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Oncology Research 2024年第3期32卷 489-502页

作者： WEIXUE WANG TONGTONG WANG YAN ZHANG TING DENG HAIYANG ZHANG YI BA Department of GI medical Oncology Tanjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerTianjin Key Iaboratory of Digestive CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell death.Apatinib is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis pathway.However,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported yet.Tumor.secreted exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered.Here,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of Apatinib.In conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

关键词： Cellular ferroptosis Exosome Tyrosine kinase inhibitor Gastrointestinal tumors miRNA

Phase II study of novel orally PI3Kα/δinhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2193-2201页

作者： Huaqing Wang Jifeng Feng Yanyan Liu Zhengzi Qian Da Gao Xuehong Ran Hui Zhou Lihong Liu Binghua Wang Meiyun Fang Hebing Zhou Zhenqian Huang Shi Tao Zhuowen Chen Liping Su Hang Su Yu Yang Xiaobao Xie Huijing Wu Ping Sun Guoyu Hu Aibin Liang Zhiming Li Department of Oncology Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China The Institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China Department of medical Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009PR China Department of medical Oncology Henan Cancer HospitalThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003PR China Department of medical Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Hematology The Affiliated Hospital of Inner Mongolia Medical College010050 HohhotPR China Department of Hematology Weifang People’s HospitalThe First Affiliated Hospital of Weifang Medical University261000 WeifangPR China Department of Lymphoma&Hematology Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University410013 ChangshaPR China Department of Hematology The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital050011 ShijiazhuangPR China Department of Lymphoma Weihai Central Hospital264400 WeihaiPR China Department of Hematology and Rheumatology The Affiliated Zhongshan Hospital of Dalian University116001 DalianPR China Department of Hematology Beijing Luhe Hospital101199 BeijingPR China Department of Hematology The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouPR China Department of Hematology The First Affiliated Hospital of Hainan Medical College570102 HaikouPR China Department of Hematology The First People’s Hospital of Foshan528000 FoshanPR China Department of Hematology Shanxi Cancer Hospital030013 TaiyuanPR China Department of Lymphoma Senior Department of HematologyThe Fifth Medical Center of Chinese PLA General Hospital100039 BeijingPR China Department of Lymphoma and Head and Neck Cancer Fujian Cancer Hospital350014 FuzhouPR China Department of Hematology The First People’s Hospit

This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

关键词： lymphoma assessed initiated

ASARA,a prediction model based on Child-Pugh class in hepatocellular carcinoma patients undergoing transarterial chemoembolization

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国际肝胆胰疾病杂志:英文版 2023年第5期22卷 490-497页

作者： Ke-Feng Jia Hao Wang Chang-Lu Yu Wei-Li Yin Xiao-Dong Zhang Fang Wang Cheng Sun Wen Shen Department of Radiology First Central Clinical CollegeTianjin Medical UniversityTianjin 300192China Department of Radiology Tianjin Third Central HospitalTianjin 300170China Department of Radiology Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300192China Department of Gastroenterology and Hepatology Tianjin Third Central HospitalTianjin 300170China

Background:Due to the high heterogeneity among hepatocellular carcinoma(HCC)patients receiving transarterial chemoembolization(TACE),the prognosis of patients varies significantly.The decisionmaking on the initiation and/or repetition of TACE under different liver functions is a matter of concern in clinical practice.Thus,we aimed to develop a prediction model for TACE candidates using risk stratification based on varied liver function.Methods:A total of 222 unresectable HCC patients who underwent TACE as their only treatment were included in this study.Cox proportional hazards regression was performed to select the independent risk factors and establish a predictive model for the overall survival(OS).The model was validated in patients with different Child-Pugh class and compared to previous TACE scoring systems.Results:The five independent risk factors,including alpha-fetoprotein(AFP)level,maximal tumor size,the increase of albumin-bilirubin(ALBI)grade score,tumor response,and the increase of aspartate aminotransferase(AST),were used to build a prognostic model(ASARA).In the training and validation cohorts,the OS of patients with ASARA score≤2 was significantly higher than that of patients with ASARA score>2(P<0.001,P=0.006,respectively).The ASARA model and its modified version“AS(ARA)”can effectively distinguish the OS(P<0.001,P=0.004)between patients with Child-Pugh class A and B,and the C-index was 0.687 and 0.706,respectively.For repeated TACE,the ASARA model was superior to Assessment for Retreatment with TACE(ART)and ALBI grade,maximal tumor size,AFP,and tumor response(ASAR)among Child-Pugh class A patients.For the first TACE,the performance of AS(ARA)was better than that of modified hepatoma arterial-embolization prognostic(mHAP),mHAP3,and ASA(R)models among Child-Pugh class B patients.Conclusions:The ASARA scoring system is valuable in the decision-making of TACE repetition for HCC patients,especially Child-Pugh class A patients.The modified AS(ARA)can be used to screen the ideal candidate for TACE init

