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Introduction: Cisplatin is extensively used in the treatment of head and neck carcinomas. Cetuximab combination therapy is employed in recurrent and metastatic settings. Sunitinib showed positive results in the treatment of head and neck carcinomas, both as monotherapy or in combination with cetuximab. Nonetheless, the mechanism governing these pharmacological interactions is largely unresolved. This study investigates the impact of cetuximab on the cytotoxicity of cisplatin and sunitinib using cells representative of head and neck carcinoma and the oral epithelium.
Methods: The uptake and efflux activities of cells were determined using the prototypical fluorescent substrates 4-[4-[dimethylamino]styryl)-1-methyl pyridinium iodide, Hoechst 33342, and calcein-AM in the presence or absence of specific inhibitors in cells pretreated with cetuximab. The expression of key uptake and efflux drug transporters was analyzed using qPCR and immunofluorescence. Cisplatin and sunitinib cytotoxicities after cetuximab pretreatment were evaluated using the PrestoBlue viability assay.
Results: Both tumor and nontumor cells showed significant active drug transport activity. Cetuximab substantially deregulated the expression of key transporters involved in drug resistance in head and neck cancer cells. Transporter expression in the nontumor cell was unaffected. Upon cetuximab pretreatment, the half maximal effective toxic concentration of cisplatin was reduced by 0.75-fold and sunitinib by 0.82-fold in cancer cells. Nontumor cells were not sensitive to cisplatin or sunitinib under the conditions tested.
Conclusion: Cetuximab regulates the expression and activity of key membrane drug transporters in head and neck cancer cells, involved in drug resistance. The deregulation of the transport mechanism behind cisplatin and sunitinib uptake reverses drug resistance and enhances the cytotoxicity of both drugs.
Purpose
Investigating whether the Acoustic Voice Quality Index (AVQI) and the Acoustic Breathiness Index (ABI) are valid and comparable to previous unmasked measurements if the speaker wears a surgical mask or a FFP-2 mask to reduce the risk of transmitting air-borne viruses such as SARS-CoV-2.
Methods
A convenience sample of 31 subjectively healthy participants was subjected to AVQI and ABI voice examination four times: Twice wearing no mask, once with a surgical mask and once with a FFP-2 mask as used regularly in our hospital. The order of the four mask conditions was randomized. The difference in the results between the two recordings without a mask was then compared to the differences between the recordings with each mask and one recording without a mask.
Results
Sixty-two percent of the AVQI readings without a mask represented perfectly healthy voices, the largest AVQI without a mask value was 4.0. The mean absolute difference in AVQI was 0.45 between the measurements without masks, 0.48 between no mask and surgical mask and 0.51 between no mask and FFP-2 mask. The results were neither clinically nor statistically significant. For the ABI the resulting absolute differences (in the same order) were 0.48, 0.69 and 0.56, again neither clinically nor statistically different.
Conclusion
Based on a convenience sample of healthy or only mildly impaired voices wearing CoViD-19 protective masks does not substantially impair the results of either AVQI or ABI results.
Objectives: To investigate the co-occurrence of 4 behavioral health risk factors (BHRFs), namely tobacco smoking, alcohol at-risk drinking, physical inactivity and unhealthy diet and their association with sick days prior to hospitalization in general hospital patients.
Methods: Over 10 weeks (11/2020-04/2021), all 18-64-year-old patients admitted to internal medicine, general and trauma surgery, and otorhinolaryngology wards of a tertiary care hospital were systematically approached. Among 355 eligible patients, 278 (78.3%) participated, and 256 (72.1%) were analyzed. Three BHRF sum scores were determined, including current tobacco smoking, alcohol use, physical inactivity and 1 of 3 indicators of unhealthy diet. Associations between BHRF sum scores and sick days in the past 6 months were analyzed using multivariate zero-inflated negative binomial regressions.
Results: Sixty-two percent reported multiple BHRFs (≥2). The BHRF sum score was related to the number of sick days if any (p = 0.009) with insufficient vegetable and fruit intake as diet indicator.
Conclusion: The majority of patients disclosed multiple BHRFs. These were associated with sick days prior to admission. The findings support the need to implement interventions targeting multiple BHRFs in general hospitals.