Pancreatic neuroendocrine tumors (PanNETs) are increasingly detected, and the optimal extent of resection remains uncertain because perioperative burden and oncologic assessment may differ by procedure. Enucleation (EN) and central pancreatectomy (CP) are often grouped together as parenchyma-sparing resections (PSRs) despite substantial differences in technical complexity, postoperative risk, and oncologic evaluation.We conducted a multicenter retrospective study of consecutive patients who underwent resection for pathologically confirmed PanNETs ≤20 mm. Procedures were categorized as EN, CP, pancreatoduodenectomy (PD), total pancreatectomy (TP), or distal pancreatectomy (DP). Primary outcomes were clinically relevant postoperative pancreatic fistula (CR-POPF) and major morbidity, defined as Clavien-Dindo grade ≥IIIa. A prespecified pairwise comparison focused on EN and CP, and pathologic assessment patterns were analyzed descriptively across procedures. Of 460 patients, 164 (35.7%) underwent EN, 40 (8.7%) CP, 84 (18.2%) PD/TP, and 172 (37.4%) DP. CR-POPF occurred in 115 patients (25.0%), major morbidity in 68 (14.8%), and 90-day mortality in 4 (0.9%). Among PSRs, CP had higher major morbidity than EN (25.0% vs 10.4%, p =.020), higher CR-POPF (50.0% vs. 24.4%, p =.003), and a longer median hospital stay (19.5 vs. 10.0 days, p <.001). Lymph node (LN) assessment was less frequent after EN than CP (40.4% vs. 87.5%, p <.001). Among assessed cases, LN metastases were identified in 44/320 patients (13.8%). EN and CP are not interchangeable as parenchyma-sparing options for small PanNETs. Among patients selected for resection, procedure selection should consider tumor location, function, technical feasibility, and oncologic requirements rather than size alone.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma most commonly involving the brain and leptomeninges. While high-dose methotrexate (HD-MTX)-based therapy has improved outcomes, relapse remains common and typically occurs within the CNS. Isolated ocular relapse after prolonged CNS remission is uncommon and diagnostically challenging. We report the case of a 78-year-old woman diagnosed in 2020 with PCSNL presenting with subacute constitutional and neurologic symptoms found to have a right frontal periventricular mass. She achieved complete radiographic remission following induction with HD-MTX and rituximab and remained free of CNS disease for nearly five years on serial surveillance imaging. Beginning in 2023, she developed progressive unilateral visual decline that was initially attributed to age-related macular degeneration, with repeatedly negative MRI studies of the brain and orbits. In 2025, further ophthalmologic evaluation with an ocular oncologist revealed vitreous and retinal involvement confirming isolated ocular relapse in the absence of systemic recurrence. She was retreated with HD-MTX and rituximab, resulting in clinical and fundoscopic improvement. This case highlights a rare pattern of delayed isolated ocular relapse following long-term remission in PCNSL. It underscores the limitations of neuroimaging in detecting ocular disease and emphasizes the importance of continued ophthalmologic surveillance with those specifically trained in ocular oncology in patients with persistent visual symptoms. Guideline-consistent systemic retreatment may provide effective disease control even in late relapse, particularly in patients with prior methotrexate sensitivity.

To identify therapeutic targets limiting glioblastoma invasion, we applied druggable genome CRISPRi screens and multiomic analysis to patient-derived glioblastoma cells in micro-dissectible biomimetic 3D hydrogels that permitted separation and analysis of core versus invasive fractions. Of 2,550 genes screened, 12 encoded druggable targets whose suppression limited invasion, of which AURKB (encoding aurora kinase B) and ACP1 (encoding low molecular weight protein tyrosine phosphatase, LMW-PTP) were validated in neurosphere assays and in vivo. Proximity labeling identified cortactin as a link between LMW-PTP and aurora B, and we observed that cortactin underwent serine phosphorylation by aurora B and tyrosine dephosphorylation by LMW-PTP. Targeting ACP1 or AURKB via CRISPRi or inhibitors in culture and in vivo shifted the cortactin phosphorylation balance in glioblastoma, reducing levels of cortactin and the actin-related protein 2/3 (Arp2/3) complex that mediates cortactin-induced actin stabilization, thereby reducing actin-cortactin-Arp2/3 colocalization and subsequent actin polymerization. AURKB or ACP1 targeting shifted actin from cytoplasm to the nucleus, reducing mesenchymal gene expression. Biophysical analysis implicated AURKB in glioblastoma cell adhesion and stiffness needed for initial migration and ACP1 in mechanical stress resistance required for later migration. These findings revealed a targetable axis balancing kinase and phosphatase activities to regulate actin polymerization during glioblastoma invasion.

This study aimed to evaluate the impact of coexisting autoimmune thyroiditis (HT) on the clinicopathological characteristics and prognosis of patients with papillary thyroid carcinoma (PTC).

