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Addressing chemoresistance with a lipid gemcitabine nanotherapeutic strategy for effective treatment of pancreatic cancer

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Nano Research 2024年第9期17卷 8377-8388页

作者： Jiawei Hong Shiyun Xian Shusen Zheng Hangxiang Wang Donghai Jiang The First Affiliated Hospital NHC Key Laboratory of Combined Multi-Organ TransplantationCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesSchool of MedicineZhejiang UniversityHangzhou 310003China Jinan Microecological Biomedicine Shandong laboratory Jinan 250117China

Resistance to gemcitabine in pancreatic cancer poses a significant clinical *** investigation is warranted to assess whether nano-formulation strategy can be employed to enhance the sensitivity of resistant strains to gemcitabine *** this study,using gemcitabine-resistant pancreatic cancer cell lines,we examined the therapeutic potential of a gemcitabine nanodelivery platform and assessed the ability to overcome drug resistance against resistant *** of human equilibrative nucleoside transporter 1(hENT1)led to reduced cellular uptake of gemcitabine,resulting in chemoresistance in pancreatic *** nanoparticles circumvented the entry blockade caused by hENT1 silencing through *** entry via clathrin-mediated endocytosis increased intracellular gemcitabine accumulation in gemcitabine-resistant pancreatic cancer ***,gemcitabine nanoparticles are preferential in vivo delivery to tumor tissues,likely due to the enhanced permeability and retention *** comparison to free gemcitabine,gemcitabine nanoparticles demonstrate a more pronounced cytotoxic effect on gemcitabine-resistant pancreatic cancer cells,with favorable *** study improved the efficacy of gemcitabine through nanotechnology,providing a novel strategy to address gemcitabine-resistant pancreatic cancer.

关键词： pancreatic cancer gemcitabine resistance gemcitabine nanoparticle human equilibrative nucleoside transporter 1

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Analysis of the potential biological value of pyruvate dehydrogenase E1 subunitβin human cancer

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World Journal of gastrointestinal Oncology 2024年第1期16卷 144-181页

作者： Yao Rong Song-Hua Liu Ming-Zheng Tang Zhi-Hang Wu Guo-Rong Ma Xiao-Feng Li Hui Cai First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina key laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina nhc key laboratory of diagnosis and therapy of gastrointestinal tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in ***,few studies have elucidated the role and mechanism of PDHB in different *** To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in *** vitro experiments were performed to examine the biological regulation of PDHB in liver *** Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)*** of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset *** regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer *** correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also *** algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)*** expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was *** study also validated the level of mRNA or protein expression of PDHB in several ***,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver *** PDHB was significantly and differently expressed in most *** was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinom

关键词： Cuprotosis Pyruvate dehydrogenase E1 subunitβ Pan-cancer Prognosis Liver cancer

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Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

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World Journal of gastrointestinal Oncology 2024年第2期16卷 436-457页

作者： Yao Rong Ming-Zheng Tang Song-Hua Liu Xiao-Feng Li Hui Cai First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina key laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina nhc key laboratory of diagnosis and therapy of gastrointestinal tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver ***,this mechanism of action has not been *** sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus *** identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were ***,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was *** Of 518 common DEGs were obtained by screening for functional *** hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”*** enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver ***,we selected 10 of the hub genes for in vitro expression validation in liver cancer *** Our study reveals a common pathogenesis of liver cancer and *** common pathways and key genes may provide new ideas for further mechanistic studies.

关键词： COVID-19 Liver cancer Differentially expressed genes Hub genes Pathogenesis

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The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

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World Journal of gastrointestinal Surgery 2024年第7期16卷 2073-2079页

作者： Ling-Zhen Gong Qian-Wen Wang Jie-Wen Zhu Department of Clinical laboratory Huangshi Central Hospital(Affiliated Hospital of Hubei Polytechnic University)Hubei Key Laboratory of Kidney Disease Pathogenesis and InterventionHuangshi Tumor Molecular Diagnosis and Treatment Key LaboratoryHuangshi 435000Hubei ProvinceChina

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)*** predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is *** To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of *** The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January *** CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver *** addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic *** The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone ***,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL *** 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL *** addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(Ptumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

关键词： Colorectal cancer Liver metastasis Serum markers Carcinoembryonic antigen Cancer antigen 125 Cancer antigen 19-9 Receiver operating characteristic analysis

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Combining systemic inflammatory response index and albumin fibrinogen ratio to predict early serious complications and prognosis after resectable gastric cancer

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World Journal of gastrointestinal Oncology 2024年第3期16卷 732-749页

作者： Jing-Yao Ren Da Wang Li-Hui Zhu Shuo Liu Miao Yu Hui Cai School of Clinical Medicine Ningxia Medical UniversityYinchuan 750000Ningxia Hui Autonomous RegionChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina key laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina nhc key laboratory of diagnosis and therapy of gastrointestinal tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Medical College of Jiangsu University Jiangsu UniversityZhenjiang 212013Jiangsu ProvinceChina The First Clinical Medical School Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of ***,patient survival rates are still low,and the incidence of major postoperative complications cannot be *** systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer *** systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical *** To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer *** We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December *** calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative *** scored the patients and categorized them into three groups based on their SIRI and AFR *** analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:Ptumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with *** Preoperative SIRI and AFR values were s

