1.Egr-1 promoter regulating effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression induced by doxorubicin and ionizing radiation
Nan DU ; Xuetao PEI ; Jinming ZHOU ; Junzhong SUN ; Yan FU ; Hui ZHAO
Chinese Journal of Radiological Medicine and Protection 2009;29(3):249-252
Objective To explore the regulating effects of Egr-1 promoter activated by ionizing radiation (IR) and doxorubicin (ADM) on the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) genes. Methods The human GM-CSF cDNA and enhanced green fluorescent protein (EGFP) cDNA were linked together with IRES(internal ribosome entry site) and then inserted into the expression vector pCIneo under control of the Egr-1 promoter(Egr-EG). The vector was transferred into human bone marrow stromal cell line HFCL by liposome transfection. And the cells were exposure to ADM and IR. The activity of EGFP in HFCL/EG cells were detected by FACS. The effect of N-acetylcysteine on the expression of EGFP following exposure to ADM and IR was examined. The amounts of GM-CSF in HFCL/EG after chemotherapy or radiation were measured with ELISA. The effects of GM-CSF in HFCL/EG cultural supernatants on expansion of CFU-GM derived from cord blood were also studied. RT-PCR analysis for the expression of GM-CSF mRNA in HFCL/EG after exposure to ADM or IR. Results The percentage of EGFP+ HFCL/EG cells exposed to ADM and IR was increased compared with non-treatment group (1.2 % and 15.2 % vs 18.2 %, t = 5.11, P < 0.01). The levels of secreted GM-CSF in HFCL/EG cells exposed to ADM and IR was increased (P < 0.01), but no difference between ADM group and IR group (P 0.05). The expression of EGFP by HFCL/EG treated with ADM and IR was significantly decreased by N-acetylcysteine. The effects of GM-CSF in HFCL/EG cultural supernatants on expansion of CFU-GM in ADM group and IR group were significantly higher than that in HFCL group and non-treatment group. However, The CFU-GM count of IR group was higher than that of ADM group. The expression of GM-CSF mRNA in HFCL/EG cells exposed to ADM and IR was significantly increased(t = 4.37, P < 0.01). Conclusions GM-CSF gene expression regulated by Egr-1 promoter induced by ADM and IR could help the recovery from hematopoietic injury.
2.Study on the relationship between serum sST2,Hey,IL-33 levels and degree of coronary artery stenosis and MACE in patients with acute myocardial infarction
Chen YANG ; Bin MENG ; Junzhong ZHOU
International Journal of Laboratory Medicine 2024;45(16):1991-1995
Objective To investigate the relationship between serum soluble growth stimulating expression gene 2 protein(sST2),homocysteine(Hcy)and interleukin(IL)-33 levels and degree of coronary artery ste-nosis and major cardiovascular adverse events(MACE)in patients with acute myocardial infarction(AMI).Methods A total of 139 patients with AMI admitted to a hospital from May 2021 to May 2023 were retro-spectively selected and divided into a good prognosis group(54 cases)and a poor prognosis group(85 cases)according to the occurrence of MACE.Spearman correlation was used to analyze the relationship between ser-um sST2,Hey,IL-33 levels and the degree of coronary artery stenosis in AMI patients.Multivariate Logistic regression was used to analyze the influencing factors of MACE occurrence in patients,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of serum sST2,Hcy and IL-33 levels for MACE occurrence in AMI patients.Results Serum levels of sST2,Hcy and IL-33 in the poor prognosis group were significantly higher than those in the good prognosis group,and the difference was statistically sig-nificant(P<0.05).Serum levels of sST2,Hcy and IL-33 in patients with severe and moderate stenosis were significantly higher than those in patients with mild stenosis,and the difference was statistically significant(P<0.05).Spearman correlation analysis showed that serum sST2,Hcy and IL-33 levels were positively cor-related with the degree of coronary artery stenosis(P<0.05).Serum Hcy,sST2 and IL-33 are risk factors for MACE in AMI patients.ROC curve analysis showed that the area under the curve(AUC)of serum sST2,Hcy and IL-33 levels for predicting the occurrence of MACE in AMI patients was 0.838,0.726 and 0.800,and the sensitivity was 87.1%,80.0%and 84.7%,respectively.The specificity was 77.8%,68.5%and 77.8%,re-spectively.The AUC of the combined prediction value of MACE in AMI patients was 0.906,and the sensitivi-ty and specificity were 88.2%and 90.7%,respectively.Conclusion Serum sST2,Hcy and IL-33 levels have certain predictive value for MACE in patients with AMI.
3.Effect of brentuximab vedotin combined with chlormethine hydrochloride on the treatment of 6 patients with relapsed and refractory Hodgkin lymphoma.
Zhigang CAO ; Zhihong WANG ; Junzhong SUN ; Chaojin PENG ; Shaomei FENG ; Xiaoyan ZHOU ; Qingming YANG
Chinese Journal of Hematology 2015;36(7):575-577
OBJECTIVETo observe the clinical efficacy and side effects of brentuximab vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and refractory Hodgkin lymphoma (HL) after failure with BV alone.
METHODSFrom March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg, iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course, and all patients received about 3-8 courses of chemotherapy, with an median of 4 courses. Clinical efficacy and adverse events were assessed and observed by radiographic examination and serological detection.
RESULTSAmong 6 patients, the overall response rate was 100% with 2 complete remission and 4 partial remission. The main adverse events were grade I (2 patients) and IV (2 patients) bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I (1 patient) increase of transaminase and myocardial enzyme and grade I (1 patient) mouth ulcers.
CONCLUSIONThe combination of BV and CH in the treatment of relapsed and refractory HL after failure with BV alone was high effective and the toxicities were well tolerable.
Antineoplastic Agents, Alkylating ; therapeutic use ; Hodgkin Disease ; drug therapy ; Humans ; Immunoconjugates ; therapeutic use ; Mechlorethamine ; therapeutic use
4.Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery
Weili ZHANG ; Chi ZHOU ; Weifeng WANG ; Weihao LI ; Jiahua HE ; Zhenhai LU ; Xiaojun WU ; Junzhong LIN ; Jianhong PENG
Chinese Journal of Gastrointestinal Surgery 2024;27(6):608-614
Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.
5.Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery
Weili ZHANG ; Chi ZHOU ; Weifeng WANG ; Weihao LI ; Jiahua HE ; Zhenhai LU ; Xiaojun WU ; Junzhong LIN ; Jianhong PENG
Chinese Journal of Gastrointestinal Surgery 2024;27(6):608-614
Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.