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Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis

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Chinese Journal of Natural Medicines 2024年第6期22卷 554-567页

作者： LI Weiming GAO Ming XUE Weili LI Xiaoli CHANG Yu ZHANG Kaixin WEN Chenyu ZHANG Mingzhi department of oncology Henan University of Traditional Chinese MedicineZhengzhou 450000China department of oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China

Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment resistance.Palmitic acid(PA)has shown promising antitumor properties.This study aims to elucidate the molecular mechanisms by which PA influences DLBCL progression.We quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell lines.Assessments were made of cell viability,apoptosis,and autophagy-related protein expression following PA administration.Interaction analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell lines.The efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse models.MiR-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control group.PA treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of DNMT3A.The luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 methylation.Subsequent experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 axis.In vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 axis.Palmitic acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.

关键词： Palmitic acid Diffuse large B-cell lymphoma MiR-429 DNMT3A FOXO1 Autophagy

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Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

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World Journal of Gastrointestinal oncology 2024年第4期16卷 1166-1179页

作者： Sebastián Díaz-López Jerónimo Jiménez-Castro Carlos Enrique Robles-Barraza Carlos Ayala-de Miguel Manuel Chaves-Conde Medical oncology department Hospital Universitario ValmeSeville 41014AndalucíaSpain

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

关键词： Mixed neuroendocrine non-neuroendocrine neoplasms Mixed adenoneuroendocrine carcinomas Mixed tumours Gastroenteropancreatic Treatment Etiology Diagnosis

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Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

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World Journal of Gastroenterology 2024年第11期30卷 1636-1643页

作者： Yoshihiro Shibata Hirofumi Ohmura Kazuki Komatsu Kosuke Sagara Atsuji Matsuyama Ryuji Nakano Eishi Baba department of Medical oncology Fukuoka Wajiro HospitalFukuoka 811-0213Japan department of oncology and Social Medicine Kyushu University Graduate School of Medical SciencesFukuoka 812-8582Japan department of Pathology and oncology University of Occupational and Environmental HealthKitakyushu 807-8555Japan department of Diagnostic Pathology Fukuoka Wajiro HospitalFukuoka 811-0213Japan

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

关键词： Spindle cell carcinoma Esophagus Myocardial metastasis Epithelial-mesenchymal transition Case report

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Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

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World Journal of Gastrointestinal oncology 2024年第2期16卷 386-397页

作者： Vilma Pacheco-Barcia Sara Custodio-Cabello Fatima Carrasco-Valero Magda Palka-Kotlowska Axel Mariño-Mendez Alberto Carmona-Bayonas Javier Gallego A J Muñoz Martín Paula Jimenez-Fonseca Luis Cabezon-Gutierrez department of Medical oncology Hospital Universitario de TorrejonMadrid 28850Spain department of Internal Medicine Hospital Universitario de TorrejonMadrid 28850Spain department of Medical oncology Hospital Universitario Central de AsturiasOviedo 33011Spain department of Medical oncology Hospital Universitario Morales MeseguerUniversity of MurciaMurcia 30001Spain department of Medical oncology Hospital General Universitario de ElcheElche 03202Spain department of Medical oncology Hospital General Universitario Gregorio MarañónUniversidad Complutense MadridMadrid 28007Spain Universidad Francisco de Vitoria Madrid 28223Spain

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not

关键词： Pancreatic cancer Nutrition Prognostic factor Inflammation Advanced cancer Systemic inflammatory response index Weight loss

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Is sarcopenia effective on survival in patients with metastatic gastric cancer?

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World Journal of Gastrointestinal oncology 2024年第5期16卷 1861-1868页

作者： Ozlem Dogan Hayriye Sahinli Yakup Duzkopru Tuba Akdag Abdulkadir Kocanoglu department of Medical oncology Adıyaman University Training and Research HospitalAdiyaman 02100Turkey department of Medical oncology Ankara Etlik City HospitalAnkara 06170Turkey department of Radiology University of Health SciencesDiskapi Yildirim Beyazit Training and Research HospitalAnkara 06000Turkey department of Medical oncology Ankara Ataturk Sanatoryum Training and Research HospitalAnkara 06170Turkey

