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Impact of the economic crisis and drug shortage on Lebanese cancer patients’care

World Journal of Clinical Oncology 2024年第5期15卷 644-652页

作者： Dollen Eid Jad Jabbour Elissar Moujaes Hampig Raphael Kourie Maissa Safieddine Joseph Kattan Department of hematology and Oncology Saint Joseph UniversityFaculty of MedicineMar MikhaëlBeirut 0000Lebanon Department of hematology and Oncology Institut Gustave RoussyVillejuif 94800France Department of hematology and Oncology Hôtel-Dieu de France University HospitalBeirut 0000Lebanon Clinical research Center Saint Joseph UniversityBeirut 0000Lebanon

BACKGROUND As a consequence of the economic crisis,the sociopolitical instability and the advent of the coronavirus disease-19 pandemic,nested challenges faced the Lebanese healthcare *** have resulted in critical shortages of essential resources,including medications vital for oncologic *** To assess the ramifications of the ongoing economic crisis on oncology patient care focusing on our outpatient oncology *** A questionnaire was distributed during the month of February 2022 to oncology patients in Hôtel Dieu de France University Hospital in Beirut during their outpatient *** primary objective was to assess the far-reaching impact of the economic crisis on patient care and the resulting psychological *** Among 182 interviewed patients,31.87%experienced treatment interruption mainly due to acute drug *** 87.91%of the patients benefiting from third-party coverage,69.60%had to self-pay for their medications leading to 69.78%of patients perceiving that healthcare was more difficult to access after ***,one-third of the patients exhibited symptoms of anxiety and/or depression,with 7 patients reporting suicidal ***,37.93%of patients who interrupted cancer treatment reported a history of comorbidities,and 89.66%who altered their treatment cited financial *** Lebanese cancer patients face complex challenges spanning economic,healthcare,and psychological *** inequalities exacerbated by the economic crisis hindered healthcare access.

关键词： Cancer care Drug shortage Economic crisis Cancer psychology Healthcare access

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Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell *** MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and *** has been well documented that MRD positivity predicts a poor prognosis and even disease ***,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical *** review assesses the common and novel MRD assessment *** addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment ***,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

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New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER Division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

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Predictive value of T cell receptor repertoire profiling for immunosuppressive therapy in severe aplastic anemia

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Genes & Diseases 2024年第1期11卷 95-98页

作者： Cunte Chen Yuling Zhang Dongpei Lu Zelong Zhang Jun Yang Xiaowei Chen Ming Zhou Wenjian Mo Caixia Wang Qinghua Cai Yumiao Li Ruiqing Zhou Shilin Xu Wei Zhou Tingfen Deng Shiyi Pan Yanli Xu Shunqing Wang Yuping Zhang Department of hematology Guangzhou First People's HospitalSouth China University of TechnologyGuangzhouGuangdong 510180China Guangzhou Junruikang Biotechnology Co. LtdGuangzhouGuangdong 510700China

Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).

关键词： anemia aplastic interferon

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Dietary lycopene mitigates nonalcoholic steatohepatitis by regulating Nrf2/PPARα-dependent ferroptosis

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Food Science and Human Wellness 2024年

作者： Xunyu Song Daotong Li Jun Sun Xiaoying Zhang Li-Shu Wang Fang Chen College of Food Science and Nutritional Engineering， National Engineering research Centre for Fruit and Vegetable Processing， Key Laboratory of Fruits and Vegetables Processing， Ministry of Agriculture Engineering research Centre for Fruits and Vegetables Processing， Ministry of Education， China Agricultural University Department of hematology and Hematopoietic Cell Transplantation Comprehensive Cancer Center， City of Hope National Medical Center

The global burden of non-alcoholic steatohepatitis (NASH) is on the rise. researchers recognize inhibiting ferroptosis， a form of cell death leading to iron-dependent oxidative damage， as a promising therapy for treating NASH. Lycopene， a natural antioxidant compound， exhibits various pharmacological properties. However， the anti-NASH efficacy of the dietary recommended concentration of lycopene and the role of lycopene in combating ferroptosis in NASH have remained unclear. Our study investigated lycopene’s impact on ferroptosis in various diet-induced mouse NASH models and corresponding cellular models， unveiling its anti-inflammatory and anti-fibrotic effects. Our findings demonstrated that lycopene notably reduced ferroptosis in MCD (methionine- and choline-deficient diet)-fed mice and a normal mouse hepatocyte cell line (NCTC1469) by restoring balanced ferrous iron levels， lipid reactive oxygen species， and normal mitochondrial morphology. These effects were linked to the regulation of ferroptosis markers GPX4 and PTGS2. Additionally， lycopene’s anti-ferroptosis action was validated in mice fed a high-fat， high-cholesterol diet and HepG2 cells treated with free fatty acid. Our transcriptomic analysis highlighted PPARα as a primary target of lycopene， crucial for activating the glutathione system because GW6471， a PPARα antagonist， blocked lycopene-induced GPX4 activation. Furthermore， Nrf2 played a crucial role in lycopene’s impact on iron metabolism-related proteins (FTH1 and TFR1). Notably， when inhibiting PPARα or Nrf2 in MCD-fed mice by GW6471 or ML385， lycopene’s protective effects against ferroptosis and NASH progression diminished. These findings underscore the crucial role of PPARα-mediated glutathione system activation and Nrf2-mediated iron metabolism modulation in lycopene's anti-ferroptosis effects.

