Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation.

Epidermal growth factor is an excellent drug for promoting wound healing; however, its conventional administration strategies are associated with pharmacodynamic challenges, such as low transdermal permeability, reduction, and receptor desensitization. Here, we develop a microneedle-based self-powered transcutaneous electrical stimulation system (mn-STESS) by integrating a sliding free-standing triboelectric nanogenerator with a microneedle patch to achieve improved epidermal growth factor pharmacodynamics. We show that the mn-STESS facilitates drug penetration and utilization by using microneedles to pierce the stratum corneum. More importantly, we find that it converts the mechanical energy of finger sliding into electricity and mediates transcutaneous electrical stimulation through microneedles. We demonstrate that the electrical stimulation applied by mn-STESS acts as an "adjuvant" that suppresses the reduction of epidermal growth factor by glutathione and upregulates its receptor expression in keratinocyte cells, successfully compensating for receptor desensitization. Collectively, this work highlights the promise of self-powered electrical adjuvants in improving drug pharmacodynamics, creating combinatorial therapeutic strategies for traditional drugs.

Clinical study of the predictors to neoadjuvant chemotherapy in patients with advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the predictive value of seven gastric cancer-associated factors on neoadjuvant chemotherapy in patients with advanced gastric cancer.</p><p><b>METHODS</b>Expressions of C-met, EGFR, HER2, Ki-67, MMP7, P53 and TOPOII were detected by immunohistochemistry in gastric cancer tissues of 53 cases before and after mFOLFOX7 neoadjuvant chemotherapy. Chemotherapy efficacy was evaluated according to RECIST 1.1 standard combined with histopathology, and the relationship between various genes and chemotherapy efficacy was analyzed by univariate and logistic multivariate regression analyses.</p><p><b>RESULTS</b>The clinical response rate was 52.8% (28/53) in neoadjuvant chemotherapy, including complete response in none, partial response in 28 cases (52.8%), stable disease in 24 cases (45.3%) and progressive disease in 1 case (1.9%). The expressions of all the genes were not significantly different before and after neoadjuvant chemotherapy (P>0.05). Neoadjuvant chemotherapy efficacy was 83.3% (10/12) in the patients of HER2 positive expression and 43.9% (18/41) in the patients of HER2 negative expression. The former was significant higher than the latter (P=0.016). Response rate of patients with P53 positive expression was 35.7% (10/28), significantly lower than 72.0% (18/25) of those with P53 negative expression (P=0.008). Six patients with both HER2 positive expression and P53 negative expression showed better efficacy. The expressions of C-met, EGFR, Ki-67, MMP7 and TOPOII were not associated with response to neoadjuvant chemotherapy (P>0.05). HER2 and P53 were independent influencing factors of neoadjuvant chemotherapy (P<0.05).</p><p><b>CONCLUSION</b>Expressions of HER2 and P53 have great value in the prediction of mFOLFOX7 neoadjuvant chemotherapy efficacy, suggesting that as independent factors, HER2 and P53 may be used to predict the efficacy before chemotherapy.</p>