Journal of Cancer最新文献

{"title":"Multi-omics Data Reveal SLC9A3R2 Promotes Breast Cancer Progression and an Immunosuppressive Microenvironment.","authors":"Zujin Chen, Yao Wang, Guixin Wang, Yue Yu, Xin Wang, Xuchen Cao","doi":"10.7150/jca.128052","DOIUrl":"10.7150/jca.128052","url":null,"abstract":"<p><p>The molecular mechanisms driving the occurrence and progression of breast cancer remain unclear, necessitating the identification of novel molecular biomarkers and therapeutic targets. This study aims to investigate the role of <i>SLC9A3R2</i> (<i>NHERF2</i>) in breast cancer progression via an integrated multi-scale approach. Analysis of The Cancer Genome Atlas (TCGA) data revealed that <i>SLC9A3R2</i> is upregulated at both protein and mRNA level in breast cancer tissues, related to advanced tumor stage and poor prognosis, especially in luminal subtypes. Functional enrichment analyses linked high <i>SLC9A3R2</i> expression to epithelial-mesenchymal transition (EMT), estrogen response, and PI3K-AKT/MAPK signaling pathways. Additionally, <i>SLC9A3R2</i> expression was negatively correlated with the infiltration level of CD8+ T cell as well as the expression of four main immune checkpoint molecules. Single-cell RNA sequencing analysis of patient samples revealed that <i>SLC9A3R2</i>-positive tumor epithelial cells mediate aberrant cellular communication with endothelial cells, fibroblasts, and macrophages via specific ligand-receptor pairs involving <i>FN1, COL1A1</i>, and <i>COL1A2</i>. Cell functional assays showed that knockdown of <i>SLC9A3R2</i> significantly impaired the proliferation, migration, and invasion capacities of breast cancer cells. Our findings establish <i>SLC9A3R2</i> as a key promoter of breast cancer progression, influencing both intrinsic oncogenic pathways and the extrinsic tumor microenvironment (TME), which provides a novel insight for breast cancer treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1018-1031"},"PeriodicalIF":3.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Machine Learning Framework Revealing TRPM4-Associated Signatures and Identifying SPATA6 as a Potential Biomarker in Prostate Cancer.","authors":"Hang Zhou, Wangli Mei, Jichen Wang, Xiang Liu","doi":"10.7150/jca.129356","DOIUrl":"10.7150/jca.129356","url":null,"abstract":"<p><strong>Background: </strong>The non-selective cation channel TRPM4 can induce necrotic cell death through sodium overload, yet its role in prostate cancer (PCa) progression remains poorly characterized.</p><p><strong>Materials and methods: </strong>Using TCGA-PCa transcriptomic data centered on TRPM4, we identified transcriptional signatures linked to sodium overload. Leveraging prognostic features, we developed robust prognostic models via ten machine learning algorithms and their combinations, training on TCGA data and validating on internal validation set, GSE46602 and GSE116918. We assessed the model's associations with clinicopathological features, prognosis, immune infiltration, and drug response. Expression of the 10 key model genes was validated in PCa cell lines versus a normal prostate epithelial cell. For SPATA6-the top-contributing gene-we overexpressed it in PCa cells to assess its functional impact.</p><p><strong>Results: </strong>We identified 91 overlapping genes from TRPM4-associated and PCa-related differentially expressed genes. Functional enrichment implicated these genes in small GTPase activity, Rap1 signaling, and cAMP signaling. A TRPM4-related signature model (TRSM) comprising 10 key genes demonstrated strong prognostic performance across training and validation cohorts. TRSM-based risk stratification revealed significant differences in disease-free survival, clinicopathological features, immune infiltration, and immunotherapy response. Drug sensitivity analysis indicated heightened docetaxel sensitivity in the high-risk group. <i>In vitro</i> assays confirmed downregulation of all 10 key genes in PCa. SPATA6 overexpression suppressed PCa cell proliferation and migration.</p><p><strong>Conclusion: </strong>Our findings underscore the importance of TRPM4-associated molecular features in PCa prognosis. TRSM shows potential as a predictive tool for patient outcomes and a guide for personalized therapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1002-1017"},"PeriodicalIF":3.