Search results for "epiderma"

Natural Products Derived from Traditional Chinese Medicine as Novel Inhibitors of the Epidermal Growth Factor Receptor

2010

The epidermal growth factor receptor (EGFR) has become an important molecular target in cancer therapy. Various small molecules and therapeutic antibodies targeting EGFR family members have been developed during recent years and are established in clinical oncology. However, increasing clinical application of EGFR tyrosine kinase inhibitors has resulted in the development of resistance to EGFR-targeting drugs due to the selection of EGFR-mutated variants. This phenomenon forced the search for novel EGFR inhibitors with activity towards EGFR-mutant tumors. This review describes recent achievements in natural products derived from medicinal plants as novel EGFR inhibitors.

Targeted Therapies for Non-Small Cell Lung Cancer

2015

The discovery of new oncogenic driver mutations and the clinical development of targeted therapies have completely changed the paradigm treatment of non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib, ALK-inhibitors, crizotinib, and ceritinib, have been already approved for clinical use, benefiting many patients whose tumors harbor, respectively, EGFR or EML4-ALK molecular alterations. However, despite an initial benefit, tumor progression inevitably occurs, due to the development of acquired resistance to the targeted treatments. Several mechanisms of resistance have been identified, such as the seco…

Epidermal Growth Factor Receptors and Downstream Signalling Pathways as Cancer Treatment Targets for Medicinal Plants

2015

Entrapment of an EGFR inhibitor into nanostructured lipid carriers (NLC) improves its antitumor activity against human hepatocarcinoma cells

2014

Background: In hepatocellular carcinoma (HCC), different signaling pathways are de-regulated, and among them, the expression of the epidermal growth factor receptor (EGFR). Tyrphostin AG-1478 is a lipophilic low molecular weight inhibitor of EGFR, preferentially acting on liver tumor cells. In order to overcome its poor drug solubility and thus improving its anticancer activity, it was entrapped into nanostructured lipid carriers (NLC) by using safe ingredients for parenteral delivery. Results: Nanostructured lipid carriers (NLC) carrying tyrphostin AG-1478 were prepared by using the nanoprecipitation method and different matrix compositions. The best system in terms of mean size, PDI, zeta…

Gefitinib in lung cancer therapy. Clinical results, predictive markers of response and future perspectives.

2009

Over the past few years, epidermal growth factor receptor has emerged as one of the most important targets in tumorgenesis and several drugs targeting signal transduction pathways have been developed. The first among these agents to be approved for the treatment of NSCLC was gefitinib, a potent, selective and reversible inhibitor of HER1/EGFR tyrosine kinase activity. The review summarizes its clinical development and the new therapeutic options, with particular focus on predictive markers of susceptibility to this drug.

ALDEN, an Algorithm for Assessment of Drug Causality in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: Comparison With Case–Control Analysis

2010

Epidermal necrolysis (EN)--either Stevens-Johnson syndrome (SJS) or toxic EN (TEN)--is a severe drug reaction. We constructed and evaluated a specific algorithm, algorithm of drug causality for EN (ALDEN), in order to improve the individual assessment of drug causality in EN. ALDEN causality scores were compared with those from the French pharmacovigilance method in 100 cases and the case-control results of the EuroSCAR study. Scores attributed by ALDEN segregated widely. ALDEN pointed to a "probable" or "very probable" causality in 69/100 cases as compared to 23/100 with the French method (P < 0.001). It scored "very unlikely" causality for 64% of medications vs. none with the French metho…

Selected Secondary Plant Metabolites for Cancer Therapy

2015

Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of a…

Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma.

2019

During wound repair, branching morphogenesis and carcinoma dissemination, cellular rearrangements are fostered by a solid-to-liquid transition, known as unjamming. The biomolecular machinery behind unjamming and its pathophysiological relevance remain, however, unclear. Here, we study unjamming in a variety of normal and tumorigenic epithelial two-dimensional (2D) and 3D collectives. Biologically, the increased level of the small GTPase RAB5A sparks unjamming by promoting non-clathrin-dependent internalization of epidermal growth factor receptor that leads to hyperactivation of the kinase ERK1/2 and phosphorylation of the actin nucleator WAVE2. This cascade triggers collective motility effe…

γ2-Adaptin, a Ubiquitin-interacting Adaptor, Is a Substrate to Coupled Ubiquitination by the Ubiquitin Ligase Nedd4 and Functions in the Endosomal Pa…

2008

gamma2-Adaptin is a putative member of the clathrin adaptor protein family with unknown physiological function. We previously reported that gamma2-adaptin acts as a ubiquitin receptor by virtue of its ubiquitin-interacting motif. Here we demonstrate that this motif mediates a specific physical interaction with the ubiquitin ligase Nedd4 and promotes ubiquitination of gamma2-adaptin. By mapping regions of Nedd4 involved in binding to gamma2-adaptin, we identified its C2 domain to be essential, whereas the WW and HECT domains are dispensable. Consistent with this, we uncovered that the C2 domain of Nedd4 is ubiquitinated itself and as such is recruited by the ubiquitin-interacting motif of ga…

Angiogenesis, immune system and growth factors: new targets in colorectal cancer therapy.

2005

Colorectal cancer is the second most common malignant human neoplasia. Over recent years, many efforts have been performed in order to develop and improve therapeutic protocols, and many advances have been accomplished in both the field of adjuvant and palliative therapy. Most of the chemotherapic agents currently used in the clinical setting are the products of decades of research aimed at inhibiting the uncontrolled growth of dysplastic cells. However, new frontiers in this field have recently been opened, with the identification of key molecules involved in physiologic mechanisms that are of fundamental importance for cancer development and progression. Tumor-induced angiogenesis, the ca…