J Cancer [JOURNAL]
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200 papers
Dehydroleucodine Induces ROS-Mediated Mitochondrial Apoptosis and G2/M Cell Cycle Arrest in Oral Squamous Cell Carcinoma.
Lee J, Chang TM, Lee CJ … +2 more , Liu JF, Chou HH
J Cancer · 2026 · PMID 42327588 · Full text
Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor clinical outcomes due largely to recurrence and therapy resistance. Dehydroleucodine (DhL) is a sesquiterpene lactone derived from species,...
Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor clinical outcomes due largely to recurrence and therapy resistance. Dehydroleucodine (DhL) is a sesquiterpene lactone derived from species, which has demonstrated anticancer activity in several tumor models. However, its therapeutic relevance in OSCC has not been established. This study investigated the antitumor effects of DhL and the mechanisms underlying its activity in OSCC using complementary and approaches. DhL significantly suppressed cell viability and clonogenic growth in HSC3 and SCC4 cells, with relatively low cytotoxicity toward normal gingival fibroblasts (HGF-1) under the tested conditions. The underlying mechanisms involved apoptotic cell death and G2/M phase arrest, accompanied by reduced cyclin B1 and CDK1 expression. DhL was also shown to promote mitochondrial dysfunction, as indicated by loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, elevated cleaved caspase-3 expression and activity, and increased intracellular reactive oxygen species (ROS) generation. Pretreatment with the antioxidant N-acetylcysteine partially attenuated apoptosis and cell cycle arrest, suggesting that ROS plays a role in both responses. Systemic DhL treatment in an xenograft model significantly inhibited tumor growth and increased cleaved caspase-3 expression in tumor tissue without a significant loss of body weight. Together, these findings identify DhL as a potent suppressor of OSCC growth, which acts through ROS-associated mitochondrial apoptosis and G2/M arrest, supporting further preclinical evaluation of DhL as a candidate therapeutic agent for OSCC.
CellVizio System for Mesothorax Lymphadenopathy Rapid on Site, 18G needle: Pros and Cons.
Zarogoulidis P, Hofenforst-Schwidt W, Huang H … +21 more , Tryfon S, Zhang Y, Ma G, Amarantidis K, Maragouli E, Papadopoulos V, Perdikouri EI, Voulgaris V, Freitag L, Margioula-Siarkou C, Tsiouda T, Ntolios P, Petousis S, Triantafylopoulou K, Tsakiridis K, Courcoutsakis N, Baka S, Baloukas D, Steiropoulos P, Zaric B, Shen X
J Cancer · 2026 · PMID 42327587 · Full text
INTRODUCTION: The best tissue sample is still very important for the diagnosis of mesothorax lymphadenopathy. In the past 20 years endobronchial ultrasound (EBUS) has been used efficiently in most cases of primary lung c...
INTRODUCTION: The best tissue sample is still very important for the diagnosis of mesothorax lymphadenopathy. In the past 20 years endobronchial ultrasound (EBUS) has been used efficiently in most cases of primary lung cancer disease or metastatic disease. Several new type of needles have been created such 19G, 18G and hybrid biopsies with cryoprobes. Rapid on-site evaluation (ROSE) is used as an additional initial diagnostic tool. Confocal microscopy is a method of rapid on-site evaluation. PATIENTS AND METHODS: One hundred patients with mesothorax lymphadenopathy were biopsied with ebus and two groups were created one with rapid on-site evaluation with confocal microscopy and one by an operator with microscopic evaluation with sample preparation on cytoglasses. Our main objective was to assess parameters such as time, false negative results between the two techniques and technical issues such as the accessibility and evaluation between the two techniques. Safety was also evaluated. RESULTS: Rapid on-site evaluation is more cost efficient with a cytologist on site, however; with a higher rate of false negative results. Accessibility with the Cellvizio catheter was less possible in a few cases due to rigid angles within the airways especially for small lymphnodes ≤ 1.5 cm (L4L mainly). DISCUSSION: Confocal is a safe and time-efficient technique for mesothorax lymphadenopathy. A high level of training is required for pulmonary physicians in order to assess the novel imaging technique. Definitely different parts of the lymphnode have to reached and evaluated in order to have a proper initial evaluation.
Epidemiological Trends and Shared Molecular Signatures of Pancreatic Ductal Adenocarcinoma and Diabetes: An Integrative Analysis Based on Global Burden of Disease and Gene Expression Omnibus Datasets.
