Search

PRAME is a prominent member of the cancer testis antigen family of proteins, which triggers autologous T cell-mediated immune responses. Integrative genomic analysis in diffuse large B cell lymphoma (DLBCL) uncovered recurrent and highly focal deletions of 22q11.22, including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME downmodulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL. In turn, PRC2-regulated genes were repressed in isogenic PRAME-KO lymphoma cell lines, and PRAME was found to directly interact with EZH2 as a negative regulator. EZH2 inhibition with EPZ-6438 abrogated these extrinsic and intrinsic effects, leading to PRAME expression and microenvironment restoration in vivo. Our data highlight multiple functions of PRAME during lymphomagenesis and provide a preclinical rationale for synergistic therapies combining epigenetic reprogramming with PRAME-targeted therapies., Introduction The current treatment standard of combined immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has achieved significant improvement in patient outcomes in diffuse large B cell lymphoma (DLBCL) [...]

The credibility and usability of lay physical activity promotion material are a persistent problem (Thomas & Cardinal, 2020, TJACM). These quality issues deter the material in promoting health literacy, a major predictor of prevention-oriented health behaviors (e.g., regular exercise, U.S. National Action Plan to Improve Health Literacy). Few studies, however, have evaluated the quality of lay material over time (Thomas et al., 2018, Quest). PURPOSE: In order to conduct a repeated-measures study of the quality of physical activity promotion web articles for lay adults, one experienced researcher (JDT) trained undergraduates on how to use the Suitability Assessment of Materials (SAM) protocol (Doak et al., 1996). METHODS: An adapted version of the SAM protocol was used (Thomas & Cardinal, 2020, Quest). Three undergraduates were part of the pilot project (ENT, SAL, CNC; Feb.-Aug. 2020). Each was introduced to the protocol and practiced its methods using six web articles that were written in English and not used in the longitudinal study. Coding by ENT was compared to JDT for analytic purposes; ENT was pre-assigned to evaluate material for the longitudinal study. Per Krippendorff's alpha and intraclass coefficient measures, ENT showed acceptable between/within coder agreement during the training phase. Jul.-Aug. 2020, ENT then tested his skills further using a random subset of 16 unique web articles that were part of the longitudinal study. RESULTS: ENT between-coder agreement ranged from Good/Substantial (both .68) to Excellent/Almost Perfect (both .86) across the SAM's main categories. Overall agreement was Excellent/Substantial (range: .76-.77). Within-coder agreement was Excellent/Almost Perfect across all main categories (both ≥ .85). CONCLUSION: This pilot study demonstrates that a novice coder can learn to code material with a high degree of fidelity. This contrasts with speculation that the SAM protocol may be too subjective for good coder agreement. Debriefing revealed key insights: (a) four "rules" that helped the novice coder achieve fidelity (e.g., review notes often) and (b) developer "bad habits" that limit the educational quality of material (e.g., jargon-filled advice). We will discuss our results and practical lessons based on post-hoc text profiles of material sampled in our pilot study. [ABSTRACT FROM AUTHOR]

PRAME is a prominent member of the cancer testis antigen family of proteins, which triggers autologous T cell-mediated immune responses. Integrative genomic analysis in diffuse large B cell lymphoma (DLBCL) uncovered recurrent and highly focal deletions of 22q11.22, including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME downmodulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL. In turn, PRC2-regulated genes were repressed in isogenic PRAME-KO lymphoma cell lines, and PRAME was found to directly interact with EZH2 as a negative regulator. EZH2 inhibition with EPZ-6438 abrogated these extrinsic and intrinsic effects, leading to PRAME expression and microenvironment restoration in vivo. Our data highlight multiple functions of PRAME during lymphomagenesis and provide a preclinical rationale for synergistic therapies combining epigenetic reprogramming with PRAME-targeted therapies. [ABSTRACT FROM AUTHOR]