The tendency for enhanced glycolysis in cancer cells presents a target for chemotherapy. In previous studies we observed that proliferation of colon and bladder cancer cells can be inhibited by treatment with either phenformin or an inhibitor of PFKFB3 namely 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO). In the present work we have examined the action of two inhibitors that are effective at lower concentrations than 3PO, namely 1-(3-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PQP) and 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15). The LDHA inhibitors that we chose to study in increasing order of IC50s were methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate (NHI-2) < isosafrole < oxamate. A synergistic anti-cancer effect of phenformin and oxamate has been reported. In the present work with colon and bladder cancer cells, additive but not synergistic growth inhibitory effects were seen with the LDHA inhibitors of which NHI-2 was effective at the lowest concentrations. Growth inhibition with PQP and PFK15 was compared in colon (Caco-2 and HT29) and bladder cancer cells (5637, HT1376, RT4, SW780, T24, TCCSUP and UM-UC-3). Apart from RT4 cells where the effects were similar, the effects were somewhat greater with PFK15 than with PQP and for both compounds the actions were seen at lower concentrations than in previous studies with 3PO. Actions on medium acidification and glucose uptake are more readily observed in the most rapidly growing cell lines. Effects of phenformin on medium pH and glucose concentration were decreased by the PFKFB3 and LDHA inhibitors that were examined. In accord with our previous studies on inhibitors of glycolysis, the increased medium acidification and glucose uptake caused by phenformin could be blocked by combined treatment with PFKFB3 or LDHA inhibitors. At the same time additive growth inhibitory effects were observed. The results supported the concept that combined treatment with phenformin and inhibitors of glycolysis can cause additive inhibition of cell proliferation while mitigating the lactic acidosis caused by phenformin as a single agent. Citation Format: Michael A. Lea, Yolanda Guzman, Charles desBordes. Inhibition of cancer cell growth by combined treatment with lactate dehydrogenase (LDHA) inhibitors and either phenformin or inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 32.
:e20170401Among the missions and functions of higher education, article 1, the World Conference on Higher Education reaffirms the generation of knowledge through research and encourages learning; as well as provide appropriate technical skills to contribute to the cultural, social and economic development of societies and to the development of scientific and technological research, 1 but in order for a person to have the capacity to produce permanent knowledge and learning, are required skills, abilities and attitudes for the research.In the context of Latin America, specifically in Colombia, the National Accreditation Council ("NAC") started talking about formative research in the second half of the 1990s as the research which is done between students and teachers in the process of developing a program's curriculum and which is distinguishing of the dynamics of the relationship with knowledge that must exist in all academic processes, both in the students' learning and in the renewal of the pedagogical practice by the teachers. 2The formative research is defined as a tool of the teaching and learning process; and its purpose is to disseminate existing information and encourage the student to incorporate it as knowledge (learning). It can also be defined as teaching through research or teaching using the research method, 3 constituting itself as a pedagogical strategy of character teaching for the development of the curriculum.According to Elliot 4 (cited by Cerda, 2007) for the development of classroom training research, there must be objective conditions in the educational institution, as a flexible, open and dynamic curriculum that accepts a diversity of skills, rhythms, cultural values, interests and demands which allow the articulation between the investigative and educational tasks and the development of the students.Stenhouse 5 proposes that the curriculum be the means by which the teacher can learn its art; can acquire knowledge and can test ideas and experience in practice, that allow one to improve the quality of teaching. In this sense, the curriculum is the tool that conditions the exercise of such experimentation in which the teacher becomes a researcher in the classroom of its own teaching experience; which has high power to influence in practice and to change obsolete educational models. This is due to the fact that it is built on teachers' real knowledge, since they address real concerns about complex hidden processes of classroom routine and because they constitute a natural process of evaluation as a research tool.The Universidad Católica los Ángeles de Chimbote (ULADECH Catholic) promotes within its didactic model the development of activities of formative research, which is based on the Institutional Educational Project, which conceives the formative research as a cross-curricular axis, since the education is a process of socialization through which research is inherent in the life of the human being. It is expressed through the insertion of pedagogical activities related to the contents of t...
Introduction Current deficiencies in children’s leisure-time physical activity in the United States and globally underscore a pressing and ongoing need to enhance child ecosystems that include school and out-of-school time settings with physical activity supports and opportunities. Marathon Kids (MK) is an international nonprofit organization that promotes children’s physical activity via school and community-based running clubs and programs. Building from the importance of indigenous knowledge and colearning with stakeholders within real-world settings for children’s physical activity promotion, we explore best practices for the implementation of children’s running clubs based on a national sample of U.S. adult volunteer MK coaches. As a secondary aim, we describe selected implementation characteristics of MK running clubs as relates to when clubs are implemented and average weekly minutes scheduled for running clubs. Methods This study was guided primarily by a phenomenological approach to qualitative research. Data were collected in 2019 from MK coaches via an online survey that included open and closed-ended items on MK delivery and best practices. Qualitative analyses were based on thematic analysis; quantitative analyses were based primarily on descriptive statistics. Results MK coaches (n = 478 out of 676 coaches; 70.7% response) from across the United States (n = 35 states) participated. Eight primary themes encapsulated the best practice recommendations: running club leadership and support network; general organization and planning; student recruitment; running club implementation; tracking/logging miles; social support; communication and public promotion of running clubs; and guiding principles for running clubs. MK coaches reported an average of 112 weekly minutes scheduled for running/walking. Conclusions MK coach best practice recommendations hold promise to enhance and further disseminate the establishment of volunteer-led running clubs for young people.
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