Colorectal cancer ranks among the most common malignancies worldwide. Rectal serrated lesions represent a significant precancerous condition, accounting for approximately 30% of sporadic colorectal carcinomas. Their flat morphology and indistinct borders often lead to missed detection during routine colonoscopy. In addition, the complex classification system and considerable molecular heterogeneity of these lesions create challenges for clinical management, including diagnostic accuracy, risk stratification, and treatment decisions. Research in recent years has progressively clarified the unique oncogenic pathway associated with serrated lesions-referred to as the serrated pathway. Characteristic molecular events include mutations in b-raf murine sarcoma viral oncogene homolog B (BRAF) or kirsten rat sarcoma viral proto-oncogene (KRAS) mutations, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI). Among these, the BRAF V600E mutation serves as the core driver event. Combination therapy with encorafenib and cetuximab, which targets this mutation, has been shown to improve outcomes in patients with BRAF-mutated metastatic colorectal cancer. Furthermore, Microsatellite Instability-High (MSI-H) lesions exhibit sensitivity to immune checkpoint inhibitors, offering novel options for personalized treatment. Concurrently, the application of technologies such as artificial intelligence (AI)-assisted endoscopy, molecular imaging, and liquid biopsy holds promise for improving the detection of early-stage lesions. This systematic review examines the current research landscape regarding rectal serrated lesions, covering an evolution of classification systems, elucidation of molecular and cellular mechanism, advances in diagnostic technology, and optimized treatment strategies. We further discussed molecular differences between the serrated pathway and the classical adenoma-carcinoma sequence, epigenetic regulatory mechanisms, tumour microenvironment characteristics, and personalized management strategies based on molecular subtyping. By synthesizing existing evidence, this review aims to provide theoretical guidance for the clinical management of rectal serrated lesions and lay the groundwork for future research.

Pancreatic ductal adenocarcinoma, which accounts for more than 90% of pancreatic cancer cases, remains one of the deadliest malignancies worldwide, with a poor 5-year survival rate of approximately 10-13% despite advances in diagnosis and treatment. Its poor prognosis is attributed to aggressive biological behavior, extensive desmoplastic stroma, profound metabolic reprogramming, and resistance to conventional therapeutic interventions. Among the hallmark metabolic alterations in PDAC, the Warburg effect enables tumor cells to sustain rapid proliferation under hypoxic and nutrient-deprived conditions. Excessive lactate accumulation within the tumor microenvironment promotes extracellular acidification, suppresses cytotoxic T-cell activity, enhances regulatory T-cell expansion, and stimulates cancer-associated fibroblast signaling, thereby facilitating immune evasion and tumour progression. Key mediators of this metabolic rewiring include glucose transporters, lactate dehydrogenase A, and monocarboxylate transporters. Consequently, integrating immunometabolic insights into therapeutic strategies has emerged as a promising approach for PDAC management. Natural compounds such as quercetin, resveratrol, curcumin, anthraquinones, and camphene have shown potential to modulate glycolytic enzymes, inhibit lactate transport, and attenuate TME-associated immunosuppression. These bioactive molecules, therefore, represent promising candidates for combination-based therapeutic interventions in PDAC. This review summarizes the molecular mechanisms underlying glucose metabolic rewiring, lactate-mediated immune evasion, and the translational potential of natural compounds as immunometabolic modulators. By highlighting the intricate interplay among glucose metabolism, lactate-driven immunosuppression, and tumor microenvironment remodeling, this review provides a mechanistic framework for the development of natural compound-based therapeutic strategies. It identifies promising directions for future preclinical and clinical investigations in PDAC.

