1.Mechanism of Weiliuan Mixture in Regulating Ferroptosis and Inhibiting Progression of Gastric Cancer Based on Transcriptome
Jingxiao LI ; Shenlin LIU ; Xi ZOU ; Minghao QI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):125-135
ObjectiveTo observe the inhibitory effect of the Weiliuan mixture (WLAHJ) on the subcutaneous xenograft tumor of MKN-74 gastric cancer cells, and explore the potential anti-gastric cancer mechanism of WLAHJ by using transcriptomic sequencing technology to reveal related genes and pathways. Methods30 Balb/c nude mice were randomly divided into model, low-, medium-, and high-dose(15,30,45 g·kg-1) WLAHJ and 5-FU (0.025 g·kg-1) groups to build a subcutaneous xenograft tumor model with MKN-74 human gastric cancer cells. After modeling,each group was continuously treated with the corresponding drugs for 28 days. During the treatment period, the body weight and tumor size of the mice were observed and recorded every 2 days. At the end of the treatment, the mice were sacrificed, and required samples were collected to calculate the tumor inhibition rate of WLAHJ on the subcutaneous xenograft tumor. High-throughput transcriptomic sequencing (RNA-seq) technology was used to analyze the differentially expressed genes in the subcutaneous tumor tissues of the model group and the medium-dose WLAHJ group, thus exploring the potential mechanism of WLAHJ in gastric cancer intervention. Immunofluorescence experiments were conducted to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein-1 (TFR-1), and acyl-CoA synthetase long-chain family member 4 (ACSL4) in subcutaneous xenograft tumors of each group. Cell counting kit-8(CCK-8) and colony formation assays were used to detect the viability and anti-proliferative ability of human gastric cancer AGS and MKN-74 cells at different concentrations of WLAHJ. Kits were used to detect the levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in cells. Western blot was used to detect the expression levels of GPX4, SLC7A11, TRF-1, ACSL4, spermidine/spermine N1-acetyltransferase 1 (SAT1), arachidonic acid 15-lipoxygenase (ALOX15), and key proteins in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. ResultsThe mechanism of WLAHJ in gastric cancer intervention may be related to ferroptosis and the PI3K/Akt /mTOR signaling pathway. The growth of subcutaneous xenograft tumors in nude mice of the WLAHJ and 5-FU groups(P<0.05,P<0.01), GPX4, and SLC7A11 dropped significantly(P<0.01), while TFR-1, ACSL4, SAT1, and ALOX15(P<0.05,P<0.01)increased significantly compared with those in the model group. The levels of ROS, Fe2+, and MDA increased in the WLAHJ and 5-FU groups and the proliferation of gastric cancer cells, SOD activity, the ratios of phosphorybation (p)-mTOR/mTOR, p-PI3K/PI3K, and p-Akt/Akt protein expressions(P<0.05,P<0.01)decreased compared with those in the blank group. ConclusionThe mechanism of WLAHJ in treating gastric cancer may be related to the regulation of the PI3K/ Akt /mTOR signaling pathway to intervene in ferroptosis.
2.Yttrium-90 selective internal radiotherapy in conversion treatment of unresectable hepatocellular carcinoma:research progress
Man ZHAO ; Qianwen NI ; Xianjie PIAO ; Xiaoqin WU ; Rui ZHOU ; Kaiting ZHANG ; Zhenguang WANG ; Minghao ZOU ; Wenxuan ZHOU ; Fuchen LIU ; Hui LIU
Academic Journal of Naval Medical University 2025;46(2):189-197
Yttrium-90(90Y)selective internal radiation therapy(SIRT)is an emerging modality for the treatment of hepatocellular carcinoma(HCC),leveraging the nuclide 90Y to deliver targeted radiation therapy.90Y has a long half-life and can be used to selectively ablate tumor cells by high-energy beta rays.It has high biological effectiveness and robust local control capabilities.In recent years,with the continuous advancement of basic and clinical research,the application of 90Y-SIRT in the conversion treatment of unresectable HCC(uHCC)has made significant progress.However,challenges remain in the clinical application of 90Y-SIRT,including how to improve the efficacy of conversion therapy and how to optimize therapy regimens.This review aims to summarize the research progress of90Y-SIRT in the conversion therapy of uHCC.
3.Morphological characteristics of hepatocellular carcinoma tumor margin:a crucial factor in clinical treatment decision-making and prognostic assessment
Rui ZHOU ; Minghao ZOU ; Wenxuan ZHOU ; Fuchen LIU ; Kaiting ZHANG ; Xiaoqin WU ; Man ZHAO ; Jin QIAN ; Ningyang JIA ; Hui LIU
Journal of Clinical Medicine in Practice 2025;29(7):127-130,137
The morphological characteristics of hepatocellular carcinoma(HCC)tumor margins are pivotal in influencing patient's prognosis and the selection of therapeutic strategies.This paper re-viewed the classification methods of HCC tumor margins,ranging from traditional macroscopic classifi-cations to refined classification systems based on multi-omics analysis,and analyzed the role of these classification methods in guiding the formulation of personalized treatment plans.Additionally,this paper emphasized the crucial role of three-dimensional imaging techniques in assessing tumor margin morphology and outlined future research directions,including validating the effectiveness of multi-omics classification systems and developing new imaging and molecular biomarkers to achieve more precise treatment plans and prolong patient survival.
4.Efficacy and Safety Analysis of the Interventional Treatment Through the Distal Transradial Access in Patients With Complex Coronary Lesions
Wei YU ; Cheng CUI ; Minghao LIU ; Ying SONG ; Tongqiang ZOU ; Jue CHEN ; Haibo LIU ; Lei SONG ; Zhan GAO ; Huanhuan WANG ; Lijian GAO
Chinese Circulation Journal 2024;39(8):775-780
Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.
5.A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression.
Cheng WANG ; Minghao ZHANG ; Shunyao LI ; Miaomiao GONG ; Ming-Yu LUO ; Mo-Cong ZHANG ; Jing-Hua ZOU ; Ningxiang SHEN ; Lu XU ; Hui-Min LEI ; Ling BI ; Liang ZHU ; Zhengting WANG ; Hong-Zhuan CHEN ; Lu ZHOU ; Ying SHEN
Acta Pharmaceutica Sinica B 2024;14(11):4819-4831
Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8+ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Result Analysis
Print
Save
E-mail