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Evaluation of sodium borocaptate(BSH)and boronophenylalanine(BPA)as boron delivery agents for neutron capture therapy(NCT)of cancer:an update and a guide for the future clinical evaluation of new boron delivery agents for NCT

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Cancer Communications 2024年第8期44卷 893-909页

作者： Rolf F.Barth Nilendu Gupta Shinji Kawabata Department of pathology The Ohio State UniversityColumbusOhioUSA Department of Radiation oncology The Ohio State UniversityColumbusOhioUSA Department of Neurosurgery Osaka Medical and Pharmaceutical UniversityTakatsukiOsakaJapan

Boron neutron capture therapy(BNCT)is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10,a stable isotope,is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form,which undergoes instantaneous nuclear fission to produce high-energy,tumoricidal alpha *** primary purpose of this review is to provide an update on the first drug used clinically,sodium borocaptate(BSH),by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug,boronophenylalanine(BPA),which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous ***,BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers,specifically brain tumors and recurrent tumors of the head and neck *** focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with highgrade ***,wewill summarize the studies thatwere carried out in Japan with BSH and subsequently at our own institution,The Ohio State University,and those of several other ***,we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for ***,although there have been intense efforts to develop new and better boron delivery agents for BNCT,none of these have yet been evaluated *** present reportwill provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

关键词： Boron neutron capture therapy(BNCT) boronophenylalanine(BPA) brain tumors head and neck cancer sodium borocaptate(BSH)

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ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling

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oncology Research 2024年第7期32卷 1209-1219页

作者： XIA DA HAN GE JUNFENG SHI CHUNHUA ZHU GUOZHU WANG YUAN FANG JIN XU Department of Breast and Thyroid Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of oncology Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of pathology Nanjing First HospitalNanjing Medical UniversityNanjingChina

Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and ***2 expression in TNBC cell lines was detected by PCR and Western blot *** migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were ***:ROR2 expression was high in metastatic TNBC ***2 knockdown suppressed the migration,invasion and chemoresistance of TNBC ***2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and ***,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to ***2 could activate PI3K/AKT/mTOR signaling in TNBC ***:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.

关键词： Receptor tyrosine kinase-like orphan receptor 2 Triplet-negative breast cancer Proliferation Apoptosis PI3K/AKT/mTOR signaling Metastasis

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Clinicopathological features,psychological status,and prognosis of 33 patients with occult breast cancer

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World Journal of Psychiatry 2024年第1期14卷 76-87页

作者： Hong-Mei Wang Ao-Yang Yu Lin-Lin Li Lu-Yao Ma Meng-Han Cao Yu-Le Yang Xiao-Bing Qin Juan-JuanTang Zheng-Xiang Han Department of oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina Graduate School Xuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of pathology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

BACKGROUND Occult breast cancer(OBC)has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast *** to the small number of cases and limited clinical experience,treatments vary greatly around the world and no standardized treatment has yet been *** To investigate the clinicopathological features,psychological status and prognostic features of patients with *** The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively *** psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression ***’emotions,stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule,the Chinese Perceived Stress Scale,and the Connor-Davidson Resilience Scale(CD-RISC),*** survival was calculated using the Kaplan-Meier method,and survival curves were plotted for analysis with the log-rank *** and multivariate survival analyses were performed using the Cox regression *** The 33 OBC patients included 32 females and 1 *** the 33 patients,30(91%)had axillary tumors,3(9%)had a neck mass as the primary symptom;18(54.5%)had estrogen receptor-positive tumors,17(51.5%)had progesterone receptor-positive tumors,and 18(54.5%)had Her-2-positive tumors;24(72.7%)received surgical treatment,including 18 patients who underwent modified radical mastectomy,1 patient who underwent breast-conserving surgery plus axillary lymph node dissection(ALND),and 5 patients who underwent ALND alone;12 patients received preoperative neoadjuvant *** 30 patients developed anxiety and depression,with low positive affect scores and high negative affect scores,accompanied by a high stress level and poor psycho

关键词： Occult breast cancer Breast cancer Perceived Stress Scale Axillary lymph node dissection

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Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees Department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States Department of pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States Division of Surgical oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic *** disease is typically associated with increased tumor diameter,multifocality,and vascular *** report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic *** SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid *** CT evaluations demonstrated steatosis,but no cirrhosis or liver *** ultrasound demonstrated a normal-appearing pancreas,biliary tree,and *** needle aspiration yielded atypical *** differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal *** review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated *** resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 *** fetoprotein was 23.3 ng/*** patient was diagnosed with HCC with portocaval nodal ***:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic *** identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic *** Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

