Project description:Here we report that Axitinib, an inhibitor of VEGFRs currently in use as a second line treatment for advanced renal cell carcinoma, promotes senescence of human endothelial cells in vitro. Mechanistically, this requires oxidative stress-dependent activation of the Ataxia Telangiectasia Mutated (ATM) kinase. Induction of oxidative stress-related genes distinguishes the response of endothelial cells to Axitinib from that to doxorubicin
Project description:This is a non-randomized, open-label, Phase II trial investigating axitinib as a single-agent maintenance therapy following standard first-line FOLFOX/bevacizumab therapy for patients with mCRC.
Project description:To understand the effect of hypoxia on vasculogenic mimicry we treated mammary tumour dervied from parental 4T1 cells with vehicle or Axitinib. Tumors were analyzed by scRNA-seq and the expression of endothelial genes assessed in these data with and wihtout Axitinib treatment.
Project description:Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10-15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. We conducted a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders had higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predicted response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features included plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario.
Project description:The purpose of this study is to evaluate and quantify the dynamic modifications of tumor blood perfusion on axitinib therapy in patients with refractory mCRC for each dose of Axitinib.
Project description:RNA sequencing analysis was used to identify changes in mouse breast cancer cells (4T1) after axitinib resistance and FACS isolation of SA-β-galHi (SM+) and SA-β-galLo (SM-) cells
Project description:Feline mammary carcinoma (FMC) is a prevalent and aggressive cancer with high metastatic potential. Few tissue biomarkers have been reported to help evaluate disease progression in FMC. This study aimed to analyze the tissue proteomic profiles of metastatic feline mammary carcinoma (mFMC) and non-metastatic FMC (NmFMC) across various histological grades (HGs) and histological types (HTs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Project description:This study is try to evaluate the effect of cetuximab monotherapy as maintenance treatment, versus continuation after 8 courses of induction therapy with cetuximab plus standard chemotherapy regimen (FOLFIRI or mFOLFOX6)in metastatic colorectal cancer (mCRC) patients. The maintenance treatments are continued until disease progression or untolerated toxicity. The aim of this study is to demonstrate that cetuximab monotherapy is non-inferior to continuation treatment, in those mCRC patients who responded to induction therapy(SD, PR, or CR), and carry biomarker-panels (KRAS, NRAS, BRAF, and PIK3CA) favor EGFR antibody.
Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC). 138 samples from patients with clear cell renal cell carcinoma, including biological replicates of nephrectomy samples. RNA extracted fresh frozen tissue samples.