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Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP

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Cancer Biology & Medicine 2022年第6期19卷 893-909页

作者： Yan Qin Haizhu Chen Peng Liu changgong zhang Jianliang Yang Lin Gui Xiaohui He Liqiang Zhou Shengyu Zhou Shiyu Jiang Hongxin Jiang Yuankai Shi Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsBeijing 100021China Department of Medical Oncology Suzhou Municipal HospitalAffiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215001China

Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients,and examine correlation of BCL2,TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL.MYC,BCL2,and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival(PFS)(5-year PFS:13.7%vs.40.8%;P=0.003)and overall survival(OS)(5-year OS:34.0%vs.70.9%;P=0.036).Importantly,patients who harbored BCL2 gain/amplifications(BCL2GA/AMP)also had a remarkably inferior 5-year PFS(11.1%vs.38.3%;P<0.001)and OS(22.1%vs.69.6%;P=0.009).In contrast,neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival.Multivariable analyses showed that the presence of BCL2 alterations,especially BCL2GA/AMP,TP53 mutations,and International Prognostic Index(IPI)were significantly associated with inferior PFS and OS.Novel prognostic models for OS were constructed based on 3 risk factors,including BCL2 alterations(Model 1)or BCL2GA/AMP(Model 2),TP53 mutations,and IPI,to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP,BCL2 alterations,especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes,which were independent of the IPI.The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP,but further validation of the prognostic models is still warranted.

关键词： BCL2 TP53 genetic alterations diffuse large B-cell lymphoma prognosis

Correlation between Expression of DcR3 on Tumor Cells and Sensitivity to FasL

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Cellular & Molecular Immunology 2007年第6期4卷 455-460页

作者： Wenzhu Li changgong zhang Caixia Chen Guohong Zhuang Anti-Cancer Research Center Medical College Xiamen University 422 Siming South Road Xiamen Fujian 361005 China School of Life Science Xiamen University 422 Siming South Road Xiamen Fujian 361005 China

To investigate the correlation between sensitivity to Fas ligand （FasL） and expression level of decoy receptor 3 （DcR3） on tumor cell surface, Fas/DcR3 mRNA expression was detected by RT-PCR. Anti-DcR3 mAb was used to detect expression level of DcR3 on surface of tumor cells by flow cytometry. Caspase-8, caspase-9, caspase-3, Bcl-2 expressions were analyzed by Western blot, respectively. Sensitivity to apoptosis induced by FasL was determined by Annexin V apoptosis kit. The expressions of DcR3 on the surface of tumor cells from high to low were approximately 35.3% in BGC823 cells, and 21.6% in MCF-7 cells, respectively. The apoptotic rates induced by FasL from low to high were 15.6% in BGC823 cells, and 58.2% in MCF-7 cells, respectively. There was a significant correlation between the expression levels of DcR3 with FasL-inducing apoptosis. Cellular ＆ Molecular Immunology.

关键词： DcR3 FasL Fas apoptosis

Intermetallic ferric nickel silicide alloy derived from magadiite by magnesiothermic reaction as bifunctional electrocatalyst for overall water splitting

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Nano Research Energy 2024年第2期3卷 20-30页

作者： Xuyang Jing Yang Mu Zhanming Gao Xueying Dong changgong Meng Chi Huang Yifu zhang School of Chemistry Dalian University of TechnologyDalian 116024China College of Environmental and Chemical Engineering Dalian UniversityDalian 116622China College of Chemistry and Molecular Sciences Wuhan UniversityWuhan 430072China

As the cleanest energy source,hydrogen energy is regarded as the most promising fuel.Water electrolysis,as the primary means of hydrogen production,has constantly been the focus of attention in the energy conversion field.Developing eco-friendly,cheap,safe and efficient catalysts for electrochemical water splitting(EWS)is the key challenge.Herein,the intermetallic silicide alloy is first synthesized via a facile magnesiothermic reduction and employed as bifunctional electrocatalysts for EWS.Ferric-nickel silicide(denoted as FeNiSi)alloy is designed and shows a good electrocatalytic performance for EWS.The lattice distortions of FeNiSi enhance the electrocatalytic activity.Besides,the porous structure affords more active sites and improves the reaction kinetics.As a consequence,FeNiSi delivers an excellent performance with overpotential of 308 mV for oxygen evolution reaction(OER)and 386 mV for hydrogen evolution reaction(HER)at 10 mA·cm−2 in 1 M KOH.The stability structure of intermetallic silicide achieves an outstanding durability with an unchanged potential of 1.66 V for overall water splitting at 10 mA·cm−2 for 15 h.This work not only provides a facile method for the synthesis of intermetallic silicide with considerable porous structures,but also develops the potential of intermetallic silicide alloy as bifunctional electrocatalysts for EWS,which opens up a new avenue for the design and application of intermetallic silicide alloy.

