RESUMO
Previously we reported that Myd88 contributed to tumor progression. To begin to decipher what may be inducing Myd88 dependent signaling we focused on proteins that could function as damage associated molecular pattern molecules (DAMPs) since DAMPs have been reported to be secreted by tumors, and certain DAMPs mediate effects through toll-like receptors. A screen of mammary carcinoma for DAMP expression showed HMGB1 and HSP60 were significantly elevated relative to normal mammary epithelium, and targeting these DAMPs, or receptors for these DAMPs influenced growth of tumor cells. Moreover, analysis using a Myd88 inhibitory peptide suggested that HMGB1 mediated its effects in a Myd88 dependent manner, and inhibiting Myd88 function decreased HMGB1 and HSP60 gene expression. Collectively, these data suggest that HMGB1 and HSP60 contribute to growth of mammary carcinoma cells, HMGB1 accomplishes this, at least in part, through Myd88 dependent signaling, and these DAMPs are expressed in a Myd88 dependent manner.
Assuntos
Proliferação de Células , Chaperonina 60/genética , Proteína HMGB1/genética , Fator 88 de Diferenciação Mieloide/genética , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Chaperonina 60/imunologia , Chaperonina 60/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/imunologia , Proteína HMGB1/metabolismo , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/patologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , Fator 88 de Diferenciação Mieloide/metabolismo , Peptídeos/farmacologia , Interferência de RNA , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismoRESUMO
PURPOSE/OBJECTIVE: The objective of this project was to evaluate the perceptions of predental students' shadowing experiences during a pandemic and further, explore innovative solutions that can be implemented to ensure that shadowing opportunities are equitable and accessible. METHODS: Data was collected via the Web 2.0 social media platform, Instagram (owned by Meta Platforms, Inc.) from 122 participants attending college in North America and are on the predental track: freshman (N = 11), sophomores (N = 25), juniors (N = 30), seniors (N = 34) and recent college graduates (N = 22). Participants completed a survey consisting of 20 questions. RESULTS: Results showed that the pandemic disrupted traditional shadowing methods; students turned to various virtual platforms, such as YouTube and Zoom, to obtain shadowing experiences. There was an increase in the number of students who shadowed virtually during the pandemic versus pre-COVID-19. The majority of the respondents (80%) agreed that dental schools have not provided sufficient guidance on how to approach shadowing during a pandemic. CONCLUSION: Innovative shadowing platforms should be implemented in order to help college students explore careers within dentistry and beyond. The development of a standardized virtual shadowing program with clear guidelines can increase equity and accessibility.
Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Estudantes , América do NorteRESUMO
In 2012, when the National Board Dental Examination (NBDE) was changed from a numerical scoring system to pass/fail, advanced dental education programs lost a metric widely used for differentiating applicants to those programs. The American Dental Association (ADA) has developed the Advanced Dental Admission Test (ADAT) to address this issue. Implementation of the ADAT began in 2016 with a pilot program, which has not yet been widely accepted in the overall admissions process. This Point/Counterpoint explores the benefits and challenges of using the ADAT for postgraduate admissions. Viewpoint 1 supports use of the ADAT, arguing that the test provides a viable, long-term solution to this immediate need. In contrast, Viewpoint 2 questions the need for and appropriateness of this additional academic measure for postgraduate admissions.
Assuntos
Educação de Pós-Graduação em Odontologia , Avaliação Educacional/normas , Critérios de Admissão Escolar , Humanos , Estados UnidosRESUMO
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth. In addition, RNA-sequencing revealed that Myd88-dependent signaling enhanced the expression of genes that could contribute to breast cancer progression and genes previously associated with poor outcome for patients with breast cancer, in addition to suppressing the expression of genes capable of inhibiting breast cancer progression. Yet, Myd88-dependent signaling in tumor cells also suppressed expression of genes that could contribute to tumor progression. Collectively, these data revealed a multifaceted role for Myd88-dependent signaling in murine mammary carcinoma.