Multikinase inhibitors modulate non-constitutive proteasome expression in colorectal cancer cells

Introduction: Proteasomes are multi-subunit protein complexes responsible for protein degradation in cells. Immunoproteasomes and intermediate proteasomes (together non-constitutive proteasomes) are specific forms of proteasomes frequently associated with immune response, antigen presentation, inflammation and stress. Expression of non-constitutive proteasome subunits has a prognostic value in several types of cancer. Thus, factors that modulate non-constitutive proteasome expression in tumors are of particular interest. Multikinase inhibitors (MKIs) demonstrate promising results in treatment of cancer. At the same time, their immunomodulatory properties and effects on non-constitutive proteasome expression in colorectal cancer cells are poorly investigated.Methods: Proteasome subunit expression in colorectal cancer was evaluated by bioinformatic analysis of available datasets. Two colorectal cancer cell lines, expressing fluorescent non-constitutive proteasomes were treated with multikinase inhibitors: regorafenib and sorafenib. The proteasome subunit expression was assessed by real-time PCR, Western blotting and flow cytometry. The proteasome activity was studied using proteasome activity-based probe and fluorescent substrates. Intracellular proteasome localization was revealed by confocal microscopy. Reactive oxygen species levels following treatment were determined in cells. Combined effect of proteasome inhibition and treatment with MKIs on viability of cells was estimated.Results: Expression of non-constitutive proteasomes is increased in BRAF-mutant colorectal tumors. Regorafenib and sorafenib stimulated the activity and synthesis of non-constitutive proteasomes in examined cell lines. MKIs induced oxidative stress and redistribution of proteasomes within cells. Sorafenib stimulated formation of cytoplasmic aggregates, containing proteolyticaly active non-constitutive proteasomes, while regorafenib had no such effect. MKIs caused no synergistic action when were combined with the proteasome inhibitor.Discussion: Obtained results indicate that MKIs might affect the crosstalk between cancer cells and immune cells via modulation of intracellular proteasome pool. Observed phenomenon should be considered when MKI-based therapy is applied

Cost analysis through the TDABC system in assembly industry Two case studies: production of motorcycles, televisions and printed circuit boards

El presente artículo investiga la aplicabilidad del sistema de costeo Tiempo Invertido por Actividad (TDABC) en la industria de ensamblaje como alternativa a los sistemas de costeo tradicionales. La metodología de la investigación tuvo un enfoque mixto con un alcance descriptivo y diseño tipo estudio de casos múltiples. La investigación fue realizada en tres líneas de ensamblaje en dos compañías. Este trabajo propone un nuevo marco metodológico del TDABC orientado a analizar las empresas de ensamblaje por completo y considerando todos los procesos necesarios para obtener los productos. Eso permitió calcular los costos de ocho procesos operativos, 40 subprocesos y 148 actividades en tres líneas de ensamblaje: televisores, motocicletas y tarjetas electrónicas. También, se establecieron los niveles de ineficiencia de los procesos. Además, se comparó la base de datos de costos de productos generada por TDABC con los datos del sistema de costos tradicional. Los resultados expuestos en este documento muestran que TDABC es una herramienta adecuada para el análisis de costos de los procesos de ensamblaje con ciertas limitaciones para el análisis de los procesos estratégicos y de soporte en cada caso de estudio.The present article investigates the applicability of Time-Driven Activity-Based Costing (TDABC) in the assembly industry as an alternative to traditional costing systems. The research methodology had a mixed approach with a descriptive scope and study design of multiple cases. The research was performed to three assembly lines in two companies. This work proposes a new extended TDABC methodological framework oriented to analyze assembly companies thoroughly and considering all the processes necessary to obtain the products. That allowed calculating the costs of eight operating processes, 40 sub-processes and 148 activities in three assembly lines: televisions, motorcycles and printed circuit boards. In addition, the inefficiency levels of the processes were established. As well as, the products cost database generated by TDABC were compared with the base of the traditional costing system. The results herein show that TDABC is an adequate tool for the cost analysis of assembly processes with certain shortcomings for the analysis of the strategic and support processes in each case of study.Magíster en Contabilidad y AuditoríaCuenc

Time-Driven Activity-Based Costing in the Assembly Industry

Costs and their determination play a critical role in all manufacturing companies. The traditional costing system has received criticism resulting from the arbitrary allocation of indirect manufacturing costs. As an important initiative to address its weaknesses, new costing methods such as the Time-Driven Activity-Based Costing (TDABC) have emerged. Unfortunately, up to our knowledge, no investigations have been applied in analyzing assembly companies thoroughly nor considering all the processes necessary to obtain the final products. This article explores the TDABC application in the assembly industry through comparison with traditional volume-based costing by focusing on manual and semi-automatized production. Since the research is descriptive, a multiple-case study design was implemented in the assembly of televisions, motorcycles, and printed circuit boards. The developed methodology allowed determining the existence of factory overhead and direct labor cost variances between two different cost accounting systems, which also affected the unit cost of the products. Findings also highlight the benefits of TDABC application in the assembly industry, along with the shortcomings and future potential of research in this area

THE INTERACTION OF COMPREHENSIVE SCHOOL AND TEACHERS’ TRAINING COLLEGE IN CONDITIONS OF FORMING A COMPLETE SOCIAL AND CULTURAL ENVIRONMENT OF A REGION