关键词： bimetallic silicide magadiite magnesiothermic reduction bifunctional electrocatalyst overall water splitting

Pathobiology of ovarian carcinomas

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Chinese Journal of Cancer 2015年第1期34卷 50-55页

作者： Yuankai Shi Ping Zhou Xiaohong Han Xiaohui He Shengyu Zhou Peng Liu Jianliang Yang changgong zhang Lin Gui Yan Qin Sheng Yang Liya Zhao Jiarui Yao Shuxiang zhang Department of Medical Oncology Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs

Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers(carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.

关键词：卵巢癌病理学卵巢肿瘤上皮细胞分子检测生殖细胞免疫组化靶向治疗

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma

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Chinese Journal of Cancer 2015年第11期34卷 522-530页

Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab(R-CHOP) by examining the stem cell mobilization in NHL patients. Factors afecting the collection of CD34+ cells were also explored.Methods: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were inancially eligible received R-CHOP for autologous peripheral blood stem cell(APBSC) mobilization; the remaining 25 patients received CHOP.Results: The median CD34+ cell yield was 7.01 × 106 cells/kg body weight(range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ber of apheresis procedures per patient was 1(range 1–3). The≥2.0 APBS× 106 cells/kg body weight. The median numC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group(P response(CR) rate in = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the completeB cell lymphoma patients as compared with CHOP(P = 0.01). No signiicant diferences in toxicity or engraftment were observed between the two groups.Conclusion: The present study demonstrated that dose-adjusted CHOP chemotherapy efectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.

关键词： Stem cell transplantation, Mobilization, CHOP regimen, Rituximab, Non-Hodgkin's lymphoma

Clinical characteristics and treatment outcomes of Chinese diffuse large B-cell lymphoma patients in the era of rituximab(2005–2018)

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Cancer Pathogenesis and Therapy 2023年第1期1卷 3-11页

作者： Yuankai Shi Haizhu Chen Yan Qin Jianliang Yang Peng Liu Xiaohui He Shengyu Zhou Liqiang Zhou changgong zhang Yongwen Song Yueping Liu Lin Gui Shulian Wang Jing Jin Hui Fang Shunan Qi Ning Li Yu Tang Xin Wang Sheng Yang Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsBeijing 100021China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

Background Rituximab combined with cyclophosphamide,doxorubicin hydrochloride,vincristine,and prednisone(R-CHOP)regimen has improved the survival of diffuse large B-cell lymphoma(DLBCL)patients worldwide,compared with CHOP alone.Several limitations were seen in previous studies of Chinese DLBCL patients treated with R-CHOP or R-CHOP-like regimens.This study aimed to investigate the clinical characteristics and treatment outcomes of Chinese DLBCL patients treated with the standard first-line treatment.Methods Clinical data were collected from DLBCL patients who received frontline R-CHOP or R-CHOP-like regimens at the Cancer Hospital Chinese Academy of Medical Sciences&Peking Union Medical College(CHCAMS)between January 1,2005,and December 31,2018.The treatment outcomes were compared with those of patients diagnosed with DLBCL between 2004 and 2017 and who received immunochemotherapy from the United States Surveillance,Epidemiology,and End Results(SEER)database.Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test.Multivariate analysis of progression-free survival(PFS)and overall survival(OS)was performed using Cox proportional hazard regression.Results Overall,1084 patients from the CHCAMS and 4013 patients from the SEER database were included in the study.As of April 30,2022,the median follow-up period for the CHCAMS group was 87.3(range:0.5-195.4)months.For the CHCAMS group,the 5-year PFS and OS rates were 61.7%(95%confidence interval[CI]:58.8-64.7%)and 70.6%(95%CI:67.8-73.4%),respectively.For the SEER group,the 5-year OS rate was 66.5%(95%CI:65.0-68.0%),which was inferior to that of the CHCAMS group(P<0.001).After adjusting for clinical factors and treatment,no significant difference was observed in the OS between the CHCAMS and SEER groups(P=0.867).In the CHCAMS group,multivariate analysis showed that an Eastern Cooperative Oncology Group performance status score≥2,presence of B symptoms,Ann Arbor stage III-IV,elevated serumβ2-microglobulin levels,and bulky mass were

