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First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang Wang Fen Guo Kangxin Wang Guangfu Jin Xiao Li Rong Wang Fengyuan Li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao Liang Liu Ling Ma Lijuan Meng Zhiguo Hou Rongrong Zheng Yang Liu Ni Guan Bei Zhang Shuang Tong Shiqing Chen Xing Li Yongqian Shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu School Nanjing medical UniversitySuzhouChina Jiangsu Key Lab of cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research Center of Precision Therapy of Gastrointestinal cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina Jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of medical Affairs 3D Medicines Inc.ShanghaiChina Shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim *** phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction *** primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and *** 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and *** regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days *** regimen 2:same as dose regimen 1,but oxaliplatin 130mg/*** regimen3:same as dose regimen 2,but apatinib 250 mg ***-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was *** 3 was set for the recommended phase 2 doses and administered in phase *** confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team *** 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse *** plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

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miR-30a-5p/PHTF2 axis regulates the tumorigenesis and metastasis of lung adenocarcinoma

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BIOCELL 2024年第4期48卷 581-590页

作者： LIJUAN ZHANG QINGYIN MENG LI ZHUANG QUAN GONG XIANDA HUANG XUEQIN LI SHIJUAN LI GUOQIN WANG XICAI WANG Department of Rehabilitation and Palliative Medicine The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Emergency Department(Outpatient Chemotherapy Center) The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of cancer BioTreatment Center The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of cancer Institute The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina

Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective *** this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung ***:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal *** experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma ***,we examined tumorigenesis and metastasis in a nude mouse ***:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma *** of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant ***,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal ***,PHTF2 was found to be a molecular target of *** PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p ***:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung ***,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.

关键词： Lung cancer Malignant phenotype Tumor formation Tumor suppressor Oncogene

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Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

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Chinese Chemical Letters 2024年第4期35卷 475-480页

作者： Lijia Xu Tong Zhong Wei Zhao Bing Yao Lin Ding Huangxian Ju State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Department of Reproductive medical Center Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China Chemistry and Biomedicine Innovation Center(ChemBIC) Nanjing UniversityNanjing 210023China Center of Clinical Laboratory Science The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210009China

Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.

关键词： Spermatozoa Glycan Chemoselective labeling Oligoasthenotspermia Fluorescence imaging

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GNAS mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma

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Oncology Research 2024年第6期32卷 1079-1091页

作者： CHAO TANG CHUNYU ZHONG JUNHAO ZHU FENG YUAN JIN YANG YONG XU CHIYUAN MA Department of Neurosurgery Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjing210002China Department of Neurosurgery Children’s Hospital of Nanjing Medical UniversityNanjing210019China affiliated Eye hospital Nanjing Medical UniversityNanjing210029China Department of Neurosurgery Jinling HospitalSouthern Medical UniversityNanjing210002China Department of Neurosurgery Jinling HospitalNanjing Medical UniversityNanjing210002China

Approximately 30%–40%of growth hormone–secreting pituitary adenomas(GHPAs)harbor somatic activating mutations in GNAS(αsubunit of stimulatory G protein).Mutations in GNAS are associated with clinical features of smaller and less invasive ***,the role of GNAS mutations in the invasiveness of GHPAs is *** mutations were detected in GHPAs using a standard polymerase chain reaction(PCR)sequencing *** expression of mutation-associated maternally expressed gene 3(MEG3)was evaluated with ***3 was manipulated in GH3 cells using a lentiviral expression *** invasion ability was measured using a Transwell assay,and epithelial–mesenchymal transition(EMT)-associated proteins were quantified by immunofluorescence and western ***,a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and *** invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type ***,the invasiveness of mutant GNASexpressing GH3 cells ***3 is uniquely expressed at high levels in GHPAs harboring mutated ***,MEG3 upregulation inhibited tumor cell invasion,and conversely,MEG3 downregulation increased tumor cell ***,GNAS mutations inhibit EMT in ***3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway,which was further validated in *** data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/β-catenin signaling pathway.

