Topical Polyethylene Glycol as a Novel Chemopreventive Agent for Oral Cancer via Targeting of Epidermal Growth Factor Response

Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR) is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG) has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide) rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall) post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat) without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells) and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis

TeleSimBox: A perceived effective alternative for experiential learning for medical student education with social distancing requirements.

INTRODUCTION: During the COVID‐19 pandemic the Association of American Medical Colleges recommended that medical students not be involved with in‐person patient care or teaching, necessitating alternative learning opportunities. Subsequently we developed the telesimulation education platform: TeleSimBox. We hypothesized that this remote simulation platform would be feasible and acceptable for faculty use and a perceived effective method for medical student education. METHODS: Twenty‐one telesimulations were conducted with students and educators at four U.S. medical schools. Sessions were run by cofacilitator dyads with four to 10 clerkship‐level students per session. Facilitators were provided training materials. User‐perceived effectiveness and acceptability were evaluated via descriptive analysis of survey responses to the Modified Simulation Effectiveness Tool (SET‐M), Net Promoter Score (NPS), and Likert‐scale questions. RESULTS: Approximately one‐quarter of students and all facilitators completed surveys. Users perceived that the sessions were effective in teaching medical knowledge and teamwork, though less effective for family communication and skills. Users perceived that the telesimulations were comparable to other distance learning and to in‐person simulation. The tool was overall positively promoted. CONCLUSION: Users overall positively scored our medical student telesimulation tool on the SET‐M objectives and promoted the experience to colleagues on the NPS. The next steps are to further optimize the tool

Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies

IntroductionFibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues.MethodsWe analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes.ResultsElevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP’s clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact.ConclusionsOur results emphasize FAP’s multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker