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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE KIM Division of hematology-oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of hematology-oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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Hypoxia inducible factor in hepatocellular carcinoma:A therapeutic target

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World Journal of Gastroenterology 2015年第42期21卷 12171-12178页

作者： Daniel Lin Jennifer Wu fellow hematology and medical oncology program NYU School of Medicine Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology NYU School of Medicine Subdivision of GI Oncology Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology

Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.

关键词： Hypoxia Hypoxia-inducible factor alpha Hepatocellu

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Ginseng-Derived Panaxadiol Saponins Promote Hematopoiesis Recovery in Cyclophosphamide-Induced Myelosuppressive Mice:Potential Novel Treatment of Chemotherapy-Induced Cytopenias

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Chinese Journal of Integrative Medicine 2018年第3期24卷 200-206页

作者： SUN Xin ZHAO Yan-na QIAN Song GAO Rui-lan YIN Li-ming WANG Li-pei CHONG Beng-hock ZHANG Su-zhan Department of oncology The Second Affiliated HospitalMedical College of Zhejiang University Department of oncology Zhejiang Provincial People's Hospital Institution of hematology Research The First Affiliated Hospital of Zhejiang Chinese Medical University Department of hematology St George Sutherland Hospital

Objective：To investigate the potential efficacy of panaxadiol saponins component（PDS-C）,a biologically active fraction isolated from total ginsenosides,to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide（CTX）.Methods：Mice with myelosuppression induced by CTX were treated with PDS-C at a low-（20 mg/kg）,moderate-（40 mg/kg）,or high-dose（80 mg/kg） for 7 consecutive *** level of peripheral white blood cell（WBC）,neutrophil（NEU） and platelet（PLT） were measured,the histopathology and colony formation were observed,the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western ***：In response to PDS-C therapy,the peripheral WBC,NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent ***,bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells（P〈0.01）.PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice,as evidenced by significantly increase in colony formation units-granulocytes/monocytes and-megakaryocytes（P〈0.01）.The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway,this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase（p-MEK） and extracellular signal-regulated kinases（p-ERK）,and receptor tyrosine kinase（C-kit） and globin transcription factor 1（GATA-1） in hematopoietic cells of CTX-treated mice（P〈0.05）.Conclusions：PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice,probably mediated by a mechanism involving MEK and ERK protein kinases,and C-kit and GATA-1 transcription ***-C may potentially be a novel treatment of mye

关键词： panaxadiol saponins component ginsenosides chemotherapy-induced myelosuppression mitogen-activated protein kinase extracellular signal-regulated kinase receptor tyrosine kinase globin transcription factor 1 Chinese medicine

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Physician approaches to drug shortages: Results of a national survey of pediatric hematologist/oncologists

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World Journal of Clinical oncology 2017年第4期8卷 336-342页

作者： Jill C Beck Baojiang Chen Bruce G Gordon Department of Pediatric hematology/oncology University of Nebraska Medical Center

AIM To evaluate personnel involved in scarce drug prioritization and distribution and the criteria used to inform drug distribution during times of shortage among pediatric hematologists/oncologists. METHODS Using the American Society of Pediatric hematology/oncology(ASPHO) membership list, a 20 question survey of pediatric hematologists/oncologists was conducted via email to evaluate personnel involved in scarce drug prioritization and distribution and criteria used to inform scarce drug distribution. RESULTS Nearly 65% of the 191 study respondents had patients directly affected by drug shortages. Most physicians find out about shortages from the pharmacist(n = 179, 98%) or other doctors(n = 75, 41%). One third of respondents do not know if there is a program or policy for handling drug shortages at their institution. The pharmacist was the most commonly cited decision maker for shortage drug distribution(n = 128, 70%), followed by physicians(n = 109, 60%). One fourth of respondents did not know who makes decisions about shortage drug distribution at their institution. The highest priority criterion among respondents was use of the shortage drug for curative, rather than palliative intent and lowest priority criterion was order of arrival or first-come *** Despite pediatric hematology/oncology physicians and patients being heavily impacted by drug shortages, institutional processes for handling shortages are lacking. There is significant disparity between how decisions for distribution of shortage drugs are currently made and how study respondents felt those decisions should be made. An institution-based, and more importantly, a societalapproach to drug shortages is necessary to reconcile these disparities.

