465 research outputs found

    The fibroblast growth factor receptors in breast cancer: From oncogenesis to better treatments

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    Breast cancer (BC) is the most frequent form of malignancy and second only to lung cancer as cause of deaths in women. Notwithstanding many progresses made in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet the needs of patients, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level and functioning on such cancer-causing molecules expressed in cancer cells of patients, or present as antigens on the surface of cancer cell membranes. Fibroblast growth factor receptor (FGFR) is one of such druggable targets, activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation. Herein we provide an update on the knowledge of genetic alterations of the receptors in breast cancer, their role in tumorigenesis and the most recent drugs against this particular receptor for the treatment of the disease

    Radiative Heat Transfer Modeling in Fibrous Porous Media

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    Phenolic-Impregnated Carbon Ablator (PICA) was developed at NASA Ames Research Center as a lightweight thermal protection system material for successful atmospheric entries. The objective of the current work is to compute the effective radiative conductivity of fibrous porous media, such as preforms used to make PICA, to enable the efficient design of materials that can meet the thermal performance goals of forthcoming space exploration missions

    Nanoparticle albumin-bound paclitaxel: a big nano for the treatment of gastric cancer

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    Gastric cancer (GC) is the third cause of cancer-related death worldwide. Patients with unresectable GC can be treated with chemotherapy such as paclitaxel, which is a microtubule stabilizer. The use of nanoparticle albumin-bound paclitaxel (nab-ptx) avoids hypersensitivity reactions due to the absence of solvent needed to dissolve paclitaxel and it can be administered at higher doses. The ABSOLUTE randomized phase-3 clinical trial showed the non-inferiority of the nab-ptx used every week compared to the solvent-based paclitaxel used every week. This review describes the current advancements of the use of nab-ptx in GC in preclinical and clinical study investigations. The possibility of combining nab-ptx with other medications to improve response of patients to their specific molecular needs will also be debated

    Updates on the CDK4/6 inhibitory strategy and combinations in breast cancer

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    Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated

    Electrochemical determination of the antipsychotic medication clozapine by a carbon paste electrode modified with a nanostructure prepared from titania nanoparticles and copper oxide

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    A nanostructure was prepared from titania nanoparticles and copper oxide (TiO2NP@CuO) and used to modify a carbon paste electrode (CPE). The modified CPE is shown to enable sensitive voltammetric determination of the drug clozapine (CLZ). The sensor was characterized by various techniques and some key parameters were optimized. Under the optimum conditions and at a working potential of 0.6 V (vs. Ag/AgCl), the modified CPE has two linear response ranges, one from 30 pmol L�1 to 4 nmol L�1 of CLZ, the other from 4 nmol L�1 to 10 μmol L�1. The detection limit is as low as 9 pM. The transfer coefficient (α) and catalytic rate constant (kcat) were calculated and the reliability of the sensor was estimated for CLZ sensing in real samples where it gave satisfactory results. Figure not available: see fulltext.. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature

    Incorporating Structural Analysis in a Quantum Dot Monte-Carlo Model

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    We simulate the shape of the density of states (DoS) of the quantum dot (QD) ensemble based upon size information provided by high angle annular dark field scanning transmission electron microscopy (HAADF STEM). We discuss how the capability to determined the QD DoS from micro-structural data allows a MonteCarlo model to be developed to accurately describe the QD gain and spontaneous emission spectra. The QD DoS shape is then studied, with recommendations made via the effect of removing, and enhancing this size inhomogeneity on various QD based devices is explored
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