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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 *** acid(PA)has shown promising antitumor *** study aims to elucidate the molecular mechanisms by which PA influences DLBCL *** 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 *** were made of cell viability,apoptosis,and autophagy-related protein expression following PA *** 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 *** efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse ***-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control *** treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of *** luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 *** experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 *** vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 *** 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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Quality assessment of surgery for colorectal cancer:Where do we stand?

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 982-987页

作者： Stefan Morarasu Cristian Livadaru Gabriel-Mihail Dimofte The Second department of Surgical oncology Regional Institute of OncologyIasi 707483Romania

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past *** has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units *** mesorectal excision,complete mesocolic excision(CME),and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical ***,there are still ongoing discrepancies in outcomes largely based on surgeon *** is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume *** markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional *** the evolution of CME surgery,various quality markers have been described,mostly based on measurements on the surgical specimen and lymph node yield,while others have proposed radiological markers(*** stumps)measured on postoperative scans as part of the routine cancer *** is no ideal marker;however,taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

关键词： Colorectal cancer Colon surgery Arterial stump Complete mesocolic excision Surgical quality

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Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

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Chinese Journal of Integrative Medicine 2024年第1期30卷 85-95页

作者： JIAO Ju-ying CHENG Chien-shan CAO Zhang-qi CHEN Lian-yu CHEN Zhen department of Integrative oncology Fudan University Shanghai Cancer CenterShanghai(200032)China department of oncology Shanghai Medical CollegeFudan UniversityShanghai(200032)China

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

关键词： cancer Chinese medicine syndrome ZHENG dampness-heat syndrome animal model pancreatic tumor evaluation methods

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STING agonist-conjugated metal-organic framework induces artificial leukocytoid structures and immune hotspots for systemic antitumor responses

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National Science Review 2024年第7期11卷 189-204页

作者： Taokun Luo Xiaomin Jiang Yingjie Fan Eric Yuan Jinhong Li Langston Tillman Wenbin Lin department of Chemistry University of Chicago department of Radiation and Cellular oncology and the Ludwig Center for Metastasis Research University of Chicago

Radiotherapy is widely used for cancer treatment, but its clinical utility is limited by radioresistance and its inability to target metastases. Nanoscale metal-organic frameworks(MOFs) have shown promise as high-Z nanoradiosensitizers to enhance radiotherapy and induce immunostimulatory regulation of the tumor microenvironment. We hypothesized that MOFs could deliver small-molecule therapeutics to synergize with radiotherapy for enhanced antitumor efficacy. Herein, we develop a robust nanoradiosensitizer,GA-MOF, by conjugating a STING agonist, 2,3-cyclic guanosine monophosphate–adenosine monophosphate(GA), on MOFs for synergistic radiosensitization and STING activation. GA-MOF demonstrated strong anticancer efficacy by forming immune-cell-rich nodules(artificial leukocytoid structures) and transforming them into immunostimulatory hotspots with radiotherapy. Further combination with an immune checkpoint blockade suppressed distant tumors through systemic immune activation. Our work not only demonstrates the potent radiosensitization of GA-MOF, but also provides detailed mechanisms regarding MOF distribution, immune regulatory pathways and long-term immune effects.

关键词： metal-organic framework radiosensitization STING agonist artificial leukocytoid structures immune hotspots immunotherapy nanomedicine

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FGFR3 alterations in bladder cancer:Sensitivity and resistance to targeted therapies

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Cancer Communications 2024年第10期44卷 1189-1208页

作者： Maxim Noeraparast Katarina Krajina Renate Pichler Dora Nieders-Beke Shahrokh F Shariat Viktor Grünwald Sascha Ahyai Martin Pichler Translational oncology II.Med Clinics Hematology and OncologyAugsburgGermany department of Urology Medical University of InnsbruckInnsbruckAustria department of Hematology and oncology Clinics OttakringViennaAustria department of Urology Medical University of ViennaViennaAustria Interdisciplinary Genitourinary oncology Clinic for UrologyClinic for Medical OncologyUniversity Hospital EssenHufelandstrase 55EssenGermany department of Urology Medical University of GrazGrazAustria

In this review,we revisit the pivotal role of fibroblast growth factor receptor 3(FGFR3)in bladder cancer(BLCA),underscoring its prevalence in both nonmuscle-invasive and muscle-invasive forms of the ***3 mutations in up to half of BLCAs play a well-established role in tumorigenesis,shaping distinct tumor initiation patterns and impacting the tumor microenvironment(TME).Emphasizing the importance of considering epithelial-mesenchymal transition profile and TME status,we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3-mutated *** writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3-mutated BLCA,stressing the pressing need to unravel resistance mechanisms and identify co-targets for future combinatorial studies.A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms,including secondarymutations,epigenetic alterations in pathway effectors,phenotypic heterogeneity,and population-specific variations within FGFR3 mutational ***,we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3-mutated BLCA.

