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Clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma: a real-world study

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cancer Biology & Medicine 2024年第9期21卷 799-812页

作者： Yuxiao Liu Xiaofan Guo Peijun Xu Yuning Song Jing Huang Xingyun Chen Wenbo Zhu Jihui Hao Song Gao Department of Pancreatic cancer Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: Little progress has been made in recent years using first-line chemotherapy, including gemcitabine combined with nabpaclitaxel, FOLFIRINOX, and NALIRIFOX, for advanced pancreatic adenocarcinoma(APC). In addition, the optimal second-line chemotherapy regimen has not been determined. This study aimed to compare the effectiveness of different types of second-line chemotherapy for ***: Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis. The primary and secondary endpoints were overall survival(OS) and progression-free survival(PFS), ***: Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment, respectively. Demographic and clinical features, except age and liver metastasis, were comparable between the two groups(P < 0.05). The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy, respectively(HR = 1.244, 95% CI = 1.090±1.419; P < 0.001). The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care, respectively(HR = 0.766, 95% CI = 0.677±0.867; P < 0.001). The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination ***: A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

关键词： 5-fluorouracil Second-line chemotherapy advanced pancreatic adenocarcinoma gemcitabine real-world study

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Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong Department of Colorectal cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

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The role of reactive oxygen species in gastric cancer

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cancer Biology & Medicine 2024年第9期21卷 740-753页

作者： Yuqi Wang Jingli Xu Zhenjie Fu Ruolan Zhang Weiwei Zhu Qianyu Zhao Ping Wang Can Hu Xiangdong Cheng College of Pharmaceutical Sciences Zhejiang University of Technology Department of Gastric Surgery Zhejiang Cancer Hospital Key Laboratory of prevention Zhejiang Provincial Research Center for Upper Gastrointestinal Tract cancer Zhejiang Cancer Hospital

Gastric cancer(GC) ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide. Reactive oxygen species(ROS) are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance. ROS are closely associated with the occurrence, development, and treatment of GC. This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction. In addition, the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized. The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC.

关键词： Gastric cancer ROS antitumor therapy natural products pharmacology reactive oxygen species

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Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

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Oncology Research 2024年第3期32卷 489-502页

作者： WEIXUE WANG TONGTONG WANG YAN ZHANG TING DENG HAIYANG ZHANG YI BA Department of GI Medical Oncology Tanjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerTianjin Key Iaboratory of Digestive CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell *** is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis ***,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported *** exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been ***,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of *** conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

关键词： Cellular ferroptosis Exosome Tyrosine kinase inhibitor Gastrointestinal tumors miRNA

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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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Biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： WANG Han Lin XUE Yan Feng CUI Bao Qiu LIU Hong SHEN Xin Xin Shandong Provincial Research Center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina Shanxi Province cancer Hospital/Shanxi Hospital Affiliated to cancer Hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State Key Laboratory of Infectious Disease prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with *** We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 *** MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for *** variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary *** The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for ***,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of *** contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against *** This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization

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Interpretation of the Standards of Basic Dataset of Chronic Diseases Behavior Risk Factor Surveillance in Adults

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Biomedical and Environmental Sciences 2024年第5期37卷 551-556页

作者： ZHAO Yan Fang ZHANG Mei WEI Wen Qiang SUN Ke Xin LI Xin Hua WANG Li Min National Center for Chronic and Noncommunicable Disease Control and prevention(NCNCD) Chinese Center for Disease Control and PreventionBeijing 100050China cancer Hospital Chinese Academy of Medical SciencesBeijing 100021China Chinese Center for Disease Control and prevention Beijing 102206China People's Medical Publishing House Beijing 100021China

BACKGROUND China’s Behavioral Risk Factor Surveillance System(BRFSS)originated from the World Bankfunded HealthⅦLoan Project in the 1990s,which conducted behavioral risk factor surveillance in seven cities and one province^([1]).Drawing on the World Health Organization’s(WHO)STEPwise approach to surveillance(STEPs)and the *** Risk Factor Surveillance System(BRFSS)^([2,3]).

