46 research outputs found
Adoptive cell therapy: a highly successful individualized therapy for melanoma with great potential for other malignancies
No full textExperimental cancer immunology and therap
Análisis financiero de la empresa E.M.E. Estructuras Metálicas S.A. y el sector metalmecánico
No full textEl presente trabajo de grado se basa en el estudio y análisis financiero de la empresa E.M.E. Estructuras Metálicas S.A., ubicada en la ciudad de Manizales, Caldas, éste tomará como referencia los últimos cuatro años de funcionamiento operativo de la empresa y se realizará una comparación en el comportamiento de los mismos. El trabajo busca identificar las fortalezas y las debilidades que presentó el desarrollo de las actividades de la empresa, a su vez se realizará un breve análisis del sector metalmecánico, al cual pertenece la empresa, para sentar bases comparativas que permitan fortalecer el análisis. El análisis financiero se realizará basado en el método tradicional utilizando indicadores como solvencia, liquidez, actividad, y rentabilidad de la empresa, a este se le sumará el análisis moderno el cual incluye indicadores de creación y/o destrucción de valor por parte de la empresa junto con su flujo de efectivo y su demás componentes. Al final se realizará una descripción de los diferentes sistemas de costos que se utilizan generalmente en las empresas y se identificará el más acorde con la empresa. Finalmente, se identificarán los principales problemas que presenta la empresa los cuales llevaran las respectivas recomendaciones de mejora que el autor definirá de acuerdo a los resultados obtenidos después del análisis.E.M.E. Estructuras Metálicas S.A.Colegio Mayor Nuestra Señora del RosarioThe following document is based on the financial study and analysis of the company E.M.E. Estructuras Metálicas S.A., which is located in the city of Manizales, Caldas. The document will take the 4 last years of operation, 2011-2014, as a reference to compare and contrast the performance of the company. The purpose of the document is to identify the strengths and weaknesses of the company in the last years. There will be included also a brief analysis of the metallurgical industry, which the company is part of, which will set the basis that will help to power the analysis. The financial analysis will include the traditional method which includes ratios of Liquidity, Activity and Profitability which will add up to the modern analysis ratios that include construction or destruction of value, free cash flow and the rest of its ratios. At the end of the analysis there will be a description of the cost systems that are frequently used and the author will recommend the most appropriate one for the company. Finally, the author will identify the most representative issues of the company and will make recommendations to the company based on the results of the analysis
The ABCs of antigen presentation by stromal non-professional antigen-presenting cells
No full textProfessional antigen-presenting cells (APCs), such as dendritic cells and macrophages, are known for their ability to present exogenous antigens to T cells. However, many other cell types, including endothelial cells, fibroblasts, and lymph node stromal cells, are also capable of presenting exogenous antigens to either CD8+ or CD4+ T cells via cross-presentation or major histocompatibility complex (MHC) class II-mediated presentation, respectively. Antigen presentation by these stromal nonprofessional APCs differentially affect T cell function, depending on the type of cells that present the antigen, as well as the local (inflammatory) micro-environment. It has been recently appreciated that nonprofessional APCs can, as such, orchestrate immunity against pathogens, tumor survival, or rejection, and aid in the progression of various auto-immune pathologies. Therefore, the interest for these nonprofessional APCs is growing as they might be an important target for enhancing various immunotherapies. In this review, the different nonprofessional APCs are discussed, as well as their functional consequences on the T cell response, with a focus on immuno-oncology.Experimental cancer immunology and therap
Harnessing neoantigens for targeted cancer treatment
No full textCancer immunotherapy has experienced remarkable advances in the last decades. Striking clinical responses have been achieved for several solid cancers, particularly cancer types with a high mutation burden, which placed tumour-mutated antigens (neoantigens) centre stage as targets of tumour immunity and cancer immunotherapy. Neoantigens can be presented in complex with HLA molecules on the tumour cell surface, where T cells with the correct specificity can recognize the neoantigen as ‘non-self’ which will trigger killing of the tumour cell by the T cell. In theory, cancers with a low/moderate mutation burden that present neoantigens in complex with HLA class molecules could still be eligible for T cell-mediated immunotherapy. This thesis, describes the finding that neoantigen-specific T cells are present in mismatch-repair proficient (MMR-p) colorectal cancer patients, a low mutation burden cancer type. Moreover, CD39 and CD103 were found as cell surface markers that pinpoint the T cell population that contains the neoantigen-specific T cells. In addition, subsequent metastasis of a melanoma patient cohort were studied and revealed that also at advanced, late-stage disease, neoantigen-directed T cell therapy is, in theory, still applicable. Taken together, the studies reveal potential for the development of neoantigen-directed cancer immunotherapy for a broader patient population. LUMC / Geneeskund