The article is devoted to the problem of creating a complete social and cultural environment of aregion by means of organizing interaction of comprehensive school and pedagogical practice, which is accomplished on three levels of the process: a research one, an innovative and practical one, and the level of professional development

Formation of Marketing Strategies and Programs in the Context of Global Change Формирование маркетинговых стратегий и программ в условиях глобальных изменений

This article gived an analysis of modern trends in globalization processes and their connection with the formation of a global business strategy. It was substantiated the topicality of forming a new conceptual approach to strategy development in a «stable instability». It was proposed a model of development strategy, which involves the formation of interconnected network of alternative strategies, and allows flexible to adapt to changing conditions.<br>В статье выполнен анализ современных тенденций глобализационных процессов и их связи с формированием глобальной стратегии предприятия. Обоснована актуальность формирования нового концептуального подхода к разработке стратегии в условиях «стабильной неустойчивости». Предложена модель разработки стратегии, которая предусматривает формирование сети взаимосвязанных альтернативных стратегий и позволяет гибко адаптироваться к изменяющимся условиям

Time-Driven Activity-Based Costing in the Assembly Industry

status: publishe

Time-driven activity-based costing in the assembly industry

Costs and their determination play a critical role in all manufacturing companies. The traditional costing system has received criticism resulting from the arbitrary allocation of indirect manufacturing costs. As an important initiative to address its weaknesses, new costing methods such as the Time-Driven Activity-Based Costing (TDABC) have emerged. Unfortunately, up to our knowledge, no investigations have been applied in analyzing assembly companies thoroughly nor considering all the processes necessary to obtain the final products. This article explores the TDABC application in the assembly industry through comparison with traditional volume-based costing by focusing on manual and semi-automatized production. Since the research is descriptive, a multiple-case study design was implemented in the assembly of televisions, motorcycles, and printed circuit boards. The developed methodology allowed determining the existence of factory overhead and direct labor cost variances between two different cost accounting systems, which also affected the unit cost of the products. Findings also highlight the benefits of TDABC application in the assembly industry, along with the shortcomings and future potential of research in this area

Integración de la responsabilidad social empresarial y la gestión de la calidad en el sistema de costeo de TDABC: un estudio de caso en la industria de ensamblaje

Propósito: este documento tiene como objetivo mostrar el potencial del costeo basado en el tiempo invertido por actividad (TDABC) para valorar e integrar la responsabilidad social corporativa (RSC) y los procesos de gestión de calidad (QM) en la industria del ensamblaje. Proporciona información valiosa sobre los procesos operativos, los subprocesos y las actividades dentro de las empresas de ensamblaje mediante el uso de las ecuaciones de tiempo de TDABC con costos más precisos para el proceso de toma de decisiones. Diseño/metodología/enfoque: el documento actual propone un nuevo marco de metodología con cuatro niveles de implementación de QM y CSR y varios escenarios de costos a través del sistema TDABC. La valoración fue construida a partir de las actividades de referentes esenciales en cada materia, como ISO, Instituto Ethos y programas de control de descargas electrostáticas. Para ello, se realizó un estudio de caso en los procesos de la industria ensambladora con datos de una ensambladora de televisores. Hallazgos: los resultados destacan que TDABC se puede ampliar para realizar un análisis de costos con procesos QM y CSR. Los procesos de gestión ambiental y administración de la seguridad y salud en el trabajo se consideraron parte de la RSE para ello. En consecuencia, los gestores pueden simular el coste e impacto de incorporar procesos de montaje de RSE y QM y así decidir el grado de implantación y su correspondiente planificación en función de las necesidades y recursos disponibles. En este caso particular, la empresa incrementa un máximo del 12% de sus recursos para ser socialmente responsable y gestionar la calidad de sus productos. Originalidad/valor: aunque se han desarrollado modelos teóricos sobre RSE, el estudio actual proporciona un marco práctico basado en escenarios TDABC que las empresas pueden implementar fácilmente para respaldar y evaluar los procesos de QM y RSE.Purpose – This paper aims to show the potential of time-driven activity-based costing (TDABC) to value and integrate corporate social responsibility (CSR) and quality management (QM) processes in the assembly industry. It provides valuable insights about operational processes, sub-process, and activities within assembly companies by using TDABC’s time equations with more accurate costs for the decision-making process. Design/methodology/approach – The current paper proposes a new methodology framework with four QM and CSR implementation levels and several costing scenarios through the TDABC system. The valuation was built based on the activities of essential referents in each subject, such as ISO, Ethos Institute, and electrostatic discharge control programs. To this end, a case study in the assembly industry processes was conducted with data from a TV assembler. Findings – The results highlight that TDABC can be extended to perform a cost analysis with QM and CSR processes. The environmental management and occupational safety and health administration processes were considered part of CSR to do so. Consequently, managers can simulate the cost and impact of incorporating CSR and QMin assembly processes and thus decide the implementation degree and its corresponding planning according to the needs and available resources. In this particular case, the company increases a maximum of 12% of its resources to be socially responsible and manage its products’ quality. Originality/value – Although theoretical models on CSR have been developed, the current study provides a practical framework based on TDABC scenarios that enterprises can easily implement to support and evaluate QM and CSR processes