Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune respons...Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.展开更多
Introduction:Hepatitis B virus(HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B(hepatitis B surface antigen[HBsAg]-negative and hepatitis B core antibody[HBcAb]-positive).This ...Introduction:Hepatitis B virus(HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B(hepatitis B surface antigen[HBsAg]-negative and hepatitis B core antibody[HBcAb]-positive).This study aimed to assess HBV reaaivation and hepatitis occurrence in diffuse large B-cell lymphoma(DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reaaivation and hepatitis occurrence and to analyze whether HBV reaaivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.Methods:We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center,China.Prediaive faaors for HBV reaaivation,hepatitis development,and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.Results:Among the 278 patients,165 were HBsAg-negative.Among these 165 patients,6(10.9%) of 55 HBcAb-positive(resolved HBV infeaion) patients experienced HBV reactivation compared with none(0%) of 110 HBcAb-negative patients(P=0.001).Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients(21.8%vs.8.2%,P = 0.013).HBcAb positivity and elevated baseline alanine aminotransferase(ALT) levels were independent risk factors for hepatitis.Among the 55 patients with resolved hepatitis B,patients with elevated baseline serum ALT or aspartate aminotransferase(AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels(P = 0.037,P = 0.005,respeaively).An elevated baseline AST level was an independent risk factor for hepatitis in these patients.Six patients with HBV reactivation recovered after immediate antiviral therapy,and chemotherapy was continued.HBcAb positivity,HBV reactivation,or hepatitis did not negatively affect the survival of DLBCL patients.Conclusions:DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reaaivation and hepatitis than HBsAg-negative/HBcAb-negative patients.Close monitoring and prompt antiviral therapy are required in these patients.展开更多
Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL pa...Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.展开更多
Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug resistance.We aimed to in...Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug resistance.We aimed to investigate the potential mechanisms of drug resistance in adults with T-LBL.Methods:Gene expression microarray was used to identify differential mRNA expression profiles between chemotherapy-resistant and chemotherapy-sensitive adult T-LBL tissues.Real-time PCR and immunohistochemistry were performed to detect the expression of bromodomain-containing protein 2(BRD2)and c-Myc in fresh-frozen T-LBL tissues from 85 adult patients.The Ras pull-down assay was performed to monitor Ras activation.Chromatin immunoprecipitation assays were used to analyze the binding of E2F transcription factor 1(E2F1)/BRD2 to the RAS guanyl releasing protein 1(RasGRP1)promoter region.The drug resistance effect and mechanism of BRD2 were determined by both in vivo and in vitro studies.Results:A total of 86 chemotherapy resistance-related genes in adult T-LBL were identified by gene expression microarray.Among them,BRD2 was upregulated in chemotherapy-resistant adult T-LBL tissues and associated with worse progressionfree survival and overall survival of 85 adult T-LBL patients.Furthermore,BRD2 suppressed doxorubicin(Dox)-induced cell apoptosis both in vitro and in vivo.The activation of RasGRP1/Ras/ERK signaling might contribute to the Dox resistance effect of BRD2.Besides,OTX015,a bromodomain and extra-terminal(BET)inhibitor,reversed the Dox resistance effect of BRD2.Patient-derived tumor xenograft demonstrated that the sequential use of OTX015 after Dox showed superior therapeutic effects.Conclusions:Our data showed that BRD2 promotes drug resistance in adult T-LBL through the RasGRP1/Ras/ERK signaling pathway.Targeting BRD2 may be a novel strategy to improve the therapeutic efficacy and prolong survival of adults with TLBL.展开更多
Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates s...Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates signifi-cantly with treatment response and survival.In the current study we examined the potential role of IL-2Rαby over-expressing IL-2Rαin representative cell lines.Methods:Levels of IL-2Rαwere evaluated in the human natural killer cell line NK-92 and the NKTCL cell line SNK-6.Lentiviral vectors were used to express latent membrane protein 1(LMP1)in NK-92 cells,and IL-2Rαin both NK-92 and SNK-6 cells.The biological effects of these genes on proliferation,apoptosis,cell cycle distribution,and chemosensitiv-ity were analyzed.Results:Expression of IL-2Rαwas significantly higher in SNK-6 cells than in NK-92 cells.Expressing LMP1 in NK-92 cells remarkably up-regulated IL-2Rαlevels,whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα.IL-2Rαoverexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution,and induced resistance to gemcitabine,doxorubicin,and asparaginase.These effects were reversed by an anti-IL-2Rαantibody.Conclusions:Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells,up-regulating IL-2Rαexpression.IL-2Rαoverexpression promotes growth and chemoresistance in NKTCL,making this interleukin receptor a potential therapeutic target.展开更多
To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and...To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women’s and Children’s Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.展开更多
基金supported by National Natural Science Foundation of China(Nos.81672686,81372883,and 81001052)Natural Science Foundation of Guangdong Province,China(No.2015A030313020)+2 种基金Science and Technology Planning Project of Guangdong Province,China(No.2011B031800222)Young Talents Key Project of Sun Yat-sen University(No.2015ykzd13)the Sister Institution Network Fund of MD Anderson Cancer Center
文摘Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.
