Search Results (29,826)

Glycosylation is essential for hematopoietic cell homeostasis and malignant transformation. Dysregulated expression of glycosylation genes in leukemia cells accelerates disease progression and fosters drug resistance. Therefore, targeting these genes offers a promising avenue for anti-leukemic therapy. In this study, we explore the roles of N-glycans in acute promyelocytic leukemia (APL) differentiation using the ATRA-induced wild-type NB4 (WT/ATRA) or HL-60 cell model. We found that expression of N-acetylglucosaminyltransferase IVa (GnT-IVa, encoded by the MGAT4A gene) and its product (β1,4-GlcNAc-branched N-glycan) increased significantly during differentiation, as evaluated by lectin blot, real-time PCR, and flow cytometry. Interestingly, analysis of the Gene Expression Omnibus (GEO) public data showed that MGAT4A expression is significantly lower in APL patients, and higher MGAT4A expression was associated with favorable survival in AML cohorts. To address the role of GnT-IVa in differentiation, we established MGAT4A- and MGAT4B-knockout (KO) NB4 cell lines using CRISPR/Cas9. Compared to WT/ATRA cells, MGAT4A KO, but not MGAT4B KO, markedly suppressed ATRA-induced differentiation, as evidenced by reduced expression of CD11b and CD11c. We found that CD11b is a major glycoprotein carrying β1,4-GlcNAc-branched N-glycans. This modification enhanced CD11b stability, as CD11b expression declined more rapidly in MGAT4A KO cells in the presence of cycloheximide. In addition, MGAT4A KO suppressed ERK/MAPK signaling, which contributed to differentiation. Our study highlights the critical role of GnT-IVa in regulating APL differentiation, which may provide a basis for developing new differentiation therapies for APL. Full article

Blood-derived extracellular vesicle (EV) biomarkers have emerged as promising liquid-biopsy analytes for monitoring treatment response and prognosis in breast cancer. This scoping review mapped the clinical evidence on blood-derived EV in breast cancer and identified key barriers to clinical translation. Following the Joanna Briggs Institute framework and PRISMA-ScR guidelines, we searched PubMed, Embase, and Web of Science for eligible studies published through November 2025. After duplicate removal, title and abstract screening, and full-text assessment, 64 clinical studies were included. Research activity increased markedly from 2020 onward, accounting for 87.5% (56/64) of included studies. The literature was concentrated in East Asia, particularly China (51.6%, 33/64). RNA-based biomarkers predominated (60.9%, 39/64), especially microRNAs (39.1%, 25/64). Prognostic outcomes were evaluated in 89.1% (57/64) of studies, treatment response in 51.6% (33/64), and both endpoints in 40.6% (26/64). Triple-negative breast cancer was the most frequently studied subtype in isolation (15.6%, 10/64). Methodological heterogeneity was substantial, and kit-based precipitation was the most common EV isolation method (57.8%, 37/64). EV biomarkers show promise for non-invasive monitoring in breast cancer, but methodological standardization, compliance with Minimal Information for Studies of Extracellular Vesicles guidelines, and large prospective validation studies remain necessary before routine clinical implementation. Full article

Hepatocellular carcinoma (HCC) incidence in Texas is 45% higher than the national average, with disproportionate burden among the Hispanic/Latino population. Despite significant health disparities, comprehensive evidence on HCC risk factors specific to this population remains limited. This scoping review of 20 primarily observational studies utilized PubMed, EbscoHost, and the PRISMA-ScR checklist to map risk factors in south Texas. Results show that metabolic dysfunction, specifically diabetes and obesity, increases advanced liver disease odds by 7- to 12-fold compared to non-Hispanic groups. Environmental exposures are also significant: aflatoxin was detected in 5.7 to 7.3% of Hispanic/Latino HCC tumors, and cases demonstrated 6-fold higher odds of aflatoxin biomarkers, while alcohol contributed to 3.0% of cancers. Furthermore, PNPLA3 genetic variants exerted synergistic effects with obesity and heavy alcohol consumption. Among four intervention studies, strategies included low-dose calcium montmorillonite clay for aflatoxin reduction, community-health-worker-integrated chronic care, and hospital-based hepatitis screening. However, critical research gaps remain regarding multirisk factor interactions, toxin dose–response characterization, dietary interventions, and longitudinal data. These findings underscore the urgent need for culturally tailored, community-engaged prevention programs and ethnicity-specific HCC guidelines for the Texas Hispanic/Latino population to effectively address these rising health disparities. Full article

Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer’s disease (AD), especially during anti-amyloid-β (Aβ) monoclonal antibody (Aβ-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate TSPO-associated neuroinflammatory responses to chronic Aβ-mAb therapy and their modulation by the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone. App^NL-G-F knock-in mice underwent TSPO-PET and Aβ-PET imaging at 5, 7.5, and 10 months of age across four treatment arms: placebo, Aβ-mAb, pioglitazone, and combination therapy. TSPO-PET detected early and progressive neuroinflammatory responses to Aβ-mAb that appeared lower with pioglitazone co-treatment. Both mono- and combination therapy were associated with altered temporal and spatial dynamics of the TSPO-PET signal. In addition, we applied a previously validated microglia desynchronization index based on TSPO-PET connectivity, which captured individual variation in regional TSPO-PET organization and correlated with cognitive performance. Together, TSPO-PET and its regional synchronicity can quantify longitudinal, region-specific treatment effects, which may help differentiate harmful from adaptive neuroinflammatory responses. These findings highlight the potential of TSPO-PET as a stratification biomarker to optimize therapeutic interventions. TSPO-PET therefore enables in vivo tracking of treatment-associated neuroinflammatory responses during anti-Aβ immunotherapy and provides a non-invasive framework for evaluating combination strategies targeting amyloid pathology and immune regulation in AD. Full article

Background: The precise identification of cancer subtypes through the integration of multi-omics data has emerged as a key research direction in bioinformatics. Among existing multi-omics integration methods, similarity graph-based clustering algorithms have attracted widespread interest owing to their capacity to effectively characterize the association patterns between samples. However, the majority of existing methods primarily focus on first-order relationships among samples while ignoring the prevalent high-order neighborhood relationships, and fail to fully exploit the complementary information from different omics. Methods: To address these limitations, we propose an innovative multi-omics integration framework termed MHSGTR, which integrates multi-omics data by combining Motif high-order similarity graphs and tensor regularization to identify cancer subtypes. Specifically, MHSGTR introduces Motif theory to construct a high-order similarity graph and designs a high-order graph learning term to obtain a hybrid similarity that integrates both first-order and high-order information, thereby capturing the latent high-order structural information among samples. For multi-omics data integration, we employ third-order tensor regularization constraints to explore complementary information across multi-omics data, coupled with an attention module to adaptively learn omics-specific weights for constructing a consensus similarity graph. Final clusters are derived via spectral clustering. Results: Comprehensive experiments on eight TCGA cancer datasets and a case study on adrenocortical carcinoma (ACC) demonstrate that MHSGTR achieves superior clustering performance and identifies cancer subtypes with significant biological differences, showcasing its effectiveness in robust multi-omics integration. Full article

Background: Colorectal cancer (CRC) represents a major global health burden, accounting for roughly 10% of all newly diagnosed cancers and cancer-related deaths worldwide. According to the World Health Organization, it is the third most diagnosed malignancy and the second leading cause of cancer mortality. Postoperative complications remain a significant concern after CRC resection, occurring in up to 50% of patients and contributing to increased morbidity, mortality, prolonged hospitalization, and substantial healthcare expenditure. Artificial intelligence (AI) has emerged as a transformative tool in modern healthcare, offering advanced capabilities in predictive analytics, clinical decision support, and personalized perioperative management. Methods: This review systematically evaluates the application of AI, specifically machine learning (ML) and deep learning (DL) algorithms, in the prediction of anastomotic leak (AL) and other major postoperative complications. In this context, AI models are generally used to refine risk stratification and enhance surgical decision-making. Results: A total of 13 studies were included, encompassing 15,105 patients. Across these studies, ML and DL algorithms consistently outperformed conventional statistical models in forecasting postoperative outcomes. Conclussions: Current evidence suggests that AI has substantial potential to improve perioperative risk prediction, support intraoperative decision-making, and personalize postoperative surveillance in patients undergoing CRC surgery. Methodological limitations, including a high risk of bias, limited external validation, heterogeneous outcome definitions, and inconsistent reporting, necessitate more robust, prospective, multicenter research before widespread clinical adoption can be realized. Full article

