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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus

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World Journal of Gastroenterology 2024年第8期30卷 843-854页

作者： Hong-Xiao Wu Xiao-Yan Ding Ya-Wen Xu Ming-Hua Yu Xiao-Mi Li Na Deng Jing-Long Chen cancer center Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

BACKGROUND Hepatocellular carcinoma(HCC)patients complicated with portal vein tumor thrombus(PVTT)exhibit poor prognoses and treatment *** To investigate efficacies and safety of the combination of PD-1 inhibitor,transcatheter arterial chemoembolization(TACE)and Lenvatinib in HCC subjects comorbid with *** From January 2019 to December 2020,HCC patients with PVTT types Ⅰ-Ⅳ were retrospectively enrolled at Beijing Ditan *** were distributed to either the PTL or TACE/Lenvatinib(TL)*** median progression-free survival(mPFS)was set as the primary endpoint,while parameters like median overall survival,objective response rate,disease control rate(DCR),and toxicity level served as secondary *** Forty-one eligible patients were finally recruited for this study and divided into the PTL(n=18)and TL(n=23)*** a median follow-up of 21.8 months,the DCRs were 88.9%and 60.9%in the PTL and TL groups(P=0.046),***,mPFS indicated significant improvement(HR=0.25;P<0.001)in PTL-treated patients(5.4 months)compared to TL-treated(2.7 months)*** were no treatment-related deaths or differences in adverse events in either *** A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types Ⅰ-Ⅳ.

关键词： Hepatocellular carcinoma Transcatheter arterial chemoembolization Lenvatinib PD-1 inhibitor Portal vein tumor thrombus

XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for Cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of Stem Cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

Retraction note to:RNA-binding protein CPSF6 regulates IBSP to affect pyroptosis in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2865-2866页

作者： Xue-Jun Wang Yong Liu Bin Ke Li Zhang Han Liang Department of Gastric Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin Clinical Research Center for CancerTianjin Key Laboratory of Digestive CancerTianjin 300060China

The authors have decided to retract the article published on World J Gastrointest Oncol(2023)for further consideration due to data errors and some misunderstandings in communication.

关键词： Retraction note

Nanoparticle delivery for central nervous system diseases and its clinical application

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Nano Research 2024年第7期17卷 6305-6322页

作者： Lin Tang Rui Zhang Yusi Wang Mohan Liu Die Hu Yuanda Wang Li Yang Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired *** a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are ***,the research process and clinical application of drugs for treating CNS diseases are still large *** barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain ***,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and ***,clinical applications of nanoparticles in CNS diseases are *** review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.

关键词： nanoparticles central nervous system(CNS)diseases clinical applications delivery carriers immunomodulators

Clinical practice guidelines for full-cycle standardized management of bone health in breast cancer patients

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cancer Innovation 2024年第1期3卷 1-28页

作者： Committee of Full-cycle Standardized Management of Bone Health in Breast cancer Patients Fei Ma 不详 Department of Medical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Bone health management for breast cancer spans the entire cycle of patient care,including the prevention and treatment of bone loss caused by early breast cancer treatment,the adjuvant application of bone-modifying agents to improve prognosis,and the diagnosis and treatment of advanced bone *** good bone health management means formulating appropriate treatment strategies and dealing with adverse drug reactions,and will help to improve patients'quality of life and survival *** Breast cancer Expert Committee of the National cancer center for Quality Control organized relevant experts to conduct an in-depth discussion on the full-cycle management of breast cancer bone health based on evidence-based medicine,and put forward reasonable suggestions to guide clinicians to better deal with health issues in bone health clinics.

关键词： bone health bone-modifying drugs breast cancer guidelines

Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasis in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1302-1316页

作者： Xinyuan Xu Qian Zhang Xufeng Wang Jing Jin Chengwei Wu Li Feng Xiuyan Yang Mingzhu Zhao Yingyi Chen Shaoyong Lu Zhen Zheng Xiaobing Lan Yi Wang Yan Zheng Xuefeng Lu Qiufen Zhang Jian Zhang State Key Laboratory of Medical Genomics National Research Center for Translational Medicine at ShanghaiRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Medicinal Chemistry and Bioinformaticscenter Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of General Surgery Huashan HospitalCancer Metastasis InstituteFudan UniversityShanghai 200040China Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medicine and Medical CenterUniversity of Science and Technology of ChinaHefei 230026China Department of Assisted Reproduction Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Pharmacy Ningxia Medical UniversityYinchuan 750004China Department of pancreatic Surgery Shanghai General HospitalShanghai Key Laboratory of Pancreatic DiseaseInstitute of Pancreatic DiseaseShanghai Jiao Tong University School of MedicineShanghai 200080China

pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour ***6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic ***,highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be ***,we developed a noveSIRT6 allosteric inhibitor,compound 11e,with maximal inhibitory potency and an IC_(50) value of 0.98±0.13μmol/***,compound 11e exhibited significant selectivity against other histone deacetylases(HADC1-11 and SIRT1-3)at concentrations up to 100μmol/*** allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural ***,we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver *** our knowledge,this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic *** not only provides a promising lead compound for subsequent inhibitor developmentargeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.

关键词： SIRT6 Inhibitor Allosteric Selectivity Cocrystal pancreatic cancer metastasis

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Mutations in Ras homolog family member A in patients with peripheral T-cell lymphoma and implications for personalized medicine

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cancer Biology & Medicine 2024年第9期 754-768页

作者： Lina Hu Xuanye Zhang Shengbing Zang Sun Yat-sen University cancer center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Department of Pathology Sun Yat-sen University Cancer Center Department of Medical Oncology Sun Yat-sen University Cancer Center

Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA) among various cancers with unique aberrant profiles and pathogenic effects, especially in peripheral T-cell lymphoma(PTCL). The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type, thereby leading to different functional and biological properties, which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors. However, the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated. Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways. The promising potential of targeting RHOA as a therapeutic modality is also outlined. This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.

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Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer

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Chinese Medical Journal 2024年第3期137卷 338-349页

作者： Feng Xu Kun Xu Lingling Fan Xintong Li Yiqiu Liu Fang Yang Chengjun Zhu Xiaoxiang Guan Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Institute of Cancer ResearchNanjingJiangsu 210009China The Comprehensive cancer center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu 210008China Jiangsu Key Lab of cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment *** androgen receptor(AR)has emerged as a potential therapeutic target for luminal androgen receptor(LAR)***,multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical *** study aimed to investigate the role of AR in TNBC and its detailed ***:Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4(NECTIN4)expression in TNBC ***,in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta(ERβ)in *** immunoprecipitation sequencing(ChIP-seq),co-immunoprecipitation(co-IP),molecular docking method,and luciferase reporter assay were performed to identify key molecules that affect the function of ***:Based on the TNBC tissue array analysis,we revealed that ERβand AR were positive in 21.92%(32/146)and 24.66%(36/146)of 146 TNBC samples,respectively,and about 13.70%(20/146)of TNBC patients were ERβpositive and AR *** further demonstrated the pro-tumoral effects of AR on TNBC cells,however,the oncogenic biology was significantly suppressed when ERβtransfection in LAR TNBC cell lines but not in AR-negative ***,we identified that NECTIN4 promoter–42 bp to–28 bp was an AR response element,and that ERβinteracted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor ***:This study suggests that ERβfunctions as a suppressor mediating the effect of AR in TNBC prognosis and cell ***,our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

关键词： Androgen receptor Estrogen receptor beta Triple-negative breast cancer NECTIN4 Oncogenic effects Tumor progression

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