IDO and galectin-3 hamper the ex vivo generation of clinical grade tumor-specific T cells for adoptive cell therapy in metastatic melanoma
No full textExperimental cancer immunology and therap
Apoptin Enhances Radiation-Induced Cell Death in Poorly Responding Head and Neck Squamous Cell Carcinoma Cells
No full textTreatment of head and neck cancers is still rather poor and worldwide new treatment options are sought. Sensitizing radioresistant tumours by combining irradiation with other therapeutics to induce apoptosis are widely investigated. We examined whether chicken anaemia virus-derived apoptin protein would have a beneficial effect on irradiation of radiosensitive SCC61 and radioresistant SQD9 human head and neck squamous carcinoma cell lines. In both cell lines, concurrent exposure to irradiation and apoptin resulted in analysed mitochondrial cytochrome c release and in cleavage of caspase-3, whereas irradiation alone of SQD9 cells under identical conditions did not. Moreover, in comparison with the irradiation, only the synchronized treatment of apoptin and irradiation resulted in increased cell death in especially the radioresistant SQD9 cells, as measured by means of a colony survival assay. Our data reveal that apoptin treatment represents an effective way for enhancing radiotherapy of tumours responding poorly to radiotherapy.Experimental cancer immunology and therap
The Potential and Challenges of Exploiting the Vast But Dynamic Neoepitope Landscape for Immunotherapy
No full textSomatic non-synonymous mutations in the DNA of tumor cells may result in the presentation of tumor-specific peptides to T cells. The recognition of these so-called neoepitopes now has been firmly linked to the clinical success of checkpoint blockade and adoptive T cell therapy. Following proof-of-principle studies in preclinical models there was a surge of strategies to identify and exploit genetically defined clonally expressed neoepitopes. These approaches assume that neoepitope availability remains stable during tumor progression but tumor genetics has taught us otherwise. Under the pressure of the immune system, neoepitope expression dynamically evolves rendering neoepitope specific T cells ineffective. This implies that the immunotherapeutic strategy applied should be flexible in order to cope with these changes and/or aiming at a broad range of epitopes to prevent the development of escape variants. Here, we will address the heterogeneous and dynamic expression of neoepitopes and describe our perspective and demonstrate possibilities how to further exploit the clinical potential of the neoepitope repertoire
The role of orthography in the revival of the Pitkern-Norf'k language
No full textThis article investigates the role played by literacy and the modes chosen to put the spoken language into writing in the vitality of endangered languages. Within the broader context of unwritten languages, in particular pidgins and creoles, the author focuses on the case of an endangered language, Pitkern/Norf'k, spoken by the descendants of the mutineers of the Bounty on Norfolk Island off the coast of Australia. © E.M.E. & InterCommunications, sprl, 2012, BE - Bruxelles - Fernelmont.Peter Mühlhäusle
Cancer immunotherapy: broadening the scope of targetable tumours
No full textCancer immunotherapy has experienced remarkable advances in recent years. Striking clinical responses have been achieved for several types of solid cancers (e.g. melanoma, non-small cell lung cancer, bladder cancer and mismatch repair-deficient cancers) after treatment of patients with T-cell checkpoint blockade therapies. These have been shown to be particularly effective in the treatment of cancers with high mutation burden, which places tumour-mutated antigens (neo-antigens) centre stage as targets of tumour immunity and cancer immunotherapy. With current technologies, neo-antigens can be identified in a short period of time, which may support the development of complementary, personalized approaches that increase the number of tumours amenable to immunotherapeutic intervention. In addition to reviewing the state of the art in cancer immunotherapy, we discuss potential avenues that can bring the immunotherapy revolution to a broader patient group including cancers with low mutation burden.</jats:p
Immunotherapy in advanced melanoma: crossing borders
No full textMonique Krystyna van der Kooij shows that a combination of treatments enhancing the immune system can conquer metastasized melanoma in heavily pre-treated patients. Immunotherapy is not a new concept. However, in Leiden a milder, and therefore better tolerated preconditioning regimen is used before the immune cells are administered. This milder preconditioning, in combination with the patient’s own immune cells and an immune checkpoint inhibitor is unique. This thesis shows that this combination is safe and preliminary data also show that some patients have (lasting) clinical responses. A second important finding described in this thesis is that treatment with immune checkpoint inhibitors can safely be prescribed to patients with common autoimmune diseases. Approximately 1 in 10 metastatic melanoma patients suffer from such an autoimmune disease. Until now clinicians were hesitant to prescribe these immune checkpoint inhibitors out of fear of unleashing the autoimmune disease. Showing that this is not the case made it possible for this large group of patients to gain access to this often-successful treatment. However, immune checkpoint inhibitor monotherapy is not indicated for all patients with metastatic melanoma. Patients with uveal melanoma do not benefit from this type of treatment, and do suffer from the adverse events. LUMC / Geneeskund
