Objective: To study the mechanisms in gambogic acid (GA) -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro. Methods: The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki...Objective: To study the mechanisms in gambogic acid (GA) -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro. Methods: The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apopt0sis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting. Results: GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo- 1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bd-2 and Bax without cell cycle arresting. Conclusions: GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle.展开更多
The PACIFIC study ushered in a“tsunami-like”therapeutic revolution for stage III inoperable non-small cell lung cancer(NSCLC)In the past,chemoradiotherapy(CRT)has been the standard of care for inoperable stage III N...The PACIFIC study ushered in a“tsunami-like”therapeutic revolution for stage III inoperable non-small cell lung cancer(NSCLC)In the past,chemoradiotherapy(CRT)has been the standard of care for inoperable stage III NSCLC.Concurrent chemoradiotherapy(cCRT),if tolerable in patients,is the optimal treatment regimen.A meta-analysis has shown that cCRT results in a 5-year survival rate 4.5%longer than that with sequential chemoradiotherapy(sCRT)1.However,within 2 years after cCRT,approximately 30%of patients experience local recurrence,and approximately 40%develop distant metastasis2.Clinicians have explored induction chemotherapy3,consolidation chemotherapy4,and combination use with targeted drugs2,and found that none improve the prognosis.展开更多
Methotrexate,etoposide,dexamethasone,and pegaspargase(MESA)with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma,nasal type(NKTCL).We explored the efficacy and...Methotrexate,etoposide,dexamethasone,and pegaspargase(MESA)with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma,nasal type(NKTCL).We explored the efficacy and safety of reduced-intensity,non-intravenous etoposide,dexamethasone,and pegaspargase(ESA)with sandwiched radiotherapy.This multicenter,randomized,phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China.Patients were randomly assigned(1:1)to receive ESA(pegaspargase 2,500 IU/m^(2)intramuscularly on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4)or MESA(methotrexate 1 g/m^(2)intravenously on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4,and pegaspargase 2,500 IU/m^(2)intramuscularly on day 5)regimen(four cycles),combined with sandwiched radiotherapy.展开更多
The integrity of lysosomes is of vital importance to survival of tumor cells.We demonstrated that LW-218,a synthetic flavonoid,induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization i...The integrity of lysosomes is of vital importance to survival of tumor cells.We demonstrated that LW-218,a synthetic flavonoid,induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy.LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D,as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents,which can alter the activity of cathepsins.Lysophagy,was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB.LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator.Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy.LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1.Moreover,LW-218 inhibited the leukemia cell growth in vivo.Thus,the necessary impact of integral lysosomal function in cell rescue and death were illustrated.展开更多
基金supported by a grant from the Key Project supported by medical science and technology development Foundation of Nanjing Department of Health (No. ZKX09016)
文摘Objective: To study the mechanisms in gambogic acid (GA) -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro. Methods: The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apopt0sis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting. Results: GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo- 1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bd-2 and Bax without cell cycle arresting. Conclusions: GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle.
基金The study was supported by the National Natural Science Foundation of China(Grant No.82072562 to QZ)the High Level Hospital Construction Project(Grant No.DFJH201810 to QZ).
文摘The PACIFIC study ushered in a“tsunami-like”therapeutic revolution for stage III inoperable non-small cell lung cancer(NSCLC)In the past,chemoradiotherapy(CRT)has been the standard of care for inoperable stage III NSCLC.Concurrent chemoradiotherapy(cCRT),if tolerable in patients,is the optimal treatment regimen.A meta-analysis has shown that cCRT results in a 5-year survival rate 4.5%longer than that with sequential chemoradiotherapy(sCRT)1.However,within 2 years after cCRT,approximately 30%of patients experience local recurrence,and approximately 40%develop distant metastasis2.Clinicians have explored induction chemotherapy3,consolidation chemotherapy4,and combination use with targeted drugs2,and found that none improve the prognosis.
基金supported by the Union for China Lymphoma Investigators,and funded by the Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine(DLY201601)the National Key R&D Program of China(2022YFC 2502600)+3 种基金the National Natural Science Foundation of China(82130004,81830007,82070204,and 81670176)Chang Jiang Scholars Program,Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152206 and 20152208)the Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1032B)the Collaborative Innovation Center of Systems Biomedicine,and the Samuel Waxman Cancer Research Foundation.
文摘Methotrexate,etoposide,dexamethasone,and pegaspargase(MESA)with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma,nasal type(NKTCL).We explored the efficacy and safety of reduced-intensity,non-intravenous etoposide,dexamethasone,and pegaspargase(ESA)with sandwiched radiotherapy.This multicenter,randomized,phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China.Patients were randomly assigned(1:1)to receive ESA(pegaspargase 2,500 IU/m^(2)intramuscularly on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4)or MESA(methotrexate 1 g/m^(2)intravenously on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4,and pegaspargase 2,500 IU/m^(2)intramuscularly on day 5)regimen(four cycles),combined with sandwiched radiotherapy.
基金supported by the Nation Natural Science Foundation of China(81873046,81830105,81903647,81503096,and 81673461)the Drug Innovation Major Project(2017ZX09301014,2018ZX09711001-003-007,and 2017ZX09101003-005-023,China)+4 种基金Natural Science Foundation of Jiangsu province(BK20190560 and BE2018711,China)Nanjing Medical Science and Technology Development Project(YKK17074 and YKK19064,China)Research and Innovation Project for College Graduates of Jiangsu Province(KYCX180803,China)China Postdoctoral Science Foundation(No.2018M642373)“Double First-Class”University project(CPU 2018GF11 and CPU2018GF05,China)。
文摘The integrity of lysosomes is of vital importance to survival of tumor cells.We demonstrated that LW-218,a synthetic flavonoid,induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy.LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D,as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents,which can alter the activity of cathepsins.Lysophagy,was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB.LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator.Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy.LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1.Moreover,LW-218 inhibited the leukemia cell growth in vivo.Thus,the necessary impact of integral lysosomal function in cell rescue and death were illustrated.