Background and Objectives: Although clinically useful, homologous recombination deficiency (HRD) testing has recently been more broadly adopted in ovarian cancer (OC) management. The VALIDATE study evaluated HRD status and treatment patterns in patients with newly diagnosed advanced OC in Bulgaria to better understand HRD prevalence and disease management. Materials and Methods: This real-world, observational, multi-centre, medical chart review study included 100 adult patients with HRD testing results available at study entry. Data collected at least 30 days after HRD results and 6 months later were descriptively analysed in the full cohort and subgroups (HRD, BRCA mutation, and genomic instability score [GIS]). Results: Mean age at diagnosis: 61.3 years; stage III: 51.0%, prevalence of HRD+ 58.0% (95% confidence intervals [CI] 47.7–67.8%) and HRD− 42.0% (95% CI 32.2–52.3%). Among the 58 HRD+ patients, 20 (34.5%) were BRCA+, whereas 38 (65.5%) were BRCA−, and 52 (89.7%) were GIS+, and 6 (10.3%) GIS−. Overall, platinum–taxane chemotherapy plus antiangiogenics was the most common front-line (FL) treatment (77.0%), regardless of subgroups (range: 66.7–85.0%). Six months later, 81 patients were alive, and 73 (90%) started maintenance therapy (MT). Antiangiogenic monotherapy (32.0%) and antiangiogenic plus PARP inhibitor (34.0%) were the most common MTs. The latter was also common across subgroups (range: 33.3–60.5%), except for HRD− (61.9% received antiangiogenic monotherapy). Conclusions: In this dataset, more than half of advanced OC patients had HRD+ status. Our study provides relevant insights into recent clinical practice patterns in advanced OC in Bulgaria that could serve as an anchor for future, more robust research in this field. Full article

Prostate cancer (PCa) is the second most frequently diagnosed solid malignancy in men and a major cause of cancer-related mortality worldwide. While localized disease is associated with excellent long-term survival, advanced and castration-resistant PCa continues to represent a major therapeutic challenge. Current management ranges from active surveillance for indolent tumors to multimodal systemic approaches for metastatic disease. In this context, natural compounds are attracting increasing interest as adjunctive or novel therapeutic agents. Among these, silymarin, a Silybum marianum-derived flavonolignan complex, has shown promising antineoplastic activity in preclinical PCa models. In vitro, silymarin compounds consistently inhibit PCa cell proliferation by inducing G1 and G2/M cell cycle arrest, upregulating cyclin-dependent kinase inhibitors, and activating caspase-dependent apoptotic pathways. They also modulate key oncogenic signaling pathways involved in cell survival, proliferation, invasion, and metastasis. In vivo xenograft and transgenic models further show reduced tumor growth, angiogenesis, and metastatic spread with limited systemic toxicity. Emerging clinical evidence, including systematic reviews and meta-analyses, suggests translational potential; however, robust randomized trials are needed to define optimal formulations, dosing strategies, and therapeutic efficacy in PCa patients. This review provides a comprehensive overview of the molecular mechanisms, preclinical efficacy, and emerging clinical evidence supporting silymarin as a candidate for future PCa research. Full article

