Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemo...Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring.This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy(HCT)for advanced patients with non-small cell lung cancer(NSCLC),especially those with malignant pleural effusion.Methods:We retrospectively evaluated medical records of 93 patients with advanced NSCLC(stage IIIB-IV)from March 2011 to January 2014.The patients were divided into HCT and chemotherapy(CT)groups.The HCT group was treated with gemcitabine and cisplatin(GP)regimen combined with regional radiofrequency deep hyperthermia,while the CT group was treated with GP regimen only.Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not.Clinical treatment results and adverse reactions were compared and analyzed after treatment.SPSS 19.0 software(SPSS Inc.,USA)was used for statistical data processing.P values less than 0.05 were accepted to be statistically significant.Results:Among the 93 patients,HCT group included 48 patients(16 patients with malignant pleural effusion),CT group included 45 patients(10 patients with malignant pleural effusion).There was no significant difference between the two groups in patient characteristics.The overall response rate(ORR)of pleural effusions was much better in HCT group than that in CT group(81.2%vs.40.0%,P=0.046).The patients in HCT group had lower incidence rate of weakness(12.5%us.46.7%,χ^2=13.16,P<0.001)and gastrointestinal(25.0%vs.77.8%,χ^2=25.88,P<0.001)adverse reactions than that in CT group.The objective tumor response and survival showed no significant differences.Conclusions:Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients.Al展开更多
In recent years,immune checkpoint inhibitors(ICIs)have made breakthroughs in the field of lung cancer and have become a focal point for research.Programmed death-1(PD-1)or programmed death-ligand 1(PD-L1)inhibitor mon...In recent years,immune checkpoint inhibitors(ICIs)have made breakthroughs in the field of lung cancer and have become a focal point for research.Programmed death-1(PD-1)or programmed death-ligand 1(PD-L1)inhibitor monotherapy was the first to break the treatment pattern for non-small cell lung cancer(NSCLC).However,owing to the limited benefit of ICI monotherapy at the population level and its hyper-progressive phenomenon,it may not meet clinical needs.To expand the beneficial range of immunotherapy and improve its efficacy,several research strategies have adopted the use of combination immunotherapy.At present,multiple strategies,such as PD-1/PD-L1 inhibitors combined with chemotherapy,anti-angiogenic therapy,cytotoxic T-lymphocyte-associated protein 4 inhibitors,and radiotherapy,as well as combined treatment with new target drugs,have been evaluated for clinical practice.To further understand the current status and future development direction of immunotherapy,herein,we review the recent progress of ICI combination therapies for NSCLC.展开更多
Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows t...Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system.The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research.Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells.Overall,these microenvironments create pre-and post-metastatic conditions for the progression of LMs.Herein,we reviewed the epidemiology,physiology,pathology and immunology,of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis.Additionally,we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations.These approaches target liver elements as the basis for future clinical trials,including combinatorial interventions reported to resolve hepatic immune suppression,such as immunotherapy plus chemotherapy,immunotherapy plus radiotherapy,immunotherapy plus anti-angiogenesis therapy,and surgical resection.展开更多
In order to improve the meat production performance of local sheep varieties in Gansu Province, Dorset was introduced to crossbreed with the local sheep varieties, including Tan sheep, Small Tail Han sheep and Mongoli...In order to improve the meat production performance of local sheep varieties in Gansu Province, Dorset was introduced to crossbreed with the local sheep varieties, including Tan sheep, Small Tail Han sheep and Mongolia sheep. The offspring of different crossbreeding combinations were sampled randomly at different growth stages, and their growth and development traits were measured so as to screen out the best crossbreeding mode. The results showed that under the same crossbreeding mode, the growth rate of F3 was higher than that of F2, and of F2 was higher than that of F1. Among the F3 population, the growth rates of Dorset ×Han and Dorset × Mongolia hybrids were higher. Compared with those of Dorset ×Tan F3 hybrids, the body weights of male and female Dorset × Han and Dorset ×Mongolia F3 hybrids were increased by 5.59%, 4.40%, 5.93% and 3.76%, respectively. Among the F2 population, the growth rates of Dorset × Han and Dorset ×Mongolia hybrids were also higher. The body weights of male and female Dorset ×Han and Dorset × Mongolia F2 hybrids were higher than those of Dorset × Tan ×Han F2 hybrids by 5.99%, 3.67%, 9.80% and 5.00%, respectively. In the F1 population, the growth rates of Dorset × Han and Dorset × Mongolia hybrids were higher.Compared with those of Tan × Han F1 hybrids, the body weights of male and female Dorset × Han and Dorset × Mongolia F1 hybrids were increased by 11.32%,5.22%, 7.60% and 7.20%, respectively. Therefore, in the feeding area of Small Tai Han sheep, Mongolia sheep and Tan sheep, Dorset was the best sire for producing hybrid lambs. The economic benefit of crossbred offspring was obvious.展开更多
Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including sm...Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including small molecule inhibitors,viral therapies,cancer vaccines,and monoclonal antibodies.Among them,the unique advantages of small molecule inhibitors have made them a focus of attention in the drug discovery of glioblastoma.Currently,the most used chemotherapeutic agents are small molecule inhibitors that target key dysregulated signaling pathways in glioblastoma,including receptor tyrosine kinase,PI3K/AKT/mTOR pathway,DNA damage response,TP53 and cell cycle inhibitors.This review analyzes the therapeutic benefit and clinical development of novel small molecule inhibitors discovered as promising anti-glioblastoma agents by the related targets of these major pathways.Meanwhile,the recent advances in temozolomide resistance and drug combination are also reviewed.In the last part,due to the constant clinical failure of targeted therapies,this paper reviewed the research progress of other therapeutic methods for glioblastoma,to provide patients and readers with a more comprehensive understanding of the treatment landscape of glioblastoma.展开更多
Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after t...Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after the first-line chemoradiotherapy. Methods: The data of 67 LS-SCLC patients who received combined treatment of Chinese medicine(CM) and Western medicine(WM) between January 2013 and May 2020 at the outpatient clinic of Guang’anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method(Kaplan–Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. Results: The median PFS in the CM and WM combination treatment group and the WM group were 19 months(95% CI: 12.36–25.64) vs. 9 months(95% CI: 5.96–12.04), respectively, HR=0.43(95% CI: 0.27–0.69, P <0.001). The median OS in the CM and WM combination group and the WM group were 34.00 months(95% CI could not be calculated) vs. 18.63 months(95% CI: 16.43–20.84), respectively, HR=0.40(95% CI: 0.24–0.66, P<0.001). Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months(P<0.001). Conclusion: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone.(Registration No. Chi CTR2200056616)展开更多
Convincing evidence indicates that the existence of cancer stem cells （CSCs） within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, s...Convincing evidence indicates that the existence of cancer stem cells （CSCs） within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, simultaneous elimin- ation of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanopartides DTXLNPsRNA for simultaneous encapsulation of the conventional chemotherapeutic agent docetaxel （DTXL） and small interfering RNA （siRNA） targeting BMI-1 （siBMI-1）. We confirmed that nanopartides vrxLNPsiBMI-l effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DVXL NPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DVXLNpsiBMI-1; consequently, the sternness was reduced and chemosensitivity of CSCs to DTXL was enhanced, resulting in the elimination of CSCs. Therefore, via DTXLNPsiBMI-1, the combination of siBMI-1 and DTXL completely inhibited tumor growth and prevented a relapse by synergistic kiUing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.展开更多
Chemoimmunotherapy(CIT)is defined as standard first line treatment for chronic lymphocytic leukemia(CLL)patients while patients with unfavorable biological characteristics such as unmutated immunoglobulin heavy chain(...Chemoimmunotherapy(CIT)is defined as standard first line treatment for chronic lymphocytic leukemia(CLL)patients while patients with unfavorable biological characteristics such as unmutated immunoglobulin heavy chain(UM-IGHV)and TP53 aberration failed to benefit from it.The emergency of the small molecular targeted agents including Bruton’s tyrosine kinase(BTK)inhibitor(BTKi)leads to a brand-new era,from a CIT to a chemo-free era in CLL.However,the treatment of target agents is not enough to attain a deep remission and high rate of complete remission(CR),especially in patients with high risks.The long duration brought about problems,such as cost,drug resistance and toxicity.To benefit CLL in progression free survival(PFS)and long-term remission,exploration of time-limited therapies,mainly with BTKi plus CIT and BCL2i based combination therapy has become a mainstream in clinical trials.The time-limited combination therapy shed light on the promising potentiality to attain sustainable deep remission and partly overcame the risk factors,although long term follow-up is required to consolidate the conclusion.In this review,we intend to introduce key results of clinical trials with combination therapy,discuss the achievements and limitations and put forward future direction for clinical trial design in this field.展开更多
基金the Scientific Research Foundation of Shanxi Province Healthy Commission(No.2017068)Shanxi Province Science Foundation for Youths(No.201801D221259).