To identify clinicopathologic predictors independently associated with cervical lymph node metastasis in pediatric papillary thyroid carcinoma.

Breast cancer remains a major cause of morbidity and mortality in women, with around 2.3 million new cases and 670,000 deaths worldwide in 2022. Daidzin, a soy isoflavone glycoside from Glycine max, is a candidate bioactive scaffold, but its breast cancer-relevant mechanisms remain poorly defined. This study used an integrated in silico strategy combining network pharmacology and molecular modeling to prioritize daidzin targets and validate key interactions, with sirtinol as a reference compound. Target prediction identified 101 putative daidzin targets, and intersection with breast cancer-associated genes yielded 97 common targets. Protein-protein interaction analysis highlighted hub genes including ALB, TNF, MMP9, CASP3, SRC, ITGB1, MMP2, ESR1, IL2, and HSP90AA1. Enrichment analyses suggested convergence on extracellular/vesicle-related functions, metallopeptidase activity, and pathway modules spanning metabolism, inflammation, endocrine signaling, and cancer circuitry. Docking against ten hub proteins produced binding energies from -6.00 to -11.49 kcal/mol, with the strongest affinity for MMP9 (6ESM; -11.49 kcal/mol), exceeding B9Z (-10.54 kcal/mol) and sirtinol (-10.59 kcal/mol). Molecular dynamics simulations indicated stable complexes, and Molecular Mechanics Generalized Born Surface Area (MMGBSA) supported stronger binding for daidzin-MMP9 (-46.86 ± 3.83 kcal/mol) than sirtinol-MMP9 (-14.12 ± 8.99 kcal/mol). Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction indicated favorable safety-related flags for daidzin, although lower predicted intestinal absorption and Caco2 permeability than sirtinol suggest potential exposure-related limitations. Density Functional Theory (DFT) analysis supported comparatively greater electronic stability. Collectively, the results prioritize a daidzin-MMP9 axis for experimental validation.

Pulmonary delivery of lipid nanoparticle (LNP)-based mRNA vaccines offers a promising strategy for localized lung cancer immunotherapy, yet how distinct pulmonary administration routes determine cellular targeting and therapeutic efficacy remains poorly understood. Here, we systematically evaluate intranasal and intratracheal delivery of mRNA-LNP vaccines and reveal a route-dependent immunological mechanism governing lung-targeted tumor vaccination. Although intratracheal administration yields only a 2.6-fold increase in total pulmonary protein expression compared to intranasal delivery, it produces a striking 26.8-fold enhancement in functional mRNA transfection efficiency within alveolar macrophages, the dominant antigen-presenting cell population in the alveolar space. This selective targeting reprograms alveolar macrophages toward an activated antigen-presenting phenotype, promoting efficient antigen presentation, robust CD8+ T-cell responses, and superior prophylactic and therapeutic efficacy in pulmonary tumor models. Notably, local depletion of alveolar macrophages completely abolishes the antitumor protection conferred by intratracheal vaccination, establishing their indispensable role in mediating pulmonary mRNA vaccine efficacy. Together, these findings provide mechanistic insights into lung-targeted mRNA cancer vaccination driven by alveolar macrophage engagement, providing critical insights for the design of next-generation LNP-based nanomedicines for lung cancer immunotherapy.

Innovations in therapeutic modalities and targeted drug delivery are two key approaches to improving the effectiveness of cancer treatment. With the development of therapeutic concepts and nanotechnology, recent research has shifted from tissue- or cell-level drug delivery to organelle-specific delivery to amplify therapeutic effects. Among these organelles, the endoplasmic reticulum (ER) has emerged as a particularly promising target because of its extensive membrane network, which serves as a major site for protein synthesis, lipid metabolism, calcium homeostasis, and intracellular signaling. The disruption of ER function can trigger severe cellular stress and apoptosis, providing a rationale for ER-targeted cancer therapy. However, traditional small-molecule drugs often exhibit poor ER specificity, rapid degradation, and limited intracellular accumulation, significantly restricting their therapeutic potential. In contrast, ER-targeting multifunctional nanoplatforms have demonstrated superior advantages, including enhanced stability, precise localization, controlled drug release, and multimodal therapeutic capabilities. In this Review, we systematically summarize the recent advances in ER-targeting nanotherapeutics and their applications in chemotherapy, phototherapy, immunotherapy, biotherapy, and combination therapy. Furthermore, we discuss the advantages, challenges, and mechanistic insights of these strategies, aiming to provide perspectives on accelerating the clinical translation of ER-targeting precision drugs.