Peptide-based cancer vaccines have emerged as a prominent focus in contemporary oncological research, as the quest for innovative cancer treatment modalities continues to gain momentum. A pivotal facet of their development is the precise delineation and characterization of immunogenic tumor antigens. In this context, VaxiJen stands out as one of the most widely used and cited computational servers for predicting immunogenicity, making it an invaluable tool for in silico antigen prediction. However, the database underpinning VaxiJen’s predictions has not undergone a comprehensive update for over fifteen years. To address this, a systematic search of the PubMed database was conducted to identify scholarly articles reporting data on novel immunogenic proteins and peptides undergoing human testing. The corresponding sequences of these proteins and peptides were subsequently curated from UniProtKB. Therefore, in this study, we introduce an updated dataset encompassing a repertoire of tumor immunogens, comprising 546 full-length human proteins and 212 human tumor peptides, as well as tumor non-immunogens, comprising 548 full-length human proteins and 181 human tumor peptides. The recently compiled VaxiGen tumor dataset is openly accessible. Researchers can conveniently download, search, and process it. This dataset, when paired with a suitable negative dataset, can further serve as a valuable training set, thereby facilitating improved predictions of the potential immunogenicity of hitherto uncharacterized protein or peptide sequences. Full article

Autophagy is a self-degradative homeostatic mechanism that plays an important role in tumor viability, metabolic reprogramming, and drug resistance. Circulating tumor DNA (ctDNA) is fragmented DNA that comes from dying tumor cells and leaks out into the blood stream. ctDNA can now be measured through blood tests and is a non-invasive way to identify cancer. ctDNA has shown promise for early detection of cancer, prognosis, and monitoring treatment response in real time. There is emerging mechanistic evidence suggesting a potential relationship between autophagy and ctDNA dynamics which has been discussed as a new autophagy–ctDNA axis. Autophagy can affect ctDNA levels by promoting or suppressing apoptosis and necrosis of tumor cells. When autophagy is cytoprotective, less DNA would be shed into the bloodstream. When autophagy is inhibited or defective, more DNA would be released because of increased genomic instability. Stressors found within the tumor microenvironment (TME) like hypoxia, oxidative stress, and nutrient depletion can also induce autophagy and indirectly affect ctDNA. Targeting autophagy therapeutically with drugs that induce or inhibit autophagy such as chloroquine (CQ) or mechanistic target of rapamycin (mTOR) inhibitors can affect ctDNA concentrations. Although emerging mechanistic evidence suggests a potential relationship between autophagy and ctDNA dynamics, direct clinical studies validating this interaction remain lacking. Therefore, this review presents the autophagy–ctDNA relationship as a hypothetical and exploratory model that warrants further mechanistic and translational investigation in cancer development, therapeutic resistance, and clinical applications. Full article

Background/Objectives: The Naxi people in Northwest Yunnan of China have used alcohol-soaked Pleione Pseudobulbus, which is the Pseudobulbus of Pleione bulbocodioides Rolfe (PBR), for lung diseases and tumors for a long period of time. This study aims to explore underlying mechanisms of bioactive ingredients in PBR, as well as to underscore the synergy between traditional medicine and modern pharmacological research. Methods: We verified the anti-tumor effects of the PBR extract through in vitro cell experiments, and explored its underlying mechanisms by combining untargeted metabolomics with network pharmacology to predict the related targets. Results: The anti-tumor potential of PBR extracts was systematically evaluated by integrating chemical profiling with in vitro cell-based assays. Untargeted metabolomics tentatively annotated metabolites spanning 12 major chemical classes, several of which have been previously reported to possess anti-tumor activity. To validate these annotations, prioritized candidates were further examined by LC-MS/MS against authentic reference standards at the nanogram scale, which confirmed the presence of sclareol—a naturally occurring diterpene with documented anti-tumor properties—as a constituent of PBR. Consistent with this chemical evidence, the PBR extract exerted multi-faceted anti-tumor effects in A549 lung cancer cells: it significantly suppressed proliferation, migration, and invasion; induced G0/G1-phase cell-cycle arrest; disrupted mitochondrial membrane potential; and modulated the expression of apoptosis-related proteins. Conclusions: By highlighting the pharmacological properties of cultivated PBR, we identified 118 overlapping targets between PBR compounds and lung disease-related targets, and we further selected 25 core lung cancer targets with high topological importance. This study suggests that the primary active compounds of Pleione bulbocodioides (Franch.) Rolfe may exert anti-lung cancer activity, potentially through targeting the EGFR tyrosine kinase inhibitor resistance pathway and the PI3K-Akt signaling pathway. Furthermore, in silico molecular docking suggested that the two major active compounds exhibited favorable predicted binding affinities with four core targets, particularly EGFR and AKT1, providing a basis for further experimental validation. These results support the potential value of Naxi traditional medicine and the need to further research onthese medicinal plants, thereby promoting Chinese herb medicine conservation efforts in the Naxi region. Full article

