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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： pin zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng zhang Richard Jones Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

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Chiral thermally activated delayed fluorescence materials for circularly polarized organic light-emitting diodes

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Science China Chemistry 2024年第4期67卷 1097-1116页

作者： Li Yuan Yi-pin zhang You-Xuan Zheng State Key Laboratory of Coordination Chemistry Collaborative Innovation Center of Advanced MicrostructuresJiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Chirality is an important natural characteristic of organic molecules,and chiral organic molecules have shown extensive application in areas such as pharmaceutical development and material science.Benefiting from the ability to achieve circularly polarized luminescence(CPL),chiral luminescent materials have shown potential applications in anti-glare display,optical communication and,3D display,etc.Due to the ability to harvest both singlet and triplet excitons by a fast reverse intersystem crossing process without involving noble metals,chiral thermally activated delayed fluorescence(TADF)materials with point chirality,axial chirality,planar chirality and helical chirality are regarded as the state-of-the-art materials for circularly polarized organic light-emitting diodes(CP-OLEDs).In recent years,the chiral TADF materials and CP-OLEDs have rapidly developed,but unfortunately,the dissymmetry factors(g)are far from the requirement of practical applications.The ideal emitters and devices should have both high efficiency and a g factor,or at least a balance between these two elements.This review gives an overview of recent progress in chiral TADF materials,with a particular focus on the chiral skeleton,CPL property and device performance.Furthermore,the molecular design concept,device structure and methods to improve the g factors of chiral materials and CP-OLEDs are also discussed.

关键词： chiral thermally activated delayed fluorescence material chiral skeleton circularly polarized luminescence circularly polarized organic light-emitting diodes dissymmetry factor

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Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation

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World Journal of Diabetes 2024年第5期15卷 958-976页

作者： Hong Xu Li-Bo zhang Yi-Yi Luo Ling Wang Ye-pin zhang Pei-Qi Chen Xue-Ying Ba Jian Han Heng Luo Department of Ophthalmology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Precision Medicine Center of Chuxiong Yi Autonomous Prefecture The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Department of Endocrinology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Department of Pathology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina

BACKGROUND Synaptotagmins(SYTs)are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones.However,few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy(DR)through Ca2+/glucose transporter-1(GLUT1)and the possible regulatory mechanism of SYTs.AIM To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR.METHODS DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells(ARPE-19).Bioinformatics analysis,reverse transcriptase-polymerase chain reaction,Western blot,flow cytometry,ELISA,HE staining,and TUNEL staining were used for analysis.RESULTS Six differentially expressed proteins(SYT2,SYT3,SYT4,SYT7,SYT11,and SYT13)were found between the DR and control groups,and SYT4 was highly expressed.Hyperglycemia induces SYT4 overexpression,manipulates Ca2+influx to induce GLUT1 fusion with the plasma membrane,promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake,induces ARPE-19 cell apoptosis,and promotes DR progression.Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR,resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane,and these effects were blocked by oe-Parkin treatment.Moreover,dysregulation of the myelin transcription factor 1(Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process,and this process was inhibited in the oe-MYT1-treated group.CONCLUSION Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

关键词： Diabetic retinopathy Glucose transporter-1 Synaptotagmin 4 Parkin Myelin transcription factor 1

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Treatment patterns and clinical outcomes in patients with metastatic breast cancer treated with palbociclib-based therapies:real-world data in the Han population

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Chinese Medical Journal 2022年第14期135卷 1734-1741页