Among 15-20 cases of breast cancer, triple-negative breast cancer (TNBC) is the deadliest form of the disease. The most effective form of treatment for this type of cancer is still targeted chemotherapy because it lacks hormone receptors. Myristicin, an active aromatic compound with anticancer properties, is mostly found in nutmeg. Antitumor, antioxidant, and antimicrobial activity are among few of the numerous properties of myristicin. On TNBC cells, the exact modes of action are mostly unidentified. This study shows that myristicin triggered the mitochondria-mediated apoptosis in MDA-MB-231 cells. The MTT assay assessed the anti-proliferative potential of myristicin on TNBC cells (IC50 0.65 mM ± 0.98). Flow cytometry analysis was used to evaluate the myristicin's effects on cell apoptosis using annexin V/PI (46.4 ± 2.31%). After evaluating the protein expression, myristicin significantly decreased the expression of Bcl2 and HSP60 while enhancing the expression of proteins such as caspase 9, caspase 3, bid, bad, caspase 7, P53, cytochrome c, and SDHA. Furthermore, our research confirmed that myristicin has a lower toxicological profile and greater in vivo therapeutic efficacy. In BALB/c mice, 4T1 cells were injected subcutaneously to develop breast tumors, and the mice subsequently received myristicin. According to in vivo results, myristicin treatment reduced tumor weight and volume when compared to the breast cancer control group. Besides, the enzyme analysis, gene, and protein expression showed significant apoptotic properties on myristicin treated group. According to these results, myristicin may be used as a therapeutic approach for the management of TNBC.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the United States. The incidence of early-onset CRC (EOCRC) has been rising in the past few decades. Given the multifaceted nature of EOCRC, the genetic and environmental factors contributing to this malignancy have remained elusive. Systems genetics is a multi-omics tool that analyzes multiple genes as a collective network. Transcriptional correlation, protein-protein interaction network, functional annotation, and drug-gene interaction analyzes enable investigators to explore the functional roles of target genes and aid with discovery of novel diagnostic biomarkers and potential therapeutics. To clarify the objective of this work, this manuscript serves three purposes: a narrative review of recent systems genetics applications in EOCRC research, a step-by-step protocol for conducting these analyses, and a discussion of current advances in systems genetics to address limitations in generalizability and context dependence. Through this manuscript, we envision a future in which emerging oncology researchers adopt these tools into their investigations of EOCRC and other malignancies.

Mediastinal sampling is essential for diagnosing and staging thoracic diseases, particularly non-small cell lung cancer (NSCLC). Traditional mediastinoscopy has been the gold standard; however, Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) has emerged as a minimally invasive alternative. This systematic review compares the economic evaluations of EBUS-TBNA to determine their cost-effectiveness, healthcare resource use, and overall economic impact.

Acquired temozolomide (TMZ) resistance remains a major challenge in glioblastoma and may involve the emergence or enrichment of cancer stem cell (CSC)-like characteristics. However, whether stem-like characteristics differ across increasing levels of acquired TMZ resistance remains unclear. This study compared stem-like characteristics among parental TMZ-sensitive glioblastoma cells and two sequentially generated TMZ-adapted populations with different levels of acquired TMZ resistance.

The systemic influence of tumor-derived secretomes on the nervous system remains poorly understood. We investigated whether differences in TP53 status are associated with altered cellular stress-handling states and amyloid precursor protein (APP) processing in colon cancer cells.

Hepatocellular carcinoma (HCC) is a malignancy with high global incidence and mortality, whose significant heterogeneity and poor prognosis pose severe clinical challenges. While artificial intelligence (AI) shows potential in HCC imaging, pathology, and prognosis, its "black-box" nature limits clinical adoption. Explainable AI (XAI) aims to reveal the decision-making logic of AI models. This narrative review synthesizes recent advances of XAI across four key domains of HCC research. In imaging diagnosis, techniques such as Grad-CAM and SHAP have enabled semantic alignment between AI outputs and clinical standards like LI-RADS, enhancing interpretability. In biomarker discovery, XAI has progressed from identifying single markers to revealing functional gene modules and molecular subtypes through multi-omics integration. In treatment efficacy prediction, XAI-based models have quantified feature contributions to therapeutic responses, supporting individualized treatment stratification. In prognosis assessment, XAI has enabled dynamic risk stratification by integrating clinical, imaging, and pathological features. However, three cross-cutting limitations persist across these domains: explanations remain predominantly correlational rather than causal, a semantic gap exists between pixel-level heatmaps and high-level clinical reasoning, and most models are static, unable to adapt to evolving clinical data. Current research is moving toward causal inference frameworks, concept-driven interpretability, and interactive, dynamic systems. In summary, XAI is transitioning from a retrospective explanation tool toward a prospective clinical decision partner, yet bridging the gap between explanation and actionable decision support remains the central challenge.

