ABSTRACT
Purpose: Long-term survival benefit of anthracyclines for human epidermal growth factor receptor 2 (HER2)-positive breast cancer is clear. In the neoadjuvant treatment, compared with the monoclonal antibody such as trastuzumab and pertuzumab, the clinical benefit of pyrotinib, a new small-molecule tyrosine kinase inhibitor (TKI), as the main anti-HER2 strategy currently requires more research to determine. Our real-world study is the first prospective observational study in China to evaluate the efficacy and safety of epirubicin (E) and cyclophosphamide (C) with pyrotinib as anti-HER2 therapy in the neoadjuvant setting of patients with stage II-III HER2-positive breast cancer. Methods: From May 2019 to December 2021, 44 untreated patients with HER2-positive nonspecific invasive breast cancer who received 4 cycles of neoadjuvant EC with pyrotinib. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included the overall clinical response, breast pathological complete response rate (bpCR), the rate of axillary lymph nodes pathological negativity and adverse events (AEs). Other objective indicators were the rate of surgical breast-conserving, the negative conversion ratios of tumor markers. Results: Thirty-seven (84.1%) of 44 patients completed this neoadjuvant therapy, and 35 (79.5%) had surgery and were included in the primary endpoint assessment. The objective response rate (ORR) of 37 patients was 97.3%. Two patients reached clinical complete response, 34 obtained clinical partial response, 1 sustained stable disease, and no one had progressive disease. Eleven (31.4%) of 35 patients who had surgery achieved bpCR and the rate of axillary lymph nodes pathological negativity was 61.3%. The tpCR rate was 28.6% (95% CI: 12.8-44.3%). Safety was evaluated in all 44 patients. Thirty-nine (88.6%) had diarrhea, and 2 developed grade 3 diarrhea. Four (9.1%) patients had grade 4 leukopenia. All grade 3-4 AEs could be improved after symptomatic treatment. Conclusion: The regimen of 4 cycles of EC combined with pyrotinib presented some feasibility in the neoadjuvant setting for HER2-positive breast cancer with manageable safety. New regimens with pyrotinib should be evaluated for higher pCR in future. Trial registration: chictr.org Identifier: ChiCTR1900026061.
ABSTRACT
BACKGROUND: The purpose of our research was to investigate the expression of epidermal growth factor receptor (EGFR) and zeste gene enhancer homolog 2 (EZH2) in breast cancer, and to explore their potential common pathways. METHODS: Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the protein and corresponding mRNA expression of EGFR and EZH2 in breast cancer tissues and benign tissues. Then, the relationship between EGFR and EZH2 along with the corresponding clinicopathological parameters were also analyzed. Bioinformatics tools were applied to explore the possible common pathways. RESULTS: The results showed that both EGFR and EZH2 protein and mRNA were highly expressed in breast cancer tissues, and there was a positive correlation between EGFR and EZH2. Moreover, we found that increased mRNA expression was correlated with lymph node metastasis and clinical stage (P<0.05). Furthermore, the enrichment results of co-expressed genes indicated that EGFR and EZH2 may work together in the FOXO signaling pathway, affecting the growth and metastasis of breast cancer cells. CONCLUSIONS: The high expression of both EGFR and EZH2 mRNA in breast cancer was related to lymph node metastasis and clinical staging. The FOXO signaling pathway may be their common signaling pathway that affects tumor cell invasion and metastasis.
ABSTRACT
This paper investigates the electroosmotic micromixing of non-Newtonian fluid in a microchannel with wall-mounted obstacles and surface potential heterogeneity on the obstacle surface. In the numerical simulation, the full model consisting of the Navier-Stokes equations and the Poisson-Nernst-Plank equations are solved for the electroosmotic fluid field, ion transport, and electric field, and the power law model is used to characterize the rheological behavior of the aqueous solution. The mixing performance is investigated under different parameters, such as electric double layer thickness, flow behavior index, obstacle surface zeta potential, obstacle dimension. Due to the zeta potential heterogeneity at the obstacle surface, vortical flow is formed near the obstacle surface, which can significantly improve the mixing efficiency. The results show that, the mixing efficiency can be improved by increasing the obstacle surface zeta potential, the flow behavior index, the obstacle height, the EDL thickness.
ABSTRACT
Enzyme-loaded nanosystems with multimodal therapeutic functions have received increasing attention in the treatment of malignant tumors. Herein, we designed and prepared cascaded dual-enzyme-augmented Fe-hemoporfin framework nanosonosensitizers for synergistic sonodynamic-starvation therapy of tumors. Amorphous Fe-hemoporfin frameworks (FeHF) with an average size of â¼85 nm were synthesized by assembling the clinical drug hemoporfin with Fe3+ ions. Then, FeHF was used to load dual enzymes (glucose oxidase (GOx) and catalase (CAT)) and modified by PEGylated folic acid-conjugated lipids. The dual-enzyme loaded FeHF (FeHF-GOx/CAT) exhibited higher efficiency not only for glucose depletion but also for ultrasound (US)-triggered 1O2 generation than that of pure FeHF, resulting from the cascaded catalytic reaction from the dual-enzyme system. As observed by magnetic resonance imaging, the intravenously injected FeHF-GOx/CAT was accumulated within tumors. The FeHF-GOx/CAT + US exhibited the highest inhibition effect compared to the FeHF-CAT + US (only SDT) or FeHF-GOx/CAT (only starvation therapy), due to the synergistic effects of SDT and starvation therapy. Therefore, the cascaded dual-enzyme loading strategy can increase the SDT efficiency of FeHF, which may guide further works in the development of efficient nanosonosensitizers.
