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Sono-assembly of folate-decorated curcumins/alginate core-shell microcomplex and its targeted delivery and pH/reduction dual-triggered release

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Particuology 2024年第1期84卷 168-177页

作者： Qingye Meng Shuangling Zhong Jingfei Wang Zhenqian Zhang Yan Gao Xuejun Cui College of Chemistry jilin University Changchun130012China College of Resources and Environment jilin Agricultural University Changchun130118China State Key Laboratory of Supramolecular Structure and Materials Jilin UniversityChangchun130012China Weihai Institute for Bionics-Jlin University Weihai264400China

In this study,sodium alginate(SA),a non-toxic natural polysaccharide with good biocompatibility and biodegradability,was developed for targeted delivery of curcumin(CUR)in tumor *** strategy is to sulfhydrylate the folic acid(FA)modified SA,and the CUR dissolved in ethyl acetate(EAC)phase is coated in microcapsules by a quick,efficient and environment-friendly sonochemical *** EAC in the microcapsule core is volatile,which can be recycled and reused to reduce *** prepared mi-crocapsules(FA-RSMCs@CUR)exhibited similar toxicity to free curcumin in anti-tumour evaluation in ***-RSMCs@CUR also exhibited effective antibacterial properties in the antibacterial evaluation in *** is expected to become a low-cost tumor targeting vector in the future,and has the potential to be promoted in clinical application.

关键词： Reductive-responsive Sodium alginate Microcapsule Targeted delivery Sonochemical

Mutational landscape of TP53 and CDH1 in gastric cancer

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 276-283页

作者： Hong-Qiao Cai Li-Yue Zhang Li-Ming Fu Bin Xu Yan Jiao Department of Hepatobiliary and Pancreatic Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Department of Critical Care Medicine The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Department of Traditional Chinese Medicine The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg.A common gene mutation in gastric cancer(GC)is the TP53 *** a tumor suppressor gene,TP53 is implicated in more than half of all tumor ***53 gene mutations in GC tissue may be related with clinical pathological *** TP53 mutation arose late in the progression of GC and aided in the final switch to ***1 encodes E-cadherin,which is involved in cell-to-cell adhesion,epithelial structure maintenance,cell polarity,differentiation,and intracellular signaling pathway ***1 mutations and functional loss can result in diffuse GC,and CDH1 mutations can serve as independent prognostic indicators for poor *** patients can benefit from genetic counseling and testing for CDH1 *** therapy may assist to postpone the onset and progression of *** investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations,as well as providing some basis for evaluating the prognosis of GC patients.

关键词： TP53 CDH1 Gastric cancer Gene mutation Methylation

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

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BIOCELL 2024年第6期48卷 945-958页

作者： YUNBAO GUO XU LIU QI XU XIAOTONG ZHOU JIAWEI LIU YANYAN XU YAN LU HAIYAN LIU The Department of Neurosurgery First Hospital of Jilin UniversityChangchun130021China The Department of Anatomy College of Basic Medical SciencesJilin UniversityChangchun130021China The Third College of Clinical Medicine Jilin UniversityChangchun130021China

Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve *** is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae *** also has anti-infection,antitumor,and immunomodulatory *** this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and ***,the mechanism through which honokiol regulates glioma cell apoptosis is still ***:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control ***-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative ***,MAPK signaling and ferroptosis were detected via western ***:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased *** of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were veriﬁ***:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling *** data could lead to new ideas for future research and therapy for patients with glioma.

关键词： Human glioma Honokiol RNA-seq Apoptosis Ferroptosis MAPK

Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog(KRAS)-mutant tumors

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Chinese Journal of Cancer Research 2024年第4期36卷 421-441页

作者： Dongsheng He Rilan Bai Naifei Chen Jiuwei Cui Cancer Center the First Hospital of Jilin UniversityChangchun 130021China

Kirsten rat sarcoma viral oncogene homolog(KRAS)is the most frequently mutated oncogene,occurring in various tumor *** extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations,resistance to these inhibitors has eventually emerged.A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome *** has developed rapidly in recent years,and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations,finding that immune factors play an essential role in KRAS-mutant(KRAS-Mut)tumor therapy and targeted drug *** and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory ***,we reviewed KRAS mutation-targeted treatment strategies and resistance issues,focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS *** aimed to guide innovative approaches combining RAS inhibition with immunotherapy,review advances in preclinical and clinical stages,and discuss challenges and future directions.