The laminin α3 chain, encoded by LAMA3, constitutes a principal component of laminin-332 (LN-332), an essential extracellular matrix (ECM) glycoprotein governing cell adhesion, proliferation, and tissue homeostasis. This systematic review consolidates current evidence on the molecular features and regulatory mechanisms of LAMA3, including its roles in PI3K/Akt, epithelial-mesenchymal transition (EMT), and Hippo-YAP signaling, as well as epigenetic and post-transcriptional modulation. Its context-dependent functions across distinct pathological states are delineated. In malignancies, including colorectal and ovarian cancers, LAMA3 functions as an oncogenic determinant that enhances invasion, metastatic dissemination, and chemotherapeutic resistance. In contrast, in hereditary diseases such as junctional epidermolysis bullosa (JEB) and chronic disorders such as idiopathic pulmonary fibrosis (IPF), LAMA3 deficiency or dysfunction constitutes a structural basis of tissue pathology. From a translational standpoint, elevated LAMA3 expression has been recognized as an independent prognostic indicator in pancreatic ductal adenocarcinoma, whereas LAMA3 promoter methylation is a candidate biomarker for platinum resistance in ovarian cancer. LAMA3-directed gene therapy for JEB has progressed to clinical evaluation. Current limitations in the field are critically examined, and emerging therapeutic approaches, including proteolysis-targeting chimeras (PROTACs), are discussed. Collectively, an integrated framework that connects LAMA3 biology with clinical applications is presented to inform future investigations and precision therapeutic strategies targeting this multifunctional molecule.

To investigate the mechanism of artemisinin liposomes regulating breast cancer metastasis and apoptosis through TIGIT/CD155 signal axis. Artemisinin liposomes were synthesized by thin film dispersion method and characterized in morphology, zeta potential, hydrodynamic size, entrapment efficiency as well as thermal stability. Furthermore, the cytotoxic effects of artemisinin liposomes on HC11 and 4T1 cell was evaluated by the MTS test. Scratch, transwell and colony formation experiment were conducted to assess the effect of artemisinin liposomes on cell metastasis. Apoptosis, cell cycle arrest were measured using flowcytometry. Meanwhile, bioinformatics analysis was used to investigate the relationship between TIGIT as a drug target for breast cancer and artemisinin liposomes, TIGIT/CD155 signal axis. Additionally, the mouse tumor model(group(saline, artemisinin, liposomes, artemisinin liposomes), dose(100 mg/kg/d)) was employed to detect the tumor-suppressive efficacy. Finally, the expression levels of Src, Akt, Mtor and Stat3 was further explored by Western Blot and RT-PCR to elucidate the regulatory mechanism of artemisinin liposomes on the TIGIT/CD155 signaling axis. The liposomes and artemisinin liposomes had average sizes of approximately 80 nm and 130 nm respectively, with a polydispersity index (PDI) of 0.225, 0.287. Artemisinin was effectively encapsulated within liposomes, as shown by the high encapsulation efficiency of 90.11% ± 0.88, with a cumulative release rate of 32.8% at pH = 5.5. In vitro studies demonstrated that artemisinin liposomes possessed significantly greater cytotoxicity against 4T1 cells, the IC₅₀ values were approximately 480 µM. In contrast to artemisinin alone, artemisinin liposomes can effectively inhibit 4T1 cell metastasis, with an inhibition rate of 93.02% at 20 µM, and also promote cell apoptosis, with an apoptosis rate of 14.17% at 20 µM. Bioinformatic analysis demonstrated that TIGIT/CD155 signal axis was highly expressed in breast cancer and had poor prognosis. In vivo results revealed that artemisinin liposomes alone produced an anti-tumor effect comparable to the combination of TIGIT/CD155 and IL-15. Ultimately, artemisinin liposomes can regulate breast cancer progression by modulating the TIGIT/CD155 signaling axis and critical factors in the SRC pathway, specifically SRC, AKT, STAT3, and mTOR. The clinical treatment of breast cancer does not rely on the use of chemotherapy drugs alone, but selects the effective ingredients of Chinese medicine with higher safety.

This paper discusses an EWSR1-SMAD3-rearranged fibroblastic tumor (ESFT) occurring in the wrist of a 5-year-old child and summarizes its clinicopathological features, immunohistochemical phenotype, and molecular characteristics to improve the accuracy of clinical diagnosis. A retrospective analysis was performed on the clinical manifestations, histopathology, immunohistochemical phenotype, and molecular characteristics of a 5-year-old patient with recurrent ESFT. Additionally, this paper presents a literature review of relevant studies on ESFT. Among the 21 cases of ESFT, including the present case, the disease primarily affects young and middle-aged adult females, with most tumors measuring 1-2 cm in diameter. It preferentially occurs in the soft tissues of the distal extremities-particularly the foot-and exhibits low-grade invasiveness. Histomorphologically, the tumor is composed of uniform spindle-shaped fibroblasts arranged in fascicular and interlacing patterns, with no prominent nucleoli or mitotic figures. A zonation pattern, focal microcalcification, and interstitial myxoid change are observed in some cases. Immunohistochemistry reveals diffuse, strong ERG expression in tumor cells; FISH molecular detection shows EWSR1 break-apart; and NGS results confirm EWSR1-SMAD3 rearrangement. ESFT is a benign neoplasm with a risk of local recurrence. It exhibits complex histomorphological features but demonstrates diffuse, strong immunoreactivity for ERG on immunohistochemistry and harbors characteristic genetic alterations.

