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| 1 | Safety and efficacy of obinutuzumab in Chinese patients with B-cell lymphomas: a secondary analysis of the GERSHWIN trial显示文摘Background:Patients with relapsed/refractory B-cell lymphomas have limited treatment options.GERSHWIN is an open-label,single-arm,phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically docu-mented CD20+relapsed/refractory chronic lymphocytic leukemia(CLL),diffuse large B-cell lymphoma(DLBCL),or follicular lymphoma(FL).The primary outcome measure of pharmacokinetics has been previously reported.We now present data on the secondary endpoint measures(e.g.,safety,and efficacy and pharmacodynamics).Methods:Patients received 1000 mg obinutuzumab intravenously on days 1,8,and 15 of cycle 1(CLL patients;first dose split over 2 days),and on day 1 of cycles 2-8.Each cycle lasted for 21 days;the treatment period was 24 weeks.All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety,efficacy,as well as pharmacodynamics.Results:A total of 48 patients(>18 years of age)were enrolled(CLL:12;DLBCL:23;FL:13).The subjects received a median of two lines of anticancer treatment prior to the enrollment.Thirty-five patients(72.9%)had at least one adverse event(AE).The most frequent AE was infusion-related reactions(15 patients;31.3%),followed by pyrexia(11 patients;22.9%).Treatment-related AEs were reported in 28 patients(58.3%),and included one death(interstitial lung disease).End-of-treatment(EoT)response rate was 33.3%.Best overall response rate was 47.9%.Most CLL patients achieved a partial response at EoT(58.3%).CD19+depletion occurred in 75.0%of the patients with CLL,and all patients with FL and DLBCL.Conclusions:The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients;no new safety signals were observed. | Yan Qin Yuqin Song Zhixiang Shen Xin Du Wei Ji Wanling Hsu Jun Zhu Yuankai Shi | 2018 | Cancer Communications2018，38，1： | 2 |
| 2 | A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma显示文摘Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation. | Zhitao Ying Ting He Shanzhao Jin Xiaopei Wang Wen Zheng Ningjing Lin Meifeng Tu Yan Xie Lingyan Ping Weiping Liu Lijuan Deng Yanping Ding Xuelian Hu Bing Bu Xin’an Lu Yuqin Song Jun Zhu | 2022 | Chinese Journal of Cancer Research2022，34，1： | 2 |
| 3 | Obinutuzumab治疗中国B细胞淋巴瘤患者的安全性和有效性:GERSHWIN试验的二次分析显示文摘背景与目的可供复发/难治性B细胞淋巴瘤患者选择的治疗方案很有限。GERSHWIN是一项研究obinutuzumab单药治疗经组织学确认的CD20+复发/难治性慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)、弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)或滤泡性淋巴瘤(follicular lymphoma,FL)中国患者的疗效的开放标签、单臂、Ib期研究。先前已经报道了药代动力学的主要结局指标,在本研究中我们将报道次要终点指标(例如安全性、有效性和药效学)。方法在第1疗程的第1、8和15 d以及第2–8疗程的第1 d分别对患者静脉注射1000 mg obinutuzumab(CLL患者的首次给药分2 d进行)。每疗程为21 d,治疗24周。注射至少1次obinutuzumab的所有受试者均被纳入安全性、有效性以及药效学分析。结果共纳入48例(> 18岁)(CLL:12例;DLBCL:23例;FL:13例)患者,入组前接受了中位数为二线的治疗。35例(72.9%)患者出现至少1次不良事件(adverse event,AE)。最常见的AE是输液相关反应(15例;31.3%),其次是发热(11例;22.9%)。有28例(58.3%)患者出现与治疗相关的AE,其中1例死亡(间质性肺病)。治疗结束时(End-of-treatment,EoT)缓解率为33.3%,最佳总缓解率为47.9%。大多数CLL患者在EoT部分缓解(58.3%)。75.0%CLL患者及全部FL和DLBCL患者均出现CD19+减少。结论 Obinutuzumab单药治疗中国B细胞淋巴瘤患者的安全性和有效性与以往非中国患者的研究结果相似,没有观察到新的安全性指标。 | Yan Qin Yuqin Song Zhixiang Shen Xin Du Wei Ji Wanling Hsu Jun Zhu Yuankai Shi | 2019 | 癌症2019，38，2： | 1 |
| 4 | Longer conserved alpine forests ecosystem exhibits higher stability to climate change on the Tibetan Plateau显示文摘Aims Vegetation dynamics are simultaneously regulated by climate change and anthropogenic activities.Since the 1980s,climate has been warming on the Tibetan Plateau(TP)at a rate higher than North Hemisphere average.Anthropogenic activities,including grazing,farming,and urbanization,are also influencing the alpine ecosystem on the TP.Especially,an ensemble of large engineering projects,such as power transported from west to east by State Grid,has been in operation on the TP.While studies disentangling effects of climate and anthropogenic activities interference are still lacking for the forest ecosystems on the TP.The overarching objectives of this study were to separate effects of natural climates and human interferences on forest ecosystem dynamics on the TP.Methods We compared vegetation activities of two typical natural reserves(Gongbu natural reserve,GNR,and Yarlung zangbo river grand canyon natural reserve,YNR)and their surroundings in southeastern Tibet(outside of the natural reserves,ONR)using long-term satel-lite normalized difference vegetation index(NDVI)dataset.Linear regression and partial correlation analyses were constructed for the relationship between vegetation activity and climates to evaluate the distinct climate effects on the two natural reserves.Important Findings The two natural reserves were established at different time,which were related to anthropogenic activities impact durations.The results showed that the annual mean NDVI fluctuated between 0.5 and 0.6 in the relatively longer reserved YNR,which was re-markably higher than