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Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 599-610页

作者： Yi Tian Zhiguang Fu Xiaosheng Zhu Chunjing Zhan Jinwei Hu Li Fan Chaojun Song Qian Yang Yu Wang Mei Shi department of Radiation oncology Xijing HospitalThe Fourth Military Medical UniversityXi’an 710032China department of oncology Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China department of Tumor Radiotherapy Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China department of Gastroenterology Air Force Hospital of Southern Theater CommandGuangzhou 510062China department of Pharmaceutical Chemistry and Analysis School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China School of Life Sciences Northwestern Polytechnical UniversityXi’an 710072China Institue of Materia Medica School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration ***,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT *** address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet *** system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after *** immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were *** the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor ***-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,*** by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,***,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

关键词： X-ray excited photodynamic therapy singlet oxygen low dose X-Ray irradiation efficient antitumor therapy anti-tumor immunity

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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan Chen Shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang Wenhai Deng Ping Li Wen Lei Aibin Liang Wenbin Qian department of hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China department of hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China department of hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β

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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-Yang Liu Song Dong Xue-Ning Yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji Yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu Si-Yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry oncology Corporation FuzhouChina Chinese Thoracic oncology Group(CTONG) GuangzhouChina department of hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

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World Journal of Clinical Cases 2024年第2期12卷 285-292页

作者： Sha-Sha Sun Xiao-Di Guo Wen-Dong Li Jing-Long Chen department of oncology Capital Medical University Affiliated Beijing Ditan HospitalBeijing 100015China

BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is *** To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced *** HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were *** patients were treated with lenvatinib every day and sintilimab once every 3 ***,TACE was performed every 4-6 wk if *** primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse *** Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January *** a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,*** ORR and DCR were 45%and 90%,*** median progressive free survival and median OS were not *** complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

关键词： Lenvatinib Sintilimab Advanced hepatocellular carcinoma Combination therapy Tumor response

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Clinical features and prognostic analysis of the blastoid variant of mantle cell lymphoma: An analysis of 20 patients from two centers

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Cancer Pathogenesis and Therapy 2024年第1期2卷 62-64页

作者： Sai Huang Shaomei Liu Hongmei Jing Ping Chen Lili Dong Xiaoyu Hao Jian Bo Lu Sun Yu Zhao department of hematology Senior Department of HematologyThe Fifth Medical Center of PLA General HospitalBeijing 100039China department of hematology The First Medical Center of PLA General HospitalBeijing 100853China medical School of Chinese PLA General Hospital Beijing 100853China department of Clinical Laboratory The First Medical Center of PLA General HospitalBeijing 100853China department of hematology Lymphoma Research CenterPeking University Third HospitalBeijing 100191China department of Pathology The First Medical Center of PLA General HospitalBeijing 100853China

Managing Editor:Peng Lyu Mantle cell lymphoma(MCL),a relatively uncommon subtype of non-Hodgkin's lymphoma(NHL),constitutes approximately 2%-10%of NHL *** by its inertness,aggressiveness,and incurability,MCL has a med... 详细信息

关键词： lymphoma NHL Clinical

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Efficacy of Yisui granule(益髓颗粒)on myelodysplastic syndromes in SKM-1 mouse xenograft model through suppressing Wnt/β-catenin signaling pathway

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Journal of Traditional Chinese Medicine 2024年第1期44卷 78-87页

作者： WU Jieya HOU Li ZHANG Xiaoyuan Elizabeth Gullen GAO Chong WANG Jing department of oncology and hematology Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China department of Pharmacology Yale Medical SchoolNew HavenCT 06510USA department of oncology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China

OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin *** amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein ***:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long ***,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s ***,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin ***:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.