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Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer:A systematic review

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 197-213页

作者： Eman Al-Balushi Amina Al Marzouqi Shima Tavoosi Amir Hossein Baghsheikhi Arash Sadri Leyla Sharifi Aliabadi Mohammad-Mahdi Salarabedi Syed Azizur Rahman Nabeel Al-Yateem Alireza Mosavi Jarrahi Aram Halimi Mohammad Ahmadvand Wael M Abdel-Rahman College of Health Sciences University of SharjahSharjah 27272United Arab Emirates Department of Biology Faculty of SciencesUniversity of IsfahanIsfahan 81746-73441Iran Department of Biology Science and Research BranchIslamic Azad UniversityTehran 11365/4435Iran Students’Scientific research Center Tehran University of Medical SciencesTehran ***Iran Cell Therapy and Hematopoietic Stem Cell Transplantation research Center Research Institute for OncologyHematologyand Cell TherapyTehran University of Medical SciencesTehran ***Iran Student research Committee School of MedicineShahid Beheshti University of Medical SciencesTehran ***Iran Department of Nursing University of SharjahSharjah 27272United Arab Emirates Cancer research Centre Shahid Beheshti University of Medical SciencesTehran ***Iran Department of Medical Laboratory Sciences University of SharjahSharjah 27272United Arab Emirates

BACKGROUND Colorectal cancer(CRC)is the third most frequent and the second most fatal *** search for more effective drugs to treat this disease is ongoing.A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic ***-specific peptidases(USPs),the largest group of the deubiquitinase protein family,have long been implicated in various *** have been numerous studies on the role of USPs in CRC;however,a comprehensive view of this role is *** To provide a systematic review of the studies investigating the roles and functions of USPs in *** We systematically queried the MEDLINE(via PubMed),Scopus,and Web of Science *** Our study highlights the pivotal role of various USPs in several processes implicated in CRC:Regulation of the cell cycle,apoptosis,cancer stemness,epithelial–mesenchymal transition,metastasis,DNA repair,and drug *** findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in *** dysregulation of USPs in CRC contributes to drug resistance through multiple *** Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

关键词： Ubiquitin-specific peptidases Colorectal cancer Deubiquitinase protein family Drug target discovery Biomarker discovery

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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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Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine

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Cancer Pathogenesis and Therapy 2024年第2期2卷 112-120页

作者： Sai Huang Peng Chen Lu Wang Lingmin Xu Nan Wang Fei Li Liping Dou Daihong Liu Department of hematology Senior Department of HematologyThe Fifth Medical Center of PLA General HospitalBejing 100039China National Clinical research Center of Geriatric Diseases Chinese PLA General HospitalBejing 100853China Chinese PLA Medical School Beijing 100853China Department of hematology The First Medical Center of PLA General HospitalBejing 100853China

Background:Acute myeloid leukemia(AML)is a heterogeneous hematopoietic malignancy whose prognosis is associated with several ***,a deoxyribonucleic acid(DNA)methyltransferase(DNMT)in-hibitor,combined with cytarabine,aclarubicin hydrochloride,and granulocyte colony-stimulating factor(DCAG),has been used in patients newly diagnosed with *** regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities,as well as those with specific gene ***,the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well ***,this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with ***:This study analyzed the clinical data and genetic mutations based on next-generation sequencing(NGS)in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army(PLA)General Hospital from January 2008 to August *** associated with the cumulative incidence of relapse(CIR)and leukemia-free survival(LFS)in patients newly diagnosed with AML were ***:The most adverse prognosis of DCAG-treated patients was observed in those with FLT3-ITD,KIT,PTPN11,GATA2,or IDH1 mutations during univariable analysis,whereas PTPN11 mutation was solely significant in multivariable analysis,with an increased likelihood of CIR(P=0.001)and reduced LFS duration(P=0.077).Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk(P=0.044)and decreased LFS duration(P=0.042)in multivariable *** this study,we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age ***:NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations,indicating the need for new therapies that target this h

关键词： Acute myeloid leukemia Next-generation sequencing Prognosis DNA methyltransferase Chemotherapy

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Favorable outcomes of front-line risk-adapted therapy in young patients with diffuse large B-cell lymphoma with clinically or biologically high-risk features

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Chinese Medical Journal 2024年第13期137卷 1620-1622页

作者： Hesong Zou Wei Liu Yi Wang Dandan Shan Ting Xie Ru Li Huimin Liu Wenyang Huang Mingwei Fu Tingyu Wang Rui Lyu Shuhui Deng Weiwei Sui Yan Xu Shuhua Yi Gang An Lugui Qiu Dehui Zou State Key Laboratory of Experimental hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Science&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China

To the Editor:Diffuse large B-cell lymphoma(DLBCL)exhibits clinical significance and biological *** the last two decades,rituximab with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)has substantially improved outcomes for DLBCL ***,approximately one-third of DLBCL cases continue to experience disease progression,resulting in long-term survival ranging from 50%to 60%.[1]Efforts to improve DLBCL patient outcomes by modifying R-CHOP dosing schedules have yielded limited success,and the addition of new drugs has benefited only specific patient ***,intensive immunochemotherapy(IIC)has demonstrated promise and cost-effectiveness in recent *** regimen of dose-adjusted etoposide.

关键词： CHOP drugs chemotherapy

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High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

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Science China(Life Sciences) 2024年第8期67卷 1635-1647页

作者： Feng-Qi Liu Qing-Yuan Qu Ying Lei Qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu Qiu-Sha Huang Hai-Xia Fu Yuan Kong Yue-Ying Li Qian-Fei Wang Xiao-Jun Huang Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China National Clinical research Center for Hematologic Disease Beijing 100044China Collaborative Innovation Centre of hematology Peking UniversityBeijing 100044China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100074China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the *** soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP *** the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T *** contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell *** a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune ***-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of *** conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of *** may offer novel targets to develop personalized immunotherapies.

关键词： immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow

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