关键词： Pediatric hematology/oncology Chemotherapy Ethics

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Immunotherapeutic approaches in biliary tract carcinoma:Current status and emerging strategies

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World Journal of Gastrointestinal oncology 2015年第11期7卷 338-346页

作者： Eric I Marks Nelson S Yee Department of Medicine Penn State Milton S.Hershey Medical Center Division of hematology-oncology Program of Experimental TherapeuticsDepartment of MedicinePenn State Hershey Medical CenterPenn State Hershey Cancer Institute

For biliary tract carcinoma(BTC),complete surgical resection of tumor is only feasible in a minority of patients,and the treatment options for patients with unresectable or metastatic disease are *** in cancer immunology have led to identification of tumor-infiltrating immune cells as indicators of prognosis and response to treatment in *** has also facilitated development of immunotherapy that focuses on enhancing the immune system against biliary *** includes peptide- and dendritic cell-based vaccines that stimulate in-vivo immune responses against tumorspecific *** immunotherapy,which entails the ex-vivo expansion of tumor-infiltrating immune cells for subsequent reintroduction,and cytokinebased therapies have been developed in *** studies indicate that this type of therapy is generally well *** therapy with dendritic cell-based vaccines and adoptive immunotherapy has shown particularly good *** strategies through discovery of novel antigen targets and by reversal of tumor-associated immunosuppression are expected to improve the efficacy of immunotherapy in *** efforts by integration of targeted immunotherapeutics with molecular profiling of biliary tumor will hopefully make a positive impact on advancing towards the goal of developing precision treatment of patients with this highly lethal disease.

关键词： Adoptive immunotherapy Cancer vaccines Biliary tra

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Immunoregulatory effects of human amniotic mesenchymal stem cells and their exosomes on human peripheral blood mononuclear cells

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BIOCELL 2023年第5期47卷 1085-1093页

作者： XIN TIAN XIANGLING HE SHUQIN QIAN RUNYING ZOU KEKE CHEN CHENGGUANG ZHU ZEXI YIN Department of hematology and oncology Children’s Medical CenterThe First Affiliated Hospital of Hunan Normal UniversityChangsha410005China

Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing *** study investigated the immunoregulatory effects of human amniotic mesenchymal stem cells(hAMSCs)and their exosomes on phytohemagglutinin(PHA)-induced peripheral blood mononuclear cells(PBMCs).Methods:The hAMSCs used in the experiment were identified by light microscopy and flow cytometry,and the differentiation ability of the cells was determined by Oil Red O and Alizarin Red *** expressions of transforming growth factor(TGF)-β,indoleamine 2,3-dioxygenase(IDO),cyclooxygenase-2(COX-2),hepatocyte growth factor(HGF),and interleukin(IL)-6 were detected by quantitative real-time polymerase chain reaction and western ***,hAMSCs,and their exosomes were collected for in vitro group *** the immunoregulatory ability of hAMSCs and their exosomes were analyzed by flow cytometry and Enzymelinked immunosorbent ***:The hAMSCs and exosomes were successfully extracted from the human amniotic ***-β,IDO,COX-2,HGF,and IL-6 were significantly expressed in *** vitro co-culture showed that hAMSCs promoted the proliferation of Th2 cells in PHA-induced PBMCs,while hAMSCs and exosomes inhibited the secretion of TNF-αin PHA-induced PBMCs,and promoted the secretion of IL-4 and IL-10,and hAMSCs had more significant effects than ***:hAMSCs or exosomes could exert immunoregulatory effects on PHA-induced PBMCs by affecting Th2 cell proliferation and cytokine secretion.