关键词： GHPAs GNAS mutation MEG3 β-catenin EMT

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A novel nomogram for predicting the prognosis of hepatocellular carcinoma patients following immune checkpoint inhibitors treatment beyond progression:a single center study based on Chinese population

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 771-787页

作者： Chao Chen Xiaoyuan Chu Hong Liu Mingzhen Zhou Zhan Shi Anfeng Si Ying Zhao Xiufeng Liu Jie Shen Baorui Liu Comprehensive cancer Center Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina Department of Oncology Jinling HospitalNanjing Medical UniversityNanjingChina Department of Cardiothoracic Surgery Nanjing Hospital Affiliated to Nanjing University of Chinese MedicineNanjingChina Department of Surgical Oncology of PLA cancer Center Jinling HospitalNanjing Medical UniversityNanjingChina Department of Radiology Jinling HospitalNanjing Medical UniversityNanjingChina

Background:Hepatocellular carcinoma(HCC)persists as a dominant cause of cancer-related mortality globally,with a notably rapid escalation in mortality *** advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has ushered in a new era in the management of liver cancer,albeit with unresolved challenges in the context of treatment beyond progression(TBP)and stratified prognosis in diverse *** study aimed to develop and validate a novel nomogram model to identify factors that predict the benefit of continued immunotherapy for hepatocellular carcinoma patients following disease progression in clinical ***:This study retrospectively analyzed the efficacy of ICIs in TBP,focusing on the Chinese population with advanced liver cancer.A nomogram was constructed based on four independent risk factors identified through Cox multivariate analysis,aiming to predict patient prognosis post-ICI *** model was validated through receiver operating characteristic(ROC)curve analysis and categorized patients into high-,intermediate-,and low-risk groups,with further validation using calibration plots and decision curve analysis(DCA).Results:The low-risk group demonstrated significantly enhanced overall survival(OS)compared to the high-risk group,with the nomogram predictions aligning closely with actual outcomes for 6-and 9-month *** model exhibited commendable predictive accuracy,achieving a C-index exceeding 0.7 in both training and validation *** DCA underscored the clinical utility of the nomogram-based prognostic model,further substantiated by the area under the ROC curve(AUC).Conclusions:The developed nomogram presents a potentially valuable tool for predicting the prognosis of HCC patients undergoing ICI therapy beyond progression,particularly within the Chinese ***,the study is constrained by its retrospective,single-center nature and necessitates further validation through large-scale,multicente

关键词： Hepatocellular carcinoma(HCC) immune checkpoint inhibitors(ICIs) novel nomogram

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White Matter Lesions in Young-Middle Aged Migraineurs with Patent Foreman Ovale: A Case-Control Study

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Congenital Heart Disease 2024年第3期19卷 279-291页

作者： Yang Hua Jinyu Sun Yuxuan Lou Hao Zhang Jing Shi Wei Sun Department of Cardiology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China

Background:White matter lesion(WML)is common in aging brain and is associated with cognitive impairment and ***,recent studies reported an association between patent foramen ovale(PFO)and WML in migraineurs,especially in young,middle-aged *** retrospective,case-control study aims to describe the clinical characteristics of WML in this population and to explore potential risk ***:226 patients with migraine and PFO were consecutively initially *** factors were selected by the least absolute shrinkage and selection operator(LASSO)regression and multivariable logistic regression model.A Nomogram was employed to visualize the prediction model *** discrimination and calibration abilities were evaluated using the Receiver Operating Characteristic(ROC)curve,the Hosmer-Lemeshow test,and calibration ***:One hundred and nineteen participants were ultimately enrolled in our study,with a median age of 36.9±12.7 years and 80.7%of *** magnetic resonance imaging MRI showed 67(56.3%)patients had WML,whereas 52(43.7%)patients were categorized into the non-WML *** regression screened out potential variables and subsequent multivariate analysisfinally identified age,mean platelet volume,andfibri-nogen(FIB)as independent predictive factors of *** area under the ROC curve(AUC)was ***-mer-Lemeshow test and calibration curve verified a consistency between the predicted and actual ***:The predictive nomogram established and validated in our study may assist clinicians in screening WML among young middle-aged migraineurs with PFO and developing individualized preventive and treatment strategies.