关键词： myelodysplastic syndromes Wnt signaling pathway beta catenin decitabine survival adverse effects sFRP5 gene methylation Yisui granule

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Analysis of the role of dihydromyricetin derived from vine tea(Ampelopsis grossedentata)on multiple myeloma by activating STAT1/RIG-I axis

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oncology Research 2024年第8期32卷 1359-1368页

作者： WEI JIANG MEI ZHOU department of hematology Shaoxing Shangyu People’s HospitalShaoxing312000China department of hematology Zhuji People’s HospitalShaoxing311800China

Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately *** study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its *** MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro *** counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,*** real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo ***,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 *** DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in ***,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in ***,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 ***,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in ***,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.

关键词： Dihydromyricetin Multiple myeloma Epithelial-mesenchymal transition Tumor growth

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Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer

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Asian Journal of Andrology 2024年第4期26卷 402-408页

作者： Shan-Shan Wang Xiao-Jie Bian Jun-Long Wu Bei-He Wang Sheng Zhang Ding-Wei Ye department of Urology Fudan University Shanghai Cancer CenterShanghai 200032China department of oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China department of medical oncology Fudan University Shanghai Cancer CenterShanghai 200032China.

This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer(mHSPC).PubMed,EMBASE,and the Cochrane Library were comprehensively searched for eligible randomized controlled trials(RCTs)published from inception to October *** included abiraterone,apalutamide,enzalutamide,docetaxel,darolutamide,and androgen deprivation therapy(ADT),either as doublet or triplet *** outcomes examined were overall survival(OS),progression-free survival(PFS),castration-resistant prostate cancer(CRPC)-free survival,time to symptomatic skeletal event(SSE),and *** surface under the cumulative ranking curve(SUCRA)was determined to identify the preferred *** RCTs were *** combination of darolutamide,docetaxel,and ADT had the highest SUCRA of 84.3 for OS,followed by combined abiraterone,docetaxel,and ADT(SUCRA=71.6).The highest SUCRAs for PFS were observed for triplet therapies(abiraterone,docetaxel,and ADT[SUCRA=74.9],followed by enzalutamide,docetaxel,and ADT[SUCRA=74.3])and other androgen receptor axis-targeted therapy-based doublet therapies(SUCRAs:26.5–59.3).Darolutamide,docetaxel,and ADT had the highest SUCRAs,i.e.,80.8 and 84.0 regarding CRPC-free survival and time to SSE,*** Grade>3 adverse events(AEs),the SUCRAs of triplet therapies(SUCRAs:14.8–31.5)were similar to that of docetaxel and ADT(SUCRA=39.5).Three studies had a low risk of bias in all categories;the remaining studies had at least an unclear risk of bias in at least one *** therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC,with acceptable safety *** might be the optimal option for triplet therapy in combination with docetaxel and ADT.

关键词： androgen antagonist androgen receptor antagonist docetaxel meta-analysis prostatic neoplasm

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High PSMA expression is associated with immunosuppressive tumor microenvironment in clear cellrenal cell carcinoma

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Precision Clinical Medicine 2024年第2期7卷 190-193页

作者： Panagiotis J.Vlachostergios Athanasios Karathanasis Konstantinos Dimitropoulos Ioannis Zachos Vassilios Tzortzis department of medical oncology IASO Thessalias HospitalLarissa 41110Greece department of Urology University of ThessalySchool of Health SciencesFaculty of MedicineUniversity Hospital of LarissaLarissa 41110Greece Division of hematology and medical oncology Department of MedicineWeill Cornell MedicineNew YorkNY 10065USA department of Urology Aberdeen Royal InfirmaryAberdeen AB252ZNUK

Dear Editor,Clear cell renal cell carcinoma(ccRCC)is a highly vascular *** surrogate markers that may reflect the neovasculature burden of ccRCC,prostate specific membrane antigen(PSMA)has emerged as a promising one,by virtue of its ability to be measured either immunohistochemically and transcriptionally or on positron emission tomography(PET)imaging[1,2].While the relationship between PSMA and neoangiogenesis in ccRCC is well established,the potential association between PSMA and the immune landscape of ccRCC is much less understood.

关键词： PSMA carcinoma cell

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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina Institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina department of hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes hematology Hospital SuzhouChina department of hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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