Purpose: Endocrine therapy is one of the main treatment options for hormone receptor (HR)-positive advanced breast cancer (ABC). However, whether the combination of endocrine therapy with chemotherapy is practicable a...Purpose: Endocrine therapy is one of the main treatment options for hormone receptor (HR)-positive advanced breast cancer (ABC). However, whether the combination of endocrine therapy with chemotherapy is practicable and more effective than endocrine therapy alone remains unknown. The aim of this study was to investigate the clinical efficacy of the aromatase inhibitors (AIs) combined with metronomic capecitabine to provide the clinical evidence for further research in patients with HR-positive ABC. Methods: Data from 407 patients with HR-positive ABC were retrospectively analyzed. A total of 305 patients were given AIs alone, and 102 patients were given AIs plus capecitabine as first-line treatment. Progression-free survival (PFS) was the primary endpoint. Results: The median follow-up for all patients was 47.0 months (range, 3 - 119 months). The median overall survival (OS) and PFS were 52.0 months and 24.2 months, respectively. The median PFS in the combination group was significantly longer than that in the AIs group (22.0 months vs. 14.0 months, p = 0.002). Additionally, patients in the combination group had significantly longer OS than patients in the AI group (66.0 months vs. 49.0 months, p = 0.003). Multivariate analysis showed that combination therapy was a significant favorable predictor for PFS and OS. Furthermore, young age (<40 years), low estrogen receptor (ER) expression level (<40%), presence of visceral metastasis, prior adjuvant AI use and long disease-free interval (DFI) (>24 months) improved the benefit from combination therapy. Conclusions: AIs plus metronomic capecitabine significantly improves PFS and OS in patients with HR-positive ABC. Thus, chemo-endocrine therapy should be further explored.展开更多
T cells are crucial for immune functions to maintain health and prevent disease.T cell development occurs in a stepwise process in the thymus and mainly generates CD4^(+)and CD8^(+)T cell subsets.Upon antigen stimulat...T cells are crucial for immune functions to maintain health and prevent disease.T cell development occurs in a stepwise process in the thymus and mainly generates CD4^(+)and CD8^(+)T cell subsets.Upon antigen stimulation,naïve T cells differentiate into CD4^(+)helper and CD8^(+)cytotoxic effector and memory cells,mediating direct killing.展开更多
Pathogen infection is the main cause of human morbidity and death.Traditional antibiotics usually sterilize bacteria in chemical ways,which tends to develop serious antibiotic resistance.Cationic polymers exhibit good...Pathogen infection is the main cause of human morbidity and death.Traditional antibiotics usually sterilize bacteria in chemical ways,which tends to develop serious antibiotic resistance.Cationic polymers exhibit good bacterial inhibition with less resistance,but often face severe cytotoxicity toward normal cells.The optimization of polymeric antimicrobials for enhanced bactericidal capacity and improved biocompatibility is quite meaningful.In addition,photodynamic therapy(PDT) is a therapeutic modality with less susceptibility to develop resistance.Herein,a typical commercial polymeric antimicrobial,polyhexamethylene guanidine(PHMG) was selected for current proof-of-concept optimization due to its excellent bactericidal capacity but moderate biocompatibility.Eosin-Y(EoS)was copolymerized to afford EoS-labeled polymer conjugates,poly(2-(dimethylamino) ethyl methacrylate-co-eosin),P(DMAEMA-co-EoS),which was conjugated with PHMG to afford a novel polymeric antimicrobial,P(DMAEMA-co-EoS)-b-PHMG-b-P(DMAEMA-co-EoS),noted as PEoS-PHMG.It could efficiently kill broad-spectrum bacteria by physical damage and photodynamic therapy.Compared with PHMG,the bacterial inhibition of PEoS-PHMG was potentiated after the functionalization.Furthermore,PEoS-PHMG exhibited low cytotoxicity and minimal hemolysis,which was demonstrated by cell viability assays toward LO2 cells and RAW 264.7 cells as well as hemolytic assays against red blood cells.These results confirmed that the resultant PEoS-PHMG could act as promising alternative antibacterial materials with excellent broad-spectrum bacterial inhibition and favorable biocompatibility.展开更多