关键词： Hepatocellular carcinoma Transarterial chemoembolization Scoring system Prognostic model Child-Pugh class Survival prediction

A pair of SARS-CoV-2 nucleocapsid protein monoclonal antibodies shows high specificity and sensitivity for diagnosis

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Virologica Sinica 2022年第6期37卷 942-945页

作者： An-Kai Zhu Sa-Sa Li Shu-Pei Yu Zhao-Yong Zhang Huan Li Jing-Feng Li Shan-Shan Gao Heng Chen Jincun Zhao Run Shi Mingjian Lu Chaoyang Li Affiliated Cancer Hospital and Institute of guangzhou medical University State Key Laboratory of Respiratory DiseaseKey Laboratory for Cell Homeostasis and Cancer Research of Guangdong High Education InstituteGuangzhou510095China State key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510182China Department of Interventional Radiology Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityGuangzhou510095China

Dear Editor,Severe Acute Respiratory Syndrome Coronavirus Type 2(SARS-CoV-2) is the pathogen of the coronavirus disease 2019(COVID-19), which has spread worldwide.SARS-CoV-2 is an enveloped virus belongs to the family of β-coronavirus(Xu et al., 2020). Its genome is a linear single-stranded positive-sense RNA about 30,000 nucleotides packed inside a virion with a diameter of 100 nm and a volume of about 10^(6)nm^(3)(Bar-On et al., 2020).

关键词： al. diagnosis specificity

Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma

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Neuroscience Bulletin 2023年第11期39卷 1717-1731页

作者： Bo Ni Yiqing Yin Zekun Li Junjin Wang Xiuchao Wang Kaiyuan Wang Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Anesthesiology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China

Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive lethal malignancy,characterized by late diagnosis,aggressive growth,and therapy resistance,leading to a poor overall prognosis.Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape.The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets.In this review,we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC,summarize the potential signaling pathways modulating the neuronal-cancer interaction,and discuss the current and future therapeutic possibilities for this condition.

关键词： PDAC Cancer-neuroscience Peripheral innervation Pain

Long-term effect of a large dose of iodinated contrast in patients with mild thyroid dysfunction:a prospective cohort study

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Chinese medical Journal 2023年第17期136卷 2044-2049页

作者： Hailong Si Kangyin Chen Qin Qin Yuanyuan Liu Bingrang Zhao Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China Department of Cardiovascular Disease Tianjin Chest HospitalTianjin 300051China Tianjin Institute of Cardiovascular Diseases Tianjin Chest HospitalTianjin 300051China Comprehensive Disease Center Tianjin Chest HospitalTianjin 300051China