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Stratification and Long-Term Care Service Patterns among Discharged Patients with Cancer: A Retrospective Study from Taiwan.","authors":"Hui-Wen Po, Ying-Chien Chu, Hui-Chen Tsai, Tzu-Yu Huang, Chung-Yu Chen","doi":"10.7150/jca.134200","DOIUrl":"10.7150/jca.134200","url":null,"abstract":"<p><strong>Background: </strong>As cancer survival improves, a growing number of patients experience functional decline and require supportive care and long-term care after hospitalization. However, the relationship between functional severity and post-discharge long-term care utilization in patients with cancer remains insufficiently characterized. This study examined long-term care service patterns across functional severity levels, as classified by a Case-Mix System, among hospitalized patients with cancer undergoing discharge planning.</p><p><strong>Methods: </strong>We conducted a retrospective single-center study of adult patients with cancer who received structured discharge planning at a tertiary hospital in Taiwan between January and December 2024. Discharge outcomes and applications for government-funded long-term care services were described for the full cohort. Exploratory multivariable analyses were restricted to patients who applied for long-term care and had complete Case-Mix System assessment data. Modified Poisson regression with robust variance was used for binary service outcomes, Poisson regression for the number of requested service types, and log-linear regression for length of stay.</p><p><strong>Results: </strong>Among 207 hospitalized patients with cancer who received discharge planning, 141 (68.1%) returned home, 26 (12.6%) were transferred to long-term care facilities, 1 (0.5%) was transferred to another hospital, and 39 (18.8%) died during hospitalization. Of 167 patients discharged home or to care facilities, 75 (44.9%) applied for long-term care services. Among applicants, 19 (25.3%) had mild disability, 36 (48.0%) moderate disability, and 20 (26.7%) severe disability according to Case-Mix System categories. Long-term care utilization showed a non-linear pattern across functional strata. After adjustment for age, sex, and length of stay, moderate disability was associated with a higher number of requested service types than mild disability (adjusted relative risk [aRR] 1.47, 95% CI 1.16-1.87; p = 0.001). Severe disability was associated with greater respite care use (aRR 2.40, 95% CI 1.40-4.09; p = 0.001), lower home-care use (aRR 0.40, 95% CI 0.17-0.95; p = 0.038), and longer hospitalization (ratio 2.82, 95% CI 1.71-4.65; p < 0.001).</p><p><strong>Conclusions: </strong>Functional stratification using a Case-Mix System was associated with distinct long-term care service patterns among discharged patients with cancer. Moderate disability was linked to broader multi-service needs, whereas severe disability was more strongly associated with respite-oriented care and prolonged hospitalization. In this single-center exploratory cohort, these findings support further validation of functional stratification approaches for post-discharge cancer care transitions.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1032-1038"},"PeriodicalIF":3.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Ganoderma lucidum</i> alcohol extract targets mutant <i>p53</i> signaling to inhibit proliferation in triple-negative breast brain metastasis cancer.","authors":"Yi-Chung Chien, Guo-Wei Wu, Yu-Heng Lin, Jia-Yan Wu, Yung-Luen Yu","doi":"10.7150/jca.133558","DOIUrl":"10.7150/jca.133558","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is among the most aggressive subtypes of breast cancer, frequently characterized by invasive growth, metastasis, and poor clinical outcomes. Brain metastasis, commonly observed in TNBC patients, significantly worsens prognosis and survival rates. Current therapeutic strategies for TNBC brain metastases remain limited and largely ineffective. Mutant p53, common in TNBC, promotes malignancy and metastasis. MDA-MB-231 cells and their brain metastatic variant (MDA-MB-231-Br) harbor a p53 R280K mutation. <i>Ganoderma lucidum</i>, historically known for anticancer properties, has unclear effects on breast cancer brain metastasis. This study evaluated the impact of alcohol-extracted <i>Ganoderma lucidum</i> on TNBC brain metastasis cells via mutant p53 inhibition. Treatment with 10% <i>G. lucidum</i> alcohol extract for 48 hours significantly reduced proliferation in MDA-MB-231 and MDA-MB-231-Br cells. Knockdown of p53 confirmed its role in cell proliferation. Additionally, MG132, proteasome inhibitor, restored p53 levels, indicating <i>G. lucidum</i> extract promotes p53 degradation. Collectively, our findings suggest that alcohol-extracted <i>G. lucidum</i> inhibits the proliferation of TNBC brain metastatic cells by promoting the degradation of mutant p53. This mechanistic insight provides a potential therapeutic strategy for mitigating brain metastasis in triple-negative breast cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1039-1049"},"PeriodicalIF":3.