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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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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN Pediatric hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological ***,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion *** and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell ***,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment ***:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological ***,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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Casual associations between blood metabolites and colon cancer

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World Journal of Gastrointestinal oncology 2024年第5期16卷 1995-2005页

作者： Ke-Yue Hu Yi-Quan Cheng Zhi-Long Shi Fu-Peng Ren Gang-Feng Xiao Department of hematology and oncology Ningbo No.2 HospitalNingbo 315000Zhejiang ProvinceChina

BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal *** To investigate causal associations between blood metabolites and colon *** The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal *** primary method of analysis used was the inverse variance weighted *** further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile *** additional analyses were conducted to ensure the reliability and robustness of the *** After rigorous selection for genetic variation,486 blood metabolites were included in the MR *** found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the *** This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk *** other five blood metabolites are protective factors.

关键词： Metabolites Colon cancer Mendelian randomization Genome-wide association studies Casual

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Chemotherapy-induced small extracellular vesicles prime the pre-metastatic niche to accelerate neuroblastoma metastasis

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Genes & Diseases 2024年第4期11卷 65-68页

作者： Carson A.Wills Xiaoming Liu Longgui Chen Yuanjun Zhao Zhenqiu Liu Vladimir S.Spiegelman Jeffrey Sundstrom Hong-Gang Wang Department of Pediatrics Division of Pediatric Hematology and OncologyThe Pennsylvania State University Collegeof MedicinePA 17033USA Department of Ophthalmology The Pennsylvania State University College of MedicinePA 17033USA Department of Public Health Sciences The Pennsylvania StateUniversityCollegeofMedicinePA 17033USA

Neuroblastoma is the most common extracranial solid tumor in children,accounting for more than 10%of cancerrelated deaths in this *** standard of care for patients diagnosed with medium-to high-risk neuroblastoma,incl... 详细信息

关键词： neuroblastoma metastatic metastasis

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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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Navigating the complex terrain of hepatitis B virus reactivation in the era of Bruton tyrosine kinase inhibitors

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World Journal of Gastroenterology 2024年第21期30卷 2748-2750页

作者： Wei-Nung Liu Ming-Shen Dai Felicia Lin Gen-Min Lin Department of Medicine Tri-Service General HospitalTaipei 114Taiwan division of hematology/oncology Department of Internal MedicineNational Defense Medical CenterTaipei 114Taiwan Community Care Minnesota OncologyMinneapolisMN 55404United States Department of Medicine Hualien Armed Forces General HospitalHualien City 970Taiwan

In this editorial,we offer a summary of the risk associated with hepatitis B reactivation(HBVr)in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase(BTK)inhibitors,with insights derived from current ***,we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such *** framework is essential for identifying those at increased risk of HBVr,enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.

关键词： Hepatitis B virus reactivation Bruton tyrosine kinase inhibitors Hematologic malignancies Solid tumors Prophylaxis guidelines

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Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma

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World Journal of Psychiatry 2024年第7期14卷 1062-1067页

作者： Qiang-Li Wang Hai-Yan Xu Yi Wang Yin-Ling Wang Pei-Nan Lin Zhong-Lei Chen Department of oncology and hematology Suzhou Kowloon HospitalShanghai Jiao Tong University School of MedicineSuzhou 215000Jiangsu ProvinceChina