文摘Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring.This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy(HCT)for advanced patients with non-small cell lung cancer(NSCLC),especially those with malignant pleural effusion.Methods:We retrospectively evaluated medical records of 93 patients with advanced NSCLC(stage IIIB-IV)from March 2011 to January 2014.The patients were divided into HCT and chemotherapy(CT)groups.The HCT group was treated with gemcitabine and cisplatin(GP)regimen combined with regional radiofrequency deep hyperthermia,while the CT group was treated with GP regimen only.Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not.Clinical treatment results and adverse reactions were compared and analyzed after treatment.SPSS 19.0 software(SPSS Inc.,USA)was used for statistical data processing.P values less than 0.05 were accepted to be statistically significant.Results:Among the 93 patients,HCT group included 48 patients(16 patients with malignant pleural effusion),CT group included 45 patients(10 patients with malignant pleural effusion).There was no significant difference between the two groups in patient characteristics.The overall response rate(ORR)of pleural effusions was much better in HCT group than that in CT group(81.2%vs.40.0%,P=0.046).The patients in HCT group had lower incidence rate of weakness(12.5%us.46.7%,χ^2=13.16,P<0.001)and gastrointestinal(25.0%vs.77.8%,χ^2=25.88,P<0.001)adverse reactions than that in CT group.The objective tumor response and survival showed no significant differences.Conclusions:Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients.Al
基金the Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China(No.2020ZX09201-024).
文摘In recent years,immune checkpoint inhibitors(ICIs)have made breakthroughs in the field of lung cancer and have become a focal point for research.Programmed death-1(PD-1)or programmed death-ligand 1(PD-L1)inhibitor monotherapy was the first to break the treatment pattern for non-small cell lung cancer(NSCLC).However,owing to the limited benefit of ICI monotherapy at the population level and its hyper-progressive phenomenon,it may not meet clinical needs.To expand the beneficial range of immunotherapy and improve its efficacy,several research strategies have adopted the use of combination immunotherapy.At present,multiple strategies,such as PD-1/PD-L1 inhibitors combined with chemotherapy,anti-angiogenic therapy,cytotoxic T-lymphocyte-associated protein 4 inhibitors,and radiotherapy,as well as combined treatment with new target drugs,have been evaluated for clinical practice.To further understand the current status and future development direction of immunotherapy,herein,we review the recent progress of ICI combination therapies for NSCLC.
基金supported by the National Natural Science Foundation of China(Nos.82202989 and 82003089)the Regional Innovation Cooperation Project of the Sichuan Science and Technology Program(No.2021YFQ0029)+4 种基金the China Postdoctoral Science Foundation(No.2022M722279)the Sichuan Science and Technology Program(No.2023YFS0163)the Postdoctoral Research Project of West China Hospital,Sichuan University,Chengdu,China(No.2021HXBH045)Fundamental Research Funds for the Central Universities(No.2022SCU12063)the Sichuan University Postdoctoral Interdisciplinary Innovation Fund(awarded to Lingling Zhu).
文摘Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system.The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research.Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells.Overall,these microenvironments create pre-and post-metastatic conditions for the progression of LMs.Herein,we reviewed the epidemiology,physiology,pathology and immunology,of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis.Additionally,we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations.These approaches target liver elements as the basis for future clinical trials,including combinatorial interventions reported to resolve hepatic immune suppression,such as immunotherapy plus chemotherapy,immunotherapy plus radiotherapy,immunotherapy plus anti-angiogenesis therapy,and surgical resection.
文摘In order to improve the meat production performance of local sheep varieties in Gansu Province, Dorset was introduced to crossbreed with the local sheep varieties, including Tan sheep, Small Tail Han sheep and Mongolia sheep. The offspring of different crossbreeding combinations were sampled randomly at different growth stages, and their growth and development traits were measured so as to screen out the best crossbreeding mode. The results showed that under the same crossbreeding mode, the growth rate of F3 was higher than that of F2, and of F2 was higher than that of F1. Among the F3 population, the growth rates of Dorset ×Han and Dorset × Mongolia hybrids were higher. Compared with those of Dorset ×Tan F3 hybrids, the body weights of male and female Dorset × Han and Dorset ×Mongolia F3 hybrids were increased by 5.59%, 4.40%, 5.93% and 3.76%, respectively. Among the F2 population, the growth rates of Dorset × Han and Dorset ×Mongolia hybrids were also higher. The body weights of male and female Dorset ×Han and Dorset × Mongolia F2 hybrids were higher than those of Dorset × Tan ×Han F2 hybrids by 5.99%, 3.67%, 9.80% and 5.00%, respectively. In the F1 population, the growth rates of Dorset × Han and Dorset × Mongolia hybrids were higher.Compared with those of Tan × Han F1 hybrids, the body weights of male and female Dorset × Han and Dorset × Mongolia F1 hybrids were increased by 11.32%,5.22%, 7.60% and 7.20%, respectively. Therefore, in the feeding area of Small Tai Han sheep, Mongolia sheep and Tan sheep, Dorset was the best sire for producing hybrid lambs. The economic benefit of crossbred offspring was obvious.
