Project description:Further to our previous study (E-MTAB-5997), here we performed transcriptome profiling on Anlotinib-resistant NCI-H1975 and Anlotinib-treated Anlotinib-resistant NCI-H1975, and would like to understand the effects of Anlotinib on Anlotinib-resistant NCI-H1975 cell, compare the different transcriptome profiling on NCI-H1975 cells and Anlotinib-resistant NCI-H1975 cells, sought to find the biomarker for explaining Anlotinib resistance.
Project description:Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors presenting a wide spectrum of different clinical and biological characteristics. In these tumors, the histological evaluation is a crucial element of clinical management. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, is the most reliable predictor of prognosis. This scoring method is time-consuming and a high reproducibility cannot be achieved. Novel approaches are needed to support histological evaluation and prognosis. In this study, starting from a microarray analysis, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. Moreover, we identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, we found miR-96-5p that raised its expression levels from grade 1 to grade 3; inversely, its target FOXO1 was decrease from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET correlates their expression with grading showing a potential advantage of miRNA quantification to aid clinicians in the classification of common GEP-NETs subtypes.
Project description:Famitinib is a tyrosin-inhibitor agent targeting at c-Kit, VEGFR2, PDGFR, VEGFR3, Flt1 and Flt3. Phase I study has shown that the toxicity is manageable.
The purpose of this study is to evaluate the efficacy and safety profile of Famitinib in patients with advanced or metastatic Gastroenteropancreatic Neuroendocrine Tumor.
Project description:This study aims to elucidate the transcriptomic changes and metabolic reprogramming in gastroenteropancreatic neuroendocrine tumor (GEP-NET) cells following PIKfyve inhibition, using both genetic (CRISPR-mediated knockdown) and pharmacological (Apilimod treatment) approaches. The research focuses on the impact of PIKfyve inhibition on lipid metabolism, cholesterol homeostasis, and mTOR signaling in QGP-1, BON-1, and GOT-1 cell lines. By analyzing RNA sequencing data from these experimental conditions, we seek to identify differentially expressed genes and enriched pathways associated with PIKfyve inhibition. This investigation is part of a broader effort to develop novel combination therapies that could potentially overcome resistance to mTOR inhibitors, the current standard of care for advanced GEP-NETs. The study's findings may provide insights into the therapeutic potential of targeting PIKfyve-driven lipid metabolism in combination with mTOR inhibition, potentially offering new strategies to improve treatment efficacy and patient outcomes in GEP-NETs and other mTOR-driven cancers.
Project description:This study aims to elucidate the transcriptomic changes and metabolic reprogramming in gastroenteropancreatic neuroendocrine tumor (GEP-NET) cells following PIKfyve inhibition, using both genetic (CRISPR-mediated knockdown) and pharmacological (Apilimod treatment) approaches. The research focuses on the impact of PIKfyve inhibition on lipid metabolism, cholesterol homeostasis, and mTOR signaling in QGP-1, BON-1, and GOT-1 cell lines. By analyzing RNA sequencing data from these experimental conditions, we seek to identify differentially expressed genes and enriched pathways associated with PIKfyve inhibition. This investigation is part of a broader effort to develop novel combination therapies that could potentially overcome resistance to mTOR inhibitors, the current standard of care for advanced GEP-NETs. The study's findings may provide insights into the therapeutic potential of targeting PIKfyve-driven lipid metabolism in combination with mTOR inhibition, potentially offering new strategies to improve treatment efficacy and patient outcomes in GEP-NETs and other mTOR-driven cancers.
Project description:The purpose of this trial is to assess time to disease progression of patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors treated with Lanreotide Depot. This is an observational study therefore all data collected will be in accordance with the routine practice of physicians.