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Chinese Journal of Chemical Engineering 2024年第1期65卷 145-157页

作者： Peizhe Cui jiafu xing Chen Li Mengjin Zhou Jifu Zhang Yasen Dai Limei Zhong Yinglong Wang College of Chemical Engineering Qingdao University of Science and TechnologyQingdao 266042China

In this work,the ternary azeotrope of tert-butyl alcohol/ethyl acetate/water is separated by extractive distillation(ED)to recover the available constituents and protect the *** on the conductor like shielding model and relative volatility method,ethylene glycol was selected as the extractant in the separation *** addition,in view of the characteristic that the relative volatility between components changes with pressure,the multi-objective optimization method based on nondominated sorting genetic algorithm II optimizes the pressure and the amount of solvent cooperatively to avoid falling into the optimal local *** on the optimal process parameters,the proposed heat-integrated process can reduce the gas emissions by 29.30%.The heat-integrated ED,further coupled with the pervaporation process,can reduce gas emission by 42.36%and has the highest exergy efficiency of 47.56%.In addition,based on the heat-integrated process,the proposed two heat pump assisted heat-integrated ED processes show good economic and environmental *** double heat pump assisted heat-integrated ED can reduce the total annual cost by 28.78%and the gas emissions by 55.83%compared with the basis process,which has a good application *** work provides a feasible approach for the separation of ternary azeotropes.

关键词： Extractive distillation Optimization Mixtures Separation

Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2024年

作者： Huanbo Zhu Longtao Huangfu Junbing Chen jiafu Ji Xiaofang xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital &Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Genomic characterization of peritoneal lavage cytology-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 66-77页

作者： Zhouqiao Wu Tingfei Gu Changxian Xiong Jinyao Shi Jingpu Wang Ting Guo Xiaofang xing Fei Pang Ning He Rulin Miao Fei Shan Yuan Zhou Ziyu Li jiafu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Biomedical Informatics Department of Physiology and PathophysiologyCenter for Noncoding RNA MedicineMOE Key Lab of Cardiovascular SciencesSchool of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric ***: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric ***: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

关键词： Cytology gastric carcinoma peritoneal metastasis whole exome sequencing

PTPRD/PTPRT mutation correlates to treatment outcomes of immunotherapy and immune landscape in pan-cancers

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Chinese Journal of Cancer Research 2023年第3期35卷 316-330页

作者： Gangjian Wang Xin Ji Haojie Wang Xiaohuan Tang Xiaofang xing jiafu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100101China

Objective: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to ***, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains ***: Clinical data and PTPRD/PTPRT mutation information from 12 cohorts were collected and classified as a discovery cohort and three validation cohorts. The association between PTPRD/PTPRT mutations and immunotherapeutic efficacy was analyzed. Then, the association between PTPRD/PTPRT mutation and immune profiles was analyzed using The Cancer Genome Atlas(TCGA) ***: A total of 2,392 patients across 20 cancer types were included in this study. Our results showed that patients harboring PTPRD/PTPRT mutation, especially co-mutations, had a significantly elevated response rate to immunotherapy in multiple cancers. Patients with PTPRD/PTPRT mutation had a higher objective response rate(ORR)(P=0.002), longer overall survival(OS)(P=0.005) and progression-free survival(PFS)(P=0.038).Importantly, the above findings were further verified in validation cohorts. In addition, we found that the PTPRD/PTPRT co-mutations(co-mut) subgroup exhibited an immune-activated phenotype, the wild-type subgroup tended to have an immune-desert phenotype, and the uni-mutation(uni-mut) subgroup might have an immune-mixed phenotype. Our further analyses suggested that combining programmed cell death ligand 1(PDL1) expression and PTPRD/PTPRT mutation can be used to screen patients who may benefit from ***: PTPRD/PTPRT mutation could serve as a potential predictive biomarker for cancer immunotherapy.

关键词： PTPRD PTPRT immune microenvironment immunotherapy biomarker

Optical dating of the Jingshuiwan Paleolithic site of Three Gorges, China

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Chinese Science Bulletin 2006年第11期51卷 1334-1342页

作者： PEI Shuwen ZHANG jiafu GAO xing ZHOU Liping FENG xingwu CHEN Fuyou Institute of Vertebrate and Paleoanthropology Chinese Academy of Sciences Beijing 100044 China College of Environmental Sciences MOE Key Laboratory for Earth Surface Processes Peking University Beijing 100871 China

The Jingshuiwan Paleolithic site occu- pies the second terrace on the right bank of the Yangtze River. The lithic assemblage is characterized by choppers and scrapers made on pebbles and large flakes——the typical lithic industry of South China. Deposits of the site are mainly composed of fluvial sediments. Quartz grains extracted from these fluvial sediments from which the artifacts were un- covered were dated using the optically stimulated luminescence/single-aliquot regenerative-dose tech- nique. The dating results show that ancient human activities at this site took place in the early Upper Pleistocene (ca. 70 ka). The successful age analysis of the Jingshuiwan site is considered as a major break- through in chronological analysis of Paleolithic open site in the Three Gorges region and even in South China. The dates obtained help to establish a more complete chronological framework of the Paleolithic cultural sequence in the region, and bear significant implica- tions in studying modern human origins in China.

