Citations

Postoperative surgical draining fluid (SDF) in oral squamous cell carcinoma (OSCC) was reported to contain circulating free DNA and extracellular vesicles (EVs). The potential role of SDF DNA as a cancer biomarker in OSCC patients is investigated. To determine whether EVs contribute to the DNA content of SDF, small EVs (sEVs) were isolated by size exclusion chromatography and compared with those in paired plasma. sEV obtained from a cohort of HPV(+) and HPV(−) patients were evaluated for the endocytic origin, size, vesicular morphology, and the DNA content. The sEV from HPV(+) and HPV(−) SDF were similar. The sEVs from SDF were larger and contained more DNA than the sEV from plasma. Treatments of sEV with the DNase/RNase cocktail established the presence of DNA on the surface and in the sEV lumen. Furthermore, 20 to 30% of the total SDF DNA was associated with sEV. Fragmentomic analyses identified the largest DNA (>10,000 bp) on the vesicle surface. The DNA in the vesicle lumen consisted of smaller (~5000 bp) DNA fragments. Electron microscopy of the enzyme-treated vesicles indicated that surface DNA/RNA may be involved in maintaining vesicular integrity and modulating the vesicle entry into cells. The sEV-carrying surface and luminal DNA emerge as significant contributors to the total SDF DNA and, following validation, might serve as useful biomarkers of disease presence/progression in OSCC.

ABSTRACT Objectives Cognitive behavioral therapy (CBT) is the most researched treatment for childhood anxiety disorders (CADs). Improving outcomes and efficiency of CBT will require identifying and optimizing the most efficacious therapeutic components. Towards this end, a recent randomized controlled trial (RCT) found that Parent Coached Exposure Therapy (PCET) led to greater symptom improvement in less time than traditional CBT. To better understand and maximize these advantages, the current study explores the timing and course of symptom improvement in these two treatments for CADs, CBT, and PCET. Methods In this secondary analysis of data from the RCT, 56 youth aged 7−17 years (73.2% female) and a parent provided weekly ratings of anxiety symptom severity. Results The mean anxiety severity ratings decreased significantly in both conditions, but a significant condition by time interaction suggested that the pace of change differed between treatment for parent report, F (6.2, 335) = 2.96, p = 0.007. A series of post‐hoc comparisons indicated that the ratings became significantly lower in the PCET group beginning in session 3 (effect size = 0.77) through post‐treatment assessment. In addition, within each treatment condition the largest change in severity ratings occurred after the introduction of exposure, effect sizes of 0.68 for PCET and 0.56 for CBT. The child severity ratings followed a similar pattern but did not reach statistical significance. Discussion The implications of these exploratory and hypothesis‐generating findings for designing treatment protocols to deliver exposure in a manner to maximize the amount, and pace, of improvement are discussed.

Background Tumor-derived small extracellular vesicles were shown to contribute to immunosuppression in various cancer types, including head and neck squamous cell carcinoma. Dendritic cells, major regulators of specific anti-tumor immune response, are often impaired in their function in the context of cancer. Methods Monocyte-derived dendritic cells were incubated with isolated small extracellular vesicles during or after maturation. Cell surface markers and antigen processing machinery were assessed by flow cytometry. Vesicle-treated dendritic cells were tested for interleukin 12p70 production by ELISA, and differences in uptake of labeled vesicles were shown by confocal microscopy. Results Small extracellular vesicles derived from HPV(+) tumor cell lines increased maturation and activation of immature dendritic cells, priming them for more rapid phagocytosis. Immature dendritic cells co-incubated with vesicles had lower levels of antigen presenting machinery components and produced less IL12p70 than controls, while similarly co-incubated mature dendritic cells remained unaffected. Vesicles in plasma of patients with head and neck cancer inhibited functions of mature dendritic cells by downregulating expression of antigen presenting machinery components. Conclusion Our results uncover mechanisms through which tumor-derived small extracellular vesicles modulate dendritic cell functions locally and systemically. These mechanisms may also affect dendritic cell-based vaccine efficacy.