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Hadhb</i> Deficiency Inhibits Lung Tumorigenesis Via Activating ER Stress.","authors":"Wuhou Dai, Dong Xu, Yubin Lei, Shujing Zhang, Tonglu Yu, Wufan Tao, Xiaofeng Chen, Xingrong Du","doi":"10.7150/jca.130384","DOIUrl":"10.7150/jca.130384","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related mortality worldwide, yet its molecular pathogenesis is not fully understood. Here, we identify <i>HADHB,</i> encoding a mitochondrial β-ketothiolase as a novel oncogene in lung cancer. Using a <i>Hadhb^PB/PB</i> mouse model, we demonstrate that <i>Hadhb</i> deficiency in mice significantly suppresses <i>K-Ras</i> ^G12D-driven lung tumor progression by impairing cancer cell proliferation and enhancing apoptosis. Mechanistically, <i>Hadhb</i> loss induces proteotoxic endoplasmic reticulum (ER) stress, as evidenced by increased ATF6(N) and phosphorylation of eIF2α and subsequent upregulation of the pro-apoptotic factor CHOP. Crucially, knockdown of <i>Chop</i> partially restores oncogenic potential in <i>Hadhb^PB/PB</i> mice and rescues the growth defect of <i>HADHB</i>-depleted cells, establishing CHOP as a key downstream mediator. Consistent with its oncogenic role, HADHB protein is upregulated in 52% (19/36) of human lung tumors compared to adjacent normal tissues, and low <i>HADHB</i> mRNA levels are correlated with good prognosis in lung cancer patients. Our findings unveil a previously unrecognized <i>HADHB</i>-<i>CHOP</i> regulatory axis in lung cancer progression and provide preclinical rationale for targeting mitochondrial metabolism in combination with ER stress modulators as a therapeutic strategy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"990-1001"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic risk factors linked to acute radiation-induced toxicities: a phenome-wide Mendelian randomization study of 12,042 cancer patients.","authors":"Wenyi Jiang, Bo Li, Siyuan Zhang, Xin Sui, Yueting Liang, Minqi Jia, Shaoran Jiang, Lijuan Li, Huajing Teng, Weihu Wang","doi":"10.7150/jca.127072","DOIUrl":"10.7150/jca.127072","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to systematically evaluate phenome-wide clinical factors contributing to radiation-induced toxicities (RITs) and provide evidence to identify acute RITs-associated risk factors for personalized radiation treatment stratification.</p><p><strong>Methods: </strong>Leveraging genome-wide association study data from 12,042 patients with prostate, head and neck, breast, or lung cancer, we conducted MR-PheWAS (phenome-wide association study integrated with Mendelian randomization) to evaluate the impact of 22,872 phenotypic traits on the susceptibility to acute RITs.</p><p><strong>Results: </strong>MR-PheWAS pinpointed diverse acute RITs-associated phenotypic traits, including previously noted and novel ones. Proteins related to infection and immunity, like C-reactive protein and Interleukin-4 receptor alpha, were found to augment the risk of acute RITs, whereas growth differentiation factor 15, fibroblast growth factor-2 and Interleukin-16 seemingly reduce it. Notably, systolic/diastolic blood pressure, and lipoprotein or cholesterol levels could elevate the risk, but fatty acids, lipids and body mass index-adjusted leptin levels offered protection. Real-world validation in 1,078 breast cancer patients who underwent radiotherapy in our department showed that red blood cell count (lowering risk), serum urea and uric acid levels (increasing risk) before radiotherapy were linked to acute RITs. Moreover, we estimated the direct causal link between the associated traits and acute RITs through multivariate MR analyses, and unveiled that systemic lupus erythematosus, and high-density lipoprotein cholesterol levels remained significantly associated with acute RITs.</p><p><strong>Conclusion: </strong>This study identified the phenome-wide risk factors linked to acute RITs, and future research was needed to clarify their underlying mechanisms for effective prevention of acute RITs.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"979-989"},"PeriodicalIF":3.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory Serum Metabolomics Identifies Metabolic Subgroups Across the Gastric Dysplasia-Early Cancer Spectrum.","authors":"Sihyun Chae, Hee Sang You, Jae Gyu Kim, Joo-Youn Cho","doi":"10.7150/jca.131608","DOIUrl":"10.7150/jca.131608","url":null,"abstract":"<p><strong>Background: </strong>Gastric carcinogenesis involves progressive molecular and metabolic alterations, yet non-invasive biomarkers for early detection and risk stratification remain limited. This study aimed to characterize systemic metabolomic changes across the gastric carcinogenesis spectrum and to investigate potential associations between serum metabolites and gastric microbiome-related pathways.