Objective:To investigate whether Buthus martensii karsch(Scorpiones),Scolopendra subspinipes mutilans L.Koch(Scolopendra)and Gekko gecko Linnaeus(Gekko)could ameliorate the hypoxic tumor microenvironment and inhibit l...Objective:To investigate whether Buthus martensii karsch(Scorpiones),Scolopendra subspinipes mutilans L.Koch(Scolopendra)and Gekko gecko Linnaeus(Gekko)could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α(PI3K/AKT/mTOR/HIF-1α)signaling pathway.Methods:Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models,with rapamycin and cyclophosphamide as positive controls.Carboxy methyl cellulose solutions of Scorpiones,Scolopendra and Gekko were administered intragastrically as 0.33,0.33,and 0.83 g/kg,respectively once daily for 21 days.Fluorescent expression were detected every 7 days after inoculation,and tumor growth curves were plotted.Immunohistochemistry was performed to determine CD31 and HIF-1αexpressions in tumor tissue and microvessel density(MVD)was analyzed.Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1αsignaling pathway-related proteins.Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor(bFGF),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in mice.Results:Scorpiones,Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α(all P<0.01).Moreover,Scorpiones,Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase(p70S6K)(P<0.05 or P<0.01).In addition,they also decreased the expression of CD31,MVD,bFGF,TGF-β1 and VEGF compared with the model group(P<0.05 or P<0.01).Conclusion:Scorpiones,Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1αsignaling pathway.展开更多
Objective:To evaluate the association between Chinese medicine(CM)therapy and disease-free survival(DFS)outcomes in postoperative patients with non-small cell lung cancer(NSCLC).Methods:This multiple-center prospectiv...Objective:To evaluate the association between Chinese medicine(CM)therapy and disease-free survival(DFS)outcomes in postoperative patients with non-small cell lung cancer(NSCLC).Methods:This multiple-center prospective cohort study was conducted in 13 medical centers in China.Patients with stage I,II,or IDA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network(NCCN)guidelines were recruited.The recruited patients were divided into a CM treatment group and a control group according to their wishes.Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression.Patients in the control group received CM therapy for less than 1 month.Follow-up was 8nducted over 3 years.The primary outcome was DFS,with recurrence/metastasis rates as a secondary outcome.Results:Between May 2013 and August 2016,503 patients were enrolled into the cohort;266 were classified in the CM treatment group and 237 in the control group.Adjusting for covariates,high exposure to CM was associated with better DFS[hazard ratio(HR)=0.417,95%confidential interval(Cl):0.307-0.567)].A longer duration of CM therapy(6-12 months,12-18 months,>24 months)was associated with lower recurrence and metastasis rates(HR=0.225,0.119 and 0.083,respectively).In a subgroup exploratory analysis,CM therapy was also a protective factor of cancer recurrence and metastasis in both stage n-MA(HR=0.50,95%Cl:0.37-0.67)and stage IDA NSCLC postoperative patients(HR=0.48,95%Cl:0.33-0.71),DFS was even longer among CM treatment group patients.Conclusions:Lon ger duration of CM therapy could be 8nsidered a protective factor of cancer recurrence and metastasis.CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China.展开更多
Objective： To observe the intervention effect of Shugan Jianpi Formula （疏肝健脾方,SGJPF） on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the developme...Objective： To observe the intervention effect of Shugan Jianpi Formula （疏肝健脾方,SGJPF） on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. Metkods： The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups： normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF＋chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine （GEM）, and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell （MDSC） in the mouse spleen, T cell subsets, and the early apoptosis of CD8~ T cells, Results： The SGJPF＋GEM group had the highest inhibition rate and the longest survival time （P〈0.01）. The MDSC level and the apoptosis rate of CD8＊ T cells was the highest in the SGJPF＋GEM group （P〈0.05）. Conclusions： Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8＊ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.展开更多
