5 research outputs found
Retinoic Acid Resistance at Late Stages of Human Papillomavirus Type 16-Mediated Transformation of Human Keratinocytes Arises Despite Intact Retinoid Signaling and Is Due to a Loss of Sensitivity to Transforming Growth Factor-β
AbstractIn our in vitro model of human cell carcinogenesis, normal human foreskin keratinocytes (HKc) transfected with human papillomavirus type 16 DNA (HKc/HPV16) progress toward malignancy through several phenotypically defined and reproducible “steps” that include immortalization, growth factor independence (HKc/GFI), differentiation resistance (HKc/DR), and ultimately malignant conversion. While HKc/HPV16 are very sensitive to growth inhibition by all-trans-retinoic acid (RA) at early passages, they lose their sensitivity to RA during progression in culture. However, gel mobility shift assays using the retinoid response elements DR1 and DR5 showed no changes in binding activity of nuclear extracts obtained from HKc/HPV16 at different stages of in vitro progression. Similarly, Western blot analyses for retinoic acid receptor γ-1 and the retinoid X receptors failed to reveal any decreases in the levels of these retinoid receptors throughout progression. In addition, luciferase activity driven by the SV40 promoter with a DR5 enhancer element was activated following RA treatment of HKc/DR that were resistant to growth inhibition by RA. Since RA induces transforming growth factor-β2 (TGF-β2) in normal HKc and HKc/HPV16, we investigated whether this response changed during progression. Again, RA induced TGF-β2 mRNA in early and late passage HKc/HPV16, HKc/GFI, and HKc/DR approximately to the same extent, confirming that the RA signaling pathways remained intact during in vitro progression despite the fact that the cells become resistant to growth inhibition by RA. We then investigated the sensitivity of HKc/HPV16 to growth inhibition by TGF-β. While early passage HKc/HPV16 were as sensitive as normal HKc to growth inhibition by TGF-β1 and TGF-β2, the cells became increasingly resistant to both TGF-β isotypes during in vitro progression. In addition, while both RA and TGF-β produced a decrease in the levels of mRNA for the HPV16 oncogenes E6 and E7 in early passage HKc/HPV16, this effect was also lost at later stages of progression. Finally, blocking anti-TGF-β antibodies partially prevented RA inhibition of growth and E6/E7 expression in early passage HKc/HPV16. Taken together, these data strongly suggest that inhibition of growth and HPV16 early gene expression in HKc/HPV16 by RA is mediated by TGF-β and that a loss of RA sensitivity is linked to TGF-β resistance rather than alterations in RA signaling
Developing a Professionalism Plan
Professionalism is a way of being which underlies all the responsibilities of a pharmacist and associated general and professional abilities. The Student Affairs Committee was charged with developing a college-wide professionalism plan to meet the Accreditation Council for Pharmacy Education (ACPE) Standards 15.1 and 23. This plan was developed concurrently with a new curriculum. The plan was developed systematically with the following goals: 1) create a definition of professionalism, 2) determine outcomes of the plan, 3) identify existing components which should be continued and new components to be added, 4) ensure existing and new components are linked to outcomes and 5) develop a continuous assessment process for the plan. The proposed plan consists of curricular, co-curricular and extra-curricular activities designed to help students gain experience in three professionalism pillars: Competence, Connection and Character, as defined by Brown et al in "Taxonomy of Professionalism". While knowledge and skills will be enhanced, the focus of development will be on student virtues, values and attitudesäóîthat what they do defines who they are. The goal is to help students develop as people and professionals who value the high ideals expected of a pharmacist.
Type: Idea Pape
Developing a Professionalism Plan
Professionalism is a way of being which underlies all the responsibilities of a pharmacist and associated general and professional abilities. The Student Affairs Committee was charged with developing a college-wide professionalism plan to meet the Accreditation Council for Pharmacy Education (ACPE) Standards 15.1 and 23. This plan was developed concurrently with a new curriculum. The plan was developed systematically with the following goals: 1) create a definition of professionalism, 2) determine outcomes of the plan, 3) identify existing components which should be continued and new components to be added, 4) ensure existing and new components are linked to outcomes and 5) develop a continuous assessment process for the plan. The proposed plan consists of curricular, co-curricular and extra-curricular activities designed to help students gain experience in three professionalism pillars: Competence, Connection and Character, as defined by Brown et al in "Taxonomy of Professionalism". While knowledge and skills will be enhanced, the focus of development will be on student virtues, values and attitudesäóîthat what they do defines who they are. The goal is to help students develop as people and professionals who value the high ideals expected of a pharmacist.
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Type:Â Idea Pape
Developing a Professionalism Plan
Professionalism is a way of being which underlies all the responsibilities of a pharmacist and associated general and professional abilities. The Student Affairs Committee was charged with developing a college-wide professionalism plan to meet the Accreditation Council for Pharmacy Education (ACPE) Standards 15.1 and 23. This plan was developed concurrently with a new curriculum. The plan was developed systematically with the following goals: 1) create a definition of professionalism, 2) determine outcomes of the plan, 3) identify existing components which should be continued and new components to be added, 4) ensure existing and new components are linked to outcomes and 5) develop a continuous assessment process for the plan. The proposed plan consists of curricular, co-curricular and extra-curricular activities designed to help students gain experience in three professionalism pillars: Competence, Connection and Character, as defined by Brown et al in “Taxonomy of Professionalism”. While knowledge and skills will be enhanced, the focus of development will be on student virtues, values and attitudes—that what they do defines who they are. The goal is to help students develop as people and professionals who value the high ideals expected of a pharmacist