those in other regions(with NDVI lower than 0.45).The vegetation vigor in the YNR showed neither a sig-nificant temporal trend nor significant relationship with climate.Nevertheless,vegetation vigor exhibited a significant increasing trend during the last three decades(0.012/decade)at the GNR.The inter-decadal analysis turned out positive relationships between vegetation vigor and annual temperature since late 1990s until early 2000s when the GNR was officially established.This study underlined the importance of considering human interference duration when assessing the relationships between vegetation dy-namics and climates. | Jian Li Nan Cong Jiaxing Zu Yuqin Xin Ke Huang Quan Zhou Yaojie Liu Lin Zhou Li Wang Yang Liu Ge Zhang | 2019 | Journal of Plant Ecology2019，12，4： | 1 |
| 5 | Review on global change status and its impacts on the Tibetan Plateau environment显示文摘The Tibetan Plateau(TP)holds fundamental ecological and environmental significances to China and Asia.The TP also lies in the core zone of the belt and road initiative.To protect the TP environment,a comprehensive screening on current ecological research status is entailed.The teased out research gap can also be utilized as guidelines for the recently launched major research programs,i.e.the second TP scientific expedition and silk and belt road research plan.The findings showed that the TP has experienced significant temperature increase at a rate of 0.2℃ per decade since 1960s.The most robust warming trend was found in the northern plateau.Precipitation also exhibited an increasing trend but with high spatial heterogeneity.Changing climates have caused a series of environmental consequences,including lake area changes,glacier shrinkage,permafrost degradation and exacerbated desertification.The rising temperature is the main reason behind the glaciers shrinkage,snow melting,permafrost degradation and lake area changes on the TP and neighboring regions.The projected loss of glacial area on the plateau is estimated to be around 43%by 2070 and 75%by the end of the century.Vegetation was responsive to the changed environments,varied climates and intensified human activities by changing phenology and productivity.Future global change study should be more oriented toward integrating various research methods and tools,and synthesizing diverse subjects of water,vegetation,atmosphere and soil. | Aamir Latif Sana Ilyas Yangjian Zhang Yuqin Xin Lin Zhou Quan Zhou | 2019 | Journal of Plant Ecology2019，12，6： | 1 |
| 6 | Ccdc57 is required for straightening the body axis by regulating ciliary motility in the brain ventricle of zebrafish显示文摘Recently,cilia defects have been proposed to contribute to scoliosis.Here,we demonstrate that coiled-coil domain-containing 57(Ccdc57)plays an essential role in straightening the body axis of zebrafish by regulating ciliary beating in the brain ventricle(BV).Zygotic ccdc57(Zccdc57)mutant zebrafish developes scoliosis without significant changes in their bone density and calcification,and the maternal-zygotic ccdc57(MZccdc57)mutant embryos display curved bodies since the long-pec stage.The expression of ccdc57 is enriched in ciliated tissues and immunofluorescence analysis reveals colocalization of Ccdc57-HA with acetylated a-tubulin,implicating it in having a role in ciliary function.Further examination reveals that it is the coordinated cilia beating of multiple cilia bundles(MCB)in the MZccdc57 mutant embryos that is affected at 48 hours post fertilization,when the compromised cerebrospinal fluid flow and curved body axis have already occurred.Either ccdc57 m RNA injection or epinephrine treatment reverses the spinal curvature in MZccdc57 mutant larvae from ventrally curly to straight or even dorsally curly and significantly upregulates urotensin signaling.This study reveals the role of ccdc57 in maintaining coordinated cilia beating of MCB in the BV. | Lu Li Juan Li Yuan Ou Jiaxin Wu Huilin Li Xin Wang Liying Tang Xiangyan Dai Conghui Yang Zehong Wei Zhan Yin Yuqin Shu | 2023 | Journal of Genetics and Genomics2023，50，4： | 0 |
| 7 | Inhibitory effect of survivin-shRNA on A431 cutaneous squamous cell carcinoma显示文摘Objective:To observe the effect of survivin-shRNA on A431 cutaneous squamous cell carcinoma(SCC)and explore the molecular biological mechanism of nuclear factorκB(NF-κB)in the inhibition of survivin-shRNA on cutaneous SCC.Methods:Survivin-shRNA adenovirus vector was constructed to screen out the best interference sequence.Nude mice were subcutaneously inoculated with the cultured A431 cell suspension to duplicate A431 transplanted tumor models.These mice were randomly divided into the blank control group,the rAd-EGFP negative control group,the rAd-survivin-shRNA transfection group and the Res positive control group,with 5 mice in each group.The corresponding reagents were injected into the tumors.All the mice were sacrificed on the 20th day.The tumor tissues were isolated,with