BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dys...BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dysfunction(EAD).Liver volumetry is performed routinely in living donor LT,but rarely in deceased donor LT(DDLT),which amplifies the adverse effects of DRSM in DDLT.Due to the various shortcomings of traditional manual liver volumetry and formula methods,a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional(IQQA-3D)for estimating the degree of DRSM is needed.AIM To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management.METHODS We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume(TLV)(sTLV)and established an estimation TLV(eTLV)index(eTLVi)model.Receiver operating characteristic(ROC)curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV(called sTLVi).The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis.Finally,the eTLVi model was compared with the sTLVi model through the ROC curve for verification.RESULTS A total of 133 patients were included in the analysis.The Changzheng formula was accurate for calculating donor sTLV(P=0.083)but not for recipient sTLV(P=0.036).Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV(P=0.221).Alcoholic liver disease,gastrointestinal bleeding,and sTLVi>1.24 were independent risk factors for massive IBL,and drug-induced liver failure was an independent protective factor for massive IBL.Male donor-female recipient combination,model for end-stage liver disease score,sTLVi≤0.85,and sTLVi≥1.32 were independent risk factors for EAD,and viral hepatitis was an independent protective factor for EAD.The overall survival of patients in the 0.85<sTLVi<1.32 group was better compared to the sTLVi≤0.85 group and sTLVi≥1.32 group(P<0.001).There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD(all P>0.05).CONCLUSION IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT.We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.展开更多
BACKGROUND Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challengi...BACKGROUND Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.展开更多
BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients ...BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.展开更多
Background:Inflammation is often related to cancer,and several inflammatory scores have been established to predict the prognosis of various types of cancer.Our study aimed to determine the prognostic value of the pre...Background:Inflammation is often related to cancer,and several inflammatory scores have been established to predict the prognosis of various types of cancer.Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio(LCR)for predicting postoperative outcomes in patients with resectable gallbladder cancer(GBC).Methods:A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital,Affiliated to Shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed.A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers.Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival.Results:Among the assessed variables,the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients(AUC:0.736).Decreased preoperative LCR was significantly associated with advanced tumor stage,including tumor invasion(P=0.018),lymph node metastasis(P=0.011)and TNM stage(P=0.022).A low preoperative LCR(cutoff threshold=145.5)was an independent risk factor for overall survival in patients with resectable GBC(P<0.001).Conclusions:The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.展开更多
Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer develop-ment and progression.The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-...Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer develop-ment and progression.The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer.Howeve-r,little is known about the functional targets and regulatory mechanism of QKI-5.Here,we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3(ADD3)significantly correlates with a poor prognosis in lung cancer.QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14.Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis,we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner.By binding to multiple sites in an upstream intron region,QKI-5 represses the splicing of ADD3 exon 14.We also identified several QKI mutations in tumors,which cause dysregulation of the splicing of QKI targets ADD3 and NUMB.Taken together,our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event,which underlies in part the tumor suppressor function of QKI.展开更多
Gallbladder cancer(GBC)is rare,but is the most malignant type of biliary tract tumor.Unfortunately,only a small population of cancer patients is acceptable for the surgical resection,the current effective regimen;thus...Gallbladder cancer(GBC)is rare,but is the most malignant type of biliary tract tumor.Unfortunately,only a small population of cancer patients is acceptable for the surgical resection,the current effective regimen;thus,the high mortality rate has been static for decades.To substantially circumvent the stagnant scenario,a number of therapeutic approaches owing to the creation of advanced technologic measures(e.g.,next-generation sequencing,transcriptomics,proteomics)have been intensively innovated,which include targeted therapy,immunotherapy,and nanoparticle-based delivery systems.In the current review,we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC.Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease,ultimately improving the efficacy of treatment.展开更多
