Translational Cancer Research
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2026
·Vol. 15
·期 7
·555
·
IF 2.1
Junjie Wu,Congxing Liu,Yaya Sun,Guangqing Jiang,Yupeng Zhao,Yihong Zhang,Yiping Yin,Xin Shi
Background Colon cancer (CC) is a heterogeneous disease with increasing morbidity and mortality. Ferroptosis, a recently identified form of regulated cell death (RCD) characterized by the massive accumulation of iron-dependent lipid peroxidation (LPO), has been proven to be closely associated with various biological behaviors of CC. Moreover, accumulating evidence reveals that ALOX12 is essential for p53-mediated ferroptosis through distinct pathways. Therefore, our study aims to explore the specific mechanisms by which ALOX12 regulates tumorigenesis in CC through ferroptosis pathway. Methods We explored the characteristics of ALOX12 expression and its correlation with prognosis in CC patients and cell lines, followed by a series of functional assays in vitro and in vivo to investigate the mechanisms underlying the functions of ALOX12 in p53-driven ferroptosis. Results We discovered that ALOX12 was downregulated in CC tissues and cell lines, which was correlated with poor prognosis. Furthermore, overexpression of ALOX12 suppressed cell proliferation and tumorigenesis by upregulating reactive oxygen species (ROS)-induced stress. We continuously found that increased ALOX12 levels enhanced the sensitivity of CC cells to a distinct ferroptosis, which required both p53 activation and additional ROS, and differed from that induced by erastin. Conclusions Our study demonstrates the oncosuppressive behavior of ALOX12 in CC. Mechanistically, we discover that p53 can indirectly activate ALOX12 function by suppressing its transcriptional target SLC7A11, resulting in an ALOX12-dependent ferroptotic pathway. Targeting ALOX12 may provide a novel biomarker or new therapeutic strategies for improving the prognosis of CC.
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高影响因子
Translational Cancer Research
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2026
·Vol. 15
·期 3
·179
·
IF 2.1
Jia-Yi Lu,Xin-Miao Zhao,Xian-Bao Liu,Li Gao
Background Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, affecting the tongue, palate, mouth floor, alveolar ridge, and buccal mucosa. Kaempferol, a natural flavonoid, exhibits anti-oral cancer properties, but its mechanisms remain unclear. This study aimed to investigate kaempferol’s therapeutic potential and molecular mechanisms in OSCC using network pharmacology, molecular docking, and experimental validation. Methods Kaempferol’s components and targets were identified via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). OSCC-related genes were sourced from GeneCards and Gene Expression Omnibus (GEO) databases. Network and molecular docking analyses were performed using Cytoscape and Autodock, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). In vitro and in vivo experiments validated kaempferol’s effects. Results Kaempferol induced ferroptosis, reducing OSCC cell viability and increasing apoptosis dose-dependently. Carbonic anhydrase IX (CA9) emerged as a core gene mediating kaempferol’s anti-OSCC effects via ferroptosis. Molecular docking confirmed strong binding affinity between kaempferol and CA9 (−6.24 kcal/mol). GO and KEGG analyses revealed kaempferol’s modulation of p53/FoxO/cellular senescence pathways. Experiments confirmed kaempferol’s inhibition of OSCC proliferation and migration through CA9/ferroptosis induction. Conclusions Kaempferol exerts anti-OSCC effects via CA9/ferroptosis, highlighting its potential as a therapeutic agent for OSCC.