Zhang J, Liu Z, Huang K … +2 more , Yi J, Kim MO
J Cancer · 2026 · PMID 42327586 · Full text
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, and diabetes mellitus has been recognized as both a risk factor for and a potential consequence of PDAC. However, the...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, and diabetes mellitus has been recognized as both a risk factor for and a potential consequence of PDAC. However, the epidemiological trends and shared molecular mechanisms underlying this association are not completely understood. METHODS: We conducted an integrative analysis combining population-level epidemiological data and transcriptomic datasets. Global trends in PDAC incidence, PDAC-related mortality, and diabetes incidence from 2013 to 2023 were obtained from the Global Burden of Disease (GBD) database. A meta-analysis was performed to quantify the association between diabetes and PDAC risk. In addition, gene expression datasets focusing on PDAC (GSE15471) and type 2 diabetes mellitus (T2DM; GSE20966) were obtained from the Gene Expression Omnibus database, differentially expressed genes were identified, and upregulated genes associated with both PDAC and T2DM were examined using heatmaps. RESULTS: Continuous increases in global PDAC incidence, mortality due to PDAC, and the incidence of diabetes were identified in the GBD data. The meta-analysis of eight studies demonstrated that diabetes was significantly associated with an increased risk of PDAC (pooled relative risk = 1.94, 95% CI: 1.78-2.11). Transcriptomic analyses identified five genes-, , , , and -that were consistently upregulated in both PDAC and T2DM-affected tissues. CONCLUSION: This integrative epidemiological and transcriptomic analysis demonstrates that diabetes and PDAC share not only similar global disease trends but also a significant epidemiological association and common molecular alterations. The identified shared genes may represent molecular links between diabetes and PDAC, providing new insights applicable to risk stratification and mechanistic studies.
Association between obesity, sex, medical comorbidities, and survival in cancer patients treated with immune checkpoint inhibitors.
Li M, Spakowicz DJ, Zhao S … +21 more , Kwon H, Chian K, Khorasanchi A, Guo Y, Wei L, Meng L, Yang Y, Alahmadi A, Memmott RM, Kaufman J, He K, Shields PG, Mace TA, Phelps MA, Coss CC, Li Z, Kendra KL, Carbone DP, Otterson GA, Presley CJ, Owen DH
J Cancer · 2026 · PMID 42327585 · Full text
BACKGROUND: Obesity's impact on cancer treatment outcomes is poorly understood, especially in the context of immuno-oncology. This study explores how obesity and medical comorbidities are associated with overall survival...
BACKGROUND: Obesity's impact on cancer treatment outcomes is poorly understood, especially in the context of immuno-oncology. This study explores how obesity and medical comorbidities are associated with overall survival in cancer patients receiving immune checkpoint inhibitors (ICIs). Additionally, considering the influence of sex on body composition in obesity, this study examines the relationship between sex, obesity, medical comorbidities, and survival. METHODS: This cohort study involved 688 patients with metastatic cancer received ICIs as first- or second-line therapy. Obesity was assessed using body mass index (BMI). Cox proportional hazard models and Kaplan-Meier survival analysis were used to examine associations between predictors and overall survival. RESULTS: Patients with higher BMI had longer overall survival, and hazard ratio (HR) for death was 0.83 (95% CI 0.73-0.95) for every 10 units increased in BMI. Additionally, patients belonged to the highest BMI group (≥ 40) had the lowest risk of death when comparing to patients with BMI 18.5 to < 30 with HR 0.58 (95% CI 0.37-0.90). In subgroup analysis, a significant association between high BMI and decreased HR for death was predominantly observed in the male cohort. In multivariate analysis, the prognostic value of BMI remained significant after adjusting for performance status, line of therapy, age-adjusted medical comorbidities, and cancer type. CONCLUSIONS: Obesity was associated with decreased mortality risk for cancer patients who had received ICIs. There could be a sex-dependent association between survival benefit and obesity.
Exosomes in Cancer Biology: Emerging Biomarkers and Therapeutic Targets.
Ahmed M, Chang CW, Ijaz S … +7 more , Qadeer A, Alzahrani KJ, Alsharif KF, Alzahrani FM, Abuderman A, Chen CC, Hussain S
J Cancer · 2026 · PMID 42327584 · Full text
Exosomes are small extracellular vesicles (EVs) that play an important role in intercellular communication among multiple cell types. In recent years, they have emerged as a novel and promising class of cancer biomarkers...