Background:Hepatopancreatoduodenectomy(HPD)has been considered the only curative treatment for metastatic cholangiocarcinoma and some locally advanced gallbladder cancers(GBCs).However,HPD has not yet been included in...Background:Hepatopancreatoduodenectomy(HPD)has been considered the only curative treatment for metastatic cholangiocarcinoma and some locally advanced gallbladder cancers(GBCs).However,HPD has not yet been included in treatment guidelines as a standard surgical procedure in consideration of its morbidity and mortality rates.The aim of this study was to evaluate the safety and effectiveness of HPD in treating biliary malignancies.Methods:The medical records of 57 patients with advanced biliary cancer undergoing HPD from January 2009 to December 2019 were retrospectively retrieved.A case-control analysis was conducted at our department.Patients with advanced GBC who underwent HPD(HPD-GBC group)were compared with a control group(None-HPD-GBC group).Baseline characteristics,preoperative treatments,tumor pathologic features,operative results,and prognosis were assessed.Results:Thirteen patients with cholangiocarcinoma and 44 patients with GBC underwent HPD at our department.Significant postoperative complications(grade III or greater)and postoperative pancreatic fistula were observed in 24(42.1%)and 15(26.3%)patients,respectively.One postoperative death occurred in the present study.Overall survival(OS)was longer in patients with advanced cholangiocarcinoma than in those with GBC(median survival time[MST],31 months vs.11 months;P<0.001).In the subgroup analysis of patients with advanced GBC,multivariate analysis demonstrated that T4 stage tumors(P=0.012),N2 tumors(P=0.001),and positive margin status(P=0.004)were independently associated with poorer OS.Patients with either one or more prognostic factors exhibited a shorter MST than patients without those prognostic factors(P<0.001).Conclusion:HPD could be performed with a relatively low mortality rate and an acceptable morbidity rate in an experienced highvolume center.For patients with advanced GBC without an N2 or T4 tumor,HPD can be a preferable treatment option.展开更多
Dear Editor,Gallbladder cancer(GBC),the most common malignant tumor of the biliary tract,is a highly invasive form of cancer.Surgical resection is currently the first line approach to effectively treat GBC;however,ver...Dear Editor,Gallbladder cancer(GBC),the most common malignant tumor of the biliary tract,is a highly invasive form of cancer.Surgical resection is currently the first line approach to effectively treat GBC;however,very few patients have the opportunity to receive radical surgical treatment due to lack of obvious symptoms.1 The median survival of patients with GBC is only 12 months and 5-year survival rate is<5%,indicating GBC is extremely poor prognosis.Therefore,it is urgent to identify novel key molecules that can potentially serve as early diagnostic biomarkers and/or therapeutic targets.The current study focused on the potential role of bone morphogenetic protein 2 inducible kinase(BMP2K),a serine/threonine kinase,which was recently identified as clathrin-coated vesicle-associated protein in the development of GBC;the outcome may hold diagnostic and therapeutic promising for clinical practice.展开更多
Background:The first-line chemotherapy regimen for advanced gallbladder cancer(GBC)is gemcitabine plus platinum(GP),despite its efficacy is limited.The current investigation is a retrospective study to compare the saf...Background:The first-line chemotherapy regimen for advanced gallbladder cancer(GBC)is gemcitabine plus platinum(GP),despite its efficacy is limited.The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX(mFOLFIRINOX)and gemcitabine plus oxaliplatin(GEMOX)as the first-line chemotherapy for unresectable locally advanced or metastatic GBC.Methods:The data of patients with unresectable locally advanced or metastatic GBC,who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,were retrieved.This retrospective study evaluated the clinical characteristics,survival outcomes and adverse events.Results:A total of 44 patients(n=25 in mFOLFIRINOX,n=19 in GEMOX)were included.There were no significant differences between groups in baseline characteristics.The median progression free survival(mPFS)was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group[P=0.021;hazard ratio(HR),0.499;95%CI,0.266 to 0.937].The median overall survival(mOS)was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group(P=0.019;HR,0.471;95%CI,0.239 to 0.929).Disease control rate(DCR)was 76.0%in the mFOLFIRINOX group and 47.4%in the GEMOX group(P=0.051).The rate of grade 3-4 adverse events was 48%in the mFOLFIRINOX group and 36.8%in the GEMOX group(P=0.459).The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group,while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group.Conclusions:mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC,and the results need to be further verified by prospective clinical studies.展开更多
