Epidural cavernous hemangioma is a rare vascular malformation, accounting for 5-12% of all spinal cord vascular malformations. We report a case of low dorsal spinal cord compression at D5-D6 due to a cavernous hemangioma mimicking the clinical and radiological features of an epidural neuroma in an hourglass shape. The clinical presentation was progressive spastic paraplegia over six months in a 41-year-old patient with no significant medical history. Magnetic resonance imaging showed a compressive D5-D6 intradural lesion with T2 hyperintensity, displaying an hourglass appearance suggestive of an epidural neuroma, with a significant extracanal component filling the ipsilateral latero-vertebral space. Histological examination confirmed cavernous hemangioma by immunohistochemistry. The postoperative outcome was favorable following total surgical removal of the lesion.

Gastrointestinal stromal tumors (GISTs), the most common sarcoma of the gastrointestinal tract, are mesenchymal tumors that generally arise in adults with a peak incidence in the sixth decade of life. Though most frequently found in the stomach or small intestine, GISTs may develop anywhere along the gastrointestinal tract. Approximately 1 in 4 GISTs are diagnosed incidentally, with imaging playing a crucial role in their detection and characterization. Due to their often clinically insidious growth, up to 25% of patients may already have metastatic disease at the time of diagnosis. In this article, we report the case of a 67-year-old woman who was incidentally diagnosed with a duodenal GIST. We analyze the computed tomography imaging findings and correlate them with the patient's clinical features.

Immunotherapy combined with chemotherapy has become the standard treatment for HER2-negative gastric cancer (GC), but its clinical benefits remain limited, with a median progression-free survival (mPFS) of 6-8 months and median overall survival (mOS) of 15-18 months. These outcomes are particularly poor in patients with CPS < 1. The marked heterogeneity of GC, along with primary and secondary resistance, presents significant clinical challenges and underscores the urgent need for novel therapeutic strategies.

To address these limitations, several combination therapies are being explored. Anti-VEGF therapy combined with immune checkpoint inhibitors (ICIs) has shown synergistic effects by enhancing immune cell infiltration and reducing tumor-mediated immunosuppression, thereby improving response rates and survival. Radiotherapy combined with ICIs also holds promise, with low-dose radiation remodeling the tumor microenvironment and high-dose radiation inducing immunogenic cell death. Other potential combinations include PD-1/PD-L1 inhibitors paired with targeted therapies against HER2, FGFR2, DKK1, PARP, LSD1, HDAC, and other emerging targets. Novel approaches such as hyperbaric oxygen therapy, oncolytic viruses, metabolic modulators, and fecal microbiota transplantation are also under investigation to further enhance immune responses.

These multimodal strategies represent a promising shift toward personalized, mechanism-driven immunotherapy sensitization. By targeting diverse pathways to overcome immune resistance, they aim to reshape the tumor microenvironment, restore immune responsiveness, and improve outcomes in GC. While many remain in early-stage development, accumulating evidence supports their potential. Future research should prioritize optimizing combination regimens, clarifying resistance mechanisms, and identifying predictive biomarkers through multi-omics and artificial intelligence to enable more precise, individualized immunotherapy.

A new group of thiadiazole-benzenesulfonamide hybrids was designed, synthesized, and biologically evaluated as potential dual inhibitors targeting B-Raf and VEGFR-2 for cancer therapy. The cytotoxic activity of the synthesized derivatives was assessed against HepG2 and Huh7 liver cancer cell lines, where compound 7a exhibited the most potent activity with IC₅₀ values of 17.89 μM and 25.07 μM, respectively. The kinase inhibition assay revealed that 7a strongly inhibited both B-Raf (IC₅₀ = 0.11 μM) and VEGFR-2 (IC₅₀ = 0.15 μM), surpassing sorafenib in B-Raf inhibition. Further mechanistic studies revealed that 7a induced G2/M phase arrest, with a significant increase in late apoptotic cells (57.08%) compared to the control group (0.15%), confirming its pro-apoptotic effect. The apoptotic pathway was further validated by caspase-3 activation, Bax upregulation, and Bcl-2 downregulation. Computational analyses verified the effective binding of compound 7a to VEGFR-2. These analyses included molecular docking, molecular dynamic (MD) simulations, molecular mechanics with generalized Born and surface area solvation (MM-GBSA), protein-ligand interaction fingerprints (ProLIF), principal component analysis (PCAT), and free energy landscape (FEL) studies. Additionally, DFT studies indicated 7a's stability and reactivity. In silico ADMET predictions indicated that the derivatives had good absorption, were non-mutagenic, non-carcinogenic, and exhibited low toxicity risks compared to sorafenib. These findings suggest that the synthesized thiadiazole-benzenesulfonamide hybrids, particularly 7a, represent promising dual BRAF/VEGFR-2 inhibitors with potent anti-cancer activity, warranting further optimization and preclinical evaluation.

