1.Clinical research of autologous hematopoietic stem cell transplantation for hematological malignancies and solid tumors
Zhenqian HUANG ; Donghua ZHANG ; Huo TAN
Chinese Journal of Practical Internal Medicine 2006;0(23):-
Objective To evaluate the therapeutic effect of autologous hematopoietic stem cell transplantation(AHSCT)on hematological malignancies and solid tumors.Methods Twenty patients with age from 18 to 50 years received AHSCT.Two or 3 of following agents,Cytarabine(Ara-C)3~4 g/m2,Cyclophosphamide(CTX)4~6 g/m2,Etoposide(VP-16)0.5~1.0 g/m2,Semustine(me-CCNU)300 mg/m2,Melphalan(Mel)140 mg/m2,Thiotep a(TSPA)600 mg/m2,Carboplatin(CBP)1.0 g/m2,Busulfan 16mg/kg,were combined as conditioning regimen in all patients.Among them 2 patients with ALL accepted additional total body irradiation(TBI).Results All the patients have reconstituted bone marrow hematopoiesis after transplantation.None of them had the transplantation-related mortality.Among 20 patients with CML and malignant lymphoma,15 achieved disease-free survival(DFS)with a median survival time of 39.5(2~109)months.Conclusion AHSCT might represent an effective approach to the treatment of some patients with chemosensitive solid tumor who are complete remission or part remission.It is suggested that the patients have got a obvious survival benefit from AHSCT.
2.Clinical research on influence of auto or allo-mesenchymal stem cells transplantation on hematopoietic recovery
Chunyan WANG ; Huo TAN ; Zhenqian HUANG ; Runhui ZHENG ; Dan LIU ; Haiming LI ; Xiaodan LUO
Cancer Research and Clinic 2010;22(z1):1-4
Objective To investigate the impact of auto and allogenic mesenchymal stem cells (MSC) transplantation on hematopoietic reconstitution. Methods MSC from auto, donor bone marrow or embryonic tissue were cultured and expanded in vitro in the serum culture system. Five patients received hematopoietic stem cell transplantation (HSCT) were investigated. Case 1 of systemic lupus erythematosus and Case 2 of non-hodgkin' s lymphoma (NHL) received auto MSC transplant before auto-HSCT. Case 3 of paroxysmal nocturnal hemoglobinuria received HLA-identical allogenic MSC transplant before HLA-identical allo-HSCT.Case 4 of chronic myelocytic leukemia and Case 5 of NHL had delayed hematopoietic reconstitution (129th and 78th day, respectively) after allo- and auto-HSCT, respectively, and received MSC from embryonic tissue.Results Case 1, 2 and 3 had no manifested side effects after MSC transplantation combined with HSCT.Neutrophil count of case 1, 2, and 3 were over 0.5 ×109/L at 1st, 10th and 10th day, respectively, platelet count were over 20 ×109/L at 1st, 8th and 33th day, respectively, and agranulocytosis at Ost, 7th and 12th day, respectively. The treatment of embryonic tissue MSC transplant was confirmed to fail for Case 4 and 5.Conclusion The time of MSC transplant has a great impact on hematopoietic reconstitution. MSC transplantation and HSCT performed simultaneously can improve hematopoietic reconstitution. However, the impact of MSC on patients with delayed hematopoietic reconstitution after HSCT needs further study.
3.Clinical diagnosis and analysis of primary pulmonary mucosa-as-sociated lymphoid tissue lymphoma:A report of seven cases
Sida PENG ; Huo TAN ; Zhenqian HUANG ; Runhui ZHENG ; Pengfei QIN ; Juhong JIANG
Chinese Journal of Clinical Oncology 2014;(14):922-924
Objective:This study aims to examine the clinicopathological features, diagnosis, and treatment of pulmonary margin-al zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT). Methods:The clinicopathological features and immu-nohistochemical staining of CD20, CD79a, CD5, CD10, CD23, CyclinD1, and Ki-67 in seven patients with PMZL-MALT were ana-lyzed. Results:These patients, with a median age of 58 years, included three males and four females. Most of the patients suffered from cough, anhelation, and irregular fever. No specific imaging manifestation was observed. Tumor cells were positive for CD19 and CD20 but negative for CD5, CD10, and CyclinD1. The positive rate of Ki-67 was low. Conclusion:PMZL-MALT cases are easily misdiag-nosed because of the absence of specific clinical characteristics and X-ray features. Final diagnosis depends on pathological examina-tions.
4.Construction of HA-1-DC nucleic-acid vaccine and induction of specific cytotoxic T lymphocytes.
Yaya, WANG ; Donghua, ZHANG ; Jinmei HU ; Wenli, LIU ; Hongsheng, ZHOU ; Lu, ZHANG ; Dan, LIU ; Zhenqian, HUANG ; Huo, TAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(3):261-4
An HA-1-DC nucleic-acid vaccine was constructed to induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT). DCs were generated from HSCT donors in vitro, and its immunologic activity was assayed by using flow cytometry and mixed lymphocytes reaction. HA-1 gene was electroporated into the cultured DCs to construct a DC nucleic-acid vaccine. After transfection for 48 h, the expression of HA-1 protein could be detected by using Western blot. The DCs were cultured with syngenic lymphocytes to induce specific cytotoxic T lymphocytes (CTLs). The cytoxicity of the CTLs was detected by LDH assay. The results showed that The DCs derived from peripheral blood monocytes (PBMCs) expressed the phenotype of DCs, and were effective in stimulating proliferation of the allogenic lymphocytes. After electroporating for 48-h, HA-1 protein was detected by using Western blot. The cytotoxicty of inducing CTLs was higher than the control group. It was suggested that minor histocompatibility antigen HA-1 could be considered as a target of immunotherapy against leukemia after HSCT.
5.Study on the distribution and clonal expansion of TCR Vβ subfamily in peripheral T cells after infusing mesenchymal stem cells in patients with chronic GVHD
Yueqiao ZHOU ; Huo TAN ; Shaohua CHEN ; Lijian YANG ; Yangqiu LI ; Chunyan WANG ; Zhenqian HUANG ; Runhui ZHENG ; Xiaodan LUO ; Dan LIU ; Pengfei QIN
Journal of Leukemia & Lymphoma 2011;20(6):362-365,369
Objective To investigate the distribution of TCR Vβ genealogy and clonal expansion in peripheral blood after infusing mesenchymal stem cells (MSC) in patients with chronic GVHD. Methods The complementarity determining region 3 (CDR3) of 24 TCR Vβ subfamily genes in peripheral blood mononuclear cell from 1 case with cGVHD after allogeneic hematopoietic stem cell transplantation (Allo-HSCT),who were treated with infusing MSC,were amplified using RT-PCR. The blood samples were taken at the first and the fifth day after 1st infusion; and the first day,the 10 th day and the 20 th day after the second infusion of MSC,as well as the MSC infused as control . The products were labelled by fluorescein and then analyzed the CDR3 size with gene scan technique to determine the clonality of T cells. Results There were no expression of TCR Vβ subfamily with the MSC infused and after the 1st day of the first infusion of MSC. Then 3,10,14,10 Vβ subfamilies clones are appeared at the other time points,of which were polyclone and oligoclone predominately. In the same time,the manifestations of cCVHD have been abated. Conclusion MSC played a certain role in reviving the immune function of the patients after Allo-HSCT and mitigating the disease of chronic GVHD. Lineage analysis of TCR Vβ subfamily showed some predominant expression.
6.Construction of HA-1-DC Nucleic-acid Vaccine and Induction of Specific Cytotoxic T Lymphocytes
Yaya WANG ; Donghua ZHANG ; Jinmei HU ; Wenli LIU ; Hongsheng ZHOU ; Lu ZHANG ; Dan LIU ; Zhenqian HUANG ; Huo TAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(3):261-264
An HA-1-DC nucleic-acid vaccine was constructed to induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT). DCs were generated from HSCT donors in vitro, and its immunologic activity was assayed by using flow cytometry and mixed lymphocytes reaction.HA-1 gene was electroporated into the cultured DCs to construct a DC nucleic-acid vaccine. After transfection for 48 h, the expression of HA-1 protein could be detected by using Western blot. The DCs were cultured with syngenic lymphocytes to induce specific cytotoxic T lymphocytes (CTLs).The cytoxicity of the CTLs was detected by LDH assay. The results showed that The DCs derived from peripheral blood monocytes (PBMCs) expressed the phenotype of DCs, and were effective in stimulating proliferation of the allogenic lymphocytes. After electroporating for 48-h, HA-1 protein was detected by using Western blot. The cytotoxity of inducing CTLs was higher than the control group. It was suggested that minor histocompatibility antigen HA-1 could be considered as a target of immunotherapy against leukemia after HSCT.
