Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinas...Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.展开更多
Si-based optical position-sensitive detectors(PSDs)have stimulated the interest of researchers due to their wide range of practical applications.However,due to the rigidity and fragility of Si crystals,the application...Si-based optical position-sensitive detectors(PSDs)have stimulated the interest of researchers due to their wide range of practical applications.However,due to the rigidity and fragility of Si crystals,the applications of flexible PSDs have been limited.Therefore,we presented a flexible broadband PSD based on a WS_(2)/Si heterostructure for the first time.A scalable sputtering method was used to deposit WS_(2)thin films onto the etched ultrathin crystalline Si surface.The fabricated flexible PSD device has a broad spectral response in the wavelength range of 450-1350 nm,with a high position sensitivity of~539.8 mV·mm^(−1)and a fast response of 2.3μs,thanks to the strong light absorption,the built-in electrical field at the WS_(2)/Si interface,and facilitated transport.Furthermore,mechanical-bending tests revealed that after 200 mechanical-bending cycles,the WS_(2)/Si PSDs have excellent mechanical flexibility,stability,and durability,demonstrating the great potential in wearable PSDs with competitive performance.展开更多
基金supported by the National Natural Science Foundation of China (No. 82072914)the Special Foundation for Taishan Scholars and the Fundamental Research Funds for the Central Universities (No. 2022JC009)。
文摘Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.
基金supported by the National Natural Science Foundation of China(No.51972341)the Shandong Natural Science Foundation,China(No.ZR2020MA069).
文摘Si-based optical position-sensitive detectors(PSDs)have stimulated the interest of researchers due to their wide range of practical applications.However,due to the rigidity and fragility of Si crystals,the applications of flexible PSDs have been limited.Therefore,we presented a flexible broadband PSD based on a WS_(2)/Si heterostructure for the first time.A scalable sputtering method was used to deposit WS_(2)thin films onto the etched ultrathin crystalline Si surface.The fabricated flexible PSD device has a broad spectral response in the wavelength range of 450-1350 nm,with a high position sensitivity of~539.8 mV·mm^(−1)and a fast response of 2.3μs,thanks to the strong light absorption,the built-in electrical field at the WS_(2)/Si interface,and facilitated transport.Furthermore,mechanical-bending tests revealed that after 200 mechanical-bending cycles,the WS_(2)/Si PSDs have excellent mechanical flexibility,stability,and durability,demonstrating the great potential in wearable PSDs with competitive performance.