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高影响因子
Translational Cancer Research
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2026
·Vol. 15
·期 8
·585
·
IF 2.1
Gennian Wang,Hua Cheng,Yaping Zhang,Xiaohu Guo,Yumin Li
Background Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, have garnered significant attention from the global scientific community due to their potential threats to human health, particularly their association with the occurrence and development of cancer. The goal of our study is to create a predictive marker for pancreatic ductal adenocarcinoma (PAAD) based on MNPs-related genes, with the purposes of predicting survival outcomes and assessing the tumor immune microenvironment. Methods Using multi-cohort data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC), we assessed the association between MNPs and PAAD prognosis through the Xiantao Academic (https://www.xiantao.love/). The development of a prognostic signature was followed by an assessment of its significance through the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and decision curve analysis (DCA). The validity of the risk model was confirmed through the ICGC and GSE71729 cohorts. The model was then assessed for levels of tumor immune infiltration. To explore MNPs-related genes expression characteristics within immune cells in PAAD, we performed single-cell RNA sequencing and spatial transcriptomics analysis through the Sparkle Platform ( https://grswsci.top/ ). Finally, in vitro experiments were conducted to investigate the biological function of interleukin 1 alpha (IL1A). Results A four-gene signature comprising XDH, IL1A, KIF20A, and ASPM, based on MNPs, was developed to stratify PAAD patients into two distinct risk groups. The high-risk group showed a significantly poorer prognosis. A similar trend was verified in the external cohorts ICGC and GSE71729 . The signature risk score affected immune cell infiltration in the PAAD microenvironment. The infiltration of B cells, CD8 + T cells, cytotoxic cells, immature dendritic cells (iDCs), mast cells, plasmacytoid dendritic cell (pDC), T cells, Tem cells, T follicular helper (TFH) cells, and T helper 17 (Th17) cells had a positive correlation with the low-risk group. In contrast, high-risk patients tended to have increased number of T helper (Th2) cells and higher expression of SIGLEC15, CD274, IGSF8. Knockdown of IL1A in PAAD cells inhibited their tumor proliferation ability in vitro . Conclusions Using MNPs-related genes, we built a prognostic model for PAAD, revealing that patients with high-risk scores are likely to have a worse prognosis. This model is designed to develop personalized treatment strategies tailored to the specific needs of each patient, thereby improving clinical outcomes for PAAD patients. Furthermore, IL1A could be a promising therapeutic candidate for PAAD.
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高影响因子
Translational Cancer Research
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2025
·Vol. 14
·期 6
·3758
·
IF 1.7
Shaojun Cai,Liyong Zhang,Tenghong Liu,Bo Wang,Shouyi Yan,Sisi Wang,Jiafan Yu,Sibin Wu,Siying Lin,Wenxin Zhao
Background Anaplastic thyroid cancer (ATC) is a rare but extremely aggressive type of thyroid cancer derived from follicular cells of the thyroid gland. Due to the rapid growth of neck masses in ATC patients, which can lead to asphyxia, multimodality therapy, including surgery, chemotherapy, and radiotherapy, is essential in the treatment of ATC. Theaflavin (TF) has anti-cancer effects; however, no study has examined whether TF inhibits the malignant progression of ATC. Therefore, this study was conducted to explore the effects of TF on ATC and to provide a preliminary exploration of its mechanism. Methods The effects of TF on the half-maximal inhibitory concentration (IC 50 ) and proliferation of 8305C cells were determined by Cell Counting Kit-8 (CCK-8) assay. The effects of TF on the invasion and migration of 8305C cells were determined by transwell assay. Cell apoptosis was evaluated by flow cytometry. Labeled 8305C cells were injected into the yolk sac of zebrafish, and the progression of the 8305C cells was observed in vivo . Fluorescence real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to detect the expression of proteins related to the lipid metabolism pathway and cell apoptosis. Network pharmacology was used to study the predicted mechanisms of the TF action on 8305C cells. Results The IC 50 of TF in the treatment of 8305C cells for 48 h was 21.79 µg/mL. TF inhibited the proliferation, migration, and invasion of the 8305C cells at a concentration of 1/2 IC 50 , and induced the apoptosis of the 8305C cells. TF also inhibited the proliferation of the 8305C cells in vivo . TF significantly increased the expression of the caspase3, caspase8, and caspase9 proteins in vivo and in vitro , and significantly inhibited the expression of the survivin protein. TF also inhibited the messenger RNA (mRNA) expression of SREBP1 and PPARD , and increased the mRNA expression of HNF4 . The network pharmacology results revealed that the PI3K/AKT signaling pathway is an important pathway by which TF acts on 8305C cells, and that TF was able to inhibit the proliferation, migration, and invasion, increase the apoptosis, inhibit the mRNA expression of SREBP1 , and increase the mRNA expression of HNF4 in the 8305C cells when the PI3K/AKT signaling pathway was activated. Conclusions This study found that TF inhibits the proliferation, migration, and invasion of ATC 8305C cells, and induces 8305C cell apoptosis by regulating lipid metabolism via the PI3K/AKT signaling pathway.