Oncolytic viruses (OVs) have emerged as a transformative approach in cancer therapy, offering tumor-specific lysis while sparing normal tissues. In addition to their direct cytolytic effects, OVs actively reshape the tumor microenvironment (TME) by enhancing immune infiltration, disrupting immunosuppressive signals, and promoting tumor antigen presentation. However, the complexity of the TME poses challenges, often necessitating combination therapies to improve OV efficacy and overcome tumor resistance. This review explores the evolution of oncolytic virotherapy, from the early use of naturally occurring viruses to the development of genetically engineered OVs. Among the most significant advancements, T-VEC, an FDA-approved herpesvirus, has been modified to express GM-CSF, enhancing immune activation in metastatic melanoma. Similarly, JX-594, a vaccinia virus, has been engineered for selective replication in tumor cells, demonstrating the potential of OVs to combine direct oncolysis with immune modulation. Other HSV-based OVs, such as HF10 and HSV1716, further highlight the ability of OVs to enhance immune cell infiltration and increase antigen presentation within the TME. Recent advances in tumor microenvironment remodeling have expanded OV therapeutic strategies. By converting immunologically "cold" tumors into "hot" tumors, OVs can overcome immune evasion through mechanisms such as enhanced antigen release, immune checkpoint inhibition, and metabolic reprogramming. To maximize therapeutic potential, researchers are developing genetically engineered OVs carrying immune-stimulatory transgenes, exploring synergistic combination therapies with immune checkpoint inhibitors, and utilizing nanoparticle-based delivery systems for improved precision. Additionally, novel OVs-including measles virus, Newcastle virus, Zika virus, and SARS-CoV-2-are being investigated for their unique ability to disrupt the TME and enhance anti-tumor immunity. Looking ahead, OV therapy will depend on optimizing TME-targeted strategies, improving viral delivery mechanisms, and identifying predictive biomarkers to personalize patient responses. Advances in viral engineering and immunomodulation hold the potential to revolutionize cancer treatment, offering more precise and effective therapeutic options. This review provides a comprehensive analysis of current progress in oncolytic virotherapy, emphasizing its potential to remodel the TME and improve clinical outcomes.

The treatment of hepatocellular carcinoma (HCC) faces challenges of low response rates to targeted drugs and immune checkpoint inhibitors, which are influenced by complicated microenvironment of HCC. In this study, the complex tumor microenvironment was identified by using tissue microarray (TMA), spatial transcriptomes and single-cell sequencing. High expression of CC chemokine receptor 7 (CCR7) in tumor cells predicted lower Overall Survival (OS). Conversely, CRISPR-Cas9-mediated knockout of CCR7 enhanced the sensitivity of HCC to sorafenib in preclinical experiments, resulting from the inhibition of epithelial-mesenchymal transition through the AKT and ERK signaling pathways. Simultaneously, we revealed CCR7 expression in stromal cells, with increased infiltration of CCR7⁺ immune cells into the tumor mesenchyme associated with high CCL21 expression at tumor sites. Subsequently, VEGF-C was identified as an independent predictor of higher patient OS and showed a significant positive correlation with CCR7 signaling. Interestingly, exogenous VEGF-C was found to promote the formation of tertiary lymphoid structures (TLSs) by activating lymphatic angiogenesis and the CCL21/CCR7 axis. As a result, VEGF-C treatment enhanced the efficacy of anti-PD-1 immunotherapy. This study highlights the opposing effects of tumor cell-derived versus stromal cell-derived CCR7 expression and guides the precision treatment for HCC.