Exosomes are small extracellular vesicles (EVs) that play an important role in intercellular communication among multiple cell types. In recent years, they have emerged as a novel and promising class of cancer biomarkers, offering significant potential to increase diagnostic and therapeutic strategies. These bilayer nano-vesicles are actively secreted by living cells into various biological fluids and carry a diverse cargo of proteins, nucleic acids, and other biomolecules that reflect the physiological and pathological state of their cells of origin. The molecular composition of exosomes mirrors the dynamic processes and unique cargo of molecular and genetic data, reflecting the complex activities within cancer cells, making them a promising alternative for cancer detection and treatment monitoring. Although the mechanisms underlying exosome biogenesis, secretion, and cargo selection in cancer remain incompletely understood, growing evidence highlights their importance in tumor progression and therapeutic response. Exosomal proteins have gained considerable attention as potential therapeutic targets. These proteins can regulate immune responses, reshape the tumor microenvironment, and influence cancer cell proliferation and survival. Consequently, targeting exosome-associated proteins represents a promising strategy for developing innovative anticancer therapies. Advances in exosomal protein analysis have provided a promising approach for unraveling the complex molecular networks underlying cancer biology. A wide range of analytical techniques is available to identify and quantify exosomal proteins, enabling characterization of cancer-specific molecular signatures. As an expanding field in cancer research, exosomes have the potential to revolutionize both therapies and diagnostics. By deciphering the diverse molecular and functional cargos of exosomes, exosomes offer new insights that may lead to more precise, effective, and personalized approaches to cancer management.
-rs9679162 Genotypes Predict Post-immunotherapy Side Effect and Survival in Patients with Hepatitis B Virus-related Hepatocellular Carcinoma.
Lin PT, Teng W, Chen WT … +8 more , Chu YD, Su CW, Hsieh YC, Lin CC, Lin YC, Lin CY, Yeh CT, Lin SM
J Cancer · 2026 · PMID 42327583 · Full text
INTRODUCTION: Genomic alterations have been reported to correlate with patients' response to immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC). The present study aimed to examine whether single...
INTRODUCTION: Genomic alterations have been reported to correlate with patients' response to immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC). The present study aimed to examine whether single nucleotide polymorphism (SNP) is associated with ICI treatment-related side effects and progression-free survival (PFS) in HCC patients. METHODS: This retrospective study included 96 patients with HBV-related HCC receiving ICI (atezolizumab plus bevazizumab) therapy between 2020 and 2023. Five SNPs derived from a previous genome-wide association study linking to chemotherapy responses in HCC patients were included. Their predictive values for PFS and side effects were examined. RESULTS: After ICI therapy, patients with -rs9679162 "GG" genotype (median PFS = 19.7 months, 95% confidence interval [CI]: 12.3-35.7; p = 0.032) had a longer PFS, whereas -rs675230, -rs6025211, -rs13338697 or -rs13333314 were not associated with PFS (all p > 0.05). -rs9679162 "GG" genotype (odds ratio [OR] = 0.298, 95% CI: 0.096-0.926; p = 0.036) was also associated with a decreased risk of post-treatment high-grade aspartate aminotransferase (AST) elevation. Multivariate analysis showed that -rs9679162 "GG" genotype (hazard ratio [HR] = 0.433, 95% CI: 0.212-0.886; p = 0.022) and high initial albumin-bilirubin (ALBI) grade (HR = 2.053, 95% CI: 1.153-3.590; p = 0.014) were independently associated with PFS. CONCLUSIONS: Genetic variant of an SNP, -rs9679162, predicts post-treatment PFS and side effect in HBV-related HCC patients receiving ICIs therapy.
Development and Validation of an m6A-Derived Prognostic Signature in Lung Adenocarcinoma.
Shao Z, Situ Y, Lai B … +7 more , Xu Y, Chen J, Deng L, Xu Q, Liang M, Liang Z, Xie Z
J Cancer · 2026 · PMID 42327582 · Full text
BACKGROUND: Lung adenocarcinoma (LUAD) exhibits extensive molecular heterogeneity and poor prognosis, necessitating novel epigenetic biomarkers. N6-methyladenosine (m6A) modification, a pivotal epigenetic regulator of RN...