Serving as a host factor for human immunodeficiency virus(HIV)integration,LEDGF/p75 has been under extensive study as a potential target for therapy.However,as a highly conserved protein,its physiological function rem...Serving as a host factor for human immunodeficiency virus(HIV)integration,LEDGF/p75 has been under extensive study as a potential target for therapy.However,as a highly conserved protein,its physiological function remains to be thoroughly elucidated.Here,we characterize the molecular function of dP75,the Drosophila homolog of LEDGF/p75,during oogenesis.dP75 binds to transcriptionally active chromatin with its PWWP domain.The C-terminus integrase-binding domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes it in vivo.Together with Jil-1,dP75 prevents the spreading of the heterochromatin mark-H3 K9 me2-onto genes required for oogenesis and piRNA production.Without dP75,ectopical silencing of these genes disrupts oogenesis,activates transposons,and causes animal sterility.We propose that dP75,the homolog of an HIV host factor in Drosophila,partners with and stabilizes Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading.展开更多
基金Supported by National Natural Science Foundation of China,No.82172628。
文摘BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dysfunction(EAD).Liver volumetry is performed routinely in living donor LT,but rarely in deceased donor LT(DDLT),which amplifies the adverse effects of DRSM in DDLT.Due to the various shortcomings of traditional manual liver volumetry and formula methods,a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional(IQQA-3D)for estimating the degree of DRSM is needed.AIM To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management.METHODS We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume(TLV)(sTLV)and established an estimation TLV(eTLV)index(eTLVi)model.Receiver operating characteristic(ROC)curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV(called sTLVi).The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis.Finally,the eTLVi model was compared with the sTLVi model through the ROC curve for verification.RESULTS A total of 133 patients were included in the analysis.The Changzheng formula was accurate for calculating donor sTLV(P=0.083)but not for recipient sTLV(P=0.036).Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV(P=0.221).Alcoholic liver disease,gastrointestinal bleeding,and sTLVi>1.24 were independent risk factors for massive IBL,and drug-induced liver failure was an independent protective factor for massive IBL.Male donor-female recipient combination,model for end-stage liver disease score,sTLVi≤0.85,and sTLVi≥1.32 were independent risk factors for EAD,and viral hepatitis was an independent protective factor for EAD.The overall survival of patients in the 0.85<sTLVi<1.32 group was better compared to the sTLVi≤0.85 group and sTLVi≥1.32 group(P<0.001).There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD(all P>0.05).CONCLUSION IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT.We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.
基金Supported by the National Natural Science Foundation of China,No.31600075
文摘BACKGROUND Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.
基金National Natural Science Foundation of China(General Program),No.31620103910National Natural Science Foundation of China(Key Program),No.81874181+3 种基金National Health Commission of China,No.2019ZX09301158Shanghai Municipal Commission of Economy and Informatization,No.2019RGZN01096Shanghai Shenkang Hospital Development Center,No.12018107and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.19XHCR13D.
文摘BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.
基金supported by grants from the National Natural Science Foundation of China(81974371)the Emerging Frontier Program of Hospital Development Center(SHDC12018107)+6 种基金the General Surgery Construction Program of Shanghai Municipal Health Commission(2017ZZ02011)the Project of Excellent Young Scholars from Shanghai Municipal Health and Family Planning Commission(2018YQ10)the Talent Development Fund from Shanghai Municipal Human Resources and Social Security Bureau(2018048)the Experiment Animal Program of Shanghai Science and Technology Committee Innovative(19140902700)Research Team of High-level Local Universities in ShanghaiShanghai Key Laboratory of Biliary Tract Disease Research Foundation(17DZ2260200)the National Science and Technology Major Project(2019ZX09301-158)。
文摘Background:Inflammation is often related to cancer,and several inflammatory scores have been established to predict the prognosis of various types of cancer.Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio(LCR)for predicting postoperative outcomes in patients with resectable gallbladder cancer(GBC).Methods:A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital,Affiliated to Shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed.A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers.Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival.Results:Among the assessed variables,the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients(AUC:0.736).Decreased preoperative LCR was significantly associated with advanced tumor stage,including tumor invasion(P=0.018),lymph node metastasis(P=0.011)and TNM stage(P=0.022).A low preoperative LCR(cutoff threshold=145.5)was an independent risk factor for overall survival in patients with resectable GBC(P<0.001).Conclusions:The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.
基金This work was supported by the National Natural Science Foundation of China(31661143035,31770881,and 32071288)the National Basic Research Program of China(2017YFA0504400)to J.H.