Background:More than 75 million procedures with intravascular iodine-based contrast media(ICM)are performed worldwide every year,and some patients undergoing these procedures do not have normal thyroid function.The long-term effects of ICM in patients with mild thyroid dysfunction(TD)are unclear.Methods:This prospective cohort study was conducted in China.Patients with stable angina pectoris with total triiodothyronine(TT3)reduction,normal thyroid-stimulating hormone,and reverse triiodothyronine(rT3)were enrolled and divided into high-dose(≥100 mL ICM)and low-dose groups(<100 mL ICM).We dynamically investigated the trends in thyroid function,rT3,and thyroid antibodies one year after ICM exposure.Results:A total of 154 patients completed 6 months of follow-up and 149 completed 1 year of follow-up.Thyroglobulin antibody(TGAB)levels were elevated in 41(26.6%)patients before ICM exposure,11(7.1%)of whom also had elevated thyroid peroxidase antibody levels.Transient subclinical TD occurred 6 months after ICM exposure;75.5%(34/45)of post-operative TD occurred in the high-dose group.One patient developed severe hypothyroidism with myxedema,requiring drug intervention 1 year after ICM exposure.The level of rT3 showed no statistically significant changes during post-operative follow-up(P=0.848).The TGAB level decreased at 6th month(P<0.001),but increased at 1 year after ICM exposure(P=0.002).Conclusions:Patients with T3 reduction are at a risk of transient subclinical TD and hypothyroidism after a single large dose of ICM.Follow-up of this population at 9-12 months after ICM exposure is warranted.

关键词： Coronary heart disease Stable angina pectoris Iodinated contrast agents Low T3 Subclinical thyroid dysfunction Non-thyroidal illness

Update on diffuse large B-cell lymphoma: highlights from the 2022 ASCO Annual Meeting

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Cancer Biology & Medicine 2022年第8期19卷 1117-1120页

作者： Minghan Qiu Shan Wu Xinrui Chen Huaqing Wang Department of Oncology Tianjin Union Medical CenterNankai UniversityTianjin 300191China The Institute of Translational Medicine Tianjin Union Medical CenterNankai UniversityTianjin 300121China

Diffuse large B-cell lymphoma(DLBCL)is the most common non-Hodgkin’s lymphoma(NHL)and has high heterogeneity.Approximately 30%–50%of patients develop relapsed/refractory(R/R)disease,which remains a major cause of mortality1-3.In recent years,a variety of novel therapies have emerged,including bispecific T-cell engagers(BiTEs),antibody–drug conjugates(ADCs),chimeric antigen receptor T cells(CAR-T),and selective BTK inhibitors,which have provided effective treatment strategies for patients with DLBCL1,4.Recently,the 58th Annual Meeting of the American Society of Clinical Oncology(ASCO)was held in Chicago,presenting cutting-edge studies in DLBCL.Here,we discuss a selection of interesting data on this topic.

关键词： lymphoma ASCO mortality

Advantages of switching to elvitegravir/cobicistat/emtricitabine/ tenofovir therapy in virologically-suppressed people living with human immunodeficiency virus/acquired immune deficiency syndrome

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Chinese medical Journal 2022年第22期135卷 2747-2749页

作者： Lina Fan Lei Li Liying Gao Yue Hu Aiping Yu Defa Zhang Chunting Qiu Rong Huang Yue Wu Ping Ma Department of Infectious Diseases Tianjin Second People's HospitalTianjin 300192China

To the Editor:With recent advances in antiretroviral therapy(ART)regimens,many patients may benefit from switching drugs.The new combination drug,elvitegravir/cobicistat/emtricitabine/tenofovir(E/C/F/TAF),has been approved for use in people living with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AID[PLWHA])in China and has also been included within the scope of medical insurance.This single-tablet regimen provides a convenient,once-daily,treatment option for many PLWHA.E/C/F/TAF was shown to increase adherence to ART and decrease the risk of drug resistance and virological failure.[1–4]However,another study showed a higher level of several lipid parameters in patients with tenofovir alafenamide(TAF)-based therapy compared with tenofovir(TDF)-based therapy in treatment-naïve and-experienced adults.[5]In 2019,a phase IV clinical study of E/C/F/TAF was conducted at our Antiviral Treatment Center,allowing us to explore the virological and immunological responses during 12 months of follow-up after switching.We also explored the changes in renal function,liver function,and lipid parameters in PLWHA.

