Immunomodulatory Agents with Antivascular Activity in the Treatment of Non-Small Cell Lung Cancer: Focus on TLR9 Agonists, IMiDs and NGR-TNF

Standard treatments for nonsmall cell lung cancer (NSCLC), such as surgery, chemotherapy, and radiotherapy, often lead to disappointing results. Unfortunately, also the various immunotherapeutic approaches so far tested have not produced satisfactory results to be widely applied in the clinical practice. However, the recent development of new immunomodulatory agents may open promising therapeutic options. This paper focuses on PF3512676, lenalidomide, and NGR-TNF, that is, drugs belonging to three different classes of immunomodulatory agents, that are also capable to affect tumor blood vessels with different mechanisms, and discusses the potential role of such agents in NSCLC treatment strategy

Factoring : Análisis de la rentabilidad del factoring para la empresa Bellilogistics en el periodo 2015

A través del presente estudio se propuso analizar la rentabilidad del factoring como financiamiento a corto plazo para la empresa BELLI LOGISTICS, en el período 2015. La empresa se encuentra en proceso de toma de decisiones ya que se le presentó una oportunidad de inversión la cual consiste en financiar a unos de sus clientes potenciales el pago de impuestos proveniente de los servicios otorgados por logística, por lo cual la gerencia financiera de la empresa está evaluando si el uso del factoring es rentable, y de esta manera poder financiar a su cliente sin presentar liquidez y poder continuar operando y generar flujos positivos. El desarrollo de este trabajo investigativo es determinar la rentabilidad del factoring, para lo cual se documentó las generalidades del factoring y su aplicación, lo que permitió detallar los antecedentes más remotos, su introducción en Nicaragua, la importancia del factoring, las ventajas, los tipos de factoring que existen, los inconvenientes que se pueden presentar al utilizar el factoring. También identificamos las normas que rigen el uso de este producto financiero, Ley 740, Ley de factoraje, se utilizó como herramienta los indicadores de rentabilidad, que permitieron dar pautas para el desarrollo del caso práctico, determinar la rentabilidad del factoring para la empresa Belli Logistics en el periodo 2015. En el cual se utilizó como referencia una empresa que por sigilo denominaremos Belli Logistics. Para el análisis de rentabilidad del factoring se realizó un estudio a los estados financieros de la empresa, lo cual determinó que el factoring es rentable, la empresa logró financiar el pago de impuestos de su cliente, y además generar un margen de ganancia. Lo cual indica que si el factoring es utilizado de manera correcta, reduce el apalancamiento, permite generar inversión, y puede utilizarse no solo para pequeñas empresas que necesitan flujo de efectivo para seguir con sus operaciones, sino que también se puede utilizar como financiamiento para generar un margen de ganancia, recuperando la inversión del producto más un margen de utilidad

Análisis comparativo de la influencia de los fondos revolventes comunitarios de ADDAC en el desarrollo humano, desarrollo comunitario y empoderamiento de los usuarios de las comunidades Azancor municipio de San Ramón y Piedra de agua municipio de Matagalpa, durante el II semestre del año 2013

El presente estudio tiene como objetivo general comparar la influencia de los fondos revolventes comunitarios de ADDAC en el desarrollo humano, desarrollo comunitario y el empoderamiento de los usuarios de Azancor municipio de San Ramón y Piedra de agua municipio de Matagalpa, durante el II semestre del año 2013. Este trabajo se clasifica como investigación comparativa, descriptiva y de corte transversal con enfoque cualitativo y cuantitativo, método teórico mediante fuentes bibliográficas, y empírico con la aplicación de encuestas y entrevista grupal. La muestra fue de 30 FRC y para esta investigación solo se trabajó en dos en concreto. Se determinó que en ambos fondos existe desconocimiento del reglamento, la participación es tomada en cuenta de manera equitativa, la información respecto al funcionamiento del fondo es transmitida a través de las asambleas comunales. La influencia del fondo en el desarrollo humano está contribuyendo en ambas comunidades en la satisfacción de las necesidades básicas de las familias asociadas (mejora de vivienda, acceso a la alimentación, educación y en el acceso al empleo), de igual manera se ha notado su contribución en el desarrollo de capacidades de las personas. En cuanto a desarrollo comunitario existe una mejor organización, que ha facilitado la creación de relaciones de amistad, adquisición de valores y principios. La influencia en el empoderamiento de las mujeres se ha notado a través del conocimiento de derechos de las mismas, la oportunidad en la toma de decisiones y una mejor distribución de las tareas del hoga