7.Investigation and analysis on the basic situation of radiotherapy application in Fujian province in 2016
Yan ZHANG ; Lihua HUANG ; Zhenqian WENG ; Qishan ZHENG ; Senxing ZHENG ; Weiqi WEI
Chinese Journal of Radiological Medicine and Protection 2020;40(11):857-861
Objective:To ascertain the basic situation of radiotherapy in Fujian in 2016.Methods:Based on the unified questionnaire, the types and quantity of radiotherapy and its corollary equipment, the number of radiotherapy staff and the work for quality control were surveyed in the radiotherapy units in the whole province, and the data on patients undergoing radiotherapy and other types of patients were collected from 26 hospitals. The total number of radiotherapy patients in the whole province was estimated by the correlation analysis and multiple linear regression analysis.Results:Radiotherapy was performed in a total of 32 hospitals in Fujian province in 2016. Among them, there were 62 sets of radiotherapy equipment, 33 sets of the simulators, 57 sets of treatment planning systems and 762 workers. The total number of 15 156 radiotherapy patients in 26 hospital were available for the survey. Multiple linear regression models showed that the frequency of application of medical electron accelerator was positively correlated with number of outpatients, emergency patients and inpatients, number of radiotherapy staff, number of electron accelerators ( r=0.311, 0.893, 0.956, P<0.05). Meanwhile, the frequency of aterloading brachytherapy was positively correlated with number of outpatients, emergency patients and inpatients, number of radiotherapy staff, number of aterloading brachytherapy units ( r=0.307, 0.966, 0.988, P<0.05). The frequency of radiotherapy was 0.54 patients per 1 000 population in Fujian in 2016. The delivered dose calibration of accelerators was performed in all hospitals involved in line with the relevant regulations, but the number of quality control equipment for radiotherapy was insufficient, such as the QA beam checker or well-type ionization chamber. Conclusions:In recent years, the rapid development of radiotherapy has been seen in Fujian province. The radiotherapy management should focus on standardenized and improved quality control and regulation in future.
8.Correlation between serum lipocalin-2 and white matter hyperintensities in patients with ischemic stroke
Zhenqian HUANG ; Yun LI ; Huaiming WANG ; Ting WAN ; Xiaohao ZHANG ; Wusheng ZHU ; Yi XIE ; Xinfeng LIU
International Journal of Cerebrovascular Diseases 2022;30(5):350-354
Objective:To investigate the correlation between the lipocalin-2 (LCN-2) level and white matter hyperintensities (WMHs) in patients with ischemic stroke.Methods:Consecutive patients with ischemic stroke admitted to the Department of Neurology, Jinling Hospital, Medical School of Nanjing University from September 2021 to November 2021 and whose duration from onset to hospitalization <14 d were prospectively enrolled. Enzyme-linked immunosorbent assay was used to detect the serum LCN-2. Fazekas scale was used to assess the severity of periventricular and subcortical WMHs. A total WMHs score ≥3 was defined as severe WMHs. Multivariate logistic regression analysis was used to determine the correlation between serum LCN-2 level and WMHs. Results:A total of 179 patients were enrolled, including 122 males (68.2%), aged 64.7±11.6 years. The median serum LCN-2 level was 387.1 g/L, and 86 patients (48.0%) had severe WMHs. Serum LCN-2 in the severe WMH group was significantly higher than that in the non-severe WMH group (505.3±342.4 g/L vs. 367.8±224.5 g/L; t=3.110, P=0.002). Multivariable logistic regression analysis showed that after adjusting for the relevant confounding factors, there was a significant correlation between higher serum LCN-2 and severe WMHs (odds ratio 2.32, 95% confidence interval 1.17-4.63; P=0.017) and higher total WMHs score (odds ratio 1.62, 95% confidence interval 1.12-2.35; P=0.011). Conclusion:Higher serum LCN-2 level is associated with severe WMHs in patients with ischemic stroke.