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高影响因子
Translational Cancer Research
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2025
·Vol. 14
·期 11
·7641
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IF 1.7
Yuan Cheng,Liu Ruiwen,Xu Xinming,Sun Jun,Zhu Yi,Lu Rongzhu,Liu Yueyu,Chen Jian
Background Because of the high malignancy and subtle early symptoms of hepatocellular carcinoma (HCC), most patients lose the opportunity for surgery and opt for drug therapy. However, the current drugs for HCC treatment remain suboptimal, underscoring the urgent need to develop a novel anti-HCC agent. Curcumin is a natural chemical compound that has anti-cancer effects on various tumor cells, attracting sustained attention from researchers and clinicians. The present study aims to further elucidate curcumin’s anti-HCC mechanisms, thereby offering a promising therapeutic candidate for HCC patients. Methods The viability of HCC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. The levels of glutathione (GSH), malondialdehyde (MDA), and total iron in the cells were detected by biochemical kits. The levels of reactive oxygen species (ROS) and Fe 2+ in the cells were detected by fluorescent probes. The protein expressions of protein kinase RNA-like endoplasmic reticulum kinase (PERK), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) in the cells were detected by western blotting. Results Curcumin exerted a notably suppressive impact on HCC cells, which could be reversed by ferrostatin-1 (Fer-1) and desferrioxamine (DFO). By detecting cellular metabolic products, we observed an increase in total iron, Fe 2+ , MDA, ROS, and a reduction in GSH levels in HCC cells after treatment with curcumin, and these effects could be attenuated by Fer-1. Western blot analysis showed that curcumin significantly downregulated GPX4 levels in HCC cells while upregulating PERK, Nrf2 and HO-1 expression. Additionally, using PERK inhibitor, HO-1 inhibitor, and endoplasmic reticulum (ER) stress inhibitor could partially reverse the inhibition of HCC cells viability by curcumin and alleviate the reduction of GPX4 expression caused by curcumin. Conclusions Curcumin may induce ferroptosis in HCC cells through the PERK/Nrf2/HO-1 signaling pathway, thereby exerting its anti-cancer effects, suggesting that curcumin could potentially be used as a drug for treating HCC.
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高影响因子
Translational Cancer Research
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2025
·Vol. 14
·期 10
·6454
·
IF 1.7
Jiaxuan Zhao,Han Wu,Zhe Sun,Yeting Cui,Nan Liu,Yixuan Wang,Youyong Wang,Jiangzhou Shi,Tongcun Zhang
Background Chimeric antigen receptor T cell (CAR-T) therapy targeting cluster of differentiation 19 (CD19) has shown promise in treating B-cell acute lymphoblastic leukemia (B-ALL), but the long-term efficacy of CD19-targeted CAR-T therapy remains limited. Programmed cell death protein 1 (PD-1), an inhibitory receptor on activated T cells, engages programmed death ligand 1 (PD-L1) in the tumor microenvironment, suppressing CAR-T cell function by impairing key signaling pathways. To address this limitation, we investigated the effect of short hairpin RNA (shRNA)-mediated PD-1 knockdown on alleviating CAR-T cell exhaustion, preserving memory phenotype, and enhancing the long-term efficacy of CD19-targeted CAR-T cells. Methods To overcome this limitation, we employed shRNA to achieve PD-1 knockdown in CD19-targeting CAR-T cells. Following screening multiple shRNA candidates, we assessed the cytotoxicity, cytokine secretion, and proliferation of PD-1 knockdown CAR-T cells. Their memory phenotype, exhaustion marker, and cytolytic function were further evaluated after repeated antigen stimulation. Therapeutic efficacy and safety were validated in NOD.Cg-PrkdC scid Il2rg tm1 /Vst (NPG) mice. Results PD-1 knockdown significantly enhanced CAR-T cell cytotoxicity and persistence against PD-L1+ RAJI (human Burkitt’s lymphoma cell line) cells. After three rounds of antigen stimulation, PD-1 knockdown CAR-T cells sustained cytotoxic activity, retained a memory-like phenotype, and displayed attenuated exhaustion markers. In vivo , they prolonged survival without inducing cytokine release syndrome (CRS), indicating improved efficacy and safety. Conclusions PD-1 knockdown mitigates tumor-induced T-cell exhaustion and represents a promising strategy to enhance the durability and potency of CAR-T cell therapy in cancer treatment.