MicroRNA (miRNA) regulation plays a pivotal role in intracellular gene expression. Analysis of miRNA profiles can provide critical insights into disease states. As cancer-associated molecules reported in previous studies, miRNAs may serve as candidate classificatory features for exploratory cancer classification. This research analyzed serum miRNA data from patients with 13 solid cancer types and individuals without cancer. The study comprised two distinct analyses: first, stratifying the dataset into cancer and non-cancer groups to identify miRNAs differentially represented in cancer patients; and second, subdividing the cancer patient data into 13 predefined solid-cancer types to identify candidate miRNA features that discriminate among these cancer types. We employed seven feature-ranking algorithms to evaluate miRNA contributions in both analyses and generate feature lists. Each list was examined using an incremental feature selection method to extract essential miRNAs and build good-performing classification models. Several candidate miRNAs were identified for distinguishing pan-cancer samples from non-cancer ones: miR-4783-3p has been linked to associated with the regulation of endocrine cell differentiation, and miR-663a has been reported in hepatocellular carcinoma and thyroid carcinoma. The analysis also highlighted miRNAs that differentiate solid cancer types, including miR-629-3p, reported to be upregulated in lung and breast cancer, and miR-6087, reported to be downregulated in osteosarcoma and bladder cancer. Full article

Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief and supportive care, population-based evidence remains limited regarding whether integrated Chinese and Western medicine (ICWM) confers measurable benefits over Western medicine (WM) alone in terms of healthcare utilization and survival. Taiwan’s National Health Insurance (NHI) system offers a unique nationwide setting to address this gap because it reimburses patients for both WM and TCM services and captures care from a large number of TCM clinics across Taiwan, allowing evaluation of adjunctive TCM use in routine clinical practice at a scale rarely possible in prior studies. We used emergency department visits, hospitalization, and length of stay as pragmatic proxy indicators of patients’ daily functioning and disease burden. Leveraging a 10-year enrollment window (2004–2013) and up to 17 years of follow-up, we hypothesized that ICWM would be associated with a reduced risk of acute care events and lower healthcare expenditures compared with WM alone. This hypothesis was examined in a large cohort of breast cancer patients treated across nearly 4000 medical facilities nationwide, encompassing the entire Taiwanese population. Methods: A retrospective cohort study was performed to analyze Taiwan’s National Health Insurance Research Database and Cancer Registry. Women newly diagnosed with breast cancer between 2004 and 2013 who subsequently developed depression (≥3 outpatient diagnoses or 1 hospitalization) were followed until death or 31 December 2021. Patients receiving ≥30 cumulative days of TCM after diagnosis were classified as the ICWM group, whereas those receiving <30 days were classified as the WM group. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for all-cause mortality. Healthcare utilization, including emergency department visits, hospitalization, and medical expenditures, was analyzed on a per-person-year basis. Results: A total of 1193 patients were included, with 488 in the WM group and 705 in the ICWM group. Compared with WM users, ICWM users were younger, had lower body mass index, and were more likely to have stage 0–II disease. ICWM was associated with lower total, inpatient, and emergency healthcare expenditures per person-year, as well as fewer emergency visits per person-year, although outpatient and overall visits were higher. In stage-stratified multivariable analyses, ICWM was associated with lower all-cause mortality in both stage 0–II disease (aHR = 0.61, 95% CI: 0.39–0.94) and stage III–IV disease (aHR = 0.38, 95% CI: 0.21–0.67). Kaplan–Meier analyses likewise showed significantly better overall survival in the ICWM group in both early-stage and advanced-stage disease. Conclusions: In this nationwide retrospective cohort of breast cancer patients with depression, adjunctive ICWM was associated with better survival, lower acute care utilization, and lower healthcare expenditures compared with WM alone. However, because quality of life was not directly measured and the study was based on observational data, QoL-related interpretations should be made cautiously, with healthcare utilization outcomes viewed as indirect proxy indicators rather than direct evidence of improved daily QoL. Full article