</p><p><strong>Methods: </strong>In this exploratory study, untargeted serum metabolomics was performed on samples from patients with gastric dysplasia or early gastric cancer (n = 40) and healthy controls (n = 14). Differential metabolite analysis, principal component analysis, and k-means clustering were used to identify metabolic alterations and potential metabolic subgroups. Microbial pathway associations were examined using metabolite origin inference based on gastric-resident taxa reported in prior studies.</p><p><strong>Results: </strong>Eighteen metabolites were significantly altered in gastric carcinogenesis compared with healthy controls. Six metabolites displayed distinct profiles that suggest two metabolic subgroups, including one subgroup showing a metabolic pattern closer to that of healthy controls, independent of histologic severity. Microbial pathway inference suggested contributions from Pseudomonadota, Actinomycetota, and Bacillota, with ornithine-related metabolites emerging as a key metabolic link previously implicated in dysplasia-to-carcinoma progression. These findings highlight inter-patient heterogeneity and potential metabolic-microbial interactions underlying gastric carcinogenesis.</p><p><strong>Conclusion: </strong>These findings suggest that serum metabolomic profiling may capture metabolic heterogeneity across the gastric dysplasia-early gastric cancer spectrum and generate hypotheses regarding microbiome-related metabolic alterations. While exploratory in nature, this study provides preliminary evidence supporting the potential of serum metabolites as non-invasive indicators of early gastric carcinogenesis, warranting validation in larger and longitudinal cohorts.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"968-978"},"PeriodicalIF":3.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Traditional Chinese Medicine in Metabolic Reprogramming, Tumor microenvironment, and Macrophage Regulation: Mechanisms and Advances in Preclinical Studies.","authors":"AnAn Yu, Donglai Yang, Hongyu Chen","doi":"10.7150/jca.126434","DOIUrl":"10.7150/jca.126434","url":null,"abstract":"<p><strong>Background: </strong>Cancer metabolism reprogramming is a hallmark of tumorigenesis, playing a critical role in tumor progression and therapeutic resistance. Macrophages in the Tumor microenvironment (TME) play a crucial role in tumor progression and immune system evasion. Traditional Chinese Medicine (TCM) has shown potential in influencing cancer metabolism and immune functions, offering new therapeutic possibilities.</p><p><strong>Objective: </strong>This review explores the intersection of TCM, metabolic reprogramming, and macrophage polarization in cancer, focusing on their molecular mechanisms and therapeutic implications. The study further seeks to summarize preclinical evidence supporting TCM's role in modulating tumor metabolism and immune microenvironments, offering a holistic approach to cancer therapy.</p><p><strong>Methods: </strong>In this study, we systematically reviewed the latest research progress in the last five years on the role of traditional Chinese medicine in regulating tumor metabolic reprogramming, TME and macrophage polarization. A comprehensive literature reviews the metabolic shifts in cancer cells, including glycolysis, oxidative phosphorylation, and lipid metabolism, and how TCM compounds restore metabolic balance. Studies on macrophage polarization (M1/M2) and their regulatory roles in cancer immunity, as influenced by TCM, were analyzed. Preclinical research highlighting TCM's dual impact on tumor metabolism and the TME was also evaluated.</p><p><strong>Results: </strong>TCM compounds demonstrate the ability to target key metabolic pathways, such as glycolysis and lipid metabolism, restoring metabolic homeostasis in cancer cells. Additionally, TCM has been shown to regulate macrophage polarization within the TME, enhancing M1 macrophage-mediated anti-tumor immunity and suppressing M2 macrophage-mediated tumor promotion. Preclinical studies further support TCM's capacity to modulate the TME and improve therapeutic outcomes when used in combination with conventional cancer therapies.