Bone and brain metastases are a very common secondary localization of disease in patients with lung cancer. The prognosis of these patients is still poor with a median survival of less than 1 year. ...Current therapeutic approaches include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents. For bone metastasis, zoledronic acid is the most commonly used bisphosphonate to prevent, reduce the incidence and delay the onset of skeletal-related events (SREs). Recently, denosumab, a fully human monoclonal antibody directed against the receptor activator of nuclear factor κB (RANK) ligand inhibiting the maturation of pre-osteoclasts into osteoclasts, showed increased time to SREs and overall survival compared with zoledronic acid. The treatment of brain metastasis is still controversial. Available standard therapeutic options, such as whole brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. More recently, novel target agents such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and afatinib have shown activity in patients with brain metastasis. Inter alia, in patients harboring EGFR mutations, the administration of EGFR TKIs is followed by a response rate of 70–80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. This review is focused on the evidence for therapeutic strategies in bone and brain metastases due to lung cancer.
Azopolymers are known to exhibit a strong light responsivity known as athermal photofluidization. Although the underlying physics is still under debate, athermal photofluidization has been ...demonstrated to trigger mass-migration according to the polarization of a proper illumination light. Here, a polymer blend is proposed wherein a commercial azo-polyelectrolyte is mixed with a passive polymer. The blend is patterned as an array of micro-pillars that are individually exposed to visible laser illumination. Thanks to the interplay between the two blend components, a reversible and controlled deformation of the micro-pillars by periodically tuning the laser polarization in time is demonstrated. A reduced mobility of the azo-compound allows to repeatibly elongate and rotate micro-pillars along specific directions, with no significant material flow outisde the initial volume and no significant degradation of the structure morphology over several cycles. The proposed work suggests new degrees of freedom in controlling the mechanical features of micro-patterned light-responsive materials that can be usefully exploited in many application fields.
Nanostructured polymeric composites are promising materials for the fabrication of piezoresistive devices because they show a huge variation in electrical resistance when subjected to mechanical ...deformation. Quantum tunneling composites feature a conduction mechanism occurring between the metallic filler and copper particles embedded in a polydimethylsiloxane (PDMS) insulating matrix, and the mechanism is enhanced by the spiky morphology of the particles. PEDOT:PSS electrodes are patterned on either side of the composite by inkjet printing, a technology that allows one-step fabrication processes. The adhesion and spreading of conductive printed ink drops are controlled and enhanced by pre-treating the samples surface in an atmospheric pressure plasma customized system. Because of an extremely high metal to polymer ratio, which results in the different surface and dielectric properties of the composite, conventional plasma conditions are not suitable to allow the control of spreading. The optimal plasma conditions for ink/surface compatibility were found using quantitative comparison based on image analysis and numerical interpretation of the adhesion/roughness properties such as bulging and spread.
Cell–substrate interactions can modulate cellular behaviors in a variety of biological contexts, including development and disease. Light‐responsive materials have been recently proposed to engineer ...active substrates with programmable topographies directing cell adhesion, migration, and differentiation. However, current approaches are affected by either fabrication complexity, limitations in the extent of mechanical stimuli, lack of full spatio‐temporal control, or ease of use. Here, a platform exploiting light to plastically deform micropatterned polymeric substrates is presented. Topographic changes with remarkable relief depths in the micron range are induced in parallel, by illuminating the sample at once, without using raster scanners. In few tens of seconds, complex topographies are instructed on demand, with arbitrary spatial distributions over a wide range of spatial and temporal scales. Proof‐of‐concept data on breast cancer cells and normal kidney epithelial cells are presented. Both cell types adhere and proliferate on substrates without appreciable cell damage upon light‐induced substrate deformations. User‐provided mechanical stimulation aligns and guides cancer cells along the local deformation direction and constrains epithelial colony growth by biasing cell division orientation. This approach is easy to implement on general‐purpose optical microscopy systems and suitable for use in cell biology in a wide variety of applications.
A platform is presented, allowing light‐controlled morphological deformations of micro‐structured substrates for cell cultures. Morphology modifications are induced with high resolution by illuminating the substrate with arbitrary light patterns that can be dynamically provided at any time during cell growth. This technique is implemented on a conventional microscope for fluorescence bio‐imaging, thus allowing direct observations while light‐triggering mechanical cues.
A one-dimensional photonic crystal (1DPC) based on a planar stack of dielectric layers is used as an optical transducer for biosensing, upon the coupling of TE-polarized Bloch Surface Waves (BSW). ...The structure is tailored with a polymeric layer providing a chemical functionality facilitating the covalent binding of orienting proteins needed for a subsequent grafting of antibodies in an immunoassay detection scheme. The polymeric layer is impregnated with Cy3 dye, in such a way that the photonic structure can exhibit an emissive behavior. The BSW-coupled fluorescence shift is used as a means for detecting refractive index variations occurring at the 1DPC surface, according to a label-free concept. The proposed working principle is successfully demonstrated in real-time tracking of protein G covalent binding on the 1DPC surface within a fluidic cell.