Volatile organic compounds (VOCs) in human biofluids are promising non-invasive cancer biomarkers. However, their potential in urological cancers, including prostate, bladder, and kidney cancers is less explored, and the relationships between urinary and cellular VOC profiles across these cancer types remain unclear.

This systematic review aimed to evaluate gas chromatography-mass spectrometry (GC-MS)-based untargeted volatolomics studies in urological cancers to investigate cancer-specific, cross-cancer, and cross-matrix (urine vs. cell culture media) VOC biomarkers, while assessing methodological factors influencing biomarker discovery.

Published urinary and cellular VOC studies in prostate, bladder, and kidney cancers were systematically reviewed. VOC biomarkers, direction of change, diagnostic performance, sampling methods, analytical platforms, compound-identification strategies, and statistical approaches were extracted and compared across cancer types and sample matrices.

A total of 12 urinary prostate, 9 urinary bladder, 5 urinary renal, and 3 cellular VOC studies were identified. Prostate cancer profiles were mainly characterized by decreased organic acids and alcohols, whereas bladder and renal cancers more frequently showed elevated ketones and aldehydes. Several VOCs, including 2-butanone, 2-heptanone, hexanal and phenol, were identified across multiple cancer types. Cellular studies showed consistent directional changes for six VOCs, and cross-matrix analysis identified 28 shared VOCs, seven of which showed aligned trends in urine and cell models. These findings suggest that VOCs reflect both unique and shared metabolic alterations in urological cancers and may serve as useful diagnostic biomarker candidates.

This review integrates urinary and cellular VOC data across major urological cancers and identifies unique, recurrent, and cross-matrix VOCs that warrant further mechanistic and clinical validation. Although methodological heterogeneity remains a challenge, VOC-based approaches have generally shown good sensitivity and specificity for distinguishing malignant from healthy controls. With improved and standardized analytical methods, VOC volatolomics may support the future development of non-invasive and accurate diagnostics for urological cancers.

Vestibular schwannoma (VS) is a benign tumor growing from Schwann cells of the vestibulocochlear nerve (cranial nerve VIII), accounting for 6-8% of brain tumors. Cystic vestibular schwannoma (cVS) represents 10% of VS cases and is characterized by unpredictable growth and worse surgical outcomes compared to solid VS (sVS). The molecular mechanisms underlying this aggressive phenotype remain poorly understood. In this context, long non-coding RNAs (lncRNAs) are gaining increased interest as biomarkers for early diagnosis and improved clinical management. lncRNAs are RNA molecules that are longer than 200 nucleotides. They are known to regulate gene transcription and participate in chromatin remodeling through various mechanisms. However, their role in cVS is largely unexplored. In this study, we identified cVS-associated lncRNAs using patient-derived samples. Whole transcriptome analysis via RNA sequencing revealed 65 differentially expressed lncRNAs and 308 protein-coding genes (PCGs) between cVS and sVS. From these, we selected the top eight lncRNAs (TENM3-AS1, ADIRF-AS1, PCA3, RP11-108K14.12, RP11-728F11.4, AC132217.4, RP11-43F13.3, and EGFLAM-AS1), each showing significant correlation with more than 20 differentially expressed PCGs. The upregulation of PCA3 and ADIRF-AS1, and the downregulation of EGFLAM-AS1 in cVS, were further validated using qRT-PCR. Here, by transcriptome-wide approach, we demonstrate that lncRNAs are prevalent in cVS disease and are likely to play critical roles in regulating important signaling pathways involved in disease pathogenesis. We believe, that detailed future investigations on this set of identified lncRNAs can provide useful insights into the biology and, ultimately, contribute to biomarker development for this neoplasm.