BACKGROUND Sarcopenia is a progressively diminishing state characterized by the reduction of muscle mass and density,which is frequently observed in malignancies of solid organs.AIM To assess how sarcopenia affects the overall survival of individuals who have been diagnosed with metastatic gastric cancer.METHODS The study retrospectively included individuals who had been diagnosed with metastatic gastric cancer between January 2008 and December 2020.Sarcopenia was identified through the calculation of the average Hounsfield units(HUAC)using computed tomography(CT)images taken at the time of diagnosis in patients.RESULTS A total of 118 patients with metastatic gastric cancer were evaluated.Sarcopenia was detected in 29 patients(24.6%).The median survival of all patients was 8(1-43)mo.The median survival of patients with sarcopenia was 2 mo,while it was 10 mo for those without sarcopenia(P<0.001).A significant relationship was found between sarcopenia and survival.CONCLUSION Sarcopenia has been observed to impact survival outcomes in various types of solid tumor cancers.Sarcopenic patients can be identified in a short time,easily and inexpensively,by HUAC measurements from CT images used for diagnosis,and survival could be promoted with nutritional support.

关键词： Hounsfield units Sarcopenia Gastric cancer Survival Psoas muscle mass Muscle density

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IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long Wu Shun Lu Gongyan Chen Jianxing He Jifeng Feng Yiping Zhang Liyan Jiang Hongming Pan Jianhua Chang Jian Fang Amy Cai Lilian Bu Jane Shi Jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China department of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China department of Thoracic oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China department of Medical oncology Jiangsu Cancer HospitalNanjing 210009China department of Medical oncology Zhejiang Cancer HospitalHangzhou 330022China department of pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China department of Medical oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China department of Medical oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China department of Thoracic oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

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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 worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved 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 primaries.The 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 pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More 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 tumors.This 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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Mapping the intellectual structure and emerging trends for the application of nanomaterials in gastric cancer:A bibliometric study

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World Journal of Gastrointestinal oncology 2024年第5期16卷 2181-2199页

作者： Bo-Na Liu Xiao-Li Gao Ying Piao department of oncology General Hospital of Northern Theater CommandShenyang 110015Liaoning ProvinceChina

BACKGROUND Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these materials.However,the research hotspots and trends in the application of nanomaterials in gastric cancer(GC)remain obscure.AIM To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in GC.METHODS Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric study.VOSviewer and CiteSpace were used for bibliometric and visualization analyses.RESULTS From 2000 to 2022,the application of nanomaterials in GC developed rapidly.The keyword co-occurrence analysis showed that the related research topics were divided into three clusters:(1)The application of nanomaterials in GC treatment;(2)The application and toxicity of nanomaterials in GC diagnosis;and(3)The effects of nanomaterials on the biological behavior of GC cells.Complexes,silver nanoparticles,and green synthesis are the latest high-frequency keywords that represent promising future research directions.CONCLUSION The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.

关键词： Nanomaterials Gastric cancer Bibliometrics Drug delivery VOSviewer CiteSpace Systematic review

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Association of previously irradiated stable brain metastases with outcomes of atezolizumab-treated non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials

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Cancer Communications 2024年第2期44卷 278-281页

作者： Tiantian Guo Yue Zhou Fei Liang Zezhou Wang Vincent Bourbonne Lukas Käsmann Nora Sundahl Abraham Jing-Ching Wu Jianjiao Ni Zhengfei Zhu department of Radiation oncology Fudan University Shanghai Cancer CenterShanghaiP.R.China department of oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Clinical Research Center for Radiation oncology ShanghaiP.R.China Shanghai Key Laboratory of Radiation oncology ShanghaiP.R.China department of Biostatistics Zhongshan HospitalFudan UniversityShanghaiP.R.China department of Cancer Prevention Fudan University Shanghai Cancer CenterShanghaiP.R.China Radiation oncology department University HospitalBrestFrance department of Radiation oncology University HospitalLMU MunichMunichGermany department of Radiation oncology AZ GroeningeKortrijkBelgium department of Radiation oncology Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA Institute of Thoracic oncology Fudan UniversityShanghaiP.R.China

Dear Editor:Brain metastasis(BM)has long been recognized as a prognostic factor associated with poor prognosis for non-small cell lung cancer(NSCLC)in the era of con-ventional chemotherapy and targeted therapy[1].In the era of immunotherapy,controversial findings have been reported regarding the prognostic significance of BM in patients with NSCLC treated with programmed death-1/programmed death-ligand 1(PD-1/PD-L1)inhibitors.

关键词： chemotherapy NSCLC metastasis death

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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 cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We 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 results.CONCLUSION 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 factors.The other five blood metabolites are protective factors.

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

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