HGP): a desmoplastic (DHGP) pattern and a replacement (RHGP) pattern where tumor cells replace parenchymal cells in the liver plates. These HGP involve distinct modes of angiogenesis and host cell responses. Namely, liver metastases with a RHGP grow by co-opting the stroma, without hypoxia-induced angiogenesis and with little perturbation of the liver architecture. In contrast, metastases with a DHGP show characteristics of ongoing, hypoxia-driven angiogenesis including increased fibrin deposition at the tumour-liver interface and increased endothelial cell proliferation. In addition RHGP is associated with poor clinical response to bevacizumab chemotherapy. These differences suggest that the two patterns trigger distinct microenvironment responses and as a consequence, may initiate and utilize different modes of vascularization and expansion. Our hypothesis is that there are distinct gene expression signatures in the tumor and/or host compartments of different HGPs, which will shed light on the biological mechanisms underlying this diversity of HGPs. To test this hypothesis we: i) have extracted high quality RNA from lesions of chemonaïve patients and through RNAseq analysis identified gene expression differences between DHGP, RHGP lesions ii.) to further understand the role of tumor associated vascularity, we have stained different lesions (chemonaïve, chemo only and chemo + bevacizumab) with vascular markers to look at tumor associated blood vessels (immature, intermediate and mature: aSMA1 & CD31) and the rate of endothelial cell proliferation (Ki67/CD34). Our preliminary data demonstrates the expression of neo-vessels in the DHGP desmoplastic ring and in the peripheral tumor along the parenchyma tissue have lower vascularity with fewer branches that are supplying the tumor. The RHGP has similar vasculature to the adjacent normal tissue with a sinusoidal network of blood supply and a higher vascularity than DHGP. We are now correlating these findings with RNAseq expression data. This work will result in the identification of targets in the HGPs that will help stratify patients in terms of treatment. We currently have less treatment options for the RHGP patients and it would be important to utilize the data from this study to develop new treatment strategies for those patients. Citation Format: Anthoula Lazaris, Abdellatif Amri, Pablo Zoroquiain, Stephanie K. Petrillo, Rafif Mattar, Zu-Hua Gao, Peter Vermeulen, Peter Metrakos. Vascularization of colorectal cancer liver metastasis: correlation with growth patterns. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1695.
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 | 0,001 | 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) | 0,004 | 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 ».