All-aqueous microfluidic fabrication of calcium alginate/alkylated chitosan core-shell microparticles with time-sequential functions for promoting whole-stage wound healing

Article

作者: Wang, Weijiang ; Ma, Qingming ; Sun, Wentao ; Xin, Huan ; Zhao, Wenbin ; Zheng, Huiyuan ; Xu, Fenglan

Wound healing comprises a series of complex physiological processes, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Designing new functional biomaterials by biological macromolecules with tailored therapeutic effects to precisely match the unique requirements of each stage is cherished but rarely discussed. Here, we employ all-aqueous microfluidics to fabricate multifunctional core-shell microparticles aimed at promoting whole-stage wound healing. These microparticles feature a core comprising calcium alginate, cellulose nanocrystals and epidermal growth factor, surrounded by a shell made of alkylated chitosan, alginate, and ciprofloxacin (EGF + CNC@Ca-ALG/CIP@ACS core-shell microparticles, D-CSMP). Response surface methodology (RSM) with a combination of central composite rotatable design (CCRD) is used to meticulously optimize the fabrication processes, endowing the resulting D-CSMP with superior capabilities for efficiently encapsulating and controlled releasing CIP and EGF tailored to each stage aligning the healing timeline. The developed D-CSMP demonstrate notable time-sequential functionalities, including promoting blood coagulation, enhancing hemostasis, and exerting antibacterial effects. Furthermore, in a skin injury model, D-CSMP significantly expedite and enhance the chronic wound healing process. In conclusion, our core-shell microparticles with notable time-sequential functions present a versatile and robust approach for wound treatment and related biomedical applications.

2024-10-01·ESMO Open

Features and efficacy of triple-targeted therapy for patients with EGFR-mutant non-small-cell lung cancer with acquired BRAF alterations who are resistant to epidermal growth factor receptor tyrosine kinase inhibitors

Review

作者: Tan, S ; Planchard, D. ; Li, Y ; Zeng, H. ; Tian, P ; Qi, C ; Planchard, D ; Li, Y. ; Li, W. ; Pu, X. ; Tan, S. ; Zeng, H ; Tian, P. ; Huang, Q. ; Li, W ; Qi, C. ; Pu, X ; Huang, Q

BACKGROUND:

The recommended first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients is EGFR-tyrosine kinase inhibitors (EGFR-TKIs). BRAF alterations have been identified as resistance mechanisms. We aimed to identify features of and subsequent treatment strategies for such patients.

PATIENTS AND METHODS:

We conducted a systematic literature review of NSCLC patients harboring acquired BRAF alterations. Additionally, BRAF-altered NSCLC patients who progressed from EGFR-TKIs at West China Hospital of Sichuan University were screened. Patient characteristics, treatment options, and outcomes were analyzed.

RESULTS:

A total of 104 patients were included, 2 of whom came from our center. Seventy-five patients (72.1%) harbored BRAF mutations (57 class I mutations, 7 class II mutations, 9 class III mutations, and 2 non-class I-III mutations), and 29 (27.9%) harbored BRAF fusions. Eighteen patients received triple-targeted therapy, including prior EGFR-TKIs plus dabrafenib and trametinib, and 23 patients received other treatments. The median progression-free survival was significantly longer in patients receiving triple-targeted therapy than in those receiving other treatments (8.0 versus 2.5 months, P < 0.001). Similar findings were observed in patients with BRAF mutations (9.0 versus 2.8 months, P = 0.004), particularly in those with BRAF class I mutations (9.0 versus 2.5 months, P < 0.001). A potential benefit was also observed among patients with BRAF fusions (5.0 versus 2.0 months, P = 0.230). Twenty patients (48.8%) experienced adverse events. Dose reduction of RAF or MEK inhibitor was required in five patients (12.2%). Five patients (12.2%) permanently discontinued treatment (three on triple-targeted therapy; one on prior EGFR-TKI plus vemurafenib; one on prior EGFR-TKI plus trametinib).

CONCLUSIONS:

BRAF alterations, specifically BRAF mutations and BRAF fusions, facilitate resistance to EGFR-TKIs. Triple-targeted therapy is effective and safe for patients with EGFR-mutant NSCLC with acquired BRAF alterations, mainly among patients with BRAF class I mutations and potentially in patients with BRAF fusions.

2024-09-01·Translational Cancer Research

Strategies and influencing factors for the treatment of advanced non-small cell lung cancer based on epidermal growth factor receptor tyrosine kinase inhibitors: a narrative review

Review

作者: Wang, Peng ; Zhou, Lin ; Li, Yangkai ; Kuang, Linwu

Background and Objective:

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the primary treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations, significantly enhancing patient prognosis. Despite the efficacy of EGFR-TKIs, monotherapy faces challenges such as variability among individuals and early drug resistance. This article aims to explore the treatment strategies and influencing factors for advanced NSCLC patients treated with EGFR-TKIs, optimize treatment plans, and improve the prognosis of patients with advanced NSCLC.

Methods:

We undertook a comprehensive, narrative review of the latest literature to define the current application and progress of EGFR-TKIs in treating patients with advanced NSCLC.

Key Content and Findings:

The efficacy and promise of EGFR-TKIs, both as monotherapy and combined with other agents, for treating patients with advanced NSCLC are outlined. The study delves into the mechanisms of resistance and the ongoing development of EGFR-TKIs. Various factors influencing the treatment of advanced NSCLC patients with EGFR-TKIs are also examined.

Conclusions:

EGFR-TKIs alone improve survival in patients with advanced NSCLC. Combined with other agents, some regimens have shown improved benefits in overcoming drug resistance and prolonging patient survival. It is imperative to focus on developing novel EGFR-TKIs and investigate innovative combination therapies to maximize patient benefit.

100 项与 Epidermal growth factor(Chang Gung Memorial Hospital) 相关的药物交易

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