Evaluación económico-financiera de una fusión en el sector cooperativo hortofrutícola de la Comunidad Valenciana: el caso de Guadacoop, Coop. V

[ES] En este Trabajo Fin de Carrera se va a realizar el análisis económico-financiero del proceso de fusión de dos cooperativas del sector hortofrutícola en la Comunidad Valenciana. Las dos cooperativas participantes en la fusión son la Cooperativa Agrícola Santísimo Cristo de la Peña, S. Coop. V. y la Cooperativa San Isidro Labrador, Coop. V. La fusión se realizó mediante la disolución de la Cooperativa San Isidro Labrador, Coop. V., y su integración en la Cooperativa Agrícola Santísimo Cristo de la Peña, S. Coop. V., que adoptó la denominación social de Guadacoop, Coop. V. Como consecuencia, todo el patrimonio, los derechos y obligaciones y los socios de la cooperativa disuelta pasaron a la cooperativa resultante. Las actividades del sector primario (agricultura, ganadería y pesca) fueron las más tradicionales y las de mayor desarrollo en la economía de la Comunidad Valenciana hasta el siglo XIX, pero a lo largo del siglo XX estas actividades han dejado paso a una economía basada en los servicios. La agricultura en la Comunidad Valenciana destaca por su gran productividad, la diversidad de productos y por ser una agricultura de exportación. En cuanto a la diversidad de productos, se distingue entre agricultura de regadío, que es la más desarrollada y se encuentra en la parte del litoral de la Comunidad (frutos cítricos, arroz y hortalizas) y agricultura de secano, que se encuentra en el interior (cereales y viña). Por tanto, en primer lugar, se va a realizar un análisis del sector agrario en general y del subsector hortofrutícola más detalladamente, en España y en la Comunidad Valenciana, ya que las cooperativas implicadas en la fusión están situadas en un municipio de la provincia de Valencia. Del sector agrario, tanto a nivel nacional como de la Comunidad Valenciana, se van a detallar las características del entorno donde se lleva a cabo, la importancia en la economía española de este sector, la superficie que ocupa, la producción obtenida y el empleo generado. Del subsector hortofrutícola también se van a analizar sus características principales para determinar sus fortalezas y debilidades. A continuación, se va a analizar el cooperativismo en el sector hortofrutícola. El proceso de fusión objeto de este TFC es llevado a cabo por dos sociedades cooperativas, por tanto, es necesario tener una visión general de la importancia del cooperativismo en este sector. Con ello, podremos llegar a entender mejor la necesidad de esta fusión. Este análisis se va a centrar en determinar el grado de concentración en el sector hortofrutícola y las principales características del cooperativismo en Europa, en España y en la Comunidad Valenciana. En la Comunidad Valenciana predomina la pequeña propiedad o minifundio (terreno de menos de 10Ha) lo cual impide una agricultura competitiva, debido a que los ingresos son bajos, y no permite la modernización de las explotaciones debido a su elevado coste. Por tanto, en los últimos años, se ha impulsado la creación de cooperativas para reducir costes y aumentar la productividad. Además, diversos estudios han puesto de manifiesto que cuanto mayor sea el volumen de negocio de la cooperativa mayor rentabilidad tendrá. Debido a este hecho, últimamente se han realizado muchas fusiones de cooperativas. También es interesante destacar que las cooperativas agrarias crean puestos de trabajo en el entorno rural, lo cual ha ayudado a minorar la despoblación de muchas áreas rurales y la migración a las ciudades. Tras haber estudiado el entorno en que se llevó a cabo la fusión de las dos cooperativas, se va a analizar cuáles son las principales características de los procesos de fusión de cooperativas y cómo se llevó a cabo la fusión del caso estudiado. También se van a detallar las necesidades para la fusión y los objetivos que se pretendían conseguir con ella. Posteriormente, se realizará un análisis económico financiero de las dos cooperativas partícipes correspondiente a los dos ejercicios anteriores a la fusión y se determinarán qué aspectos tenían en común y cuáles las diferenciaban. En este caso, el análisis económico-financiero será de los ejercicios terminados a 30 de septiembre de 2008 y 2009. Por último, se realizará un análisis económico financiero de la cooperativa resultante de los ejercicios terminados a 30 de septiembre de 2010 y 2011, con objeto de obtener conclusiones sobre el resultado de la fusión durante los dos primeros ejercicios, y se analizará también la cooperativa resultante en los dos últimos ejercicios terminados a 30 de septiembre de 2014 y 2015, para ver en qué situación se encuentra actualmente.Sais Ibiza, E. (2017). EVALUACIÓN ECONÓMICO-FINANCIERA DE UNA FUSIÓN EN EL SECTOR COOPERATIVO HORTOFRUTÍCOLA DE LA COMUNIDAD VALENCIANA: EL CASO DE GUADACOOP, COOP. V. http://hdl.handle.net/10251/84500.Archivo delegad

Silibinin Suppresses Tumor Cell-Intrinsic Resistance to Nintedanib and Enhances Its Clinical Activity in Lung Cancer

The anti-angiogenic agent nintedanib has been shown to prolong overall and progression-free survival in patients with advanced non-small-cell lung cancer (NSCLC) who progress after first-line platinum-based chemotherapy and second-line immunotherapy. Here, we explored the molecular basis and the clinical benefit of incorporating the STAT3 inhibitor silibinin-a flavonolignan extracted from milk thistle-into nintedanib-based schedules in advanced NSCLC. First, we assessed the nature of the tumoricidal interaction between nintedanib and silibinin and the underlying relevance of STAT3 activation in a panel of human NSCLC cell lines. NSCLC cells with poorer cytotoxic responses to nintedanib exhibited a persistent, nintedanib-unresponsive activated STAT3 state, and deactivation by co-treatment with silibinin promoted synergistic cytotoxicity. Second, we tested whether silibinin could impact the lysosomal sequestration of nintedanib, a lung cancer cell-intrinsic mechanism of nintedanib resistance. Silibinin partially, but significantly, reduced the massive lysosomal entrapment of nintedanib occurring in nintedanib-refractory NSCLC cells, augmenting the ability of nintedanib to reach its intracellular targets. Third, we conducted a retrospective, observational multicenter study to determine the efficacy of incorporating an oral nutraceutical product containing silibinin in patients with NSCLC receiving a nintedanib/docetaxel combination in second- and further-line settings (n = 59). Overall response rate, defined as the combined rates of complete and partial responses, was significantly higher in the study cohort receiving silibinin supplementation (55%) than in the control cohort (22%, p = 0.011). Silibinin therapy was associated with a significantly longer time to treatment failure in multivariate analysis (hazard ratio 0.43, p = 0.013), despite the lack of overall survival benefit (hazard ratio 0.63, p = 0.190). Molecular mechanisms dictating the cancer cell-intrinsic responsiveness to nintedanib, such as STAT3 activation and lysosomal trapping, are amenable to pharmacological intervention with silibinin. A prospective, powered clinical trial is warranted to confirm the clinical relevance of these findings in patients with advanced NSCLC

Correction : Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance

Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin

Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patient

Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance