Chemical eye burns remain one of the most severe ophthalmic emergencies, capable of causing irreversible vision loss and disability. The annual incidence reaches approximately 51 cases per million population, predominantly affecting working-age males, with occupational injuries accounting for 45–52% of cases. This review systematizes data from the literature published between 2013 and 2025 on the key aspects of the problem: pathogenesis (differences in injury mechanisms between alkali and acid burns, the role of limbal stem cell deficiency), evolution of classification systems (from Roper-Hall to the Dua classification and the global consensus on LSCD), current approaches to emergency care and medical therapy (including biological agents — autologous serum, platelet-rich plasma, anti-angiogenic agents), surgical rehabilitation (amniotic membrane transplantation, limbal stem cell transplantation, keratoprosthesis), and emerging directions (cell-based therapies, nanotechnology-based drug delivery systems). A dedicated section addresses quality of life and psychological consequences: chemical burns are shown to be accompanied by a marked decline in vision-related and overall quality of life, a high prevalence of anxiety-depressive disorders, and post-traumatic stress disorder. The need tointegrate psychological screening into standard patient management protocols is substantiated. Key unresolved challenges are identified: the conduct of large multicenter randomized trials, standardization of treatment protocols, and the development of pharmacological methods to stimulate residual limbal stem cells.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare and highly malignant variant of gastric cancer, distinguished by histological features resembling hepatocellular carcinoma and frequent elevation of serum alpha-fetoprotein (AFP). It demonstrates aggressive biological behavior, early metasta-tic potential, and intrinsic resistance to conventional platinum-based chemotherapy, resulting in poor outcomes. No standard systemic therapy exists for initially unresectable HAS, making conversion strategies a critical therapeutic goal. We present a 56-year-old male with biopsy-proven locally advanced HAS and markedly elevated AFP (1 729.53 μg/L). Imaging revealed bulky lymphadenopathy (largest node: 39 mm×27 mm), rendering the tumor unresectable. Molecular profiling confirmed human epidermal growth factor receptor 2 (HER2) amplification. First-line conversion therapy with oxaliplatin, fluoropyrimidine, sintilimab (a programmed death-1 inhibitor), and later trastuzumab yielded only transient stabilization followed by clear progression: After six cycles, AFP rose to 1 546.07 μg/L and target lymph nodes enlarged to 46 mm×31 mm on CT. Given treatment failure and persistent HER2 positivity, a second-line, biology-informed regimen was initiated: Disitamab vedotin (an HER2-targeted antibody-drug conjugate delivering monomethyl auristatin E), lenvatinib (a multi-targeted tyrosine kinase inhibitor blocking vascular endothelial growth factor receptor and other pro-angiogenic pathways), tislelizumab (a programmed death-1 inhibitor), and short-course capecitabine (discontinued after 7 days due to grade 3 thrombocytopenia). This combination produced rapid and sustained antitumor activity. Serum AFP declined drama-tically to 102.3 μg/L after two cycles. Radiological reassessment showed progressive shrinkage of metastatic lymph nodes (from 46 mm to 25 mm after cycle two, and further to 14 mm after cycle three) consistent with partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) confirmed reduced metabolic activity in residual lesions. These results enabled successful R0 radical distal gastrectomy in June 2024. Final pathology revealed minimal residual disease (ypT1bN1) with hepatoid morphology and positive immunostaining for AFP, glypican-3, Sal-like protein 4, and HER2 (2 +). The patient received two adjuvant cycles of the same targeted-immunotherapy backbone before transitioning to observation due to cumulative toxicity. Eighteen months postoperatively, he remained free of recurrence. This case underscores that in HER2-positive, chemotherapy-refractory HAS, a rationally designed, multimodal regimen integrating an HER2-directed antibody-drug conjugate, antiangiogenic agent, and immune checkpoint blockade can overcome therapeutic resistance, achieve meaningful downstaging, and enable long-term disease control. Early molecular characterization and aggressive, persona-lized intervention are essential for improving outcomes in this rare malignancy.