关键词： White matter lesion migraine patent foreman ovale nomogram predictive model

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Bortezomib depended on PRDM1 and TP53 to exert therapeutic effect in activated B-cell-like diffuse large B-cell lymphoma

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Genes & Diseases 2024年第2期11卷 550-553页

作者： Jing Tang Yue Li Jiazhu Wu Haorui Shen Hua Yin Jinhua Liang Li Wang Jianyong Li Yi Xia Wei Xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of nanjing medical university NanjingJiangsu 210029China Collaborative Innovation Center for cancer Personalized Medicine NanjingJiangsu 210029China

PR/SET domain 1(PRDM1)gene is located on chromosome 6q21,encoding the B lymphocyte-induced maturation protein 1(BLIMP1).1 It is reported that loss of PRDM1 function is exacerbated in activated B-cell-like(ABC)-diffuse large B cell lymphoma(DLBCL)and associated with inferior ***,it remains unclear what leads to PRDM1 inactivation and the drug resistance mechanism caused by abnormal inactivation of *** investigated the contribution of PRDM1 gene as a prognosis and potential therapeutic target for ABC-DLBCL patients and further clarified the possible mechanism of PRDM1 abnormal *** first proposed that TP53 could regulate PRDM1 by histone ubiquitination modification at the post-transcriptional level.

关键词： PRDM1 TP53 therapeutic

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Genotyping on circulating tumor DNA improves mutation detection rate in high-risk diffuse large B-cell lymphoma

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Genes & Diseases 2024年第4期11卷 116-119页

作者： Yi Xia Li Wang Jinhua Liang Haorui Shen Jiazhu Wu Hua Yin Yue Li Huayuan Zhu Jianyong Li Wei Xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of nanjing medical university NanjingJiangsu 210029China Collaborative Innovation Center for cancer Personalized Medicine NanjingJiangsu 210029China

Diffuse large B-cell lymphoma(DLBCL)is the most common lymphoma with heterogeneous clinical *** who are primarily refractory to the frontline therapy or relapse less than 12 months after diagnosis have an extremely di... 详细信息

关键词： lymphoma diagnosis clinical

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Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

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National Science Review 2024年第5期11卷 170-185页

作者： Yong Zhou Shanlan Mo Heyang Cui Ruifang Sun Weimin Zhang Xiaofei Zhuang Enwei Xu Hongyi Li Yikun Cheng Yongsheng Meng Meilin Liu Ting Yan Huijuan Liu Ling Zhang Bin Yang Yanfeng Xi Shubin Wang Xiaolong Cheng Shuai Cheng Li Zhihua Liu Qimin Zhan Zheng Hu Yongping Cui cancer Institute Department of Pathology Peking University Shenzhen Hospital Shenzhen Peking University-the Hong Kong University of Science and Technology(PKU-HKUST) Medical Center Institute of Cancer ResearchShenzhen Bay Laboratory Key Laboratory of Cellular Physiology of the Ministry of Education Department of Pathology Shanxi Medical University City university of Hong Kong Shenzhen Research Institute CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of Sciences Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Department of Tumor Biobank Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Research Unit of Molecular cancer Research Chinese Academy of Medical Sciences Department of Thoracic Surgery Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Department of Pathology Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University College of Letters & Science University of California Berkeley State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Esophageal squamous cell carcinoma（ESCC） is a poor-prognostic cancer type with extensive intra-and inter-patient heterogeneity in both genomic variations and tumor microenvironment（TME）. However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2,accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the ***, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted ***, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

关键词： squamous cell carcinoma heterogeneity multi-omics evolution tumor microenvironment

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Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

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Journal of Biomedical Research 2024年第4期38卷 397-412页

作者： Jiaqi Tang Lin Luo Bakwatanisa Bosco Ning Li Bin Huang Rongrong Wu Zihan Lin Ming Hong Wenjie Liu Lingxiang Wu Wei Wu Mengyan Zhu Quanzhong Liu Peng Xia Miao Yu Diru Yao Sali Lv Ruohan Zhang Wentao Liu Qianghu Wang Kening Li Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsu 211166China Department of Hematology of the affiliated Huai'an No.1 People's hospital of nanjing medical university Northern Jiangsu Institute of Clinical MedicineHuai'anJiangsu 223300China Collaborative Innovation Center for Personalized cancer Medicine Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentNanjing Medical UniversityNanjingJiangsu 211166China Department of Hematology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of nanjing medical university NanjingJiangsu 210029China Department of Pharmacology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China The affiliated cancer hospital of nanjing medical university Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchNanjingJiangsu 210002China

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is *** surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and *** the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression *** using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML *** predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome *** Cox regression analysis showed that the risk score was an independent prognostic factor for the AML *** AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low ***,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy ***,PI3K inhibitors were identified as potential treatments for these high-risk *** conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

关键词： acute myeloid leukemia cell surface markers prognosis drug sensitivity multi-model analysis

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