Abstract Lung cancer is the leading cause of cancer-related death worldwide. Despite several chemotherapeutic agents, a survival plateau has been reached, so new treatment strategies are clearly ...needed. A strong interest is now focused on the use of targeted therapies for the management of non–small-cell lung cancer. Monoclonal antibodies against the epidermal growth factor receptor (EGFR; cetuximab) or vascular endothelial growth factor receptor (VEGFR; bevacizumab) and EGFR tyrosine kinase inhibitors (gefitinib, erlotinib) are generally well tolerated and do not have the severe systemic side effects usually seen with cytotoxic drugs. A considerable number of treated patients develop dermatologic side effects, such as acneiform eruption, xerosis, and eczema, and unfortunately, this is often one cause of negative impact on a patient's quality of life. No controlled clinical trials have been performed to manage rash, so it is necessary to provide suggestions for managing this frequent side effect. The main problems related to the class of angiogenesis inhibitors affecting VEGFRs are the exclusion of patients with brain metastases and/or squamous histology, and vascular adverse effects, such as hypertension, proteinuria, thrombosis, and hemorrhage. There are other new agents in clinical development, such as sorafenib, sunitinib, vorinostat, vandetanib, everolimus, panobinostat, and ASA404. They are all associated with a spectrum of toxicities, often reversible with interruption of dosing. Further research is required to clarify the role of targeted therapies and toxicities management.
Abstract Pemetrexed, a new cytotoxic agent, is a potent inhibitor of thymidylate synthase and other folate-dependent enzymes. Firstly, pemetrexed was approved in combination with cisplatin for the ...treatment of malignant pleural mesothelioma. Successively, it has been studied, as single-agent, in phase II and III trials for second-line therapy of non-small cell lung cancer (NSCLC). Based on these results, pemetrexed has been registered for the treatment of recurrent NSCLC. The next step was to test pemetrexed plus cisplatin versus gemcitabine plus cisplatin, as first-line therapy in advanced NSCLC patients, in a phase III, non-inferiority, randomized trial. This trial reported the pemetrexed plus cisplatin regimen to be not inferior, in terms of activity and efficacy, to the control arm but statistically better tolerated. The role of pemetrexed as maintenance therapy after first-line therapy for advanced NSCLC is currently being evaluated into a phase III trial. The consistency of the results of these recent studies has identified a predictive effect of NSCLC non-squamous histology for pemetrexed. To date, pemetrexed is registered, at the dose of 500 mg/m2 on day 1 of a 3-week schedule, in combination with cisplatin, for first-line therapy and, as single-agent, for second-line treatment of patients with non-squamous NSCLC.This review shows the latest and indicates the future developments of pemetrexed in the treatment of advanced NSCLC patients.
The rapid detection of enteropathogens with high sensitivity and selectivity continues to be a significant challenge, especially in order to transfer laboratory analyses to the Point-Of‐Care (POC) by ...developing simple and reliable diagnostic kits. Bacterial infections are already detected, in analytical labs, by means of high-density microarray biochips based both on RNA/DNA fragments and antibodies as probes and antigens receptors, respectively, immobilized on the chip surface. Many efforts to obtain a high efficiency of the surface chemical properties for a stable probes grafting in order to avoid unspecificity or non-selectivity of the bio-recognition are still under way. The aim of this work is to show the advantages of applying a low pressure plasma polymerized acrylic acid (exposing COOH groups) thin coating to a low-density microarray biochip for the efficient grafting of suitable NH2 terminated probes able to match complementary DNA oligonucleotides of Listeria monocytogenes by means of a novel hybridization protocol and a commercial simple and low-cost colorimetric detection method compatible with POC applications.
The chemical properties of the obtained polyacrylic acid thin films are characterized by means of ATR FT-IR spectroscopy, XPS and contact angle (OCA) measurements. The surface density of the carboxylic functionalities is quantified by colorimetric titration with Toluidine Blue O (TBO).
The optimized functional thin film is shown to provide good advantages for DNA microarray diagnostics in terms of chemical stability, density of readily accessible COOH groups and at the same time low hydrophilicity, crucial for reducing the dilution of spotted probes on the surface and thus resulting in higher and satisfying intensity of the detect signals in the microarray test.
► Stable and active polyacrylic acid coatings give advantages to DNA microarray diagnostics. ► COOH groups irreversibly bind DNA properly 5′ NH2-modified single strands. ► Plasma polymerization can be applied in novel Point-of-Care or biomedical applications. ► Properties of polyacrylic acid thin films can be tailored by tuning plasma parameters. ► ATR-FTIR spectroscopy and XPS analysis are used to study chemical properties.
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► Anhydride surface functionalization of polystyrene cell culture carriers facilitates a simple and versatile way to protein binding. ► Different techniques (plasma and electron beam ...based) are introduced and compared. ► All techniques are capable of lateral microstructuring.
Physico-chemical and topographical cues allow to control the behavior of adherent cells. Towards this goal, commercially available cell culture carriers can be finished with a laterally microstructured biomolecular functionalization. As shown in a previous study Biomacromolecules 4 (2003) 1072, the anhydride moiety facilitates a simple and versatile way to protein binding. The present work addresses the technical issue of anhydride surface functionalization of polystyrene, the most common material for cell culture ware. Different approaches based on low pressure plasma, electron beam and ultraviolet light techniques (i.e. maleic anhydride plasma reactions; plasma, electron beam and UV immobilization of functional polymer thin films; grafting of functional polymers to plasma activated surfaces) are introduced and briefly illustrated with examples. Results are characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and ellipsometry. The different routes are compared in terms of technical feasibility and achievable surface properties.
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