关键词： hAMSCs Exosomes Immunomodulatory effects

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Moving from late to early stage disease: lessons learned from erlotinib in pancreatic cancer

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Hepatobiliary Surgery and Nutrition 2018年第5期7卷 406-408页

作者： Andrew H. Ko Division of hematology/oncology Gastrointestinal Oncology Program Helen Diller Family Comprehensive Cancer Center University of California San Francisco San Francisco CA USA

At the time the CONKO-005 trial was originally conceived, there was an inherent rationale to its design;it represented the next logical step in trying to move the needle in the treatment of early-stage pancreatic aden... 详细信息

关键词： needle adenocarcinoma rational

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Compound Zhebei granules combined with chemotherapy for the treatment of refractory acute leukemia: a randomized clinical trial

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Journal of Traditional Chinese Medicine 2016年第5期36卷 606-612页

作者： Hou Li Yang Shulian Yang Wenhua Zhou Yuhong Liu Feng Yang Hongyong Sun Weizheng Li Dongyun Xu Yamei Chen Xinyi Department of oncology and hematology Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine Department of hematology Langfang Chinese Medicine Hospital Affiliated to Hebei Medical University Department of hematology First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Department of hematology Chinese Medicine Hospital of Zhejiang Province Department of hematology Xiyuan Hospital Affiliated to China Academy of Chinese Medical Sciences Department of hematology First Affiliated Hospital of Guangzhou University of Chinese Medicine Department of hematology First Affiliated Hospital of Heilongjiang University of Chinese Medicine

OBJECTIVE: To observe the effect of compound Zhebei granules(CZBG) with chemotherapy in the treatment of refractory acute ***: In this multicenter, double-blind, placebo-controlled clinical trial, we used a central(online) randomization system to assign 235 patients to two treatment groups. A total of 118 patients received chemotherapy combined with CZBG(4 g,twice daily) and 117 patients received chemotherapy plus placebo. The clinical efficacy was evaluated at the end of one chemotherapeutic ***: In the full analysis set, in which deaths due to disease progression were regarded as inefficacy, the rates of complete remission(CR) and partial remission(CR + PR) were 32.35% and 50.00%,respectively, for the chemotherapy combined with CZBG group, and 23.08% and 35.58%, respectively,for the chemotherapy plus placebo group. There was a statistically significant difference between the two groups according to a ysis set(PPχ2test(P < 0.05). In the per protocol analS), the CR(33.67%),CR+PR(52.04%) response rates for the chemotherapy plus CZBG group were significantly different from the response rates of the control group(CR:24.24% and CR+PR: 37.37%), respectively(P < 0.05).CONCLUSION: CZBG plus chemotherapy can improve the clinical remission rate of refractory acute leukemia after one just one therapeutic cycle.

关键词： Refractory acute leukemia Zhebei granules Chemotherapy remission rate Randomized clinical trial

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WJSC 6^(th) Anniversary Special Issues(1):Hematopoietic stem cell transplantation Allogeneic hematopoietic cell transplant for acute myeloid leukemia:Current state in 2013 and future directions

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World Journal of Stem Cells 2014年第2期6卷 69-81页

作者： Abraham S Kanate Marcelo C Pasquini Parameswaran N Hari Mehdi Hamadani Osborn Hematopoietic Malignancy and Transplantation program Section of Hematology/OncologyWest Virginia University Division of hematology and oncology Medical College of Wisconsin

Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable *** remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free *** pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on *** hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk *** we review the published data regarding the role of allo-HCT in adults with *** searched MEDLINE/PubMed and EMBASE/*** addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial *** discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory *** the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord *** also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of *** we explore recent advances and future possibilities and directions of allo-HCT in *** therapeutic recommendations have been made where possible based on available data and expert opinion.

关键词： Acute myeloid leukemia Allogeneic hematopoietic cell transplantation Reduced intensity conditioning Myeloablative conditioning Haploidentical Umbilical cord blood

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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(*** *** 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 *** 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 *** received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at *** stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete *** control rate was 95.1%due to 7(8.5%)stable *** time to response was 1.8 *** 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)*** 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 *** 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 ***-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

关键词： lymphoma assessed initiated

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