9.Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT)
Huiqiang HUANG ; Zhiming LI ; Lihong LIU ; Liang HUANG ; Jie JIN ; Hongyan TONG ; Hui ZHOU ; Zengjun LI ; Zhenqian HUANG ; Wenbin QIAN ; Kaiyang DING ; Quande LIN ; Ming HOU ; Yunhong HUANG ; Jingbo WANG ; Pengcheng HE ; Xiuhua SUN ; Xiaobo WANG ; Zunmin ZHU ; Yao LIU ; Jinhai REN ; Huijing WU ; Liling ZHANG ; Hao ZHANG ; Liangquan GENG ; Jian GE ; Ou BAI ; Liping SU ; Guangxun GAO ; Xin LI ; Yanli YANG ; Yijian CHEN ; Aichun LIU ; Xin WANG ; Yi WANG ; Liqun ZOU ; Xiaobing HUANG ; Dongping HUANG ; Shujuan WEN ; Donglu ZHAO ; Jun MA
Journal of Leukemia & Lymphoma 2023;32(8):457-464
Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
10.Impact of siRNA-mediated down-regulation of CD147 on human breast cancer cells.
Zhenqian LI ; Daoming LI ; E-mail: LIDAOMING@ZZU.EDU.CN. ; Jiangwei LI ; Pei HUANG ; Hui QIN
Chinese Journal of Pathology 2015;44(10):734-738
OBJECTIVETo investigate the influence of siRNA-mediated down-regulation of CD147 on growth, proliferation and movement of human breast cancer cell line MDA-MB-231.
METHODSThe protein expression of CD147, MMP-2 and TIMP-2 of the MDA-MB-231 cells were analyzed by ABC. Lentiviral expression vector of CD147 gene was constructed and transfected into MDA-MB-231 cells. RT-PCR and Western blot were used to detect the mRNA and protein level changes of CD147 genes to identify the optimal time point, followed by detection of changes of mRNA and protein expression of MMP-2 and TIMP-2 genes. CCK-8 reagent method and cell scratch test were used to detect the proliferation and migration change of MDA-MB-231 cells. The nude mouse model of breast cancer by hypodermic injection with MDA-MB-231 cells was established to document the effect of CD147 siRNA on the tumor transplants.
RESULTSAfter transfection of lentiviral expression vector of CD147 gene, protein of CD147, MMP-2 and TIMP-2 were weakly or negative expressed, significantly weaker than those of control group (P < 0.01). After 72 hours of transfection, average down-regulation rate of CD147 and MMP-2 were 96.03% ± 0.84% and 96.03% ± 0.84%, respectively. Both CD147 mRNA and MMP-2 mRNA expression were down-regulated (P < 0.05), while TIMP-2 mRNA expression showed no significant deference (P > 0.05). No less than 2 days after transfection, cell growth of MDA-MB-231 cell line was found significantly inhibited (P < 0.05). After 24 hours of transection, average migration distance of MDA-MB-231 cell line and control group were (0.64 ± 0.12) mm and (4.69 ± 0.85) mm, respectively, which indicated a lower migrate speed. Down regulation of CD147 led to reduction of volume and mass of nude mouses. The growth of the carcinoma transplant was inhibited upon siRNA-mediated down-regulation of CD147 (P < 0.05), with an average tumor mass of (1.85 ± 0.98) g and both reduction of tumor size and tumor mass.
CONCLUSIONSCD147 may alter the MMP-2/TIMP-2 balance in MDA-MB-231 cells. CD147 gene silencing inhibits the proliferation and migration of MDA-MB-231 cells and the growth of carcinoma transplants in nude mice.
Animals ; Basigin ; metabolism ; Blotting, Western ; Breast Neoplasms ; genetics ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Nude ; Neoplasm Transplantation ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Transfection