BACKGROUND: Lung adenocarcinoma (LUAD) exhibits extensive molecular heterogeneity and poor prognosis, necessitating novel epigenetic biomarkers. N6-methyladenosine (m6A) modification, a pivotal epigenetic regulator of RNA, is frequently dysregulated in LUAD, yet its systematic roles in clinical prognosis and the tumor microenvironment (TME) remain poorly elucidated. METHODS: Transcriptomic profiles and clinical data from large-scale cohorts were integrated and analyzed. Unsupervised consensus clustering based on 47 m6A-related genes (MRGs) was performed to distinguish distinct molecular subtypes. A prognostic model was developed via LASSO-Cox regression algorithm and further validated in multiple independent cohorts. Immune infiltration, tumor mutational burden (TMB), immunotherapy response (TIDE/IPS), and chemotherapy sensitivity were analyzed, complemented by single-cell RNA sequencing. RESULTS: Two distinct m6A-related gene clusters (mRGclusters A and B) were identified. Patients in cluster B exhibited inferior survival outcomes, higher m6A pathway activity, and significant enrichment of cell cycle-related pathways. The eight-gene signature successfully stratified patients into high-risk (HR) and low-risk (LR) subgroups. Patients in the HR group presented significantly worse overall survival (P < 0.05), higher TMB levels, and upregulated expression of multiple immune checkpoint genes such as and . mutations were capable of improving the survival of HR patients by facilitating the infiltration of natural killer cells and follicular helper T cells. The signature independently predicted prognosis (AUC: 0.70-0.84) and treatment response: LR patients favored immunotherapy (lower TIDE, higher IPS), while HR patients were sensitive to chemotherapy (e.g., Bosutinib, Tozasertib). CONCLUSION: This transcriptome-derived m6A-associated prognostic model can effectively predict clinical survival outcomes and therapeutic response in LUAD patients. Combined with immune landscape, genomic mutation profiles and single-cell transcriptomic evidence, this signature provides a reliable basis for personalized risk stratification and rational treatment choice.
The Emerging Role of CACNA1E in Cancer: Molecular Mechanisms and Therapeutic Implications.
Hou W
J Cancer · 2026 · PMID 42327581 · Full text
Voltage-gated calcium channels (VGCCs) are crucial membrane proteins that mediate calcium influx. The CACNA gene family, which encodes the alpha subunits of VGCC complexes, is essential for forming functional calcium cha...
Voltage-gated calcium channels (VGCCs) are crucial membrane proteins that mediate calcium influx. The CACNA gene family, which encodes the alpha subunits of VGCC complexes, is essential for forming functional calcium channels and plays significant roles in various cancers. This review focuses on the CACNA1E gene, which encodes the Cav2.3 channel α1E subunit, and systematically elaborates its role in cancer. Studies have identified CACNA1E as a key prognostic stemness-related gene in bladder cancer. Its somatic mutations are associated with the development of air pollution-related lung cancer and non-small cell lung cancer. In breast cancer, genetic variations and DNA methylation differences in CACNA1E have also been reported. Functionally, CACNA1E drives tumor progression by regulating calcium signaling. For example, in osteosarcoma, METTL3-mediated m⁶A modification stabilizes CACNA1E mRNA, activating the WNT7B/Ca²⁺ signaling pathway and thereby promoting tumor progression and chemoresistance. The expression of CACNA1E is closely linked to patient prognosis, with its amplification and overexpression correlating with relapse in favorable histology Wilms' tumor. Additionally, CACNA1E is involved in therapy resistance, as evidenced by its downregulation being associated with temozolomide resistance in glioblastoma. Collectively, this evidence suggests that CACNA1E, along with other VGCC members, may serve as a potential prognostic biomarker and therapeutic target in cancer. Future research should further explore their molecular mechanisms, interactions with the tumor microenvironment, and clinical translation potential.
Emerging Oncolytic Viruses: Beyond Adenoviruses and Herpes Simplex Virus.
Chokkakula S, Yin C, Yang B … +7 more , Chong S, Pathakumari B, Zhang YQ, Nirmala PV, Lai KW, Naveen B, Tang Q
J Cancer · 2026 · PMID 42327580 · Full text
Oncolytic virotherapy represents an innovative therapeutic modality in oncology, exploiting the selective tropism of viruses to target and eradicate malignant cells. Unlike conventional cancer treatments such as chemothe...