文摘Purpose: Endocrine therapy is one of the main treatment options for hormone receptor (HR)-positive advanced breast cancer (ABC). However, whether the combination of endocrine therapy with chemotherapy is practicable and more effective than endocrine therapy alone remains unknown. The aim of this study was to investigate the clinical efficacy of the aromatase inhibitors (AIs) combined with metronomic capecitabine to provide the clinical evidence for further research in patients with HR-positive ABC. Methods: Data from 407 patients with HR-positive ABC were retrospectively analyzed. A total of 305 patients were given AIs alone, and 102 patients were given AIs plus capecitabine as first-line treatment. Progression-free survival (PFS) was the primary endpoint. Results: The median follow-up for all patients was 47.0 months (range, 3 - 119 months). The median overall survival (OS) and PFS were 52.0 months and 24.2 months, respectively. The median PFS in the combination group was significantly longer than that in the AIs group (22.0 months vs. 14.0 months, p = 0.002). Additionally, patients in the combination group had significantly longer OS than patients in the AI group (66.0 months vs. 49.0 months, p = 0.003). Multivariate analysis showed that combination therapy was a significant favorable predictor for PFS and OS. Furthermore, young age (<40 years), low estrogen receptor (ER) expression level (<40%), presence of visceral metastasis, prior adjuvant AI use and long disease-free interval (DFI) (>24 months) improved the benefit from combination therapy. Conclusions: AIs plus metronomic capecitabine significantly improves PFS and OS in patients with HR-positive ABC. Thus, chemo-endocrine therapy should be further explored.
基金This work was supported by the National Key Research and Development Program of China grants 2021YFA1100702(to B.Z.)Major International(Regional)Joint Research Project grants 81820108017(to B.Z.)+2 种基金National Natural Science Foundation of China grants 82271792(to L.S.)32200727(to L.S.)Innovation Capability Support Program of Shaanxi 2021TD-38(to B.Z.).
文摘T cells are crucial for immune functions to maintain health and prevent disease.T cell development occurs in a stepwise process in the thymus and mainly generates CD4^(+)and CD8^(+)T cell subsets.Upon antigen stimulation,naïve T cells differentiate into CD4^(+)helper and CD8^(+)cytotoxic effector and memory cells,mediating direct killing.
基金supported by the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province(No.2016A030306013)the Pearl River Young Talents Program of Science and Technology in Guangzhou(No.201906010047)the National Key Research and Development Program of China(No.2017YFA0205200)。
文摘Pathogen infection is the main cause of human morbidity and death.Traditional antibiotics usually sterilize bacteria in chemical ways,which tends to develop serious antibiotic resistance.Cationic polymers exhibit good bacterial inhibition with less resistance,but often face severe cytotoxicity toward normal cells.The optimization of polymeric antimicrobials for enhanced bactericidal capacity and improved biocompatibility is quite meaningful.In addition,photodynamic therapy(PDT) is a therapeutic modality with less susceptibility to develop resistance.Herein,a typical commercial polymeric antimicrobial,polyhexamethylene guanidine(PHMG) was selected for current proof-of-concept optimization due to its excellent bactericidal capacity but moderate biocompatibility.Eosin-Y(EoS)was copolymerized to afford EoS-labeled polymer conjugates,poly(2-(dimethylamino) ethyl methacrylate-co-eosin),P(DMAEMA-co-EoS),which was conjugated with PHMG to afford a novel polymeric antimicrobial,P(DMAEMA-co-EoS)-b-PHMG-b-P(DMAEMA-co-EoS),noted as PEoS-PHMG.It could efficiently kill broad-spectrum bacteria by physical damage and photodynamic therapy.Compared with PHMG,the bacterial inhibition of PEoS-PHMG was potentiated after the functionalization.Furthermore,PEoS-PHMG exhibited low cytotoxicity and minimal hemolysis,which was demonstrated by cell viability assays toward LO2 cells and RAW 264.7 cells as well as hemolytic assays against red blood cells.These results confirmed that the resultant PEoS-PHMG could act as promising alternative antibacterial materials with excellent broad-spectrum bacterial inhibition and favorable biocompatibility.
