CDK-Inhibitors as New Therapeutic Treatment for Human Bronchial Carcinoids Abstract #1494

Introduction: Bronchial Carcinoids (BC) are still orphan of medical therapy. We previously demonstrated that 70% of primary BC cultures are sensitive to Everolimus (E), an mTOR inhibitor, while 30% are not. We also observed that in 2 human BC cell lines, the NCI-H720 (sensitive to E) and NCI-H727 (resistant to E), mTOR resistance may be linked to a differential cell cycle protein expression (CyclinD1/E, CDK2/4, p27kip1/p27kip1phospho-Ser10), which is higher in BC resistant to E as compared to sensitive ones, suggesting an impaired p27 function
Aim(s): Evaluate the response of BC immortalized cell lines and primary culture to Dinaciclib (D), a novel and potent CDK inhibitor
Materials and methods: We have assessed cell viability and apoptosis activation assay on BC primary cultures and immortalized cell lines, resistant or sensitive to mTOR inhibitor
Conference: 13th Annual ENETS conference 2016 (2016)
Category: Medical treatment - Others
Presenting Author: MASTER DEGREE Katiuscia Benfini

To read results and conclusion, please login ...

Further abstracts you may be interested in

#962 Cyclin D1 Levels are Involved in the Resistance to m-TOR Inhibitors in Human Bronchial Carcinoids
Introduction: Bronchial carcinoids (BC) are still orphans of medical therapy. We previously demonstrated that the typical BC human cell line NCI-H727 is sensitive to Everolimus, in terms of cell viability reduction, while the atypical human BC cell line NCI-H720 is not. However, the mechanisms underlying this phenomenon have not been fully clarified.
Conference: 11th Annual ENETS Conference 2014 (2014)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: Master degree Katiuscia Benfini
Keywords: BC, mTOR
#1090 p27kip1 Is Involved in the Resistance of Human Bronchial Carcinoids to m-TOR Inhibitors
Introduction: Bronchial carcinoids (BC) are still orphan of medical therapy. We previously demonstrated that the typical BC human cell line NCI-H727 is sensitive to Everolimus (E), in terms of cell viability reduction, with a G0 cell-cycle arrest, while the atypical human BC cell line NCI-H720 is not. The mechanisms underlying this phenomenon have not been clarified
Conference: 12th Annual ENETS Conference 2015 (2015)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: Master Degree Katiuscia Benfini
Keywords: RAD001, BC, p27kip1, Cell cycle
#1999 Study of Cell Cycle Protein Expression Pattern in Bronchial Carcinoids: A New Potential Target for Medical Therapy?
Introduction: Bronchial Carcinoids (BCs) are rare neuroendocrine neoplasms arising from respiratory epithelium. The only effective treatment option is surgery, but its efficacy is frequently limited by metastatic spread. Everolimus prolongs progression free survival but patients may develop resistance. Previous studies demonstrated that Everolimus reduces viability of NCI-H720 cells (Atypical Carcinoid) but not of NCI-H727 cells (Typical Carcinoid). Everolimus decreases Ciclyn D1 protein levels in both cell lines but NCI-H727 cells survive, indicating a derangement in cell cycle control.
Conference: 15th Annual ENETS conference 2018 (2018)
Category: Basic Science - Signaling pathways, receptors, biomarkers
Presenting Author: Giulia Bresciani
#2785 Inhibition of Cyclin Dependent Kinases Overcomes MYC-Driven Secondary Resistance to Everolimus in Digestive NETs
Introduction: Dysregulation of the mTOR pathway in digestive neuroendocrine tumours (d-NETs) led to the introduction of Everolimus (EVE) as treatment. EVE significantly increases PFS, but most patients acquire resistance, due to activation of feedback loops.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Signaling pathways, receptors, biomarkers
Presenting Author: Md, PhD Gabriele Capurso
#2983 Differential TGF-β Signalling in Typical and Atypical Bronchial Carcinoids
Introduction: Typical and atypical bronchial carcinoids (TBC and ABC) are well-differentiated neuroendocrine neoplasms (NEN). Metastatic BC having low to moderate mitotic count may still be treated with somatostatin analogues and mTOR inhibitors; however, TBC and ABC have been reported to respond very differently to therapy and an effective treatment algorithm is still lacking. TGF-β is known for its ability to activate mTOR pathway and induce epithelial mesenchymal transition, affecting cell pathophysiological capabilities such as proliferation, migration and tissue invasiveness.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Signaling pathways, receptors, biomarkers
Presenting Author: Patricia Borges de Souza