关键词：旧石器时代光学定年河成阶地人类起源

SDCBP-AS1 destabilizesβ-catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis

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Cancer Communications 2022年第11期42卷 1141-1161页

作者： Jing Han Menglin Nie Cong Chen Xiaojing Cheng Ting Guo Longtao Huangfu Xiaomei Li Hong Du Xiaofang xing jiafu Ji Department of Gastrointestinal Cancer Translational Research Laboratory Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijing Institute for Cancer ResearchBeijing 100142P.R.China Department of Radiation Oncology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070P.R.China Department of Gastrointestinal Surgery Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijing Institute for Cancer ResearchBeijing 100142P.R.China

Background:Gastric cancer(GC)is among the most malignant tumors,yet the pathogenesis is not fully understood,especially the lack of detailed information about the mechanisms underlying long non-coding RNA(lncRNA)-mediated post-translational ***,the molecular mechanisms and clinical significance of the novel lncRNA syndecan-binding protein 2-antisense RNA 1(SDCBP2-AS1)in the tumorigenesis and progression of GC were ***:The expression levels of SDCBP2-AS1 in 132 pairs of GC and adjacent normal tissues were compared,and the biological functions were assessed in vitro and in *** pull-down and immunoprecipitation assays were conducted to clarify the interactions of SDCBP2-AS1 and heterogeneous nuclear ribonucleoprotein(hnRNP)***-sequencing,immunoprecipitation,immunofluorescence,and luciferase analyses were performed to investigate the functions of ***:SDCBP2-AS1 was significantly downregulated in GC tissues and pre-dictive of poor patient *** of SDCBP2-AS1 promoted the proliferation and migration of GC cells both in vitro and in ***,SDCBP2-AS1 physically bound to hnRNP K to repress SUMOylation of hnRNP K and facilitated ubiquitination of hnRNP K andβ-catenin,thereby promoting the degradation ofβ-catenin in the *** of SDCBP2-AS1 caused SUMOylation of hnRNP K and stabilizedβ-catenin activity,which altered tran-scription of downstream genes,resulting in tumorigenesis and metastasis of ***,the knockdown of hnRNP K partially abrogated the effects of ***:SDCBP2-AS1 interacts with hnRNP K to suppress tumorigenesis and metastasis of GC and regulates post-transcriptional modifications of hnRNP K to destabilizeβ-*** findings suggest SDCBP2-AS1 as a potential target for the treatment of GC.

关键词： SDCBP2-AS1 gastric cancer hnRNP K β-catenin post-transcriptional modifications tumori-genesis

TRIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3512-3523页

作者： Xiaoxiao Ma Shuqin Jia Gangjian Wang Min Liang Ting Guo Hong Du Sisi Li Xiaomei Li Longtao Huangfu Jianping Guo Xiaofang xing jiafu Ji Department of Gastrointestinal Cancer Translational Research Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer Hospital&InstituteBeijingChina Department of Molecular Diagnostics Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer Hospital&InstituteBeijingChina Institute of Precision Medicine the First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510275China Department of Gastrointestinal Surgery Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer Hospital&InstituteBeijingChina

Immune checkpoint blockade(ICB)offers a new opportunity for treatment for gastric cancer(G.C.).Understanding the upstream regulation of immune checkpoints is crucial to further improve the efficacy of ICB ***,using the CRISPR-Cas9-based genome-wide screening,we identified TRIM28 as one of the most significant regulators of PD-L1,a checkpoint protein,in ***.

关键词： cancer gastric immune

Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer

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Science China(Life Sciences) 2023年第2期66卷 298-312页

作者： Longtao Huangfu Xiaoyang Wang Shanshan Tian Junbing Chen Xueying Wang Biao Fan Qian Yao Gangjian Wang Cong Chen Jing Han Xiaofang xing jiafu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Department of Pharmacy Peking University Cancer Hospital&InstituteBeijing 100142China National Institute on Drug Dependence Peking UniversityBeijing 100191China Gastrointestinal Cancer Center Peking University Cancer Hospital&InstituteBeijing 100142China Department of Pathology Peking University Cancer Hospital&InstituteBeijing 100142China

The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.

关键词： piceatannol Beclin-1 autophagy everolimus gastric cancer drug synergy

Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications

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Chinese Journal of Cancer Research 2014年第1期26卷 104-111页

作者： Zhixue Zheng Zhaode Bu Xijuan Liu Lianhai Zhang Ziyu Li Aiwen Wu Xiaojiang Wu Xiaojing Cheng Xiaofang xing Hong Du Xiaohong Wang Ying Hu jiafu Ji Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal Surgery Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Central Laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Clinical Gastric Cancer Translational Research Laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Biological Tissue BankPeking University Cancer Hospital&Institute

Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host *** study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric ***：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present *** PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed ***：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.

关键词： Programmed cell death-1 ligands (PD-L1) tumor immunity advanced gastric cancer enzyme-linked immunosorbent assay (ELISA)

LGR5 is a promising biomarker for patients with stage Ⅰ and Ⅱ gastric cancer

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Chinese Journal of Cancer Research 2013年第1期25卷 79-89页

作者： Zhaode Bu Zhixue Zheng Lianhai Zhang Ziyu Li Yu Sun Bin Dong Aiwen Wu Xiaojiang Wu Xiaohong Wang Xiaojing Cheng Xiaofang xing Yingai Li Hong Du jiafu Ji Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal Surgery Peking University Cancer Hospital & Institute Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Pathology Peking University Cancer Hospital & Institute Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Clinical Gastric Cancer Research Laboratory Peking University Cancer Hospital & Institute Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Tissue Bank Peking University Cancer Hospital & Institute

Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results： The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues （P〈0.001）, and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II （P〈0.05）. Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn＇t meet statistical significance （P〉0.05）. LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients （P〈0.05）. Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival （P〈0.05）. Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer （P〈0.05）. Conclusions： Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.

关键词： Leucine-rich repeat-containing G protein-coupled receptor 5 (LGRS) gastric cancer cancer stemcell biomarker prognosis