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
A highly-sensitive in-situ diagnosis approach for nitrogen dioxide (NO2) has been developed in dielectric barrier discharge (DBD) based on pulsed cavity ring-down spectroscopy (CRDS). Absorption bands of NO2 in ...A highly-sensitive in-situ diagnosis approach for nitrogen dioxide (NO2) has been developed in dielectric barrier discharge (DBD) based on pulsed cavity ring-down spectroscopy (CRDS). Absorption bands of NO2 in a spectral region from 508 nm to 509 nm were used, and a detection limit of 17.5 ppb was achieved. At this level of sensitivity, the quantitative and real-time monitoring of the production and removal of NO2 are accomplished for the first time in the discharge region. By measuring the removal amount and rate at different NO2 initial number densities from 1.54 ×10^13 cm^-3 to 2.79 × 10^14 cm^-3, we determined the relationship between them and NO2 initial number densities. The removal amount linearly increases with the initial number density, while the removal rate increases logarithmically. At a lower initial number density, the removal rate is limited. By considering the chemical kinetic mechanism in plasma, a qualitative explanation for the above phenomena is proposed: the additional NO2 produced by discharge limits the removal rate, since the NO2 concentration is dominated by the competition between the forward reactions (production) and the reverse reactions (removal).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 Magnetic Confinement Fusion Science Program of China(No.2013GB109005)National Natural Science Foundation of China(Nos.11175035,10875023)+2 种基金Chinesisch-Deutsches Forschungs Project(GZ768)the Fundamental Research Funds for the Central Universities(DUT12ZD(G)01)Mmlab Research Project of China(DP1051208)
文摘A highly-sensitive in-situ diagnosis approach for nitrogen dioxide (NO2) has been developed in dielectric barrier discharge (DBD) based on pulsed cavity ring-down spectroscopy (CRDS). Absorption bands of NO2 in a spectral region from 508 nm to 509 nm were used, and a detection limit of 17.5 ppb was achieved. At this level of sensitivity, the quantitative and real-time monitoring of the production and removal of NO2 are accomplished for the first time in the discharge region. By measuring the removal amount and rate at different NO2 initial number densities from 1.54 ×10^13 cm^-3 to 2.79 × 10^14 cm^-3, we determined the relationship between them and NO2 initial number densities. The removal amount linearly increases with the initial number density, while the removal rate increases logarithmically. At a lower initial number density, the removal rate is limited. By considering the chemical kinetic mechanism in plasma, a qualitative explanation for the above phenomena is proposed: the additional NO2 produced by discharge limits the removal rate, since the NO2 concentration is dominated by the competition between the forward reactions (production) and the reverse reactions (removal).