Managing unresectable metastatic colorectal cancer (mCRC) requires a comprehensive strategy. While chemotherapy, anti-angiogenic, and anti-epidermal growth factor receptor (EGFR) agents are available, strategy trials are needed to optimize their use and sequencing. The STRATEGIC-1 phase III trial (NCT01910610) was designed to determine the optimal treatment sequence in patients with untreated, unresectable wild-type RAS/BRAFV600E mCRC. Patients were randomized (1:1) to FOLFIRI-cetuximab then mFOLFOX6-bevacizumab (arm A) or OPTIMOX-bevacizumab then FOLFIRI-bevacizumab followed by EGFR monoclonal antibody +/- irinotecan (arm B). The primary endpoint was the duration of disease control (DDC). Secondary endpoints were overall survival (OS), time to failure of strategy (TFS), progression-free survival (PFS), overall response rate (ORR), salvage surgery rate, safety, and health-related quality of life (HRQoL). Overall, 263 patients (arm A:131, arm B:132) were randomized. After 68.4 months of median follow-up (95% CI, 76.5-98.0), the median DDC was 22.8 months (95% CI, 20.4-28.8) in arm A and 23.5 months (95% CI, 17.9-26.3) in arm B (HR = 1.01, 95% CI, 0.76-1.34; log-rank P = 0.945). The median OS was 40.4 months (95% CI, 32.4-51.1) in arm A and 34.4 months (95% CI, 27.5-42.2) in arm B (HR = 1.30, 95% CI, 0.99-1.72). The ORR was higher in arm A (82.4% versus 65.4%) in the first-line group but not in the second-line group (20.7% versus 16.4%). Adverse events were consistent with the well-known safety profiles. STRATEGIC-1 did not meet its primary endpoint and was inconclusive in identifying the optimal treatment strategy in wild-type RAS/BRAFV600E mCRC.

Simlukafusp alfa (FAP-IL2v) was engineered to preferentially activate CD8+ T and natural killer (NK) cells in tumor microenvironments overexpressing fibroblast activation protein (FAP). Checkpoint inhibitors combined with antiangiogenic agents are standard therapy for metastatic renal cell carcinoma (mRCC), which overexpresses FAP. Here, we explored the efficacy, safety, and pharmacodynamic effects of FAP-IL2v in combination with atezolizumab with or without bevacizumab in patients with mRCC. Patients with treatment-naïve or pretreated clear cell and/or sarcomatoid mRCC were eligible. Dose escalation explored FAP-IL2v every 2 weeks (Q2W) with atezolizumab Q2W (doublet, arm A), and with atezolizumab and bevacizumab Q2W (triplet, arm B) in patients treated with up to one prior systemic therapy. Dose extension explored in untreated patients the recommended FAP-IL2v dose administered Q2W (doublet, arm A; and triplet, arm B) or 3-weekly (doublet, arm C; and triplet, arm D). Primary objectives were the recommended FAP-IL2v dose and antitumor activity. Secondary objectives included safety, pharmacodynamics, and exploratory biomarkers in peripheral blood and paired biopsies. By the data cut-off date (31 August, 2021), 66 patients were enrolled. The median duration of treatment was 11.0 months. Objective response rates (ORRs) were 25% for the doublet and 47% for the triplet, and median progression-free survival was 6.3 and 18.3 months, respectively. Safety profiles were consistent with the individual drugs, including expected interleukin-2 (IL-2) class-specific adverse events (AEs). Two deaths were recorded caused by AEs related to study treatment (acute kidney injury, n=1; pancytopenia, n=1). Expansion and activation of NK and T cells, but not regulatory T cells, was observed in peripheral blood, leading to increased tumor infiltration and inflammation in paired biopsies. The addition of bevacizumab led to a reduced angiogenesis signature score and reduced vessel density. The combination of FAP-IL2v plus atezolizumab with or without bevacizumab was consistent with the known safety profile of the individual drugs. The maximum tolerated dose was not reached, with a recommended FAP-IL2v dose of 10 mg. ORR was higher among patients receiving the triplet therapy compared with the doublet. Pharmacodynamic results were consistent with the mechanism of action of IL-2, supporting further research in this field.