关键词： Diffuse large B-Cell lymphoma Treatment Prognosis SEER database

Single‑Atom Catalysts:Advances and Challenges in Metal‑Support Interactions for Enhanced Electrocatalysis

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Electrochemical Energy Reviews 2022年第1期5卷 145-186页

作者： Yang Mu Tingting Wang Jian zhang changgong Meng Yifu zhang Zongkui Kou School of Chemical Engineering Dalian University of TechnologyDalian 116024LiaoningChina State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070HubeiChina School of Chemistry and Chemical Engineering Huazhong University of Science and TechnologyWuhan 430074HubeiChina

Single-atom catalysts(SACs),which contain a single metal atom supported on a well-confined substrate,are among the most promising heterogeneous catalysts owing to their unique advantages,such as high intrinsic activity and selectivity,tunable bonds and coordination,abundant metal-containing active sites,and atomic economy.Since metal-support interactions(MSIs)in SACs exert a substantial influence on the catalytic properties,gaining a profound understanding and recognition of catalytic reactions depends greatly on investigating MSIs both experimentally and computationally.Hence,the engineer-ing and modulation of MSIs are regarded as one of the most efficient methods to rationally design SACs with disruptively enhanced catalytic properties.In this review,we track the recent advances in SACs from an MSI perspective.We then discuss the existing MSIs in SACs and elucidate the significant role of strong MSIs in catalytic properties and mechanisms.The chal-lenges hindering the rational design of supported SACs with strong MSIs,which are currently still far from being completely understood and overcome,are described.In addition,the correlation between strong MSIs and electrocatalytic activities in SACs,including an outlook to increase our understanding of MSIs,is discussed.Finally,the present review provides some perspectives and an in-depth understanding of strong MSIs to advance high-performing SACs.

关键词： Metal-support interaction Single-atom catalysts Electrocatalysis ORR and OER HER and HOR

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

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Chinese Journal of Cancer Research 2015年第1期27卷 66-73页

作者： Youwu Shi Shengyu Zhou Xiaohui He Xiaohong Han Shikai Wu Feng Pan Peng Liu Yinyu Liu Yingheng Lei Hongzhi zhang Jianliang Yang Yan Qin changgong zhang Sheng Yang Liya Zhao Kehuan Luo Guanqing Wu Yan Sun Yuankai Shi Department of Medical Oncology Cancer Institute/Hospital Chinese Academy of Medical Sciences & Peking Union Medical College National Center for Anticancer Drugs Clinical Study Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs Department of Radiation Oncology Cancer Institute/Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation （HSCT） from December 1989 to December 2009 in a single institution. Results： HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months （range, 24.6-173.1 months）. The 5-year overall survival （OS） and event-free survival （EFS） rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow （BM） involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission （CR1）.

关键词： Lymphoblastic lymphoma （LL） high-dose therapy （HDT） hematopoietic stem cell transplantation（HSCT） autologous allogeneic

Clinical features and outcomes of diffuse large B-cell lymphoma based on nodal or extranodal primary sites of origin:Analysis of 1,085 WHO classified cases in a single institution in China

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Chinese Journal of Cancer Research 2019年第1期31卷 152-161页

作者： Yuankai Shi Ying Han Jianliang Yang Peng Liu Xiaohui He changgong zhang Shengyu Zhou Liqiang Zhou Yan Qin Yongwen Song Yueping Liu Shulian Wang Jing Jin Lin Gui Yan Sun Department of Medical Oncology Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Departement of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.Results: In the 1,085 patients, 679(62.6%) cases were nodal DLBCL(N-DLBCL) and 406 cases(37.4%) were extranodal DLBCL(EN-DLBCL). The most common sites of N-DLBCL were lymphonodus(64.8%), Waldeyer's ring(19.7%), mediastinum(12.8%) and spleen(2.7%), while in EN-DLBCL, stomach(22.4%), intestine(16.0%),nose and sinuses(8.9%), testis(8.4%), skin(7.9%), thyroid(6.9%), central nervous system(CNS)(6.4%), breast(5.7%), bone(3.4%), and salivary gland(2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival(OS) rate and progression-free survival(PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9%(P=0.008), and the 5-year PFS were57.0% and 49.0%(P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate(83.6%) and PFS rate(76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach,breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%,respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.Conclusions: In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.

关键词： Diffuse large B-cell lymphoma(DLBCL) distribution nodal extranodal