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高影响因子
Translational Cancer Research
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2026
·Vol. 15
·期 2
·90
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IF 2.1
Zhao Yubo,Zhang Digun,Zheng Hongqun,Chen Xuejian,Xu Lishan
Background N6-methyladenosine (m6A) regulators are involved in hepatocellular carcinoma (HCC) development. However, the functions of m6A regulators in HCC have not yet been elucidated. This study aimed to evaluate the potential of m6A methylation regulators as biomarkers and immunotherapeutic targets in HCC. Methods RNA sequencing data were obtained from publicly available databases including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Bioinformatics analysis was conducted, including Kaplan-Meier (KM) survival analysis, univariate and multivariate Cox regression, receiver operating characteristic (ROC) curve analysis and immune-related signatures were assessed using single-sample gene set enrichment analysis (ssGSEA) and drug sensitivity prediction was performed to identify potential small-molecule compounds. In vitro , small interfering RNA (siRNA)-mediated knockdown of selected m6A regulators was performed in three HCC cell lines (HepG2, HuH7 and MHCC-97H). Quantitative polymerase chain reaction (qPCR) and Western blot (WB) were subsequently conducted to validate gene expression changes. Additionally, WB was performed after treatment with candidate drugs to evaluate their functional impact. Results The five upregulated m6A regulators in HCC, KIAA1429, METTL3, PRRC2A, RBMX, and ZC3H3, were related to worse outcomes in HCC. ROC curves showed that m6A regulators could accurately distinguish between normal and HCC tumor tissues. Furthermore, differential m6A regulator expression was affected by immune infiltration. In advanced HCC patients, m6A regulators were important in determining clinical outcomes. Drug response analysis demonstrated m6A regulators as potential therapeutic agents that could be used as guidance for patients with HCC. PCR and WB analysis showed that m6A regulators could act on immune-related sites, interact with immune tolerance, and inhibit it. Conclusions This study indicates that KIAA1429, METTL3, PRRC2A, RBMX, and ZC3H3 may be potential immunotherapeutic targets and biomarkers in HCC.
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高影响因子
Translational Cancer Research
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2021
·
IF 1.241
Dong Luo,Wenzhi Chen,Wei Wang,Junlin Chen,Haopeng Xu,Jinyun Chen,Yan Wang
Background Our team has previously reported that low intensity pulsed ultrasound (LIPUS) can alleviate myelosuppression in rats induced by single chemotherapy drugs. But in clinics, chemotherapy is often performed with multiple drugs simultaneously. To be closer to the clinical status quo, this experiment was designed to show whether it was the same effect of LIPUS on myelosuppression caused by combination therapy of chemotherapy drugs. Methods The rat model of myelosuppression was established by continuous injection of paclitaxel and carboplatin for 4 days. These myelosuppressive rats were randomly divided into LIPUS group (n=40) and control group (n=40). The LIPUS group was given continuous LIPUS irradiation for 7 days, while the control group was given sham irradiation (no energy output). The evaluation of blood cells counts, Hematoxylin-Eosin staining (H&E staining), scanning electron microscopy, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qPCR) was then performed. Results The results showed in the LIPUS group the blood cells count, hematopoietic tissue of bone marrow, the colonies formed from adhering of bone marrow stromal cells, levels of hematopoietic regulators and adhesion molecules all increased (LIPUS group vs. control group, P<0.05). Conclusions The results indicated that LIPUS can relieve myelosuppression induced by combined treatment of paclitaxel and carboplatin. The mechanisms may be LIPUS can increase the levels of hematopoietic regulators and adhesion molecules.
研究领域:
肿瘤学
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药理学
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实验医学
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高影响因子
MICROELECTRONICS RELIABILITY
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2026
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IF 2.5
Tao Yang,Guoyou Gan,Xianglei Yu,Hu Sun,Junpeng Li
This study investigates the electrical properties and stability of resistor pastes formulated from RuO 2 –CuO composites doped with La 2 O 3 . The pastes exhibit an approximately linear positive temperature coefficient (PTC) of resistance behavior, referred to as near-linear positive temperature coefficient of resistance (TCR) in this work, to emphasize the linearity of the resistance-temperature relationship, with optimal performance achieved at 1.2 wt% La 2 O 3 doping. Microstructural analyses indicate that La 2 O 3 promotes densification of the resistive layer, enhancing the stability of the conductive network. After 1000 h of storage at room temperature, the resistance change rate is approximately 0.5%. Under high-temperature conditions (150 °C for 240 h), the rate increases slightly to about 2%, demonstrating satisfactory preliminary stability.
