Search results for "EGFR"
showing 10 items of 150 documents
Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR
2014
Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR. PHD3 silencing in human gliomas or genetic deletion in a murine high-grade astrocytoma model markedly promotes tumour growth and the ability of tumours to continue growing under unfavourable conditions. The growth-suppressive function of PHD3 is independent of the established PHD3 targets HIF and NF-κB and its hydroxylase activity. Instead, l…
Roles of signaling pathways in drug resistance, cancer initiating cells and cancer progression and metastasis
2014
The EGFR/PI3K/PTEN/Akt/mTORC pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance, cancer initiating cells (CICs) and metastasis. The expression of this pathway is frequently altered in breast and other cancers due to mutations at or aberrant expression of: HER2, EGFR1, PIK3CA, and PTEN as well as other oncogenes and tumor suppressor genes. miRs and epigenetic mechanisms of gene regulation are also important events which regulate this pathway. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathw…
Epidermal Growth Factor Receptor (EGFR) Cell Expression During Adjuvant Treatment After Transurethral Resection for Non-Muscle-Invasive Bladder Cance…
2019
Abstract Background The aim of the study was to investigate the feasibility of Epidermal Growth Factor Receptor (EGFR) measurement in bladder washings of patients affected by non–muscle-invasive bladder cancer (NMIBC) and its prognostic role in identifying risk subgroups and predicting disease recurrence and progression. Patients and Methods Patients with NMIBC treated with transurethral resection of bladder tumor (TURBT) from 2012 to 2015 were enrolled. Samples of bladder washings were collected and stored at −80°C until RNA extraction. The cDNA obtained from RNA was used to perform a gene expression analysis by a real time polymerase chain reaction. Results An adequate cellular pellet was…
Investigation of new 2-aryl substituted Benzothiopyrano[4,3-d[pyrimidines as kinase inhibitors targeting vascular endothelial growth factor receptor 2
2015
Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most important positive modulators of Angiogenesis, a central process implicated in tumour growth and metastatic dissemination. This led to the design and development of anti-VEGF monoclonal antibodies and small-molecule ATP-competitive VEGFR-inhibitors. In this study, we describe the synthesis and the biological evaluation of novel 2-aryl substituted benzothiopyrano-fused pyrimidines 1a-i, 2a-i and 3a-i. The ability of the compounds to target the VEGF pathway was determined in vitro exploiting the compounds' antiproliferative efficacy against HUVEC cells. The VEGFR-2 inhibition was confirmed by enzymatic assays on …
Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project
2021
Abstract Background Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods Clinica…
Safety and Pharmacokinetics/Pharmacodynamics of the First-in-Class Dual Action HER3/EGFR Antibody MEHD7945A in Locally Advanced or Metastatic Epithel…
2015
Abstract Purpose: The novel dual-action humanized IgG1 antibody MEHD7945A targeting HER3 and EGFR inhibits ligand-dependent HER dimer signaling. This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of MEHD7945A. Experimental Design: Patients with locally advanced or metastatic epithelial tumors received escalating doses of MEHD7945A (1–30 mg/kg) every 2 weeks (q2w) until disease progression or intolerable toxicity. An expansion cohort was enrolled at the recommended phase II dose (14 mg/kg, q2w). Plasma samples, tumor biopsies, FDG-PET were obtained for assessment of pharmacokinetics, and pharmacodynamic modulation downstream of EGFR and HER3. …
Triple-negative breast cancer: Molecular features, pathogenesis, treatment and current lines of research
2010
Breast cancer is a heterogeneous disease with different morphologies, molecular profiles, clinical behaviour and response to therapy. The triple negative is a particular type of breast cancer defined by absence of oestrogen and progesterone receptor expression as well as absence of ERBB2 amplification. It is characterized by its biological aggressiveness, worse prognosis and lack of a therapeutic target in contrast with hormonal receptor positive and ERBB2+ breast cancers. Given these characteristics, triple-negative breast cancer is a challenge in today's clinical practice. A new breast cancer classification emerged recently in the scientific scene based in gene expression profiles. The ne…
Abstract 3363: Pharmacodynamic (PD) assessment of drug activity in tumor tissue from patients (pts) enrolled in a Phase I study of MEHD7945A (MEHD), …
2013
Abstract Background Members of the human epidermal growth factor receptor (HER) family of oncogenes are often co-expressed and heterodimerized, suggesting that simultaneous blockade of multiple HER family receptors may be more effective than targeting single receptors. MEHD is a dual-action human IgG1 antibody that can bivalently bind to HER3 and EGFR and block ligand binding to either. FDG-PET imaging is a recognized method of assessing PD modulation with EGFR inhibitors in the clinic. HER3 and EGFR signaling via the MAPK and PI3K pathways can be monitored in tissue by examining phosphorylation of downstream markers. Methods A Phase 1, multicenter, open-label study was conducted to evaluat…
Comprehensive cross-platform comparison of methodologies for noninvasive EGFR mutation testing: Results of the RING observational trial.
2020
e21518 Background: Several platforms for non-invasive EGFR testing are currently used in the clinical setting, with sensitivities ranging from 30 to 100%. Comparison studies in prospective cohorts remain limited and reports evaluating mutant allelic fractions (MAFs) are particularly scarce. The RING observational trial (ClinicalTrials.gov identifier NCT03363139) was designed to comprehensively analyze the concordance between methodologies for EGFR mutation detection in blood. Methods: Seventy-two EGFR mutant NSCLC patients were enrolled in the trial. Plasma samples were prospectively collected at progression to first line Tyrosine Kinase Inhibitor and tested for EGFR mutations by 7 methodo…
Panitumumab in combination with gemcitabine/cisplatin (GemCis) for patients with advanced kRAS WT biliary tract cancer: A randomized phase II trial o…
2015
4082 Background: Biliary tract cancer encompasses a group of genetically heterogeneous tumors. Panitumumab is a human EGFR inhibitor and has shown anti-tumor activity in RAS WT colorectal cancer. M...