基金We gratefully thank the support from the grants(Nos.82173652,81872728,81830105 and 81973207)of National Natural Science Foundation of China(Nos.BK20191411)of Natural Science Foundation of Jiangsu Province.
文摘Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including small molecule inhibitors,viral therapies,cancer vaccines,and monoclonal antibodies.Among them,the unique advantages of small molecule inhibitors have made them a focus of attention in the drug discovery of glioblastoma.Currently,the most used chemotherapeutic agents are small molecule inhibitors that target key dysregulated signaling pathways in glioblastoma,including receptor tyrosine kinase,PI3K/AKT/mTOR pathway,DNA damage response,TP53 and cell cycle inhibitors.This review analyzes the therapeutic benefit and clinical development of novel small molecule inhibitors discovered as promising anti-glioblastoma agents by the related targets of these major pathways.Meanwhile,the recent advances in temozolomide resistance and drug combination are also reviewed.In the last part,due to the constant clinical failure of targeted therapies,this paper reviewed the research progress of other therapeutic methods for glioblastoma,to provide patients and readers with a more comprehensive understanding of the treatment landscape of glioblastoma.
基金the Science and Technology Innovation Project of the China Academy of Chinese Medical Sciences(No.CI2021A01808)the Natural Science Foundation of Beijing(No.7212189)the Outstanding Young Scientific and Technological Talents(Innovation)Training Program of China Academy of Chinese Medical Sciences(No.ZZ15-YQ-026)。
文摘Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after the first-line chemoradiotherapy. Methods: The data of 67 LS-SCLC patients who received combined treatment of Chinese medicine(CM) and Western medicine(WM) between January 2013 and May 2020 at the outpatient clinic of Guang’anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method(Kaplan–Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. Results: The median PFS in the CM and WM combination treatment group and the WM group were 19 months(95% CI: 12.36–25.64) vs. 9 months(95% CI: 5.96–12.04), respectively, HR=0.43(95% CI: 0.27–0.69, P <0.001). The median OS in the CM and WM combination group and the WM group were 34.00 months(95% CI could not be calculated) vs. 18.63 months(95% CI: 16.43–20.84), respectively, HR=0.40(95% CI: 0.24–0.66, P<0.001). Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months(P<0.001). Conclusion: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone.(Registration No. Chi CTR2200056616)
文摘Convincing evidence indicates that the existence of cancer stem cells （CSCs） within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, simultaneous elimin- ation of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanopartides DTXLNPsRNA for simultaneous encapsulation of the conventional chemotherapeutic agent docetaxel （DTXL） and small interfering RNA （siRNA） targeting BMI-1 （siBMI-1）. We confirmed that nanopartides vrxLNPsiBMI-l effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DVXL NPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DVXLNpsiBMI-1; consequently, the sternness was reduced and chemosensitivity of CSCs to DTXL was enhanced, resulting in the elimination of CSCs. Therefore, via DTXLNPsiBMI-1, the combination of siBMI-1 and DTXL completely inhibited tumor growth and prevented a relapse by synergistic kiUing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.
基金grants from the National Natural Science Foundation of China(No.81970146)National Science Foundation of China International Cooperation and Exchange Program(No.81720108002)+1 种基金National Science and Technology Major Project(No.2018ZX09734007)Six Talent Peaks Project in Jiangsu Province,2019(No.WSN-001).
文摘Chemoimmunotherapy(CIT)is defined as standard first line treatment for chronic lymphocytic leukemia(CLL)patients while patients with unfavorable biological characteristics such as unmutated immunoglobulin heavy chain(UM-IGHV)and TP53 aberration failed to benefit from it.The emergency of the small molecular targeted agents including Bruton’s tyrosine kinase(BTK)inhibitor(BTKi)leads to a brand-new era,from a CIT to a chemo-free era in CLL.However,the treatment of target agents is not enough to attain a deep remission and high rate of complete remission(CR),especially in patients with high risks.The long duration brought about problems,such as cost,drug resistance and toxicity.To benefit CLL in progression free survival(PFS)and long-term remission,exploration of time-limited therapies,mainly with BTKi plus CIT and BCL2i based combination therapy has become a mainstream in clinical trials.The time-limited combination therapy shed light on the promising potentiality to attain sustainable deep remission and partly overcame the risk factors,although long term follow-up is required to consolidate the conclusion.In this review,we intend to introduce key results of clinical trials with combination therapy,discuss the achievements and limitations and put forward future direction for clinical trial design in this field.