Oncolytic virotherapy represents an innovative therapeutic modality in oncology, exploiting the selective tropism of viruses to target and eradicate malignant cells. Unlike conventional cancer treatments such as chemotherapy and radiotherapy, oncolytic viruses (OVs) exhibit a dual mechanism of action: direct tumor cell lysis and potent immune activation. This approach transforms tumors into vaccines, generating durable anti-tumor immune memory. The field has garnered substantial attention following the regulatory approval of talimogene laherparepvec (T-VEC), a genetically engineered herpes simplex virus, for metastatic melanoma treatment-a watershed moment in oncolytic virotherapy. Recent advances in genetic engineering have significantly enhanced OV specificity and efficacy, addressing critical challenges including tumor-selective targeting and immune evasion. This review comprehensively examines the complex mechanisms underlying OV therapeutic action, clinical applications, and recent developments that position oncolytic virotherapy as a transformative strategy in contemporary cancer treatment.
Assessing the Association Between Genetic Variants in ACE, SOD1, and PER3 and their Role in Breast Cancer Risk among Jordanian Women.
Al-Eitan LN, Almomani FA, Alorjani MS … +3 more , Alasmar MK, Ali HO, Alghamdi MA
J Cancer · 2026 · PMID 42327579 · Full text
BACKGROUND: Genetic and environmental factors regulate many physiological processes in the human body, and alterations in these processes may contribute to the development of various diseases, including breast cancer (BC...
BACKGROUND: Genetic and environmental factors regulate many physiological processes in the human body, and alterations in these processes may contribute to the development of various diseases, including breast cancer (BC), which is considered the most prevalent cancer among women and a leading cause of cancer-related mortality in the Jordanian population. Genes such as , and play important roles in regulating essential biological functions. These genes are involved in key physiological pathways, including blood pressure regulation, oxidative stress response and circadian rhythm maintenance, and genetic variants within them may influence susceptibility to cancer. Therefore, this study investigates the association between polymorphisms in the , and genes and the risk of breast cancer, with the aim of evaluating how these genetic variations relate to breast cancer susceptibility and clinical outcomes in Jordanian women. METHODS: Blood samples of 300 women diagnosed with breast cancer, along with 300 healthy participants, were collected, and DNA was extracted from them. Genetic variants in the (rs1799752), (rs36232792) and (rs57875989) genes are examined through employing direct PCR to amplify the target regions. RESULTS: The (rs1799752) variant was observed to be associated with breast cancer susceptibility, with the I/I genotype increasing risk of breast cancer (OR = 5.138, 95% CI = 1.38-19.03, p = 0.014). No associations were observed for (rs36232792) and (rs57875989) variants. CONCLUSION: The rs1799752 polymorphism is suggested to have the potential of serving as a biomarker for breast cancer susceptibility in Jordanian women, as it is associated with elevating the risk.
miR-150-5p at the Interface of Cancer Biology and Immune Regulation: Dual Roles, Mechanisms, and Therapeutic Opportunities.
Lin I, Shirkani P, Garnis C
J Cancer · 2026 · PMID 42327578 · Full text
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally and play crucial roles in cancer biology and immune function. Among them, miR-150-5p has emerged as a key regulator with...
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally and play crucial roles in cancer biology and immune function. Among them, miR-150-5p has emerged as a key regulator with complex, context-dependent roles in both tumorigenesis and immune cell differentiation. This review provides a comprehensive synthesis of current knowledge on miR-150-5p, highlighting its dual function as a tumor suppressor or oncogene depending on cancer type and cellular context. We examine its involvement in hematologic malignancies and solid tumors, detailing the molecular mechanisms through which it influences proliferation, apoptosis, and metastasis. Particular emphasis is placed on the role of extracellular vesicle (EV)-associated miR-150-5p as a modulator of the tumor microenvironment (TME), including its impact on angiogenesis, immune evasion, and intercellular communication. We further explore miR-150-5p's regulation of key immune cell subsets-such as macrophages, dendritic cells, T cells, and natural killer cells-and its implications for anti-tumor immunity. Finally, we discuss the therapeutic potential and challenges of targeting miR-150-5p, including delivery barriers, off-target effects, and opportunities for personalized medicine. By integrating recent findings, this review underscores miR-150-5p's value as both a biomarker and a therapeutic target in cancer immunology.
Development of nasopharyngeal carcinoma target delineation: from two-dimensional radiotherapy to adaptive precision radiotherapy.