The METTL3-METTL14 protein-protein interaction (PPI) plays an important role in tumour progression, and disruption of this interaction has been explored as a potential strategy. In this study, four peptides were identified from a peptide database through virtual screening and molecular docking. Among them, peptide-1 showed the lowest K_d value among the tested peptides in MST analysis (K_d = 0.76 ± 0.02 μM). Binding mode analysis, molecular dynamics simulations, and MM/PBSA calculations suggested that peptide-1 might form a binding-related conformation with METTL3 under the simulated conditions. In lung cancer cells, peptide-1 showed growth-inhibitory activity, whereas weaker effects were observed in BEAS-2B cells. Peptide-1 also reduced the METTL3-METTL14-associated NanoBRET signal, decreased cellular m⁶A levels and JUNB mRNA expression, and its antiproliferative effect was attenuated by METTL3 knockdown. These findings suggest that peptide-1 may represent a METTL3-targeting peptide candidate for further evaluation.

Hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options, underscoring the urgent need for novel therapeutic targets. The copper transporter ATP7A has been implicated in cancer, but its precise role and regulatory mechanisms in HCC pathogenesis remain poorly understood. ATP7A expression was analyzed using public databases and validated in clinical HCC tissues and cell lines via qPCR and western blot. Functional assays were performed following ATP7A knockdown. Sensitivity to cuproptosis was assessed by measuring intracellular copper/ROS levels and IC50 of elesclomol-Cu. The upstream regulatory axis was identified through bioinformatic prediction and verified by dual-luciferase reporter and rescue experiments. The role of the LINC02038/miR-506-3p/ATP7A axis was further confirmed both in vitro and in a xenograft mouse model. ATP7A was significantly upregulated in HCC tissues and cell lines. ATP7A knockdown markedly inhibited HCC cell proliferation, migration, and invasion, while simultaneously sensitizing cells to cuproptosis. Mechanistically, LINC02038, which was highly expressed in HCC, functioned as a competing endogenous RNA (ceRNA) to sponge tumor-suppressive miR-506-3p, thereby upregulating ATP7A expression. This LINC02038/miR-506-3p/ATP7A axis was demonstrated to coordinately regulate malignant phenotypes and the expression of key cuproptosis-related proteins (DLAT, FDX1, LIPT1). In vivo, silencing LINC02038 effectively suppressed tumor growth and recapitulated the molecular alterations of this axis and cuproptosis regulators. Our findings reveal that the LINC02038/miR-506-3p/ATP7A axis played a crucial oncogenic role in HCC by driving tumor progression and modulating cuproptosis. This axis represents a promising prognostic biomarker and a potential therapeutic target for HCC intervention.

Background/Objectives: Virtual Bronchoscopic Navigation is used to guide bronchoscopes toward peripheral pulmonary lesions, but broad clinical and research adoption remains limited by the cost of proprietary software and by segmentation failures in small distal airways that can interrupt path planning. This study presents Virtual Bronchoscopic Pathfinder, an open-source, web-based system designed to provide automated airway segmentation, robust path generation, and browser-based three-dimensional visualization. Methods: The system integrates five components: a connectivity-aware deep learning model for pulmonary airway segmentation using Connectivity-Aware Surrogate and Local-Sensitive Distance modules; TotalSegmentator for automated tumor localization; a topology-preserving three-dimensional thinning algorithm implemented in C++ for centerline extraction; a bidirectional Dijkstra algorithm operating on a three-tier anatomical cost field with centerline, airway lumen, and parenchymal costs; and a zero-footprint visualization interface built on vtk.js with synchronized axial viewing and interactive volume rendering. VBP was validated on 306 thin-section CT series from 154 subjects in the public Lung-PET-CT-Dx dataset. Results: Among the 306 CT series, 33 series (10.8%) were excluded because of scanner-specific segmentation artifacts. In the remaining 273 anatomically valid series, the system successfully generated complete end-to-end navigation paths for all cases. The overall pipeline success rate was therefore 273 of 306 series (89.2%). The web-based interface was also confirmed to operate without client-side installation across desktop, laptop, and mobile device configurations. Conclusions: Virtual Bronchoscopic Pathfinder demonstrates that a reliable and accessible virtual bronchoscopic navigation workflow can be constructed entirely from open-source components. By combining connectivity-aware segmentation, cost-field path planning, and browser-based visualization, the system provides a practical foundation for imaging informatics research and future development of intra-procedural bronchoscopic guidance.