文摘Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer develop-ment and progression.The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer.Howeve-r,little is known about the functional targets and regulatory mechanism of QKI-5.Here,we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3(ADD3)significantly correlates with a poor prognosis in lung cancer.QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14.Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis,we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner.By binding to multiple sites in an upstream intron region,QKI-5 represses the splicing of ADD3 exon 14.We also identified several QKI mutations in tumors,which cause dysregulation of the splicing of QKI targets ADD3 and NUMB.Taken together,our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event,which underlies in part the tumor suppressor function of QKI.
基金thank Andy Cumming for providing language assistance.This study was supported in part by Sao Paulo Research Foundation(FAPESP),Grants#2015/09324-9,#15/02200-2,#14/50947-7,and#13/08135-2support also came in part from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior—Brasil(CAPES),and support also came in part from the National Counsel of Technological and Scientific Development(CNPq).
文摘Gallbladder cancer(GBC)is rare,but is the most malignant type of biliary tract tumor.Unfortunately,only a small population of cancer patients is acceptable for the surgical resection,the current effective regimen;thus,the high mortality rate has been static for decades.To substantially circumvent the stagnant scenario,a number of therapeutic approaches owing to the creation of advanced technologic measures(e.g.,next-generation sequencing,transcriptomics,proteomics)have been intensively innovated,which include targeted therapy,immunotherapy,and nanoparticle-based delivery systems.In the current review,we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC.Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease,ultimately improving the efficacy of treatment.
基金the Shanghai Key Laboratory of Biliary Tract Disease Research Foundation(No.17DZ2260200)the National Natural Science Foundation of China(Nos.81502433,81773043,91440203,81702315)+3 种基金the Clinical research program of Xinhua Hospital(No.19XHCR3D)the Multi-center clinical research project of Shanghai Jiaotong University School of Medicine(No.DLY201507)the Project of Excellent Young Scholars from Shanghai Municipal Health and Family Planning Commission(No.2018YQ10)the Talent Development Fund from Shanghai Municipal Human Resources and Social Security Bureau(No.2018048).
文摘Background:Hepatopancreatoduodenectomy(HPD)has been considered the only curative treatment for metastatic cholangiocarcinoma and some locally advanced gallbladder cancers(GBCs).However,HPD has not yet been included in treatment guidelines as a standard surgical procedure in consideration of its morbidity and mortality rates.The aim of this study was to evaluate the safety and effectiveness of HPD in treating biliary malignancies.Methods:The medical records of 57 patients with advanced biliary cancer undergoing HPD from January 2009 to December 2019 were retrospectively retrieved.A case-control analysis was conducted at our department.Patients with advanced GBC who underwent HPD(HPD-GBC group)were compared with a control group(None-HPD-GBC group).Baseline characteristics,preoperative treatments,tumor pathologic features,operative results,and prognosis were assessed.Results:Thirteen patients with cholangiocarcinoma and 44 patients with GBC underwent HPD at our department.Significant postoperative complications(grade III or greater)and postoperative pancreatic fistula were observed in 24(42.1%)and 15(26.3%)patients,respectively.One postoperative death occurred in the present study.Overall survival(OS)was longer in patients with advanced cholangiocarcinoma than in those with GBC(median survival time[MST],31 months vs.11 months;P<0.001).In the subgroup analysis of patients with advanced GBC,multivariate analysis demonstrated that T4 stage tumors(P=0.012),N2 tumors(P=0.001),and positive margin status(P=0.004)were independently associated with poorer OS.Patients with either one or more prognostic factors exhibited a shorter MST than patients without those prognostic factors(P<0.001).Conclusion:HPD could be performed with a relatively low mortality rate and an acceptable morbidity rate in an experienced highvolume center.For patients with advanced GBC without an N2 or T4 tumor,HPD can be a preferable treatment option.