</p><p><strong>Conclusions: </strong>TCM integrates metabolic reprogramming and immunomodulation to provide a comprehensive treatment strategy for cancer. However, translating these findings into clinical practice remains challenging. Future research should focus on validating the exact mechanisms of TCM in tumor metabolism and immunity through clinical trials and investigating the synergistic effects of TCM with modern cancer therapies, such as immunotherapy and targeted therapies. This may facilitate the use of TCM as an adjuvant therapy to improve the efficacy of existing cancer treatments.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"952-967"},"PeriodicalIF":3.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of protein markers of inflammasome formation and ferroptosis in thyroid cancer based on gender.","authors":"Raúl Díaz-Pedrero, Oscar Fraile-Martinez, Cielo García-Montero, Diego Liviu Boaru, Patricia De Castro-Martinez, Diego De Leon-Oliva, Laura López-Gonzalez, Beatriz García-González, Isabel Pérez-González, Majd N Michael Alhaddadin, Silvestra Barrena-Blázquez, Connie Ferrara-Coppola, Ana María Villar-Carrillo, Laura Gutierrez-Gonzalez, Miguel Pascual-Casero, Félix Mañez, Tomás Ratia Giménez, Inmaculada Lasa-Unzúe, Manuel Díez Alonso, Alberto Gutiérrez-Calvo, Luis G Guijarro, Melchor Álvarez-Mon, Montserrat Chao Crecente, Miguel A Saez, Miguel A Ortega","doi":"10.7150/jca.128886","DOIUrl":"10.7150/jca.128886","url":null,"abstract":"<p><p>Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, with a globally increasing incidence. The disease exhibits significant sex-related clinical and biological differences: while incidence is approximately three times higher in women, men face a greater risk of lymph node metastasis, recurrence, and mortality. This gender disparity may be associated with hormonal factors, particularly estrogens, which are known to modulate cellular proliferation, invasion, migration, and adhesion in thyroid tumor cells. However, the molecular pathways underlying these effects remain poorly understood. In this context, the hallmarks of cancer proposed by Hanahan-such as sustained proliferative signaling, evasion of cell death, and reprogramming of the tumor microenvironment-provide a valuable framework to investigate sex-based disparities. This study assessed, via immunohistochemistry, the expression of molecular markers related to ferroptosis (GPX4, ALOX5, ACSL4, TFRC), the NLRP3 inflammasome and its components (NLRP3, ASC, caspase-1, caspase-5, caspase-8, IL-1β, and IL-18), proliferation (IRS-4), and tumor suppression (KLOTHO) in PTC samples from 25 men and 25 women. Our results demonstrated increased expression of ferroptosis-related markers, components of the NLRP3 inflammasome, and IRS-4 in female-derived samples, whereas male samples exhibited higher KLOTHO expression levels. These findings support the hypothesis of a molecular basis for sexual dimorphism in PTC and highlight the need for further research with larger cohorts and mechanistic approaches to elucidate these pathways and their therapeutic potential.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"937-951"},"PeriodicalIF":3.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Effects of Cepharanthine: an Updated Minireview.","authors":"Pei-Yin Yang, Jyun-Xue Wu, Ya-Hui Chen, Shun-Fa Yang, Yi-Tzu Chu, Yi-Hsuan Hsiao","doi":"10.7150/jca.118647","DOIUrl":"10.7150/jca.118647","url":null,"abstract":"<p><p>Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid, has a long history of clinical use in Japan for various diseases. Over the past few decades, it is potent anticancer activities have garnered significant attention. In this review shows CEP exhibits anti-cancer activity via diverse mechanisms: it induces programmed cell death via intrinsic mitochondrial pathways, extrinsic death receptor signaling, and endoplasmic reticulum stress. It also arrests uncontrolled cell proliferation by causing G0/G1 and G2/M phase cell cycle arrest. Furthermore, CEP inhibits tumor progression by suppressing metastasis, invasion, and angiogenesis. It effectively modulates crucial oncogenic signaling pathways such as PI3K/Akt/mTOR, NF-κB, and JAK2/STAT3, MAPK, and plays a role in regulating oxidative stress within cancer cell. Notably, CEP can reverse multidrug resistance by inhibiting drug efflux transporters, thereby enhancing the efficacy of conventional chemotherapies, this review shows the diverse molecular targets of CEP and elucidates the complex network of pathways it modulates, positioning it as a promising natural compound for further investigation in cancer therapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"925-936"},"PeriodicalIF":3.4,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}