Yang X, Liu L, Zhang H … +2 more , Ren H, Fu J
J Cancer · 2026 · PMID 42327577 · Full text
Nasopharyngeal carcinoma (NPC) is mainly treated with radiotherapy. With the advancements of imaging and radiotherapy techniques, the delineation of NPC target areas has evolved from empirical field setting in the two-di...
Nasopharyngeal carcinoma (NPC) is mainly treated with radiotherapy. With the advancements of imaging and radiotherapy techniques, the delineation of NPC target areas has evolved from empirical field setting in the two-dimensional era to three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), and image-guided adaptive radiotherapy (ART), significantly improving treatment accuracy and safety. This review systematically explores the development process of target area delineation in NPC, focusing on the evolution and standardization of target areas in the nasopharynx and neck lymph nodes, and combines the role of multimodal imaging such as MRI and PET-CT in target area delineation. The article further examines the clinical response strategies and research trends of target area changes after induction chemotherapy (IC), and looks forward to the potential of ART and artificial intelligence in future target area delineation. The review aims to provide clinical practitioners with a scientific, rational, and personalized approach to target delineation, optimizing treatment plans and improving clinical outcomes.
Anticancer Effects of Cepharanthine: an Updated Minireview.
Yang PY, Wu JX, Chen YH … +3 more , Yang SF, Chu YT, Hsiao YH
J Cancer · 2026 · PMID 42179796 · Full text
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....
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.
alcohol extract targets mutant signaling to inhibit proliferation in triple-negative breast brain metastasis cancer.
Chien YC, Wu GW, Lin YH … +2 more , Wu JY, Yu YL
J Cancer · 2026 · PMID 42179795 · Full text
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 TNB...
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. , historically known for anticancer properties, has unclear effects on breast cancer brain metastasis. This study evaluated the impact of alcohol-extracted on TNBC brain metastasis cells via mutant p53 inhibition. Treatment with 10% 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 extract promotes p53 degradation. Collectively, our findings suggest that alcohol-extracted 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.
Serum Thyroid Biomarkers for Diagnosing Malignant Thyroid Nodules: A Machine Learning Approach with External and Causal Validation.
Gu Q, Xue F, Shi X … +8 more , Zheng Z, Wang W, Yang Z, Zhang Y, Huang W, Huang M, Wang Z, Li J
J Cancer · 2026 · PMID 42179794 · Full text
BACKGROUND: Thyroid nodules (TNs) are common, and accurate malignancy risk stratification is critical for clinical decision-making. Although serum thyroid biomarkers are routinely measured, their contribution to malignan...
BACKGROUND: Thyroid nodules (TNs) are common, and accurate malignancy risk stratification is critical for clinical decision-making. Although serum thyroid biomarkers are routinely measured, their contribution to malignancy discrimination remains insufficiently characterized. Thus, we aimed to develop a practical and biologically grounded model for identifying malignant TNs using routinely clinical data. METHODS: We retrospectively analyzed 5537 patients initially diagnosed with TNs from two hospitals, including 66.23% with malignant TNs. Diagnostic models were developed using logistic regression and machine learning approaches with internal and external validation. Causal associations were assessed using Mendelian randomization (MR), and biological relevance was further examined based on TCGA data. RESULTS: Younger age (OR = 0.96 [0.95-0.97], P < 0.001) and lower thyroglobulin (Tg) levels (OR = 0.64 [0.61-0.67], P < 0.001) were identified as key risk factors for malignant TNs. The two-factor model achieved AUCs of 0.755 (training), 0.735 (internal validation), 0.76 (temporal validation), and 0.784 (external validation) among various cohorts, and demonstrated incremental value to TI-RADS. An interactive web-based nomogram was developed as a proof-of-concept tool to support clinical utility. MR analysis supported a positive causal relationship between Tg and benign TNs (β = 0.62, P = 0.006), while TCGA data confirmed the inverse association between Tg and malignant TNs (OR = 0.14, P < 0.001). CONCLUSION: A simple model integrating age and routine serum Tg demonstrates robust and generalizable performance for malignancy risk stratification of TNs. By integrating clinical prediction with causal inference and biological validation, this study provides a complementary tool to existing ultrasound-based risk stratification systems.
Functional Stratification and Long-Term Care Service Patterns among Discharged Patients with Cancer: A Retrospective Study from Taiwan.
Po HW, Chu YC, Tsai HC … +2 more , Huang TY, Chen CY
J Cancer · 2026 · PMID 42179793 · Full text
BACKGROUND: 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 sever...