tumor volume and tumor weight measured,the tumor growth curves were accordingly plotted and the tumor inhibition rate was consequently calculated.Hematoxylin-eosin(HE)staining was used to observe the cellular morphology of the tumors.TUNEL was applied to the detection of cell apoptosis.Western blot was applied to the detection of the expression of Survivin,inhibitor of NF-κB(IκB),P65,P53 and Caspase-3.Results:As to the transplanted tumors,tumor volume and tumor weight were decreased in nude mice in the rAd-survivinshRNA transfection group and the Res positive control group,in comparison with the blank control group and the rAd-EGFP negative control group,the differences were of statistical significance(p<.05);The results of TUNEL showed that the apoptosis rates were significantly increased in the rAd-survivin-shRNA transfection group and the Res positive control group,in comparison with the blank control group and the rAd-EGFP negative control group,the difference was statistically significant(p<.05);In the rAd-survivin-shRNA transfection group and the Res positive control group,the microscopic observation showed a small amount of sparsely-distributed tumor cells,degenerative liquefactive necrosis,cancer cell shrinkage and round-shape,and karyopycnosis;The expressions of Survivin and P65 proteins were decreased in the rAd-survivin-shRNA transfection group and the Res positive control group,in comparison with the blank control group and the rAd-EGFP negative control group,the differences were statistically significant(p<.05),while the expressions of IκB,P53 and Caspase-3 proteins were significantly increased,in comparison with the blank control group and the rAd-EGFP negative control group,the differences were statistically significant(p<.05).Conclusions:Survivin-shRNA can inhibit the growth of the transplanted tumors in cutaneous SCC nude mice,one of the mechanisms is to promote the apoptosis of tumor cells and inhibit the growth of SCC transplanted tumors by inhibiting the NF-κB signaling pathway and then activating the tumor suppressor gene P53. | Yuqin Hao Xia Liu Shuxia Kang Xin Zhang Kun Zhang Yongmeng Zhu | 2018 | Discussion of Clinical Cases2018，5，4： | 0 |
| 8 | MAPK/ERK regulation of P53 in human epidermoid carcinoma cell line A431显示文摘Objective:To observe the impact of activation and inhibition of mitogen activated protein kinases(MAPK)/extracellular signalregulated protein kinase(ERK)signaling pathway on the proliferation and apoptosis of cutaneous squamous cell carcinoma(SCC).cells and investigate the interaction mechanism between MAPK/ERK signaling pathway and tumor suppressor gene P53 in SCC.Methods:Human A431 cells were cultured and divided into MAPK/ERK inhibition groups with low-,medium-and highconcentration of inhibitors(PD98059+DMSO),MAPK/ERK activation groups with low-,medium-and high-concentration of stimuli(IGF+PBS)and blank control group(DMSO).The cell proliferation in vitro was detected by MTT assay,with the cell apoptosis detected by flow cytometry(FCM)and the protein expression of P-ERK and P53 detected by western blot in each group.Results:The A431 cell proliferation was inhibited by different concentrations of PD98059 with a clear concentration-effect and time-effect relationship(p<.05);and the cell proliferation was promoted by the different concentrations of IGF with a clear concentration-effect and time-effect relationship(p<.05).The FCM results showed a significant increase in the apoptosis rate of A431 cells which were treated with PD98059,with a clear concentration-effect relationship(p<.05);while the apoptosis rate was decreased significantly after A431 cells were treated with IGF,also with a concentration-effect relationship(p<.05).The western blot results showed that the expression of P-ERK protein was decreased but the expression of P53 was increased after A431 cells were treated with PD98059.With the concentration of PD98059 going up,the decrease in P-ERK and the increase in P53 were more significant(p<.05);while the expression of P-ERK protein was increased but the expression of P53 was decreased after A431 cells were treated with IGF.With the concentration of IGF going up,the increase in P-ERK and the decrease in P53 were more significant(p<.05).According to Pearson correlation analysis,the expression of P53 was negatively correlated to that of P-ERK(p<.05).Conclusions:After MAPK/ERK signaling pathway was activated by IGF in A431 cells,the expression of pro-apoptotic factor P53 was decreased with the ability of cell proliferation enhanced and the ability of apoptosis reduced.However,after the inhibition of MAPK/ERK signaling pathway,the expression of pro-apoptotic factor P53 was increased with the ability of cell proliferation reduced and the ability of apoptosis increased. | Yuqin Hao Chunyi Kang Xin Zhang Shuxia Kang Xia Liu | 2018 | Discussion of Clinical Cases2018，5，4： | 0 |
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