关键词： immunodeficiency drugs treatment

Negative effects of enlarging internal limiting membrane peeling for idiopathic macular hole surgery

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International Journal of Ophthalmology(English edition) 2022年第11期15卷 1806-1813页

作者： Ze-Tong Nie Bo-Shi Liu Yong Wang Qiong Chen Jiao-Ting Wei Meng Yang Shao-Fang Pang Xiao-Rong Li Bo-Jie Hu Tianjin key Laboratory of Retinal Functions and Diseases Tianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University EyeHospitalTianjin 300384China

AIM: To observe the effects of the different extents of internal limiting membrane(ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole(IMH).METHODS: In this retrospective cohort study, 36 patients were reviewed and divided into two groups according to the extent of ILM peeling: group A(18 patients), with the peeling area within one-half of the optic disc macular distance as the radius;group B(18 patients), with the peeling area larger than that of group A but did not exceed the optic disc macular distance as the radius. The main outcomes included the best corrected visual acuity(BCVA), light-adaptive electroretinography, macular hole(MH) closure rate, central macular thickness(CMT), retinal nerve fiber layer(RNFL) and ganglion cell complex(GCC) thickness [nine regions based on the Early Treatment of Diabetic Retinopathy Study(ETDRS) ring] before and 1, 3, and 6mo after surgery.RESULTS: The closure rate was 94.4%(17/18) both in groups A and B. The BCVA in both groups improved significantly compared with the preoperative values, but there was no difference between the two groups. The b-wave amplitude of the electroretinogram analysis was significantly improved in both groups compared to that of the preoperative period, with a greater increase in group A than in group B at 6mo(P=0.017). The CMT in both groups gradually decreased after surgery, and there was no difference between the two groups. The RNFL thickness of the temporal outer ring region in group B was significantly lower than that in group A at 3 and 6mo after surgery(P=0.010, 0.032). The GCC thickness of the temporal outer ring region in group B was significantly lower than that in group A at 6mo after surgery(P=0.038).CONCLUSION: Enlarging the extent of ILM peeling doesn’t affect the IMH closure rate and visual acuity recovery, but the greater the extent of peeling, the greater the damage to the inner retinal structures.

关键词： idiopathic macular hole internal limiting membrane light-adapted electroretinography retinal nerve fiber layer ganglion cell complex

p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3592-3608页

作者： Mingyang Ma Shuyao Hua Xiangde Min Liang Wang Jun Li Ping Wu Huifang Liang Bixiang Zhang Xiaoping Chen Shuai Xiang Department of General Surgery Tianjin Medical University General HospitalTianjinChina Hepatic Surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Clinical Nutrition Shanghai Jiao Tong University Affliated Sixth People's HospitalShanghaiChina Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Wuhan Pulmonary Hospital Wuhan Institute for Tuberculosis ControlWuhanChina Department of Pathophysiology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Hubei key Laboratory of Hepato-Pancreato-Biliary Disease WuhanChina key Laboratory of Organ Transplantation Ministry of EducationWuhanChina key Laboratory of Organ Transplantation National Health CommissionWuhanChina key Laboratory of Organ Transplantation Chinese Academy of Medical SciencesWuhanChina

Hepatic progenitor cells(HPCs)hold tremendous potential for liver regeneration,but their well-known limitation of proliferation hampers their broader use.There is evidence that laminin is required for the proliferation of HPCs,but the laminin isoform that plays the dominant role and the key intracellular downstream targets that mediate the regulation of HPC proliferation have yet to be determined.Here we showed that p53 expression increased gradually and reached maximal levels around 8 days when lamininα4,α5,β2,β1,andγ1 subunit levels also reached a maximum during HPC activation and expansion.Laminin-521(LN-521)promoted greater proliferation of HPCs than do laminin,matrigel or other laminin isoforms.Inactivation of p53 by PFT-αor Ad-p53^(V143A) inhibited the promotion of proliferation by LN-521.Further complementary MRI and bioluminescence imaging analysis showed that p53 inactivation decreased the proliferation of transplanted HPCs in vivo.p53 was activated by LN-521 through the Integrinα6β1/FAK-Src-Paxillin/Akt axis.Activated p53 was involved in the nuclear translocation of CDK4 and inactivation of Rb by inducing p27^(Kip1).Taken together,this study identifies LN-521 as an ideal candidate substrate for HPC culture and uncovers an unexpected positive role for p53 in regulating proliferation of HPCs,which makes it a potential target for HPC-based regenerative medicine.

关键词： laminin progenitor inhibited