基金Supported by the Special Scientific Research Project of the Chinese Medicine Industry of the State Administration of Traditional Chinese Medicine of China(No.201307006)National Natural Science Foundation of China(No.82104656,82004179,82074405)Fundamental Research Funds for the Central Public Welfare Research Institutes(No.ZZ14-YQ-013,ZZ15-YQ-024)。
文摘Objective:To investigate whether Buthus martensii karsch(Scorpiones),Scolopendra subspinipes mutilans L.Koch(Scolopendra)and Gekko gecko Linnaeus(Gekko)could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α(PI3K/AKT/mTOR/HIF-1α)signaling pathway.Methods:Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models,with rapamycin and cyclophosphamide as positive controls.Carboxy methyl cellulose solutions of Scorpiones,Scolopendra and Gekko were administered intragastrically as 0.33,0.33,and 0.83 g/kg,respectively once daily for 21 days.Fluorescent expression were detected every 7 days after inoculation,and tumor growth curves were plotted.Immunohistochemistry was performed to determine CD31 and HIF-1αexpressions in tumor tissue and microvessel density(MVD)was analyzed.Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1αsignaling pathway-related proteins.Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor(bFGF),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in mice.Results:Scorpiones,Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α(all P<0.01).Moreover,Scorpiones,Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase(p70S6K)(P<0.05 or P<0.01).In addition,they also decreased the expression of CD31,MVD,bFGF,TGF-β1 and VEGF compared with the model group(P<0.05 or P<0.01).Conclusion:Scorpiones,Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1αsignaling pathway.
基金Supported by Special Funded Projects of the TCM Industry(No.201307006)National Natural Science Foundation of China(No.81473467)Beijing Natural Science Fund(No.7192181)
文摘Objective:To evaluate the association between Chinese medicine(CM)therapy and disease-free survival(DFS)outcomes in postoperative patients with non-small cell lung cancer(NSCLC).Methods:This multiple-center prospective cohort study was conducted in 13 medical centers in China.Patients with stage I,II,or IDA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network(NCCN)guidelines were recruited.The recruited patients were divided into a CM treatment group and a control group according to their wishes.Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression.Patients in the control group received CM therapy for less than 1 month.Follow-up was 8nducted over 3 years.The primary outcome was DFS,with recurrence/metastasis rates as a secondary outcome.Results:Between May 2013 and August 2016,503 patients were enrolled into the cohort;266 were classified in the CM treatment group and 237 in the control group.Adjusting for covariates,high exposure to CM was associated with better DFS[hazard ratio(HR)=0.417,95%confidential interval(Cl):0.307-0.567)].A longer duration of CM therapy(6-12 months,12-18 months,>24 months)was associated with lower recurrence and metastasis rates(HR=0.225,0.119 and 0.083,respectively).In a subgroup exploratory analysis,CM therapy was also a protective factor of cancer recurrence and metastasis in both stage n-MA(HR=0.50,95%Cl:0.37-0.67)and stage IDA NSCLC postoperative patients(HR=0.48,95%Cl:0.33-0.71),DFS was even longer among CM treatment group patients.Conclusions:Lon ger duration of CM therapy could be 8nsidered a protective factor of cancer recurrence and metastasis.CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China.
基金Supported by the National Natural Science Foundation of China(No.81273946 and No.81072802)the National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(No.2013ZX09303301)
文摘Objective： To observe the intervention effect of Shugan Jianpi Formula （疏肝健脾方,SGJPF） on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. Metkods： The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups： normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF＋chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine （GEM）, and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell （MDSC） in the mouse spleen, T cell subsets, and the early apoptosis of CD8~ T cells, Results： The SGJPF＋GEM group had the highest inhibition rate and the longest survival time （P〈0.01）. The MDSC level and the apoptosis rate of CD8＊ T cells was the highest in the SGJPF＋GEM group （P〈0.05）. Conclusions： Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8＊ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.