Alpha-fetoprotein (AFP) is a glycoprotein primarily produced by the fetal liver and yolk sac during development. It is a multifaceted biomarker with significant applications in the prenatal screening of congenital abnormalities, cancer, and other disorders. The level of AFP in maternal blood may indicate several obstetric concerns and complications during pregnancy. Atypical AFP levels are commonly utilized as a biomarker for detecting fetal anomalies, placental complications, and other pregnancy-related issues. These findings raise concerns regarding the effectiveness of screening maternal serum alpha-fetoprotein (MS-AFP) as a primary indicator of pregnancy problems and underscore the need for further investigation into the functional role of AFP throughout pregnancy. The measurement of MS-AFP has been utilized for the past four decades. It is anticipated that MS-AFP measurement will continue to be utilized as a component of integrated or sequential tests for chromosomal abnormalities and may serve as a prognostic indicator for adverse obstetric outcomes. Critically, whether AFP functions solely as a passive marker or plays active biological roles in pregnancy physiology and pathology remains unresolved, necessitating additional mechanistic investigation and discourse. This review consolidates critical data from numerous studies on AFP, focusing specifically on its diagnostic and prognostic applications for congenital abnormalities and problems during pregnancy. This review also identifies key research gaps regarding the functional biology of AFP, particularly whether AFP functions as a passive biomarker or an active participant in the pathophysiology of adverse pregnancy outcomes. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide despite advances in screening, navigational bronchoscopy, and systemic therapies. Diagnostic and therapeutic limitations persist, including uncertainty regarding intraprocedural tissue adequacy during biopsy sampling and constraints of existing ablative modalities for tumors located near critical thoracic structures. This review examines two emerging technologies: Full-Field Optical Coherence Tomography-based Dynamic Cell Imaging (DCI) and monopolar biphasic Pulsed Electric Field (PEF) ablation as complementary emerging technologies that may address these gaps. The Van Gogh™ Microscopy System (CellTivity Scientific, Inc.) utilizes DCI to enable real-time visualization of cellular metabolic activity without tissue destruction, providing functional information regarding tissue viability and microstructural morphology. The Aliya^® PEF ablation system (Galvanize Therapeutics, Inc.) delivers biphasic high-voltage electrical pulses that induce non-thermal tumor cell death while preserving extracellular matrix architecture, potentially allowing treatment near sensitive thoracic structures such as airways, vasculature, and pleura. Early preclinical studies and initial clinical experience suggest that DCI can facilitate rapid intraprocedural assessment of biopsy adequacy, while PEF ablation may provide reproducible focal tumor destruction with a favorable safety profile near critical structures. Although the current evidence base remains limited to early-phase studies and feasibility trials, the convergence of real-time biologic tissue assessment with structurally preserving ablation technologies introduces the possibility of integrating diagnostic confirmation and local therapy within a single procedural workflow. This review summarizes the mechanistic rationale, emerging evidence, and potential clinical applications of these technologies and proposes a conceptual “See and Strike” framework within these two emerging technologies. The methodological limitations, workflow considerations, and future research directions required to validate this approach are also discussed. Prospective multicenter trials and long-term oncologic outcomes will be necessary before widespread clinical adoption. Full article