基金supported by Shanghai Key Laboratory of Biliary Tract Disease Research Foundation(17DZ2260200)the National Natural Science Foundation of China(Nos.81572819,91940305,81773043,91440203,81702315)+4 种基金the Peak Plateau Discipline Construction Project of Shanghai Jiao Tong University School of medicine(No.20181808)the development fund for Shanghai talents(No.201608)Shanghai Sailing Program(17YF1411700)the Program of Shanghai Academic Research Leader(No.19XD1422700)the Precision Medicine Research Program of Shanghai Jiao Tong University School of Medicine(Nos.15ZH4003,DKY201507)。
文摘Dear Editor,Gallbladder cancer(GBC),the most common malignant tumor of the biliary tract,is a highly invasive form of cancer.Surgical resection is currently the first line approach to effectively treat GBC;however,very few patients have the opportunity to receive radical surgical treatment due to lack of obvious symptoms.1 The median survival of patients with GBC is only 12 months and 5-year survival rate is<5%,indicating GBC is extremely poor prognosis.Therefore,it is urgent to identify novel key molecules that can potentially serve as early diagnostic biomarkers and/or therapeutic targets.The current study focused on the potential role of bone morphogenetic protein 2 inducible kinase(BMP2K),a serine/threonine kinase,which was recently identified as clathrin-coated vesicle-associated protein in the development of GBC;the outcome may hold diagnostic and therapeutic promising for clinical practice.
基金This work was supported by the National Natural Science Foundation of China(grant numbers 31620103910,81874181,82073206,81773043)the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(grant number 2019ZX09301158)+4 种基金Emerging Frontier Projects of Shanghai-Level Hospitals(grant number SHDC12018107)“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(grant number 20SG14)the Program of Shanghai Academic Research Leader(grant number 19XD1422700)the Peak Plateau Discipline Construction Project of Shanghai Jiaotong University School of Medicine(grant number 20181808)Clinical Research Program of Xinhua Hospital(19XHCR3D).
文摘Background:The first-line chemotherapy regimen for advanced gallbladder cancer(GBC)is gemcitabine plus platinum(GP),despite its efficacy is limited.The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX(mFOLFIRINOX)and gemcitabine plus oxaliplatin(GEMOX)as the first-line chemotherapy for unresectable locally advanced or metastatic GBC.Methods:The data of patients with unresectable locally advanced or metastatic GBC,who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,were retrieved.This retrospective study evaluated the clinical characteristics,survival outcomes and adverse events.Results:A total of 44 patients(n=25 in mFOLFIRINOX,n=19 in GEMOX)were included.There were no significant differences between groups in baseline characteristics.The median progression free survival(mPFS)was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group[P=0.021;hazard ratio(HR),0.499;95%CI,0.266 to 0.937].The median overall survival(mOS)was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group(P=0.019;HR,0.471;95%CI,0.239 to 0.929).Disease control rate(DCR)was 76.0%in the mFOLFIRINOX group and 47.4%in the GEMOX group(P=0.051).The rate of grade 3-4 adverse events was 48%in the mFOLFIRINOX group and 36.8%in the GEMOX group(P=0.459).The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group,while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group.Conclusions:mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC,and the results need to be further verified by prospective clinical studies.
基金supported by the National Natural Science Foundation of China(2019XH004,81874181,82073206,21705108,and 81773043)the Emerging Frontier Program of Hospital Development Centre(SHDC12018107)+4 种基金the Key Program of Shanghai Science and Technology Commission(YDZX20193100004049)the State Key Laboratory of Oncogenes and Related Genes(KF2120)the National Key Research and Development Program of China(2021YFE0203300)the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG14)he Program of Shanghai Academic Research Leader(19XD1422700)。
基金supported by the grant from the NIH to Z.Z.(DP5OD021355)the National Natural Science Foundation of China(91940302 and 31870741 to Y.H.)。
文摘Serving as a host factor for human immunodeficiency virus(HIV)integration,LEDGF/p75 has been under extensive study as a potential target for therapy.However,as a highly conserved protein,its physiological function remains to be thoroughly elucidated.Here,we characterize the molecular function of dP75,the Drosophila homolog of LEDGF/p75,during oogenesis.dP75 binds to transcriptionally active chromatin with its PWWP domain.The C-terminus integrase-binding domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes it in vivo.Together with Jil-1,dP75 prevents the spreading of the heterochromatin mark-H3 K9 me2-onto genes required for oogenesis and piRNA production.Without dP75,ectopical silencing of these genes disrupts oogenesis,activates transposons,and causes animal sterility.We propose that dP75,the homolog of an HIV host factor in Drosophila,partners with and stabilizes Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading.