The concept of vascular normalization represents a promising strategy for antitumor therapy. However, clinical translation of antiangiogenic agents to induce and sustain tumor vascular normalization remains hampered by acquired drug tolerance and dose-limiting systemic toxicities. Here, we demonstrate that focused ultrasound-stimulating oxygen nanobubbles (ONB_FUS) can effectively alleviate tumor hypoxia and drive vascular normalization, evidenced by improved intratumoral perfusion, reduced microvascular density, and increased pericyte coverage. During this normalization window, key proangiogenic signaling pathways, including VEGFA and ANGPT2, were significantly downregulated. Single-cell RNA sequencing of tumor endothelial cells (TECs) identified capillary endothelial cells (CapECs) as the primary responsive population, with selective depletion of the proangiogenic CapEC_Spp1+ subset. Clinical tumor samples corroborated these findings, showing elevated CapEC abundance and heightened ANGPT/VEGF pathway activity, specifically in high-proliferation CapECs. Functionally, ONB_FUS-mediated vascular repriming significantly enhanced intratumoral drug delivery and potentiated chemotherapy efficacy. Collectively, ONB_FUS offers a spatiotemporally controllable approach to vascular remodeling that complements standard-of-care therapeutics. Moreover, the identification of functionally distinct TEC subpopulations reveals mechanistically guided targets for precision antiangiogenic intervention.

Antiangiogenic combination therapy-antiangiogenic agents combined with immune checkpoint inhibitors and/or chemotherapy-has become an important treatment strategy for advanced driver-negative non-small cell lung cancer (NSCLC). We conducted a network meta-analysis to compare efficacy and safety and identify optimal antiangiogenic combinations. We searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) that evaluated antiangiogenic combination therapies. Primary outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and incidence of grade ≥ 3 treatment-related adverse events (TRAEs). Nine treatment regimens comprising 5954 patients were included. The network meta-analysis indicated that the chemotherapy-free regimen of sintilimab + anlotinib achieved the greatest progression-free survival (PFS) benefit, compared with chemotherapy (HR = 0.39, 95% CI 0.23-0.67), and the lowest incidence of grade ≥ 3 treatment-related adverse events (TRAEs) (RR = 0.57, 95% CI 0.32-0.95). Recombinant human endostatin (Endostar) + chemotherapy provided the largest overall survival (OS) benefit vs. chemotherapy (HR = 0.46, 95% CI 0.36-0.58). The triplet regimen of atezolizumab, bevacizumab, and chemotherapy yielded the largest improvement in objective response rate (ORR) vs. bevacizumab + chemotherapy (OR = 1.90, 95% CI 1.40-2.60). Across most subgroup analyses, regimens combining immunotherapy, an antiangiogenic agent, and chemotherapy conferred the greatest PFS and OS benefits. This network meta-analysis demonstrates that antiangiogenic combinations improve outcomes in driver-negative advanced NSCLC. Endostar + chemotherapy offers the greatest OS benefit, atezolizumab-bevacizumab-chemotherapy improves ORR, and sintilimab-anlotinib provides superior PFS with lower toxicity. Treatment should be tailored based on clinical factors, with further validation in multiethnic trials.

Benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for PD-L1-positive, advanced non-small-cell lung cancer (CAMPASS): a blinded, randomised, controlled, phase 3 trial.