关键词： Cancer KRAS mutation targeted therapy immunotherapy immune microenvironment

Hypoxic tumor microenvironment:Destroyer of natural killer cell function

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Chinese Journal of Cancer Research 2024年第2期36卷 138-150页

作者： Yongfei Zhang Feifei Guo Yufeng Wang Cancer Center the First Hospital of Jilin UniversityChangchun 130021China

In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.

关键词： Hypoxia immunotherapy NK cell tumor microenvironment

Manufacturing CAR-NK against tumors: Who is the ideal supplier?

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Chinese Journal of Cancer Research 2024年第1期36卷 1-16页

作者： Feifei Guo Yi Zhang Jiuwei Cui The First Hospital of jilin University Cancer CenterChangchun 133021China

Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical ***, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.

关键词： CAR-NK cells cord blood iPSC NK-92 cells peripheral blood

抗原改造联合纳米肿瘤疫苗用以克服肿瘤新抗原短缺及在多种肿瘤类型上激起强效抗肿瘤免疫反应

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Science Bulletin 2024年第7期69卷 922-932页

作者：陈宏宇黄子超李佳玄董思徐玉笛马胜赵佳雨刘丽萍孙天盟宋万通陈学思 School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China Key laboratory of Polymer Ecomaterials Changchun Institue of Applied ChemistryChinese Academy of SciencesChangchun 130022China Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin UniversityChangchun 130021China jilin Biomedical Polymers Engineering Laboratory Changchun 130022China

Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer ***,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen ***,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide *** demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in ***,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was *** combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen *** approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.

关键词： Cancer immunotherapy Cancer vaccine Neoantigen Nanocarrier Poly(2-oxazoline)s

AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy

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Chinese Medical Journal 2024年第2期137卷 222-231页

作者： Yichun Yin Jian Wang Junxuan Yi Kaiyue Zhang Zimeng Yin Shunzi Jin Baisong Zheng Public Health of College Jilin UniversityJilinChangchun 130021China Institute of Virology and AIDS Research The First Hospital of Jilin UniversityJilinChangchun 130021China NHC Key Laboratory of Radiobiology(jilin University) JilinChangchun 130021China

Background:Radiation(IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment(TME).Wee1,a cell cycle regulator,can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1(CDK1).Meanwhile,programed death-1/programed death ligand-1(PD-1/PDL-1)blockade is closely related to *** study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody(anti-PD-1 Ab)on radiosensitization of ***:The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide(MTT)assay on human and mouse hepatoma cells HepG2,Hepa1-6,and *** anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro.A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice,which were divided into control group,IR group,AZD1775 group,IR+AZD1775 group,IR+anti-PD-1 Ab group,and the IR+AZD1775+anti-PD-1 Ab *** CD8^(+)T cells in TME were analyzed by flow ***:Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in ***1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA ***1775 treatment also reduced the proportion of PD-1^(+)/CD8^(+)T cells in the spleen of hepatoma subcutaneous xenograft *** studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferonγ(IFNγ)^(+)or Ki67^(+)CD8 T cells and decreasing the levels of CD8^(+)Tregs cells in the tumor and spleen of the hepatoma mice model,indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγexpression,enhancing CD8^(+)T cells proliferation,and weakening CD8^(+)T cells ***:This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiothera

关键词： Hepatoma Radiation AZD1775 Anti-PD-1 antibody DNA damage tumor microenvironment

Impact of immunotherapy on liver metastasis

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 1969-1972页

作者： Zhuo Fu Ming-Wei Wang Ya-Hui Liu Yan Jiao Medical College Inner Mongolia Minzu UniversityTongliao 028000Inner Mongolia Autonomous RegionChina Ministry of Health Key Laboratory of Radiobiology School of Public Health of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Hepatobiliary and Pancreatic Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

This editorial discusses the article“Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis”published in the latest edition of the World Journal of Gastrointestinal *** has achieved outstanding success in tumor ***,the presence of liver metastasis(LM)restrains the efficacy of immunotherapy in various tumors,including lung cancer,colorectal cancer,renal cell carcinoma,melanoma,and gastric cancer.A decrease in CD8+T cells and nature killer cells,along with an increase in macrophages and regulatory T cells,was observed in the microenvironment of LM,leading to immunotherapy *** studies are necessary to determine the best strategy for enhancing the effectiveness of immunotherapy in patients with LM.

关键词： Immunotherapy Liver metastasis tumor microenvironment Resistance T cells