作者： Hongnan Mo Fei Ma Qing Li pin zhang Peng Yuan Jiayu Wang Yang Luo Ruigang Cai Qiao Li Binghe Xu Department of Medical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive(ER+)metastatic breast cancer in routine clinical practice.Methods:The clinical data of patients with ER+metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database.The efficacy profile of palbociclib in this Han population was evaluated,especially for various combination regimens.The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed.Results:A total of 186 patients from 89 cities in 18 provinces in China were enrolled.The median progression-free survival(PFS)was similar among different palbociclib-combined groups(P=0.566):10.0 months(95%confidence interval[CI]3.8-16.1)in the+exemestane group,9.7 months(95%CI 6.3-13.1)in the+letrozole group,7.8 months(95%CI 5.5-10.2)in the+fulvestrant group,7.2 months(95%CI 3.2-11.3)in the+toremifene group,and 6.1 months(95%CI 1.2-11.0)in the+anastrozole group.Thirty-four patients(18.3%)had received everolimus for their metastatic disease before the prescription of palbociclib.The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group(50.0%vs.82.2%,P<0.001).Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group(3.4 months vs.8.8 months,P=0.001).After propensity score matching,patients pre-treated with everolimus had similar PFS(4.4 months,95%CI 0.5-8.2)compared with everolimus-naïve patients(6.1 months,95%CI 4.7-7.5,P=0.439).Conclusions:Various palbociclib-based regimens have promising efficacy in ER+metastatic breast cancer in real-world settings,even in patients who had been pre-treated with everolimus.

关键词： Metastatic breast cancer Palbociclib Progression-free survival Real-world data

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Combined chemo-endocrine therapy as a potential new option for HR+/HER2−advanced breast cancer:a prospective study of fulvestrant plus oral vinorelbine

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Cancer Biology & Medicine 2023年第4期20卷 287-296页

作者： Xue Wang Jian Yue Yikun Kang Zhong Dai Jie Ju Jiayu Wang pin zhang Fei Ma Binghe Xu Peng Yuan Department of VIP Medical Services National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Comprehensive Oncology Huanxing Cancer HospitalBeijing 100026China Department of Medical Oncology and Clinical Trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.

关键词： HR+/HER2−breast cancer recurrence metastasis fulvestrant oral vinorelbine

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A two-step strategy for constructing stable gel polymer electrolyte interfaces for long-life cycle lithium metal batteries

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Journal of Materiomics 2022年第5期8卷 1048-1057页

作者： Qiujun Wang pin zhang Weiqi Zhu Di zhang Zhaojin Li Huan Wang Huilan Sun Bo Wang Li-Zhen Fan Hebei Key Laboratory of Flexible Functional Materials School of Materials Science and EngineeringHebei University of Science and TechnologyShijiazhuang050018China Beijing Advanced Innovation Center for Materials Genome Engineering Institute of Advanced Materials and TechnologyUniversity of Science and Technology BeijingBeijing100083China

Due to the high reactivity between the lithium metal and traditional organic liquid electrolyte,the reaction of lithium metal electrode is usually uneven and there are also unexpected side reactions.Therefore,construction of a stable solid electrolyte interface(SEI)is highly essential to improve the performance of lithium metal anode.Herein,a sandwich-like gel polymer electrolyte(GPE)is accurately prepared by in-situ polymerization of Polyacrylonitrile(PAN)nanofiber membrane with trihydroxymethylpropyl trimethylacrylate(TMPTMA)and 1,6-hexanediol diacrylate(HDDA).The resulting GPE with a tightly cross-linked gel skeleton exhibits high ionic conductivity and electrochemical window of 5.6 V versus Li/Li^(+).In particular,the pretreatment of Li metal anode can improve the interfacial wettability,and the synergy of the chemically pretreated Li metal anode surface and the GPE can electrochemically in situ generate SEI with compositionally stable and fluorine-rich inorganic components.Owing to these unique advantages,the interfacial compatibility between the GPE and lithium metal is greatly improved.Meanwhile,the formed SEI can inhibit the formation of lithium dendrites,and decomposition of GPE would be alleviated.The assembled Li-FEC|GPE|LiFePO_(4) full cell shows a high initial discharge capacity of 157.1 mA h g^(-1),and maintains a capacity retention of 92.3%after 100 cycles at 0.2C.

