Despite of remarkable progress made in the head and neck cancer (HNC) therapy, the survival rate of this metastatic disease remain low. Tailoring the appropriate therapy to patients is a major challenge and highlights the unmet need to have a good preclinical model that will predict clinical response. Hence, we developed an accurate and time efficient drug screening method of tumor ex vivo analysis (TEVA) system, which can predict patient-specific drug responses. In this study, we generated six patient derived xenografts (PDXs) which were utilized for TEVA. Briefly, PDXs were cut into 2 × 2 × 2 mm3 explants and treated with clinically relevant drugs for 24 h. Tumor cell proliferation and death were evaluated by immunohistochemistry and TEVA score was calculated. Ex vivo and in vivo drug efficacy studies were performed on four PDXs and three drugs side-by-side to explore correlation between TEVA and PDX treatment in vivo. Efficacy of drug combinations was also ventured. Optimization of the culture timings dictated 24 h to be the time frame to detect drug responses and drug penetrates 2 × 2 × 2 mm3 explants as signaling pathways were significantly altered. Tumor responses to drugs in TEVA, significantly corresponds with the drug efficacy in mice. Overall, this low cost, robust, relatively simple and efficient 3D tissue-based method, employing material from one PDX, can bypass the necessity of drug validation in immune-incompetent PDX-bearing mice. Our data provides a potential rationale for utilizing TEVA to predict tumor response to targeted and chemo therapies when multiple targets are proposed.
Objectives: Evaluate the relationship between clinical findings and course of disease among patients with necrotizing otitis externa (NOE). Study Design: Retrospective case series review. Setting: Tertiary referral center. Patients: Adult patients with no previous history of chronic ear disease, hospitalized due to NOE between the years 1990 to 2015. Main Outcome Measures: 1) Duration of hospitalization and 2) necessity for surgery. Results: Eighty-one patients were included in the study, corresponding to 83 effected ears. Thirty-two patients (38.5%) were hospitalized longer than 20 days and 20 patients (24.0%) underwent surgery. Otalgia was the most common complaint (n = 71, 85.5%). Pseudomonas Aeruginosa (PA) was the most common isolated bacteria (n = 40, 48.1%). Shifting incidence of culture results was noted, as rates of PA NOE decreased and rates of sterile culture and fungal NOE increased. Duration of complaints and presence of aural discharge at admission were associated with prolonged hospitalization (p = 0.010, p = 0.011, respectively). Advanced age, duration of hospitalization, and rates of readmission were associated with surgery (p = 0.037, p < 0.001, p < 0.001 respectively). Conclusions: Duration of complaints and presence of aural discharge may indicate advanced NOE and require longer in-hospital treatment. Elderly patients are at increased risk for conservative treatment failure and are more likely to require surgery. With shifting incidence of pathogens, a wider empirical treatment covering nontraditional pathogens should be considered.
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