Radioactive trace in semi natural grassland. Effect of 40K in soil and potential remediation

The uptake of radionuclides by plant roots constitutes the main pathway for the migration of radiocaesium from soil to humans, via food chain. In this study we assessed radiocaesium uptake by plant in order to piece together information on factors affecting uptake processes, particularly K supply and differential uptake among different plant species. Soil contaminated by the Chernobyl accident and forage from a semi-natural alpine grassland, situated in Tarvisio, Italy, were sampled during 1999. Under field conditions, 137 Cs uptake for Graminaceae and Taraxacum officinale seem to behave in a comparable way. Higher 40K soil activity concentration leads to a lower 137Cs plant uptake, suggesting an inhibitory pattern of potassium on radiocaesium plants uptake. For forage samples, a similar tendency was observed. We analyzed the influence of the ratio of 137Cs/ 40K in soil on 137Cs plant uptake. Under field conditions, the ratio observed varied in a range of 0.5 to 1.3. For most of the species, at higher 40K soil concentration a lower 137Cs uptake was observed, a fact that reflects the resulting effect of the complexity of factors controlling ion absorption from soil

Radioactive trace in semi natural grassland. Effect of 40K in soil and potential remediation

The uptake of radionuclides by plant roots constitutes the main pathway for the migration of radiocaesium from soil to humans, via food chain. In this study we assessed radiocaesium uptake by plant in order to piece together information on factors affecting uptake processes, particularly K supply and differential uptake among different plant species. Soil contaminated by the Chernobyl accident and forage from a semi-natural alpine grassland, situated in Tarvisio , Italy , were sampled during 1999. Under field conditions, 137Cs uptake for Graminaceae and Taraxacum officinale seem to behave in a comparable way. Higher 40K soil activity concentration leads to a lower 137Cs plant uptake, suggesting an inhibitory pattern of potassium on radiocaesium plants uptake. For forage samples, a similar tendency was observed. We analyzed the influence of the ratio of 137Cs/ 40K in soil on 137Cs plant uptake. Under field conditions, the ratio observed varied in a range of 0.5 to 1.3. For most of the species, at higher 40K soil concentration a lower 137Cs uptake was observed, a fact that reflects the resulting effect of the complexity of factors controlling ion absorption from soil

Primary systemic treatment and concomitant low dose radiotherapy for breast cancer: final results of a prospective phase II study.

Abstract Background To evaluate the efficacy of preoperative low dose fractionated radiotherapy (LD-FRT) and chemotherapy in breast cancer. Materials and methods Patients with stage IIA–IIIA breast cancer, received LD-FRT (0.40 Gy bid, on day 1 and 2, for 6 cycles) to primary tumor volume and concurrent chemotherapy with non-pegylated liposomal anthracycline and docetaxel. Pathological response was assessed by Mandard Tumor Regression Grade (TRG). We evaluated the pathological major response rate (PMRR) as TRG1 and TRG2. The expected outcome was a PMRR of 60%. The accrual was determined by the single proportion powered analysis ( α = 0.05, power = 0.8). Results Twentyone patients were enrolled. No grade 2–4 acute skin and hematological toxicity was observed. TRG1 was obtained in 3 patients (14.3%), TRG2 in 4 patients (19%). The PMRR was 33.3%; it does not concur with the expected result, but is similar to that of chemotherapy alone. According to molecular subtype, 2/11 luminal A patients and 4/6 luminal B patients obtained a PMRR to preoperative treatment (35.3%); 1/4 basal like patients reported TRG1 (25%). Conclusions LD-FRT concomitant with primary systemic treatment has a good toxicity profile. The response rate is consistent with that of chemotherapy alone, and suggests different interactions between low dose radiotherapy and molecular subtypes. Additional investigations are planned

