c-Src and cooperating partners in human cancer

AbstractThe proto-oncogene c-src is rarely mutated in human cancers, and when overexpressed in normal cells is non- or weakly oncogenic. These observations have raised doubts about the involvement of c-src in the etiology of human tumors. However, recent studies have shown that c-Src, a non-receptor tyrosine kinase, exhibits elevated protein levels and activity in numerous types of human cancers. Furthermore, it has been found to be a critical component of multiple signaling pathways that regulate proliferation, survival, metastasis, and angiogenesis. Because of its important role in these oncogenic processes, it represents a therapeutic target ripe for exploitation

Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer

Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. Because these molecules are plasma membrane-associated and involved in mitogenesis, it has been speculated that they function in concert with one another to promote breast cancer development and progression. Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic signaling initiated by the EGF receptor itself, as well as by several G-protein coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus, c-Src appears to have pleiotropic effects on cancer cells by modulating the action of multiple growth-promoting receptors

Virtual Learning and Assessment in Rheumatology Fellowship Training: OSCE Revisited

OBJECTIVE: With the onset of the COVID-19 pandemic, an annual multi-institutional face-to-face Rheumatology Objective Structured Clinical Examination (ROSCE) was transformed into a virtual format. The educational goals of the virtual ROSCE (vROSCE) were to reproduce the educational value of the previous in-person ROSCE, providing a valuable formative assessment of rheumatology training activities encompassing the six Accreditation Council for Graduate Medical Education (ACGME) Core Competencies for fellows-in-training (FITs). This report describes the novel design, feasibility, and stakeholder value of a vROSCE. METHODS: Through an established collaboration of five rheumatology fellowship training programs, in February 2021, a vROSCE was created and conducted using a Zoom® platform. Station development included learning objectives, FIT instructions, faculty proctor instructions, and a checklist by which to provide structured formative feedback. An anonymous, optional web-based survey was sent to FIT participants to evaluate the experience. RESULTS: Twenty-three rheumatology FITs from 5 institutions successfully rotated through six stations in the vROSCE. Immediate feedback was given to each FIT using standardized rubrics structured around ACGME Core Competencies. Sixty-five percent (15/23) of FITs responded to the survey. Ninety-three percent of survey respondents agreed or strongly agreed that the vROSCE was a helpful educational activity and identified individualized opportunities for improvement. CONCLUSIONS: A vROSCE is an innovative, feasible, valuable, and well-received educational technology tool. The vROSCE enriched Rheumatology FITs\u27 education and offered collaborative learning experiences across institutions. This article is protected by copyright. All rights reserved

Incorporating Telemedicine in Rheumatology Fellowship Training Programs: Needs Assessment, Curricular Intervention, and Evaluation

OBJECTIVE: To increase rheumatology fellows\u27 in training (FITs) confidence in delivering virtual care (VC) and prepare them for independent practice, we developed educational materials addressing gaps in their skills. METHODS: We identified gaps in telemedicine skills based on FIT performance in a virtual rheumatology observed structured clinical examination (vROSCE) station on VC delivery using videoteleconference technology and survey (Survey1) responses. We created educational materials including videos of mediocre and excellent VC examples, discussion/reflection questions, and a document summarizing key practices. We measured change in FITs\u27 confidence levels for delivering VC with a post-intervention survey (Survey2). RESULTS: Thirty-seven FITs (19 first-year, 18 second + third-year fellows) from seven rheumatology fellowship training programs participated in a vROSCE and demonstrated gaps in skills mapping to several Rheumatology Telehealth Competency domains. FITs\u27 confidence levels improved significantly from Survey1 to Survey2 for 22 of 34 (65%) questions. All participating FITs found the educational materials helpful for learning and reflecting on their own VC practice; 18 FITs (64%) qualified usefulness as moderately or a lot . Through surveying, 17 FITs (61%) reported implementing skills from the instructional videos into VC visits. DISCUSSION: Continually assessing our learners\u27 needs and creating educational materials addressing gaps in training is requisite. Using a vROSCE station, needs assessments, and targeted learning with videos and discussion-guidance materials enhanced the confidence level for FITs in VC delivery. It is imperative to incorporate VC delivery into fellowship training program curricula to ensure breadth in skills, attitudes, and knowledge of new entrants into the rheumatology workforce. This article is protected by copyright. All rights reserved

Fas-Activated Serine/Threonine Phosphoprotein Promotes Immune-Mediated Pulmonary Inflammation

We generated Fas-activated serine threonine phosphoprotein (FAST)-deficient mice $(FAST^{−/−})$ to study the in vivo role of FAST in immune system function. In a model of house dust mite-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes, and neutrophils. $FAST^{−/−}$ mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in $FAST^{−/−}$ mice compared with wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-α and IL-6 and -23) and chemoattractants (MIP-2 and keratinocyte chemoattractant) in bronchoalveolar lavage fluids. Because $FAST^{−/−}$ neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g., pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a proinflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation