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Cancer Biology & Medicine 2024年第2期21卷 132-138页

作者： Xiumei Wang Jun Chen Guangshuai Jia department of immunology and microbiology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Jinfeng Laboratory Chongqing 401329China GMU-GIBH Joint School of Life sciences Guangzhou Medical UniversityGuangzhou 510182China

Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate *** orchestrate sophisticated processes in development,homeostasis,immunity,and *** residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.

关键词： immunity homeostasis tumor

Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2119-2136页

作者： Li Peng Yanyi Jiang Hengxing Chen Yongqiang Wang Qiusheng Lan Shuiqin Chen Zhanwang Huang Jingyuan Zhang Duanqing Tian Yuntan Qiu Diankui Cai Jiangyun Peng Daning Lu Xiaoqing Yuan Xianzhu Yang Dong Yin Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China medical Research Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Hefei Institutes of Physical Science Chinese Academy of SciencesHefei 230031China department of Gastrointestinal Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China department of Hepatobiliary Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biomedical sciences.and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug ***,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of *** is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor *** this study,we found that ETS homologous factor(EHF)expression is promoted by a core transcriptional regulatory circuitry(CRC),specifically ELF3-KLF5-GATA6,and interference with its expression suppressed the malignant biological behavior of GEA ***,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in ***,we identified KRAS signaling as a common pathway downstream of EHF and ***,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in *** conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS *** of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.

关键词： EHF AJUBA KRAS pathway Enhancer Core transcriptional regulatory circuitry Gastroesophageal adenocarcinoma Gastric adenocarcinoma Esophageal adenocarcinoma Transcription factor Coactivator Lipid nanoparticles

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

Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1730-1744页

作者： Zhenzhen Fang Gang Shen Yina Wang Fuyan Hong Xiumei Tang Yongcheng Zeng Ting Zhang Huanyi Liu Yanmei Li Jinhong Wang Jing Zhang Anton Gao Weiwei Qi Xia Yang Ti Zhou Guoquan Gao department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China department of VIP medical Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Physical Examination Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China department of Clinical Laboratory Guangzhou First People's HospitalGuangzhou 510080China Guangdong Key Laboratory of Liver Disease Research the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 51008China department of Health sciences College of Health SolutionsArizona State UniversityTempeUSA Guangdong Engineering&Technology Research Center for Gene Manipulation and Biomacromolecular Products Sun Yat-Sen UniversityGuangzhou 510080China Guangdong Province Key Laboratory of Diabetology Guangzhou 510o80China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic ***(HLP)is the leading risk factor for *** study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were *** plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver ***,KAL levels of NAFLD patients were significantly *** transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)*** contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD ***,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),***-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa ***,hepatic CGl-58-overexpress reverses NASH in KAL transgenic ***,free fatty acids up-regulated KAL against thyroid hormone in ***,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating *** results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

关键词： GSK3β inflammation elevated

RNA ac^(4)C modification in cancer biology:from regulatory mechanisms to clinical applications

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Science China(Life sciences. 2024年第4期67卷 832-835页

作者： Lijun Tao Yunqing Lu Zhuojia Chen Lichen Ge Junming He Jianxin Peng Hongsheng Wang School of Pharmaceutical sciences Sun Yat-sen UniversityGuangzhou 510006China sun yat-sen university Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China department of Hepatobiliary Surgery Guangdong Province Traditional Chinese Medical HospitalGuangzhou 510120China

RNA modifications are increasingly recognized for their significance in diverse physiological and pathological processes,with over 170 types of chemical modifications having been discovered since *** these modifications,N4-acetylcytidine(ac^(4)C)is the first acetylated modification identified on eukaryotic RNAs,previously reported in transfer RNA(t RNA)and ribosomal RNA(rRNA)。

关键词： clinical (4) modification

Roles of cancer-associated fibroblast functional heterogeneity in shaping the lymphatic metastatic landscape:new insights and therapeutic strategies

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Cancer Biology & Medicine 2024年第6期21卷 445-450页

作者： Hanhao Zheng Daiyin Liu Zhicong Liu Mingjie An Yuming Luo Changhao Chen Tianxin Lin department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510003China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalState Key Laboratory of Oncology in South ChinaGuangzhou 510003China department of General Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510003China

Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system.

关键词： metastasis lymphatic landscape

Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2091-2103页

作者： Ri-Xin Chen Shui-Dan Xu Min-Hua Deng Shi-Hui Hao Jie-Wei Chen Xiao-Dan Ma Wei-Tao Zhuang Jing-Hua Cao Yong-Rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-Wei Wang department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China

RNA-binding proteins(RBPs)-RNA networks have contributed to cancer *** RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still *** bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and *** evidence suggests a connection between PBs dynamics and cancer *** the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in ***,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient *** MEX3A accelerates malignance and inhibits autophagy of CRC ***,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the ***,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs *** MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC ***,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall *** findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关键词： colorectal inhibiting MPP

Development of antibody-drug conjugates in cancer:Overview and prospects

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Cancer Communications 2024年第1期44卷 3-22页

作者： Dan-Yun Ruan Hao-Xiang Wu Qi Meng Rui-Hua Xu department of Clinical Research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdongP.R.China department of medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China

In recent years,remarkable breakthroughs have been reported on antibody-drug conjugates(ADCs),with 15 ADCs successfully entering the market over the past *** substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs,demonstrating their efficacy in treating awide array of ***,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of *** ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and ***,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side *** this review,we comprehen-sively reviewed the current development and the prospects of ADC,provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China,highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies,and also discussed the new related technologies,possibility of next-generation ADCs and the directions of clinical research.

关键词： companies breakthrough payload

Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling

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Genes & Diseases 2024年第2期11卷 964-977页

作者： Chengzhi Wu Hengyu Liu Dongmei Zhong Xiaoming Yang Zhiheng Liao Yuyu Chen Shun Zhang Deying Su Baolin Zhang Chuan Li Liru Tian Caixia Xu Peiqiang Su Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spine SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Research Center for Translational Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Precision Medicine Institute The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China department of Orthopedics Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Guangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China

Mutation of the MAPK7 gene was related to human ***7 regulated the development of limb bones and skulls in ***,the role of MAPK7 in vertebral development is still *** this study,we constructed Col2a1-cre;Mapk7 f/f transgenic mouse model to delete Mapk7 in cartilage,which displayed kyphosis and ***,Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes,which impaired chondrocyte hypertrophy and attenuated vertebral *** vivo,systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 *** study firstly clarified the mechanism by which MAPK7 was involved in vertebral development,which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.

关键词： Chondrocyte hypertrophy Growth plate Kyphosis MAPK7 MEF2C Osteopenia PI3K/AKT PTEN

Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

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Neural Regeneration Research 2024年第10期19卷 2281-2289页

作者： Wang Liao Jiana Wei Chongxu Liu Haoyu Luo Yuting Ruan Yingren Mai Qun Yu Zhiyu Cao Jiaxin Xu Dong Zheng Zonghai Sheng Xianju Zhou Jun Liu department of Neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Special medical Service Center Neuroscience CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangdongGuangdong ProvinceChina department of Rehabilitation The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of Neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

关键词： Alzheimer's disease APP/PS1 double-transgenic Alzheimer's disease mouse model inflammation intestinal barrier dysfunction magnesium-L-threonate microbiome microbiota-gut-brain axis oxidative stress serum metabolites