BACKGROUND Chemotherapy for malignant tumors can cause brain changes and cognitive impairment,leading to chemotherapy-induced cognitive impairment(CICI).Current research on CICI has focused on breast cancer and Hodgkin’s *** patients with non-Hodgkin’s lymphoma(NHL)undergoing chemo-therapy have cognitive impairment has not been fully *** have cognitive impairment has not been fully *** To investigate whether NHL patients undergoing chemotherapy had cognitive *** The study included 100 NHL patients who were required to complete a compre-hensive psychological scale including the Brief Psychiatric Examination Scale(MMSE)at two time points:before chemotherapy and within 2 wk of two chemo-therapy courses.A language proficiency test(VFT),Symbol Number Pattern Test(SDMT),Clock Drawing Test(CDT),Abbreviated Daily Cognition Scale(ECog-12),Prospective and Retrospective Memory Questionnaire,and Karnofsky Perfor-mance Status were used to assess cognitive changes before and after *** The VFT scores for before treatment(BT)and after treatment(AT)groups were 45.20±15.62,and 42.30±17.53,respectively(t-2.16,P<0.05).The CDT scores were 8(3.5-9.25)for BT and 7(2.5-9)for AT groups(Z-2.1,P<0.05).Retrospective memory scores were 13.5(9-17)for BT and 15(13-18)for AT(Z-3.7,P<0.01).The prospective memory scores were 12.63±3.61 for BT and 14.43±4.32 for AT groups(t-4.97,P<0.01).The ECog-12 scores were 1.71(1.25-2.08)for BT and 1.79(1.42-2.08)for AT groups(Z-2.84,P<0.01).The SDMT and MMSE values did not show a significant difference between BT and AT *** Compared to the AT group,the BT group showed impaired language,memory,and subjective cognition,but objec-tive cognition and execution were not significantly affected.

关键词： Non-Hodgkin’s lymphoma Hodgkin lymphoma Lymphoma cognitive impairment Chemotherapy-related cogni-tive impairment Clinical study

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Management Practices of Locally Advanced and Metastatic Urothelial Carcinoma: A Questionnaire-Based Survey among Lebanese Oncologists

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Open Journal of Urology 2024年第2期14卷 138-149页

作者： Joseph Kattan Sally Temraz Fadi Nasr Arafat Tfayli Christina Khater Anas Mugharbel Hady Ghanem Hampig Raphael Kourie Georges Hachem Sarah Masri Jamil Debs Ali Shamseddine Department of hematology-oncology H&#244tel-Dieu de France University Hospital Faculty of Medicine Saint-Joseph University of Beirut Beirut Lebanon Department of Internal Medicine Hematology-Oncology Division American University of Beirut Medical Center Beirut Lebanon hematology-oncology division American University of Beirut Medical Center Beirut Lebanon Department of hematology-oncology Saint Charles Hospital Beirut Lebanon Department of Internal Medicine Makassed General Hospital Beirut Lebanon hematology-oncology division Lebanese American University Medical Center - Rizk Hospital Beirut Lebanon Department of hematology-oncology Saint George Hospital University Medical Center Beirut Lebanon Pfizer Medical Affairs Beirut Lebanon

Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.

关键词： Clinical Practice Chemotherapy Immune Checkpoint Inhibitors PDL1 Urothelial Carcinoma

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Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

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World Journal of Gastrointestinal oncology 2024年第8期16卷 3521-3528页

作者： Shin Woo Kang Sung Hee Lim Min-Ji Kim Jeeyun Lee Young Suk Park Ho Yeong Lim Won Ki Kang Seung Tae Kim division of hematology oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Samsung Biomedical Research Institute Samsung Medical CenterSeoul 06351South Korea

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor *** VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab *** cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and *** To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of *** This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with *** A total of 124 patients was included in this *** all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line *** 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line *** numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),*** results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

关键词： Bevacizumab Colorectal cancer Programmed cell death ligand 1 expression First-line chemotherapy Metastatic colorectal cancer

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A multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： Meng-Jie Tang Xiao-Li Ma Xiang-Ling He Wei-Hua Pan Xiao-Hong Zhang Sha-Yi Jiang Ju Gao Fu Lie Wei Yao Song Gu Wei-Ling Zhang Qiang Zhao Shi-Hao Huang Yong-Jun Fang Wei Liu Hui-Zhong Niu Chun-Mei Wang Li-Rong Sun Hui Gao Yun-Peng Dai Shun-Gen Huang Zhi-Yong Zhong Xi-Ge Wang Zhong-Rong Li Liang-Chun Yang Ye-Ming Wu Huan-Min Wang Xin Sun Xiao-Jun Yuan Department of Pediatric hematology/oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical oncology Department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of hematology/oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China Department of Pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of hematology/oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China Department of hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of hematology/oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China Department of Pediatric Surgery Children's Hospital of Fudan UniversityShanghai 201102China Department of General Surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pediatric oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of hematology/oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of hematology/oncology Henan Children's HospitalZhengzhou 450018China Department of Pediatric General Surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's Hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Paediatric

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,*** 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0S was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study Survival

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