关键词： Inflammation Albumin fibrinogen ratio Gastric cancer Complications Prognosis

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Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

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Animal Models and Experimental Medicine 2024年第1期7卷 3-11页

作者： Hanwei Yue Lin Bai nhc key laboratory of Human Disease Comparative Medicine Institute of Laboratory Animal SciencesCAMS and PUMCChao-yang DistrictBeijingChina

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient *** better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor *** exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and *** believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient *** characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid *** study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

关键词： antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research

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Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia:Long-term outcomes of a prospective trial(PKUCH-R03 trial)

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Chinese Journal of Cancer Research 2024年第4期36卷 410-420页

作者： Nan Chen Minghe Zhao Yunfeng Yao Lin Wang Yifan Peng Tingting Sun Tiancheng Zhan Jun Zhao Aiwen Wu key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China State key laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF).Methods:This prospective,single-arm phaseⅡtrial was designed and conducted at Peking University Cancer *** patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR).Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5%of whom experienced grade 3-4 adverse events during *** pCR rate was 17.0%for the entire cohort,and the overall rate of postoperative complications was 37.7%(1.9%of gradeⅢa patients).The 3-year disease-free survival rate was 91.4%,and 23.5%(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major ***:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable *** fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

关键词： Neoadjuvant chemotherapy rectal cancer mesorectal fascia disease-free survival anal function

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Clinical significance of peripheral blood immune cells in patients with gastric cancer after surgery

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World Journal of gastrointestinal Surgery 2024年第8期16卷 2521-2527页

作者： Qian-Wen Wang Jie-Wen Zhu Ling-Zhen Gong Department of Clinical laboratory Huangshi Central Hospital(Affiliated Hospital of Hubei Polytechnic University)Huangshi 435000Hubei ProvinceChina Hubei key laboratory of Kidney Disease Pathogenesis and Intervention Huangshi 435000Hubei ProvinceChina Huangshi tumor Molecular diagnosis and Treatment key laboratory Huangshi 435000Hubei ProvinceChina

BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,and surgical resection is one of the main ways to treat gastric ***,the immune status of postoperative patients is crucial for prognosis and survival,and immune cells play an important role in this ***,it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells,especially total T cells(CD3+),helper T cells(CD3+CD4+),and suppressor T cells(CD3+CD8+),and its relationship to *** To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery,detect the levels of total T cells,helper T cells and suppressor T *** A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective *** cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells,helper T cells and inhibitory T *** explore the relationship between these immune markers and patient *** The results showed that the levels of total T cells,helper T cells,and suppressor T cells changed in patients after gastric cancer *** was a significant positive correlation between total T cells,helper T cells and suppressor T cells(r=0.35,P<0.01;r=0.56,P<0.01).However,there was a negative correlation between helper T cells and suppressor T cells(r=-0.63,P<0.01).Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group(28.87±24.98 months vs 18.42±16.21 months).The survival curve shows that the curve of patients in the high-level group is shifted to the upper right,and that of the low-level group is shifted *** was no significant difference between the levels of helper T cells and suppressor T cells and patient survival *** By detecting peripheral blood immune c

关键词： Gastric cancer surgery Peripheral blood immune cells Flow cytometry Survival analysis Immune monitoring

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Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer

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National Science Review 2024年第4期11卷 216-227页

作者： Da-Yong Hou Ni-Yuan Zhang Lu Wang Mei-Yu Lv Xiang-Peng Li Peng Zhang Yue-Ze Wang Lei Shen Xiu-Hai Wu Bo Fu Peng-Yu Guo Zi-Qi Wang Dong-Bing Cheng Hao Wang Wanhai Xu nhc and CAMS key laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University Department of Urology Harbin Medical University Cancer Hospital CAS key laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST) School of Chemistry Chemical Engineering & Life Science Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases Wuhan University of Technology

Mitochondriopathy inspired adenosine triphosphate(ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration(IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites,leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like ***, the reported transformable nucleopeptide(NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei,which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines(T24,EJ and RT-112) revealed that the half-maximal inhibitory concentration(IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

关键词： self-assembly nucleopeptide nanomaterial bladder cancer mitochondriopathy

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Distal margin distance in radical resection of locally advanced rectal cancer after neoadjuvant therapy

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Chinese Journal of Cancer Research 2024年第2期36卷 226-232页

作者： Jun Luo Mingxuan Zhu Long Zhao Meiwen He Bei Li Yifan Liu Yuhan Sun Guoqing Lyu Zhanlong Shen Department of gastrointestinal Surgery Peking University Shenzhen HospitalShenzhen 518036China Department of Gastroenterological Surgery Laboratory of Surgical OncologyBeijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment ResearchPeking University People's HospitalBeijing 100044China School of Medicine the Chinese University of Hong KongShenzhen 518172China

Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more *** tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal ***, there is currently no consensus on the specific distance of distal resection margin.

关键词： Colorectal cancer distal resection margin neoadjuvant therapy

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