The tyrosine kinase inhibitors effects on metastatic tumor graft in the chick chorioallantoic membrane assay

Vol. 58 No. 4, 2017

ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Alexandru Ciolofan, Octavian Marius Cretu, Stelian Stefanita Mogoanta, Eduard Mihai Ciuca

Background: Due to its heterogeneous nature, pancreatic cancer has a higher incidence and a clinical treatment failure. In this study, we present the effects of Avastin, Rapamycin and their combination on the pancreatic liver metastatic human tumor graft in the chick chorioallantoic membrane (CAM) assay. Materials and Methods: We conducted this study with 33 fertilized chicken eggs, incubated at 37 degrees C, divided into three working groups: control (three eggs), first (10 eggs), second (10 eggs), and third group (10 eggs). A cell suspensions derived from human liver metastasis of pancreatic tumor were implanted on the CAM, in the ring. First group was treated with 2 micro-L Avastin (Bevacizumab 25 mg/mL), the second with Rapamycin and the third with Avastin and Rapamycin combination on days 10, 12, 14 of incubation. The immunohistochemical techniques using vascular endothelial growth factor A (VEGFA), CD34, podoplanin, platelet-derived growth factor subunit A (PDGFA) and epidermal growth factor receptor (EGFR) as primaries antibodies were performed on metastatic tumor and metastatic tumor graft. Results: Our results showed that the unique treatment with Avastin gave rise to metastases on CAM xenograft, due likely to inflammatory infiltrate and vascular remodeling. The lowest immunoexpression of CD34, podoplanin, PDGFA, EGFR has been noticed in the Rapamycin-treated group without important differences correlated to dosage and time. In the third group, decreased value was found for PDGFA only. The periphery of the tumor graft malignant cells intensely expressed VEGFA, podoplanin and EGFR. Conclusions: The inhibitory therapy with mechanistic target of Rapamycin (mTOR) and Avastin may favor the epithelial to mesenchymal transition by podoplanin and phosphatase and tensin homolog (PTEN) pathways in liver metastasis pancreatic graft to CAM.

Corresponding author: Octavian Marius Cretu, Professor, MD, PhD; e-mail: tavicretu@yahoo.com

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