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Phenotypic risk factors linked to acute radiation-induced toxicities: a phenome-wide Mendelian randomization study of 12,042 cancer patients.
Jiang W, Li B, Zhang S … +7 more , Sui X, Liang Y, Jia M, Jiang S, Li L, Teng H, Wang W
J Cancer · 2026 · PMID 42179792 · Full text
OBJECTIVE: 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...
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Determination of protein markers of inflammasome formation and ferroptosis in thyroid cancer based on gender.
Díaz-Pedrero R, Fraile-Martinez O, García-Montero C … +22 more , Boaru DL, De Castro-Martinez P, De Leon-Oliva D, López-Gonzalez L, García-González B, Pérez-González I, Alhaddadin MNM, Barrena-Blázquez S, Ferrara-Coppola C, Villar-Carrillo AM, Gutierrez-Gonzalez L, Pascual-Casero M, Mañez F, Giménez TR, Lasa-Unzúe I, Alonso MD, Gutiérrez-Calvo A, Guijarro LG, Álvarez-Mon M, Crecente MC, Saez MA, Ortega MA
J Cancer · 2026 · PMID 42179791 · Full text
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 a...
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.
Integrative Bulk and Single-Cell Transcriptome Profiling of Telomere-Related Genes Reveals a Robust Prognostic Signature and Immunotherapeutic Landscape in Neuroblastoma.
Aierken Y, Zheng L, Liu T … +2 more , Tan K, Lv Z
J Cancer · 2026 · PMID 42179790 · Full text
PURPOSE: Neuroblastoma (NB) is the most common extracranial solid tumor in children with poor overall survival. Increasing evidence indicates that telomeres contribute to tumorigenesis and influence cancer prognosis. How...
PURPOSE: Neuroblastoma (NB) is the most common extracranial solid tumor in children with poor overall survival. Increasing evidence indicates that telomeres contribute to tumorigenesis and influence cancer prognosis. However, the biological and clinical implications of telomere-related genes (TRGs) in NB remain poorly defined. MATERIALS AND METHODS: We integrated data from multiple independent cohorts to elucidate the roles of TRGs in NB. Differential expression and weighted gene co-expression network analyses (WGCNA) were performed to identify telomere-related differentially expressed genes (TRDEGs) linked to patient survival. Consensus clustering based on TRDEG expression patterns was conducted to stratify molecular subtypes, followed by functional enrichment analysis. A prognostic signature was then built using machine-learning algorithms to predict clinical outcomes and potential therapeutic responses. Single-cell RNA sequencing (scRNA-seq) data were used for signature gene expression validation and to guide functional candidate selection. Quantitative RT-PCR was performed to verify the TRDEG signature, and functional assays were performed to explore the role of in NB progression. RESULTS: First, we identified 103 telomere-related differentially expressed genes (TRDEGs) significantly linked to NB patient survival. Consensus clustering of TRDEGs revealed two NB molecular subtypes with distinct biological processes and clinical outcomes. We established an eight-gene prognostic signature ( and ) that demonstrated high predictive accuracy, with 1-, 3-, and 5-year survival AUCs of 0.885, 0.903, and 0.911, respectively. The model showed consistent robustness across validation cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Integrating the risk score with clinical parameters within a nomogram yielded superior prognostic performance compared with traditional stratification schemes. High-risk patients showed decreased immune cell infiltration and increased immune evasion patterns, corresponding to poorer immunotherapy response. Distinct chemosensitivity profiles characterized the two risk groups. Quantitative RT-PCR validated the TRDEG signature. Last, was identified as a representative gene within the TRDEG signature through integration of scRNA-seq data, exhibited tumor-cell-specific expression, and was experimentally confirmed to promote NB cell proliferation, inhibit apoptosis, and enhance migratory capacity. CONCLUSION: TRGs play a pivotal role in shaping NB prognosis and treatment response. The validated TRDEG signature provides a foundation for individual risk assessment and future development of precision therapies and immunotherapeutic strategies. Among these genes, emerges as a key oncogenic driver.
The Role of Traditional Chinese Medicine in Metabolic Reprogramming, Tumor microenvironment, and Macrophage Regulation: Mechanisms and Advances in Preclinical Studies.
Yu A, Yang D, Chen H
J Cancer · 2026 · PMID 42179789 · Full text
BACKGROUND: 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...
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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