基金supported by the National Natural Science Foundation of China (No.81372883,No.81001052)the Science and Technology Planning Project of Guangdong Province,China(No.2011B031800222)+4 种基金the Young Talents Project of Sun Yat-sen University Cancer Center(to QC)the Young Talents Project of Sun Yat-sen University(to QC)the Natural Science Foundation of Guangdong Province,China(No.8151008901000043)the Sister Institution Network Fund of MD Anderson Cancer Center(to HR)partly supported by the NIH through MD Anderson's Cancer Center Support Grant (No.CA016672)
文摘Introduction:Hepatitis B virus(HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B(hepatitis B surface antigen[HBsAg]-negative and hepatitis B core antibody[HBcAb]-positive).This study aimed to assess HBV reaaivation and hepatitis occurrence in diffuse large B-cell lymphoma(DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reaaivation and hepatitis occurrence and to analyze whether HBV reaaivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.Methods:We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center,China.Prediaive faaors for HBV reaaivation,hepatitis development,and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.Results:Among the 278 patients,165 were HBsAg-negative.Among these 165 patients,6(10.9%) of 55 HBcAb-positive(resolved HBV infeaion) patients experienced HBV reactivation compared with none(0%) of 110 HBcAb-negative patients(P=0.001).Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients(21.8%vs.8.2%,P = 0.013).HBcAb positivity and elevated baseline alanine aminotransferase(ALT) levels were independent risk factors for hepatitis.Among the 55 patients with resolved hepatitis B,patients with elevated baseline serum ALT or aspartate aminotransferase(AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels(P = 0.037,P = 0.005,respeaively).An elevated baseline AST level was an independent risk factor for hepatitis in these patients.Six patients with HBV reactivation recovered after immediate antiviral therapy,and chemotherapy was continued.HBcAb positivity,HBV reactivation,or hepatitis did not negatively affect the survival of DLBCL patients.Conclusions:DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reaaivation and hepatitis than HBsAg-negative/HBcAb-negative patients.Close monitoring and prompt antiviral therapy are required in these patients.
基金supported by the National Natural Science Foundation of China(81372883,81001052)Natural Science Foundation of Guangdong Province,China(2015A030313020 and 8151008901000043)+3 种基金Science and Technology Planning Project of Guangdong Province,China(2011B031800222)Young Talents Key Project of Sun Yat?sen University(2015ykzd13,to Qing-qing Cai)Young Talents Project of Sun Yat-sen University(11ykpy56,to Qing-qing Cai)the Sister Institution Network Fund of MD Anderson Cancer Center(to Qing-qing Cai and Hui-Rao)
文摘Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.
基金supported by the grants from National Key R&D Program of China(2017YFC1309001 and 2016YFC1302305)National Natural Science Foundation of China(81603137,81672686,and 81973384)Special Support Program of Sun Yat-sen University Cancer Center(PT19020401).
文摘Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug resistance.We aimed to investigate the potential mechanisms of drug resistance in adults with T-LBL.Methods:Gene expression microarray was used to identify differential mRNA expression profiles between chemotherapy-resistant and chemotherapy-sensitive adult T-LBL tissues.Real-time PCR and immunohistochemistry were performed to detect the expression of bromodomain-containing protein 2(BRD2)and c-Myc in fresh-frozen T-LBL tissues from 85 adult patients.The Ras pull-down assay was performed to monitor Ras activation.Chromatin immunoprecipitation assays were used to analyze the binding of E2F transcription factor 1(E2F1)/BRD2 to the RAS guanyl releasing protein 1(RasGRP1)promoter region.The drug resistance effect and mechanism of BRD2 were determined by both in vivo and in vitro studies.Results:A total of 86 chemotherapy resistance-related genes in adult T-LBL were identified by gene expression microarray.Among them,BRD2 was upregulated in chemotherapy-resistant adult T-LBL tissues and associated with worse progressionfree survival and overall survival of 85 adult T-LBL patients.Furthermore,BRD2 suppressed doxorubicin(Dox)-induced cell apoptosis both in vitro and in vivo.The activation of RasGRP1/Ras/ERK signaling might contribute to the Dox resistance effect of BRD2.Besides,OTX015,a bromodomain and extra-terminal(BET)inhibitor,reversed the Dox resistance effect of BRD2.Patient-derived tumor xenograft demonstrated that the sequential use of OTX015 after Dox showed superior therapeutic effects.Conclusions:Our data showed that BRD2 promotes drug resistance in adult T-LBL through the RasGRP1/Ras/ERK signaling pathway.Targeting BRD2 may be a novel strategy to improve the therapeutic efficacy and prolong survival of adults with TLBL.
基金the National Natural Science Foundation of China(81400159,81873450,81700196,81672686)Pearl River Nova Program of Guangzhou(201710010161)+1 种基金Sister Institution Net-work Fund of the MD Anderson Cancer Center(to Qingqing Cai)the Fundamental Research Funds for the Central Universities(17ykpy77).
文摘Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates signifi-cantly with treatment response and survival.In the current study we examined the potential role of IL-2Rαby over-expressing IL-2Rαin representative cell lines.Methods:Levels of IL-2Rαwere evaluated in the human natural killer cell line NK-92 and the NKTCL cell line SNK-6.Lentiviral vectors were used to express latent membrane protein 1(LMP1)in NK-92 cells,and IL-2Rαin both NK-92 and SNK-6 cells.The biological effects of these genes on proliferation,apoptosis,cell cycle distribution,and chemosensitiv-ity were analyzed.Results:Expression of IL-2Rαwas significantly higher in SNK-6 cells than in NK-92 cells.Expressing LMP1 in NK-92 cells remarkably up-regulated IL-2Rαlevels,whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα.IL-2Rαoverexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution,and induced resistance to gemcitabine,doxorubicin,and asparaginase.These effects were reversed by an anti-IL-2Rαantibody.Conclusions:Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells,up-regulating IL-2Rαexpression.IL-2Rαoverexpression promotes growth and chemoresistance in NKTCL,making this interleukin receptor a potential therapeutic target.
文摘To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women’s and Children’s Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.