Denosumab is a humanized monoclonal antibody targeting receptor activator of nuclear factor-κB ligand (RANKL) and is commonly used in the treatment of osteoporosis and cancer-related bone metastases. However, the persistent use of denosumab has been associated with an increasing incidence of denosumab-related osteonecrosis of the jaw (DRONJ), particularly following tooth extraction. This expert consensus aims to develop clinical management guidelines for the perioperative period of tooth extraction in patients who are currently receiving or have previously received denosumab therapy. The consensus covers the definition, etiology, epidemiology, staging, and risk factors of DRONJ, focusing on preoperative assessment, risk-based prevention strategies, minimally invasive surgical techniques, and postoperative follow-up protocols. The core management strategy for DRONJ emphasizes individualized decision-making based on a comprehensive preoperative assessment of medication history, local infection, and systemic conditions. The main risk factors for DRONJ include high-dose and long-term denosumab therapy, preexisting oral infections, such as periodontitis and periapical periodontitis, and invasive dental procedures, including tooth extraction, diabetes, and concomitant use of glucocorticoids or antiangiogenic agents. Core preventive measures include strict perioperative oral care, risk assessment-based antibiotic prophylaxis, long-term drug holidays, which were developed by dentists and physicians prio-ritizing the primary disease, and minimally invasive surgical techniques for managing trauma, preserving local blood supply, thoroughly removing infected tissues, and ensuring tight wound closure. This consensus highlights the importance of multidisciplinary collaboration between dental and clinical medicine experts in managing DRONJ. High-quality research is necessary to provide an evidence-based foundation for optimizing DRONJ prevention and treatment strategies.

Open-label, single-arm, phase II trial to investigate the efficacy of sitravatinib plus tislelizumab combination as a second-line treatment for advanced biliary tract cancer.

Cuproptosis is a regulated, copper-dependent form of cell death driven by mitochondrial protein lipoylation and disruption of the tricarboxylic acid (TCA) cycle. Increasing evidence in gynecologic oncology indicates that copper transport, lipoate metabolism, and respiratory-chain phosphorylation influence tumor fitness and treatment response. This review evaluates cuproptosis as a therapeutic hypothesis across gynaecologic cancers and outlines actionable targets and strategies based on this mechanism. Mechanistically, ferredoxin 1 (FDX1)-mediated lipoylation enables copper excess to precipitate TCA enzyme-dependent proteotoxic stress that is distinct from apoptosis and ferroptosis. Therapeutic concepts arising from this biology include modulation of copper flux with ionophores or chelators, inhibition of lipoic acid synthases, and disruption of mitochondrial proteostasis. Clinically, cuproptosis-related transcriptional signatures and imaging markers of mitochondrial respiration may help stratify patients for combination regimens that incorporate poly (ADP-ribose) polymerase inhibitors, anti-angiogenic agents, or immune checkpoint blockade. By synthesizing available mechanistic and translational evidence and highlighting trials-ready strategies, this review positions cuproptosis as a tractable, precision-oriented pathway for ovarian, cervical, and endometrial cancers.

Dual potential of tetrandrine: Antiangiogenic efficacy and safety liabilities revealed through in silico, in vitro, and zebrafish models.

Glioblastoma (GBM) is an aggressive and treatment-resistant primary brain tumor with a poor prognosis. Conventional therapies are limited by tumor heterogeneity, therapy resistance, and restricted Blood-Brain Barrier (BBB) penetration, highlighting the need for novel multi-targeted therapeutic strategies. This review assesses the therapeutic potential of curcumin analogs in GBM, with a focus on their molecular mechanisms, in silico predictions, preclinical efficacy, and potential synergistic strategies with standard treatments. A comprehensive search of published in vitro, in vivo, and computational studies on curcumin analogs was conducted. Mechanistic investigations included apoptosis induction, cell-cycle arrest, autophagy, ferroptosis, and inhibition of key oncogenic pathways such as STAT3, NF-κB, PI3K/Akt/mTOR, and EGFR. Pharmacokinetic optimization and BBB permeability were also assessed. Curcumin analogs demonstrate enhanced cytotoxicity in GBM cells, including temozolomide-resistant lines, through multi-target modulation of apoptosis, oxidative stress, oncogenic signaling, and glioma stem cell pathways. in silico docking and network pharmacology reveal strong binding to GBM-relevant targets, corroborating experimental efficacy. Preclinical studies show that analogs such as C-150, ALZ003, and DMC-BH suppress tumor growth, inhibit angiogenesis, and prolong survival in orthotopic and xenograft models. Combination with temozolomide, radiotherapy, or anti-angiogenic agents exhibits synergistic anti-tumor effects. Curcumin analogs are promising multi-targeted agents capable of overcoming GBM heterogeneity, therapy resistance, and invasiveness. Optimization of pharmacokinetics and targeted delivery, along with clinical evaluation, is necessary to translate preclinical findings into effective GBM therapies. Glioblastoma (GBM) is a highly aggressive type of brain cancer characterized by treatment resistance and a poor prognosis. The efficacy of conventional treatment approaches is limited by treatment resistance, heterogeneity, and inability to cross the Blood-Brain Barrier (BBB). Therefore, there is a need to develop new multi-targeting treatment approaches. This review aims to describe the therapeutic potential of curcumin analogs for GBM treatment, focusing on their molecular mechanisms, in silico studies, and their potential to act synergistically with conventional treatment approaches. A comprehensive literature review of published studies on curcumin analogs was conducted. Mechanistic studies of curcumin analogs included induction of apoptosis, cell cycle inhibition, induction of autophagy, and ferroptosis, as well as inhibition of key oncogenic pathways, including STAT3, NF-κB, PI3K/Akt/mTOR, and EGFR. In addition, studies aimed at improving their pharmacokinetics and permeability through the BBB were included. Evidence from various studies indicates that curcumin analogs exhibit superior cytotoxic effects against GBM cells, including temozolomide-resistant GBM cells, through multi-targeting approaches. In addition, in silico studies have demonstrated high binding affinities to key GBM-related targets. Preclinical studies have demonstrated the efficacy of curcumin analogs, including C-150, ALZ003, and DMC-BH, in inhibiting GBM growth, angiogenesis, and improving survival in orthotopic and xenograft mouse models. These compounds have demonstrated synergistic effects with temozolomide, radiotherapy, and anti-angiogenic therapy. Therefore, curcumin analogs have demonstrated significant therapeutic potential as multi-targeting agents to address heterogeneity, treatment resistance, and invasiveness of GBM. However, to realize this potential, there is a need to improve their pharmacokinetics and permeability through the BBB.

This review aims to review the efficacy and toxicity of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in the management of glioblastoma. A systematic review was completed utilizing PubMed, Cochrane, and Embase databases up to February 2025. Boolean operators and the MeSH term "glioma" were used, along with relevant keywords related to EGFR. First- and second-generation EGFR-focused TKIs performed poorly in patients with GBM. The use of erlotinib in combination with radiotherapy, alkylating agents, and anti-angiogenic agents yielded the best outcomes in patients with newly diagnosed GBM. EGFR-focused TKIs were largely disappointing as a treatment for GBM. Longstanding issues, including treatment resistance, tumor heterogeneity, and blood-brain barrier penetration persist. Future efforts must focus on tackling these issues, and prioritizing patient selection via biomarkers.

Efficacy of EGFR inhibitor-anti-angiogenic combination therapy varies substantially in RAS wild-type advanced colorectal cancer (CRC), and current clinical guidelines lack individualized predictive tools to identify optimal candidates and tailor regimens. This study aimed to develop and externally validate a multi-dimensional efficacy prediction model to address this unmet clinical need. This retrospective multi-center study included 600 RAS wild-type advanced CRC patients (development cohort: 420 patients from two centers; external validation cohort: 180 patients from an independent center) treated with EGFR inhibitors (cetuximab/panitumumab) plus anti-angiogenic agents (bevacizumab/fruquintinib/regorafenib) between 2018 and 2021. Candidate variables encompassed clinical, laboratory, radiomic, and biological indices. Radiomic features were screened via ANOVA-dimensionality reduction, and LASSO-Cox regression was used for variable selection and nomogram construction (with shrinkage calibration to reduce overfitting). Model performance was evaluated by discrimination (AUC), calibration (Hosmer-Lemeshow test), and clinical utility (decision curve analysis [DCA]); the overfitting risk was assessed by calculating events per variable (EPV), and model stability was verified by multi-step internal validation (tenfold cross-validation, bootstrap resampling) and subgroup/risk stratification analyses. The final nomogram integrated five core predictors: vascular density, neutrophil-to-lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), metastatic sites, and ECOG score. The model exhibited moderate discrimination with clinical practical value (development cohort AUC = 0.641, 95%CI 0.588-0.691; validation cohort AUC = 0.532, 95%CI 0.445-0.617), which is consistent with the performance of most multi-dimensional clinical prediction models for advanced colorectal cancer reported in similar studies (AUC range 0.58-0.68). Meanwhile, the model showed excellent calibration in the external validation set (H-L χ2 = 1.12, p = 0.572), indicating a high consistency between the predicted PFS probability and the actual clinical outcome. The limited discrimination of the model is mainly due to the inherent biological heterogeneity of advanced colorectal cancer and the lack of dynamic monitoring indicators (e.g., circulating tumor DNA) in the study variables. Risk stratification identified low (0.7%), intermediate (57.3%), and high-risk (42.0%) groups with significantly distinct progression-free survival (PFS) and overall survival (OS) (all log-rank p < 0.001). High-risk patients who switched regimens achieved longer median PFS (11.1 vs. 5.9months, p < 0.001). DCA confirmed superior net benefit over "treat all/none" strategies, and the model outperformed guidelines (median PFS: 9.3months [both recommended] vs. 6.7months [guideline-only], p < 0.05). Key biomarkers (vascular density, tumor mutational burden) correlated with treatment response and risk stratification, providing biological rationale. This externally validated nomogram integrating five readily available clinical and laboratory indicators can realize individualized PFS prediction and risk stratification for RAS wild-type advanced CRC patients receiving EGFR inhibitor-anti-angiogenic combination therapy, and provide preliminary reference for clinical regimen adjustment of high-risk patients. As a supplementary tool to current clinical guidelines, the model can partially address the problem of clinical response heterogeneity in combination therapy and provide simple decision support for clinicians in primary and secondary hospitals with limited detection conditions. However, the model has certain limitations in long-term prognostic prediction and needs to be further optimized and validated in larger, multi-center prospective cohorts before it can be translated into clinical practice of precision oncology.

ObjectiveRecent years have seen breakthrough progress in the use of immune checkpoint inhibitors in cancer therapy, offering new hope for patients with advanced gastric cancer. However, there remains insufficient real-world evidence regarding the efficacy and safety of combining immune checkpoint inhibitors with anti-angiogenic drugs and chemotherapy in the second-line setting. There is a pressing clinical need for dedicated studies to validate its application value. The present investigation systematically evaluated the clinical efficacy and safety profile of a multimodal therapeutic strategy integrating second-line immunotherapeutic agents, cytotoxic chemotherapy, and anti-angiogenic therapy in patients with metastatic gastroesophageal junction adenocarcinoma.MethodsA retrospective analysis was conducted on 84 patients treated in the oncology department. Patients were divided into two groups: the observation group (sintilimab + apatinib + albumin-bound paclitaxel, n = 42) and the control group (apatinib + albumin-bound paclitaxel, n = 42). Outcomes included median overall survival (mOS), median progression-free survival (mPFS), objective response rate (ORR), disease control rate (DCR), and adverse event incidence.ResultsBaseline characteristics (age, gender, Eastern Cooperative Oncology Group score, tumor location, histology, Lauren classification, human epidermal growth factor receptor 2 status, programmed death-ligand 1 expression, metastatic status, and prior treatment) showed no significant differences (P > 0.05), ensuring comparability. After follow-up, there was no significant difference in ORR or DCR between the two groups (P > 0.05): the observation group exhibited an ORR of 42.85% and DCR of 85.71%, compared to 38.09% and 75.57% in the control group, respectively. Furthermore, there was no significant difference in the overall incidence of adverse events or immune-related adverse events between the groups (P > 0.05). The incidence of immune-related adverse events was 21.43% (observation group) vs. 23.81% (control group), with no statistical significance (P = 0.798). The observation group had significantly longer mPFS (12.0 months vs. 9.0 months, hazard ratio (HR) = 0.455, 95% confidence interval [CI]: 0.217–0.956; P = 0.028), though mOS showed no difference (HR = 0.384, 95% CI: 0.131–1.125; P = 0.062). Kaplan-Meier analysis confirmed superior PFS in the observation group.ConclusionThe combination of an anti-PD-1 monoclonal antibody with chemotherapy and anti-angiogenic agents demonstrated preliminary efficacy and favorable safety in second-line gastric cancer patients. This study, using real-world data, validates the clinical benefit of this triple regimen, addresses the evidence gap in second-line treatment options, provides new insights for personalized combination strategies in advanced gastric cancer, and holds significant value for guiding clinical practice.