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Remodeling Tumor Immune Microenvironment by Using Polymer-Lipid-Manganese Dioxide Nanoparticles with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer

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Research 2024年第3期2023卷 83-96页

作者： Abdulmottaleb E.Zetrini HoYin Lip Azhar Z.Abbasi Ibrahim Alradwan Taksim Ahmed Chunsheng He Jeffrey T.Henderson Andrew M.Rauth Xiao Yu Wu Advanced Pharmaceutics and Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoM5S 3M2TorontoONCanada. departments of medical Biophysics and Radiation oncology University of TorontoM5G 1L7TorontoONCanada.

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer–lipid manganese dioxide nanoparticles (PLMDs) to remodel the tumor immune microenvironment (TIME) by increasing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD treatment sensitized hypoxic human and murine CRPC cells to radiation, significantly increasing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the secretion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress. Reoxygenation via PLMDs also polarized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor alpha release, and thus reducing the viability of murine CRPC TRAMP-C2 cells. In a syngeneic TRAMP-C2 tumor model, intravenous injection of PLMDs suppressed, while radiation alone enhanced recruitment of regulatory T cells and myeloid-derived suppressor cells. Pretreatment with PLMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor CD8+ T cells and M1 macrophages to tumor sites. Taken together, TIME modulation by PLMDs plus radiation profoundly delayed tumor growth and prolonged median survival compared with radiation alone. These results suggest that PLMDs plus radiation is a promising treatment modality for improving therapeutic efficacy in radioresistant and immunosuppressive solid tumors.

关键词： RAW264.7 alone treatment

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New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO SOOK HEE HONG HYUNG SOON PARK IN-HO KIM HO JUNG AN BYOUNG YONG SHIM JIN HYOUNG KANG Division of medical oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Department of pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Division of medical oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)*** cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival ***,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing ***:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with *** APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot *** blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B *** viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with ***:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with *** with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B *** treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B *** to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B ***:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR *** result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

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The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

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oncology Research 2024年第4期32卷 785-797页

作者： MENNA AL-ADL MAGDY MYOUSSEF AHMED EL-SEBAIE SHERIF REFAAT AFAF EL-SAID Division of Biochemistry Department of ChemistryFaculty of ScienceMansoura UniversityMansoura35511Egypt Hematology Unit Department of Clinical PathologyFaculty of MedicineMansoura UniversityMansoura35511Egypt medical oncology Unit Oncology Center Mansoura UniversityMansoura35511Egypt Department of Genetics Mansoura University Children’s HospitalMansoura35511Egypt

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including *** gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used *** research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide *** was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy *** presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed *** CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT ***,OR=5.4,p<0.001)*** cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian *** variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

关键词： B-CLL Xenobiotics Cytochromes P450 CYP2B6

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Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer(RATICAL):a nationwide multicenter retrospective study

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Cancer Communications 2024年第9期44卷 992-1004页

作者： Lin Li Wencai Li ChunyanWu Yanfeng Xi Lei Guo Yuan Ji Lili Jiang Ji Li Jingping Yun Gang Chen Yuan Li Yueping Liu DianbinMu Yuchen Han Leina Sun Qingxin Xia Xiaodong Teng Nanying Che WeiWu Xueshan Qiu Chao Liu Xiaochu Yan Daiqiang Li Zhihong Zhang ZheWang Yujun Li ZhengWang Lingchuan Guo Xiu Nie Jingshu Geng Jianhua Zhou Jianming Ying Department of pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking UnionMedical CollegeBeijingP.R.China Department of pathology the First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of pathology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiP.R.China Department of pathology Cancer Hospital Affiliated to Shanxi Medical UniversityShanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesTaiyuanShanxiP.R.China Department of pathology Zhongshan HospitalFudan UniversityShanghaiP.R.China Department of pathology West China Hospital of Sichuan UniversityChengduSichuanP.R.China Department of pathology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Department of pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of pathology Fujian Cancer HospitalFujian Medical University Cancer HospitalFuzhouFujianP.R.China Department of pathology Department of OncologyFudan University Cancer CenterShanghaiMedical College of Fudan UniversityShanghaiP.R.China Department of pathology The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebeiP.R.China Department of pathology Shandong Cancer HospitalJinanShandongP.R.China Department of pathology Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiP.R.China Department of pathology Tianjin Medical University Cancer Institute and HospitalTianjinP.R.China Department of pathology the Affiliated Cancer Hospital of Zhengzhou UniversityHenan Provincial Cancer HospitalZhengzhouHenanP.R.China Department of pathology the First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Department of pathology Bei

Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene *** study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced ***:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively *** training was conducted before the study was *** controls were performed at participating centers using immunohistochemistry(IHC)-*** positive ALK gene rearrangement rate and consistency rate were *** associated clinicopathological characteristics of ALK gene rearrangement were investigated as ***:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung *** quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma *** specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for *** overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high co

关键词： anaplastic lymphoma kinase diagnosis gene fusion non-small cell lung cancer

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Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

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oncology Research 2024年第7期32卷 1141-1162页

作者： PAULINA CHMIEL ALEKSANDRA SŁOWIKOWSKA ŁUKASZ BANASZEK ANNA SZUMERA-CIEĆKIEWICZ BARTŁOMIEJ SZOSTAKOWSKI MATEUSZ J.SPAŁEK TOMASZŚWITAJ PIOTR RUTKOWSKI ANNA M.CZARNECKA Department of Soft Tissue/Bone Sarcoma and Melanoma Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland Faculty of Medicine Medical University of WarsawWarsaw02-091Poland Department of pathology Maria Sklodowska Curie National Research Institute of OncologyWarsaw02-781Poland Department of Radiotherapy Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland

Inﬂammatory myoﬁbroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic *** challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging ***,IMT is identiﬁed by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows conﬁrmation of the *** surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difﬁcult to deﬁ*** therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in ***,an ALK tyrosine kinase inhibitor(TKI),was ofﬁcially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK ***,most patients face resistance and disease progression,requiring consideration of sequential *** radiotherapy with targeted therapy appears to be beneﬁcial in this *** promising results have also been achieved with immunotherapy,indicating potential for combined therapy ***,deﬁned recommendations are still *** review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.

关键词： Inﬂammatory myoﬁbroblastic tumor(IMT) Epithelioid inﬂammatory myoﬁbroblastic sarcoma Tyrosine kinase inhibitors(TKI) Anaplastic lymphoma kinase(ALK)

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Sintilimab(anti-PD-1 antibody)plus chidamide(histone deacetylase inhibitor)in relapsed or refractory extranodal natural killer T-cell lymphoma(SCENT):a phase Ⅰb/Ⅱ study

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2765-2773页

作者： Yan Gao Haixia He Xueping Li Liling Zhang Wei Xu Ru Feng Wenyu Li Yin Xiao Xinxiu Liu Yu Chen Xiaoxiao Wang Bing Bai Huijing Wu Qingqing Cai Zhiming Li Jibin Li Suxia Lin Yanxia He Liqin Ping Cheng Huang Jiaying Mao Xiujin Chen Baitian Zhao Huiqiang Huang State Key Laboratory of oncology in South China&Collaborative Innovation Center of Cancer Medicine Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Department of medical oncology Sun Yat-sen University Cancer CenterGuangzhouChina Department of Radiation oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina Department of Hematology Sun Yat-sen University Cancer CenterGuangzhouChina Cancer Center Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingChina Department of Hematology Nanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Lymphoma Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouChina Department of pathology Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouChina Department of medical oncology Hubei Cancer CenterWuhanChina Department of Clinical Research Sun Yat-sen University Cancer CenterGuanzhouChina Department of pathology Sun Yat-sen University Cancer CenterGuangzhouChina

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be *** phase 1b/2 study investigated the safety and efficacy of sintilimab,a fully human anti-PD-1 antibody,plus chidamide,an oral subtype-selective histone deacetylase inhibitor in 38 patients with *** objective response rate(ORR)of combination treatment was 80%.Patients received escalating doses of chidamide,administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 *** dose-limiting events were observed,RP2D of chidamide was 30 mg twice a ***-nine patients were enrolled in phase *** the intention-to-treat population(n=37),overall response rate was 59.5% with a complete remission rate of 48.6%.The median DOR,progression-free survival(PFS),and overall survival(OS)were 25.3,23.2,and 32.9 months,*** most common grade 3 or higher treatment-emergent adverse events(AEs)were neutropenia(28.9%)and thrombocytopenia(10.5%),immune-related AEs were reported in 18(47.3%)*** biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic ***3 mutation shows an unfavorable *** outcome of anticipate ORR was not achieved,sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first *** is a promising therapeutic option for this population.

关键词： killer lymphoma doses

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