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CERAMICS INTERNATIONAL
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2023
·
IF 5.2
Shaozheng Wang,Ruiting Hou,Lanlan Tian,Hui Zhang,Yule Li,Qingming Chen
La 0.67 Ca 0.33 MnO 3 (LCMO) ceramics exhibit high temperature coefficient of resistance (TCR) and colossal magnetoresistance effect (CMR). Increasing their TCR and MR values can enhance potential applications in uncooled infrared detectors and magnetic storage devices. However, presence of inherent grain boundaries and defects within these ceramics significantly limits their performance. Therefore, this work proposed modifying grain boundaries of LCMO ceramic using low-resistivity and stable Au to enhance its electrical transport and improve magnetoresistance performance through competition between antiferromagnetic Au and ferromagnetic La 0.67 Ca 0.33 MnO 3 . A series of La 0.67 Ca 0.33 MnO 3 : Au x ( x = 0, 0.05, 0.10, 0.15) composite ceramics was prepared by sol-gel and solid-state methods. Introduction of Au increased TCR from 40.1 %·K −1 to 55.2 %·K −1 and MR from 60.4 % to 74.2 %, when x = 0.10. This study demonstrates that proposed strategy involving multiphase interactions can significantly improve electrical transport and magnetic properties of functional materials , with promising applications in areas such as thermoelectric and magnetoelectric conversion.
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高影响因子
CERAMICS INTERNATIONAL
·
2026
·
IF 5.6
Zifeng Li,Shuang Ding,Changchun Yu,Hao Yang,Xuting Sun,Hui Zhang,Qingming Chen,Yule Li
This study focuses on the improvement of magnetoresistance (MR) in a two-phase composite systems. The spin-polarization tunneling caused by the introduction of metal oxides (Fe 2 O 3 ) coating grains is a key link to enhance magnetoresistance performance. Two-phase composite ceramics La 0.67 Ca 0.33 MnO 3 @ x Fe 2 O 3 (LCMOF) (0 ≤ x ≤ 0.009) were prepared by sol-gel method, and the microstructure, electrical transport and magnetoresistance (MR) properties under the composite system were systematically studied. The XRD results indicate that the recombination of the second phase causes subtle structural distortion but still presents an orthogonal perovskite structure. The surface SEM results show that the grain boundaries of the material are clear, and the grain connections are tight. The coexistence of LCMOF and MnO phases exists in the sectional SEM images, which proves the occurrence of ion substitution. The ρ - T curve shows a drastic metal-insulator transition. The continuous recombination of Fe 2 O 3 increases the resistivity, which can be explained by the grain boundary effect and the dual-channel model. A noteworthy phenomenon was observed, when x = 0.009, the optimized MR was significantly enhanced to 72.94 %, and the sample performance was significantly improved, which was attributed to the spin-polarization tunneling effect. This study expands the application prospects of LCMOF composite phases in fields such as magnetic sensors, magnetic storage, and thermistors.
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高影响因子
CERAMICS INTERNATIONAL
·
2024
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IF 5.1
Zimeng Pan,Jiachen Wang,Zihao Chen,Zhenyu Wang,Yao Wang,Xiaolu Liang,Haitao Wang,Yiliang Liu,Yufei Du,Jiamei Han,Jiabin Jiang,Xin Gu,Xiang Liu
For uncooled infrared bolometers, the traditional thermal sensing materials such as vanadium oxide and amorphous silicon have a relative low value of temperature coefficient of resistivity ( TCR ). In contrast, perovskite manganese oxide films exhibit 3–5 times higher TCR values than traditional materials. The important challenge is to achieve both high TCR and peak TCR temperatures ( T k ) at room temperature. Herein, La 0.7 Ca 0.3− x K x MnO 3 (LCKMO, 0.22 ≤ x ≤ 0.28) films were fabricated on La 0.3 Sr 0.7 Al 0.65 Ta 0.35 O 3 (00 l ) substrates using a combined sol–gel and spin coating process. It was found that by optimizing the K doping amount at x = 0.24, on the one hand, double exchange mechanism becomes the strongest. On the other hand, with minimal lattice strain, electron scattering is inhibited, and the electron-lattice coupling effect improves. Furthermore, the film exhibits a dense surface structure and a uniform distribution of grains. Finally, TCR value reaches 15.95 % K −1 at the corresponding temperature of 283.28 K. Obviously, the prepared LCKMO films effectively combine the high TCR of La 1− x Ca x MnO 3 with the high T k of La 1− x K x MnO 3 by optimizing the K doping level. The results show that LCKMO films are a promising candidate for fabricating uncooled infrared bolometers.
研究领域:
材料科学
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凝聚态物理
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电子器件
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薄膜技术
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红外传感
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