Glioblastoma (GBM) is the most prevalent primary malignant tumor of the adult central nervous system, characterized by pronounced vascularity that facilitates tumor proliferation, invasion, and progression. Although anti-angiogenic therapy has emerged as a potential treatment strategy for GBM, currently available anti-angiogenic agents, such as bevacizumab targeting VEGF, have demonstrated limited efficacy in improving patient survival. This underscores the urgent need for novel therapeutic targets and strategies. In this study, we identified that the expression of maternally expressed gene 3 (MEG3), a tumor-suppressive long non-coding RNA (lncRNA), is negatively correlated with patient prognosis. Spatial transcriptomics sequencing and RT-qPCR analyses revealed that MEG3 is highly expressed in glioma stem cells (GSCs). In vitro tube formation assays further demonstrated that MEG3 in GSCs promotes angiogenesis in human brain microvascular endothelial cells (HBMECs). Transcriptome sequencing identified VGF nerve growth factor inducible (VGF), a secreted pro-angiogenic protein, as a downstream target, and showed that MEG3 regulates the pro-angiogenic activity of GSCs by modulating VGF expression. RNA pull-down assays revealed that MEG3 binds to far upstream element-binding protein 1 (FUBP3), which also regulates VGF expression. In vivo, knockdown of MEG3 significantly extended survival in orthotopic xenograft models of GSCs. Immunohistochemical analysis of mouse tumor tissues showed a corresponding reduction in VGF levels and microvessel density following MEG3 knockdown. In conclusion, this study demonstrates that MEG3 in GSCs promotes GBM angiogenesis through a FUBP3-dependent induction of VGF expression, highlighting MEG3 as a potential therapeutic target for anti-angiogenic intervention in GBM.

Classic Kaposi sarcoma (CKS) is a rare vascular neoplasm driven by infection with Kaposi sarcoma-associated herpesvirus (KSHV) and characterized by a heterogeneous geographic distribution. While the etiology of other Kaposi's sarcoma (KS) variants is well established, the underlying mechanisms of CKS appear multifactorial, with several risk factors, among which advanced age and male sex are most significant. Due to the rarity of CKS and its often indolent clinical course, clinical trials are sparse, and current knowledge of therapeutic approaches remains limited. Most available clinical trials and practice guidelines focus on human immunodeficiency virus (HIV) -related Kaposi sarcoma. Therefore, specific recommendations for the classic form are restricted and rely on a low level of evidence, as categorized by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines, making disease management more challenging. Current approaches to treating CKS include both local and systemic therapies, selected based on disease stage, patient comorbidities, and individual preferences. Systemic treatment options may include immunotherapy, chemotherapy, or antiangiogenic agents. This review summarizes current management strategies and highlights emerging therapeutic approaches for CKS. It aims to support clinicians in optimizing therapeutic decision-making, including the use of novel and investigational therapies. Although several novel therapies are currently under investigation in clinical trials, significant gaps remain. Therefore, further research is needed to improve disease management.