Oral squamous cell carcinoma (OSCC) arises in the context of diverse etiological exposures, such as tobacco, alcohol, areca nut use and viral infections. This etiological heterogeneity drives distinct molecular alterations, contributing to tumor complexity and significant challenges in identifying robust, clinically applicable biomarkers.

The cingulate cortex (CC) and cingulum bundle (CB) are key structures involved in pain processing. Thus, we explored the correlations between cortical morphometry of the CC, white matter integrity of the CB, and pain-related assessments in lung cancer patients with cancer pain (CP+). Structural and diffusion spectrum imaging, along with emotion and pain-related assessments, were collected from 45 CP+ patients, 47 lung cancer patients without pain (CP-), and 35 healthy controls (HC). Cortical morphometry and tract-based automatic analysis evaluated the CC and CB. One-way ANOVA revealed significant group differences in sulcal depth (SD) within the CC, as well as in fractional anisotropy (FA) and radial diffusivity (RD) within the CB. Post-hoc tests indicated that the CP+ group had greater SD than the CP- group, and smaller FA as well as greater RD than both the CP - and HC groups. In the CP+ group, RD of the CB was positively correlated with SD of the CC, and the anxiety score was positively correlated with RD of the CB and SD of the CC. In the HC group, the anxiety score was negatively correlated with SD of the CC. This study revealed distinct patterns of structural alterations across the three groups. Differences in both CB and CC structures were observed in CP+ relative to CP - and HC groups, were interrelated, and were associated with anxiety. These findings highlight the significant contribution of CC and CB in cancer pain processing, while also serving as potential biomarkers for negative emotion.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, largely due to the supportive role of the tumor microenvironment (TME). Tumor-associated macrophages, particularly the M2 phenotype, are pivotal in promoting NSCLC progression. Exosomes, key mediators of intercellular communication, can transfer functional cargo from M2 macrophages to cancer cells, thereby regulating malignant behaviors. However, the specific mechanisms by which M2 macrophage-derived exosomes modulate NSCLC progression are not fully understood.

To evaluate the impact of probable sarcopenia on overall survival (OS), toxicity, and quality of life (QoL) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving androgen receptor pathway inhibitors (ARPIs), adjusting for geriatric and inflammatory markers.

Carboxylic metabolites and drugs play essential roles in biological regulation and disease progression. Their simultaneous quantification remains analytically challenging due to their low ionization efficiency and poor chromatographic retention. Here, we synthesized a pair of secondary amine-based chemical isotope labeling reagents, N-(piperidin-4-ylmethyl)benzamide (PMBA) and d5-N-(piperidin-4-ylmethyl)benzamide (d5-PMBA), for the simultaneous labeling of carboxylic metabolites and drugs. The secondary amine moiety on PMBA/d5-PMBA can efficiently react with carboxyl groups on carboxylic compounds, substantially improving the reversed-phase (RP) chromatographic retention and separation, along with the enhancement of the MS sensitivity. Upon this strategy, the limits of detection (LODs) of 32 carboxylic metabolites and drugs were determined to range from 0.001 to 0.13 ng mL-1. The chemical isotope labeling approach with liquid chromatography-mass spectrometry (LC-MS) analysis enabled reliable quantification of diverse carboxylic compounds in serum samples and revealed significant alterations in their abundances during hepatocellular carcinoma progression. This method provides a sensitive and robust analytical platform for the simultaneous quantification of carboxylic metabolites and drugs and facilitates investigations of their biological and pharmacological functions in diseases.

DNAzymes capable of RNA-cleaving are attractive, protein-independent candidates for biosensing and gene regulation. However, precise modulation of their activity remains a significant obstacle to biomedical applications. Herein, we uncovered a cyclization-provoked, size-reliant topological barrier that suppresses the catalytic core folding of DNAzymes, thereby governing their catalytic activity. Leveraging this underlying topological insight, we engineered a catalytically inert, minimal-sequence circular DNAzyme bearing a cleavable apurinic/apyrimidinic (AP) site and revealed that its substrate-cleavage potential could be restored through miRNA-10b-responsive circular-to-linear switching. The smallest circular size confers the strongest topological barrier for catalytic activity self-blocking in the circular DNAzyme, providing the most effective means for stimuli-specific activity restoration. This topology-informed strategy facilitated the design of an orthogonally activated circular DNAzyme-metal nanohybrid via Zn2+-mediated coordination self-assembly of the circular DNAzyme with its substrates. The nanohybrid allowed accurate discrimination of metastatic triple-negative breast cancer in various complex biological settings, including a heterogeneous population of cell subtypes, an in vivo subcutaneous tumor model, an in vivo sentinel lymph node metastasis model, and clinical human breast tissue samples. Our findings provide a flexible and robust framework for conditional manipulation of DNAzyme activity, enabling more accurate, spatiotemporal regulation for future therapeutic interventions.