Estrategias del marketing digital en el siglo XXI

El presente trabajo de seminario de graduación trata del marketing digital y las estrategias de marketing digital en el siglo XXI, es un tema muy amplio donde se realizan todas las actividades del marketing tradicional implementadas en las redes y diferentes medios digitales. El objetivo del documento es describir la importancia de aplicar estrategias de marketing digital en el siglo XXI para la efectiva comercialización de productos y servicios, ya que el avance tecnológico está haciendo una nueva era de la economía tanto nacional como internacional. El marketing digital hace uso de comunicación digital, nuevas tendencias de comercialización de productos y servicios online mantiene conectada a las empresas u organizaciones con su segmento de mercado y clientes. La base teórica que sustenta este informe hace énfasis en tres capítulos tales como: conceptos generales del marketing, herramientas esenciales en la estrategia de marketing digital y el proceso para definir, implementar y monitorear estrategias de digitales. Para la elaboración de esta investigación documental, se hace uso de las normativas para esta modalidad de graduación, normas APA 6ta edición y las orientaciones del departamento de administración de empresas

Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: a phase II randomised trial

Background: New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Methods: Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status >50%, no progression after 6 months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5mg daily until progression or a maximum of 6 months (arm B). The primary outcome measure was the probability of being progression-free at 6 months (PFS-6) from randomisation. Assuming P0 = 10%; P1 = 30%, α .10; β .10, the target accrual was 26 patients per arm. Results: 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91 days (7-186). Main grade 3-4 toxicity was thrombocytopenia, neutropenia and hand-foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0-10.6%) and 22.2% (95% CI: 6.2-38.2%; P<0.01); 2 y overall survival was 7.1% (95% CI: 0-16.8%) and 22.9% (95% CI: 5.8-40.0%; P = 0.11), stable disease 21.4% and 51.9% (P = 0.02). Conclusion: This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2 y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population

Baseline Tumor Size as Prognostic Index in Patients With Advanced Solid Tumors Receiving Experimental Targeted Agents

Abstract Background Baseline tumor size (BTS) has been associated with outcomes in patients with cancer treated with immunotherapy. However, the prognostic impact of BTS on patients receiving targeted therapies (TTs) remains undetermined. Methods We reviewed data of patients with advanced solid tumors consecutively treated within early-phase clinical trials at our institution from 01/2014 to 04/2021. Treatments were categorized as immunotherapy-based or TT-based (biomarker-matched or not). BTS was calculated as the sum of RECIST1.1 baseline target lesions. Results A total of 444 patients were eligible; the median BTS was 69 mm (IQR 40-100). OS was significantly longer for patients with BTS lower versus higher than the median (16.6 vs. 8.2 months, P < .001), including among those receiving immunotherapy (12 vs. 7.5 months, P = .005). Among patients receiving TT, lower BTS was associated with longer PFS (4.7 vs. 3.1 months, P = .002) and OS (20.5 vs. 9.9 months, P < .001) as compared to high BTS. However, such association was only significant among patients receiving biomarker-matched TT, with longer PFS (6.2 vs. 3.3 months, P < .001) and OS (21.2 vs. 6.7 months, P < .001) in the low-BTS subgroup, despite a similar ORR (28% vs. 22%, P = .57). BTS was not prognostic among patients receiving unmatched TT, with similar PFS (3.7 vs. 4.4 months, P = .30), OS (19.3 vs. 11.8 months, P = .20), and ORR (33% vs. 28%, P = .78) in the 2 BTS groups. Multivariate analysis confirmed that BTS was independently associated with PFS (P = .03) and OS (P < .001) but not with ORR (P = .11). Conclusions Higher BTS is associated with worse survival outcomes among patients receiving biomarker-matched, but not biomarker-unmatched TT