Histological analysis remains the gold standard for tissue diagnosis and evaluation, but it often relies on subjective visual interpretation and limited field of view areas. In this study, we present a macroscopic, wide-field Mueller polarimetric imaging approach for the quantitative analysis of histological sections of melanoma induced with the B16F10 cell line in mice. By using the depolarization index, our method enables objective tissue discrimination based on intrinsic tissue properties. A color-coded segmentation mask derived from the depolarization index values was implemented to classify tissue into strongly depolarizing regions, associated with blood vessels, and weakly depolarizing regions, which predominantly correspond to tumor cell-dominated tissue. This pixel-wise classification allowed for quantitative mapping and statistical analysis of spatial heterogeneity across several mm² of entire histological sections, significantly extending the field of view compared to conventional microscopy. As a potential application, the technique was applied to evaluate histological sections from a preclinical murine melanoma model subjected to a treatment regimen including antiangiogenic agents. The results demonstrated measurable differences in the amount of strongly depolarizing tissue, associated with blood vessels, in the treatment group, supporting the method's sensitivity to antiangiogenic effects in the tumor microenvironment. These findings highlight the potential of Mueller polarimetry as a complementary tool for histological assessment, enabling reproducible, large-area tissue characterization beyond visual inspection.

Anti-angiogenic agents are widely used to treat solid tumors. We previously demonstrated that nicorandil, an angina pectoris medication, counteracted the effects of bevacizumab in a human mini-tumor model. To further elucidate the potential pharmacodynamic interactions and possible clinical implications, we conducted an integrative investigation combining an in vivo mouse model and a large-scale analysis of clinical adverse event reports. In tumor-bearing nude mice, aflibercept treatment markedly increased systemic blood pressure and substantially reduced tumor volume, whereas co-administration of nicorandil mitigated both responses. Additionally, an analysis of the Unites States Food and Drug Administration Adverse Event Reporting System data (FAERS [JAPIC AERS]) was conducted. Concomitant use of anti-angiogenic agents and nicorandil was infrequently reported; therefore, this data must be interpreted with caution. However, the tendency of reduced reporting odds ratios of hypertension and proteinuria and instances of hypotension were documented. Collectively, these findings suggest that nicorandil may counteract the pharmacodynamic effects of anti-angiogenic agents when administered concurrently. Therefore, further clinical validation is warranted.

Esophageal squamous cell carcinoma (ESCC) remains a highly aggressive malignancy with dismal clinical outcomes and limited treatment options. NAD(P)H quinone oxidoreductase 1 (NQO1) is classically characterized as a cytosolic oxidoreductase that prevents the formation of reactive oxygen species. Here, we demonstrated that NQO1 promoted ESCC progression and lung colonization via an enzymatic activity-independent mechanism. Integrated transcriptomic and direct RNA-binding analyses revealed that NQO1 acted as an RNA-binding protein to stabilize the mRNA encoding agrin (AGRN), thereby increasing AGRN expression. Upregulation of AGRN enhanced endothelial cytoskeletal organization by interacting with filamin A (FLNA) and stimulated angiogenesis through selective extracellular vesicle-mediated transfer. Structure-based screening identified the clinically approved agent panobinostat as a direct NQO1-binding compound that destabilized NQO1 and suppressed AGRN-dependent angiogenic signaling. Importantly, combined treatment with panobinostat and the anti-angiogenic agent anlotinib resulted in superior inhibition of tumor growth and vascularization compared with either monotherapy in patient-derived organoid xenograft models. Together, these findings uncover an enzymatic activity-independent RNA regulatory function of NQO1 in ESCC and provide a mechanistic rationale for targeting the NQO1/AGRN axis.