关键词： Bladder Cancer Erdafitinib FGFR inhibition FGFR3 mutations Resistance to Erdafitinib Tumor Microenvironment

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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang department of Medical oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

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Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study

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Chinese Journal of Integrative Medicine 2024年第6期30卷 489-498页

作者： CAO Ni-da ZHU Xiao-hong MA Fang-qi XU Yan DONG Jia-huan QIN Meng-meng LIU Tian-shu ZHU Chun-chao GUO Wei-jian DING Hong-hua GUO Yuan-biao LIU Li-kun SONG Jin-jie WU Ji-ping CHENG Yue-lei ZENG Lin ZHAO Ai-guang oncology department I Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghai200032China oncology department Zhongshan HospitalFudan UniversityShanghai200032China Gastrointestinal Surgery department Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China oncology department Fudan University Shanghai Cancer CenterShanghai200032China oncology department Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080China Traditional Chinese Medicine department Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China oncology department Shanxi Traditional Chinese Medicine HospitalTaiyuan030012China oncology department Xiyuan HospitalChina Academy of Chinese Medical ScienceBeijing102445China oncology department Yunnan Province Hospital of Traditional Chinese MedicineKunming650021China oncology department Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai201203China Shanghai NewCore Biotechnology Co. Ltd.Shanghai200240China

Objective To describe the treatment patterns and survival status of advanced gastric cancer(AGC)in China in the past two decades,and objectively evaluate the impact of standardized Chinese medicine(CM)treatment on the survival of AGC *** This multicenter registry designed and propensity score analysis study described the diagnosis characteristics,treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1,2000 and July 31,*** survival(OS)was evaluated between non-CM cohort(standard medical treatment)and CM cohort(integrated standard CM treatment≥3 months).Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to adjust any difference in average outcomes for *** A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were *** them,1,607 received systemic chemotherapy,215(10.74%)accepted molecular targeted therapy,44(2.2%)received checkpoint inhibitor therapy,and 769(38.43%)received ***-drug regimen was the main choice for first-line treatment,with fluoropyrimidine plus platinum as the most common regimen(530 cases,60.09%).While 45.71%(16 cases)of patients with HER2 amplification received trastuzumab in *** application of apatinib increased(33.33%)in *** application of checkpoint inhibitors has increased since *** analysis showed that Lauren mixed type(P=0.017),cycles of first-line treatment>6(P=0.000),CM(P=0.000),palliative gastrectomy(P=0.000),trastuzumab(P=0.011),and apatinib(P=0.008)were independent prognostic factors for the OS of *** PSM and IPTW,the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months,respectively(P<0.001).Conclusions In real-world practice for AGC in China,therapy choices consisted with ***-drug regimen was the main first-line *** CM treatment was an independent

关键词： advancedgastriccancer real-world study treatment pattern survival analysis Chinese medicine

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A lysosomal-targeted Pt(Ⅱ) metallacycle for NIR-Ⅱ fluorescence imaging guided highly efficient tumor immunogenic cell death

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Science China Chemistry 2024年第11期67卷 3508-3509页

作者： Qihang Ding Shuai Zhang Jong Seung Kim department of Chemistry Korea University department of Medical oncology Harbin Medical University Cancer Hospital

Cisplatin, carboplatin, and oxaliplatin are well-known firstline antineoplastic drugs that have been approved worldwide. Recently, the successful integration of chemotherapy and immunotherapy in clinical trials has hi...

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Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

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Biomedical and Environmental Sciences 2024年第6期37卷 581-593页

作者： Nani Li Xiaoting Qiu Jingsong Xue Limu Yi Mulan Chen Zhijian Huang department of Medical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina department of Breast Surgical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina Departmen of Pathology Shenzhen Longhua Maternity and Child Healthcare HospitalShenzhen 518109GuangdongChina

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment ***8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing *** leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to *** Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC *** the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T ***,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic *** accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)***,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic ***,we investigated the potential underlying biological pathways that contribute to divergent treatment *** We successfully developed a model capable of predicting the prognosis of patients with *** areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,*** this risk model,we stratified the samples into high-and low-risk *** KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine ***,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that o

关键词： Breast Cancer Immunotherapy Prognosis CD8+T cells PD-L1

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Targeting RAF dimers in RAS mutant tumors:From biology to clinic

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1895-1923页

作者： Huanhuan Yin Qiulin Tang Hongwei Xia Feng Bi Division of Abdominal Cancer Department of Medical OncologyCancer Center and Laboratory of Molecular Targeted Therapy in OncologyWest China HospitalSichuan UniversityChengdu 610041China

RAS mutations occur in approximately 30%of tumors worldwide and have a poor prognosis due to limited *** targeting of KRAS G12C has achieved significant success in recent years,but there is still a lack of efficient therapeutic approaches for tumors with non-G12C KRAS mutations.A highly promising approach is to target the MAPK pathway downstream of RAS,with a particular focus on RAF ***-generation RAF inhibitors have been authorized to treat BRAF mutant tumors for over a ***,their use in RAS-mutated tumors is not recommended due to the paradoxical ERK activation mainly caused by RAF *** address the issue of RAF dimerization,type II RAF inhibitors have emerged as leading *** clinical studies have shown the initial effectiveness of these agents against RAS mutant ***,type II RAF inhibitors in combination with MEK or ERK inhibitors have demonstrated impressive efficacy in RAS mutant *** review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treatment in tumors with RAS mutations,as well as recent progress in therapeutic approaches to address the problem of RAF dimerization in RAS mutant tumors.

关键词： RAS mutations RAF dimerization RAF inhibitors Cancer therapy Drug resistance

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