关键词： Gel polymer electrolyte Pre-lithiation Lithium-metal batteries In-situ polymerization

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Pyrotinib plus capecitabine could significantly improve overall survival in HER2-positive metastatic breast cancer

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1378-1380页

作者： Xiuwen Guan Fei Ma Qiao Li Shanshan Chen Ying Fan Jiayu Wang Yang Luo pin zhang Qing Liand Binghe Xu Department of Medical Oncology and State Key Laboratory of Molecular Oncology National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Dear Editor,The irreversible pan-ErbB tyrosine kinase inhibitors(TKIs),including neratinib and pyrotinib,demonstrated more complete inhibition towards ErbB-family and promising antitumor activity compared to lapatinib,a reversible TKI.1 In the phase III NALA study for HER2-positive metastatic breast cancer(MBC)who were progressed after two lines of HER2-targeted regimens,2 significant improvement was observed in progression-free survival(PFS)in patients receiving neratinib combined with capecitabine when compared to lapatinib plus capecitabine(L+C)group.However,the 2.2-month PFS improvement in neratinib plus capecitabine cohort failed to translate to a significant benefit in the overall survival(OS,24.0 vs 22.2 months,P=0.2086).2 While another irreversible TKI,pyrotinib combined with capecitabine(P+C)achieved clinically and statistically significant improvement in the PFS and a trend of benefits in the OS when compared to the L+C group,based on the interim analysis(with the cutoff of March 31,2019)of the phase III PHOEBE study.3 Generally speaking,current evidence was still limited regarding the survival data of irreversible TKIs.

关键词： capecitabine HER2 breast

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Metabolic surgery in China: present and future

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Journal of Molecular Cell Biology 2021年第8期13卷 594-609页

作者： Yinfang Tu Yuqian Bao pin zhang Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth Peopled HospitalShanghai Diabetes InstituteShanghai Clinical Center of DiabetesShanghai Key Laboratory of Diabetes MellitusShanghai Key Clinical Center for Metabolic DiseaseShanghai 200233China Department of Endocrinology and Metabolism Jinshan District Central Hospital of Shanghai Sixth People's HospitalShanghai 201599China Department of Bariatric and Metabolic Surgery Shanghai Jiao Tong University Affiliated Sixth Peopled HospitalShanghai 200233China

Obesity and its related complications comprise a serious public health problem worldwide,and obesity is increasing in China.Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications.The pathogenesis of obesity is complex and not yet fully understood.Here,we review the current efficacy and safety of metabolic surgery,as well as recent progress in mechanistic studies and surgical procedures in China.The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.

关键词： metabolic surgery type 2 diabetes mellitus obesity metabolic syndrome

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Newly Identified Silicate Carbon Stars from IRAS Low-Resolution Spectra

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Chinese Journal of Astronomy and Astrophysics 2006年第6期6卷 697-704页

作者： Pei-Sheng Chen pin zhang National Astronomical Observatories / Yunnan Observatory Chinese Academy of Sciences Kunming 650011 Cosmic Ray Institute Yunnan University Kunming 650091

The discovery of silicate carbon star poses a challenge to the theory of stellar evolution in the late stage, hence it is important to look for more silicate carbon stars. To this end we have carried out cross-identifications between the new IRAS Low-Resolution Spectrum （LRS） database and the new carbon star catalog, CGCS3. We have found nine new silicate carbon stars with silicate features around 10μm and/or 18 μm. These newly identified stars are located in the Regions Ilia and VII in the IRAS two-color diagram, which means they indeed have typical far infrared colors of silicate carbon stars. The infrared properties of each of these sources are discussed.

关键词： stars AGB and post-AGB - star carbon - infrared stars

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An infrared study of Be stars based on ISO SWS01 spectra

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Research in Astronomy and Astrophysics 2009年第7期9卷 770-776页

作者： pin zhang Zai-Qi Fu Cosmic Ray Institute Yunnan University Kunming 650091 China Department of Physics Zhaotong Teachers College Zhaotong 657000 China

The Infrared Space Observatory （ISO） Short-Wavelength Spectrometer （SWS） spectra of 10 Be stars are presented. It can be seen that the Be stars show a diversity in their ISO SWS01 spectral classifications by Kraemer et al., from naked stars, stars associated with dust, stars with warm dust shells, stars with cool dust shells to very red sources. In addition, the Brα/HI（14-6） line flux ratio derived for the sample stars is compared with that of P Cyg, and it is found that the line ratio of Be stars which were investigated show not only lower values as suggested by Waters et al., but also larger values. Therefore, the line ratio cannot be used to judge whether a star is a Be star or not.

关键词： stars circumstellar matter - infrared stars - stars emission-line Be

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