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Extracellular vesicles and nanoparticles (EVPs) are now recognized as a novel form of cell–cell communication. All cells release a wide array of heterogeneous EVPs with distinct protein, lipid, and RNA content, dependent on the pathophysiological state of the donor cell. The overall cargo content in EVPs is not equivalent to cellular levels, implying a regulated pathway for selection and export. In cancer, release and uptake of EVPs within the tumour microenvironment can influence growth, proliferation, invasiveness, and immune evasion. Secreted EVPs can also have distant, systemic effects that can promote metastasis. Here, we review current knowledge of EVP biogenesis and cargo selection with a focus on the role that extracellular RNA plays in oncogenesis and metastasis. Almost all subtypes of RNA have been identified in EVPs, with miRNAs being the best characterized. We review the roles of specific miRNAs that have been detected in EVPs and that play a role in oncogenesis and metastasis.

BackgroundHospitalized patients with complex care needs require an interprofessional team of health professionals working together to support their care in hospitals and during discharge planning. However, interprofessional communication and collaboration in inpatient settings are often fragmented and inefficient, leading to poor patient outcomes and provider frustration. Health information technology can potentially help improve team communication and collaboration; however, to date, evidence of its effectiveness is lacking. There are also concerns that current implementations might further fragment communication and increase the clinician burden without proven benefits. ObjectiveIn this study, we aimed to generate transferrable lessons for future designers of health information technology tools that facilitate team communication and collaboration. MethodsA secondary analysis of the qualitative component of the mixed methods evaluation was performed. The electronic communication and collaboration platform was implemented in 2 general internal medicine wards in a large community teaching hospital in Mississauga, Ontario, Canada. Fifteen inpatient clinicians in those wards, including nurses, physicians, and allied health care providers, were recruited to participate in semistructured interviews about their experience with a co-designed electronic communication and collaboration tool. Data were analyzed using the Technology Acceptance Model, and themes related to the constructs of perceived ease of use (PEOU) and perceived usefulness (PU) were identified. ResultsA secondary analysis guided by the Technology Acceptance Model highlighted important points. Intuitive design precluded training as a barrier to use, but lack of training may hinder participants’ PEOU if features designed for efficiency are not discovered by users. Organized information was found to be useful for creating a comprehensive clinical picture of each patient and facilitating improved handovers. However, information needs to be both comprehensive and succinct, and information overload may negatively impact PEOU. The mixed paper and electronic practice environment also negatively impacted PEOU owing to unavoidable double documentation and the need for printing. Participants perceived the tool to be useful as it improved efficiency in information retrieval and documentation, improved the handover process, afforded another mode of communication when face-to-face communication was impractical, and improved shared awareness. The PU of this tool depends on its optimal use by all team members. ConclusionsElectronic tools can support communication and collaboration among interprofessional teams caring for patients with complex needs. There are transferable lessons learned that can improve the PU and PEOU of future systems.

Although some cancers are initially sensitive to EGFR tyrosine kinase inhibitors (TKIs), resistance invariably develops. We investigated mechanisms of acquired resistance to the EGFR TKI gefitinib by generating gefitinib-resistant (GR) A431 squamous cancer cells. In GR cells, gefitinib reduced phosphorylation of EGFR, ErbB-3, and Erk but not Akt. These cells also showed hyperphosphorylation of the IGFI receptor (IGFIR) and constitutive association of IRS-1 with PI3K. Inhibition of IGFIR signaling disrupted the association of IRS-1 with PI3K and restored the ability of gefitinib to downregulate PI3K/Akt signaling and to inhibit GR cell growth. Gene expression analyses revealed that GR cells exhibited markedly reduced IGF-binding protein 3 (IGFBP-3) and IGFBP-4 RNA. Addition of recombinant IGFBP-3 restored the ability of gefitinib to downregulate PI3K/Akt signaling and to inhibit cell growth. Finally, gefitinib treatment of mice with A431 xenografts in combination with an IGFIR-specific monoclonal antibody prevented tumor recurrence, whereas each drug given alone was unable to do so. These data suggest that loss of expression of IGFBPs in tumor cells treated with EGFR TKIs derepresses IGFIR signaling, which in turn mediates resistance to EGFR antagonists. Moreover, combined therapeutic inhibition of EGFR and IGFIR may abrogate this acquired mechanism of drug resistance and is thus worthy of prospective clinical investigation. [ABSTRACT FROM AUTHOR]