关键词： funded Basic originated

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Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4001-4013页

作者： Ziqi Huang Kun Zhang Yurui Jiang Mengmeng Wang Mei Li Yuda Guo Ruolin Gao Ning Li Chenyang Wang Jia Chen Jiefu Wang Ning Liu Xiang Liu Shuangwei Liu Mingming Wei Cheng Yang Guang Yang The State Key Laboratory of Medicinal Chemical Biology College of Life SciencesCollege of PharmacyNankai UniversityTianjin 300071China Tianjin Medical University cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

cancer stem cells(CSCs)play a pivotal role in tumor initiation,proliferation,metastasis,drug resistance,and ***,targeting CSCs has emerged as a promising avenue for cancer ***,3-phosphoglycerate dehydrogenase(PHGDH)has been identified as being intricately associated with the regulation of numerous cancer stem ***,reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are *** this study,the novel“molecular glue”LXH-3-71 was identified,and it robustly induced degradation of PHGDH,thereby modulating the stemness of colorectal cancer cells(CRCs)both in vitro and in ***,LXH-3-71 was observed to form a dynamic chimera,between PHGDH and the DDB1-CRL E3 *** insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH ***,compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase,facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

关键词： Molecular glue Targeted protein degradation PHGDH cancer stem cells PROTACs

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Deep insight into the B-cell associated tertiary lymphoid structure and tumor immunotherapy

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cancer Biology & Medicine 2024年第2期21卷 125-131页

作者： Jilong Yang Jin Xu Haotian Liu Wanyi Xiao Gengpu Zhang Department of Bone and Soft Tissue Tumor Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Molecular Cancer EpidemiologyTianjin 300060China Department of Anaesthesiology Tianjin University Tianjin HospitalTianjin 300211China

Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other *** a promising supplemental immunotherapy to mainstream method... 详细信息

关键词： immunotherapy immunity

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2024年

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian cancer Institute Linzhou cancer Hospital Center for Disease Control and prevention of Sheyang County Department of cancer prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Luoshan Center for Disease Control and prevention Office for cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer(GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates(CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic(atrophic gastritis/intestinal metaplasia) and neoplastic lesions(low-grade/high-grade dysplasia), respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients(≥3 risk factors) with non-neoplastic lesions showed higher GC risks(adjusted HR=7.73, 95%CI: 4.29–13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions(aHR=3.07, 95%CI: 1.67–5.64) and high-risk patients with mild lesions(aHR=7.29, 95%CI: 3.58–14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Beta-lactam antibiotic resistance among Escherichia coli isolates from patients with urinary tract infections in Vietnam:A systematic review and meta-analysis

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Asian Pacific Journal of Tropical Medicine 2024年第6期17卷 243-255,I0001-I0003页

作者： Dat T Nguyen Princess Margaret cancer centre University Health NetworkTorontoOntarioCanada

Objective:To investigate the evolving patterns of antimicrobial resistance against beta-lactam antibiotics in Escherichia coli isolates from urinary tract infection patients in Vietnam,covering the period from 2005 to ***:29 Descriptive studies published between 2010 and 2022 in English and Vietnamese were included in the *** on resistance rates to beta-lactam antibiotics,including cephalosporins and carbapenems,were extracted and *** pooled resistance rates were calculated using random-effects *** trends in resistance were assessed using linear regression ***:Among the beta-lactam antibiotics studied,Escherichia coli exhibited varying levels of resistance,with cephalosporins showing higher resistance rates compared to *** pooled resistance rates were 66%for cefotaxime,65%for ceftriaxone,54%for ceftazidime,and 56%for *** contrast,carbapenems demonstrated lower resistance rates,with weighted pooled resistance rates ranging from 3%to 4%for meropenem,ertapenem,and *** rates were also observed for amoxicillin/clavulanate(35%),ticarcillin/clavulanate(26%),and piperacillin/tazobactam(12%).Significant annual increases in resistance were noted for imipenem(0.56%,P<0.001).Conclusions:This study highlights the critical issue of antimicrobial resistance in urinary tract infections in Vietnam and emphasizes the importance of prudent antibiotic use and the regular monitoring of resistance *** insights are useful for guiding healthcare professionals in optimizing treatment strategies and for policymakers in formulating evidence-based clinical guidelines to combat antibiotic resistance effectively.

关键词： Antimicrobial resistance Urinary tract infection Vietnam

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