Ciprofol, an innovative anesthetic derived from propofol, has not yet been studied in detail regarding its effects in colorectal cancer (CRC). This study mainly explored the effects of Ciprofol on the epithelial-mesenchymal transition (EMT) process, glycolysis, and the Wnt/β-catenin signaling pathway in CRC cells. Through in vitro and in vivo experiments, we successfully demonstrated that Ciprofol can inhibit the proliferative capacity of CRC cells and tissues. It can also suppress the invasion, metastasis, and EMT process of CRC cells. In addition, treatment with Ciprofol decreased the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in CRC cells, thereby inhibiting cellular glycolysis. However, knockdown of APC could reverse the effects of Ciprofol. Regarding the mechanism, overexpression of APC was able to activate the Wnt/β-catenin signaling pathway. Ciprofol could activate the expression of APC, subsequently activating the Wnt/β-catenin signaling pathway. The addition of Derivative83 could reverse Ciprofol - mediated regulation of this pathway. This study still has certain limitations. For example, the verification through clinical trials, as well as issues such as the safety and efficacy of ciprofol, remain the key focuses of future research.

Sorafenib is an antiangiogenic and antiproliferative chemotherapeutic drug that plays a crucial role in the treatment of patients with advanced hepatocellular carcinoma (HCC). However, resistance to sorafenib greatly limits its therapeutic efficacy. This highlights the importance of determining the mechanisms underlying resistance to antiangiogenic therapy. In this study, we found that the extracellular matrix (ECM) stiffness was closely related to the prognosis of HCC patients and chemotherapy resistance. Using atomic force microscopy, we assessed ECM stiffness in tumor samples from 30 HCC patients treated with sorafenib, and the ECM stiffness in sorafenib-resistant patients was significantly greater than that in those who responded to sorafenib treatment. In a liver orthotopic xenograft model, reducing tumor ECM stiffness by inhibiting LOX enzyme activity significantly enhanced the efficacy of sorafenib and suppressed tumor progression. We found that glucose-6-phosphate dehydrogenase (G6PD) is regulated by ECM stiffness and is involved in resistance to sorafenib. Further in vitro and in vivo experiments confirmed that ECM stiffness can upregulate G6PD expression through the ITGB1-PI3K/AKT pathway, mediating sorafenib resistance in HCC. Clinical tissue microarray analysis revealed that the expression of collagen I, α-SMA, ITGB1, p-AKT, and G6PD was associated with sorafenib resistance in HCC patients. These results indicated that reducing ECM stiffness can increase the sensitivity of HCC to sorafenib and that the ITGB1-PI3K/AKT-G6PD cascades may serve as potential therapeutic targets for reversing sorafenib resistance.

The immunosuppressive tumor microenvironment (ITME) and inherent radioresistance of tumor cells limit the effectiveness of radioimmunotherapy and exacerbate immune evasion. To address these challenges, PEGylated Azacitidine-loaded and Mn²⁺-doped calcium carbonate nanoparticles (A@MCP NPs) are synthesized as multifunctional nanoagent to enhance radioimmunotherapy outcomes. Upon acidic TME, the release of Ca²⁺ and Mn²⁺ from A@MCP NPs co-triggers intracellular reactive oxygen species (ROS) generation via Ca²⁺ overload and Fenton-like reactions, inducing cytochrome C release and caspase-3 activation. Concurrently, released Azacitidine inhibits DNA methylation, upregulating GSDME expression in irradiated tumor cells, which synergistically amplifies caspase-3/GSDME-induced pyroptosis. The resulting pyroptotic cell damage, coupled with radiotherapy (RT)-induced DNA, activates Mn²⁺-sensitized cGAS-STING pathways, amplifying immune responses. Collectively, A@MCP, as a nano radiosensitizer, together with RT, co-activates pyroptosis and cGAS-STING to further amplify anti-tumor immune response, overcome ITME-mediated resistance and offer significant potential for improved cancer radioimmunotherapy.

The design of prodrugs aims to address the issues of systemic toxicity and poor specificity associated with traditional chemotherapy drugs, thereby improving patient survival rates. However, effectively controlling the activation of prodrugs and further improve the efficacy remains a significant challenge that needs to be addressed. Photodynamic therapy (PDT) is a non-invasive cancer treatment that utilizes photosensitizers (PS) to generate reactive oxygen species (ROS) under light irradiation, selectively killing tumor cells, but PDT still faces challenges such as limited therapeutic efficacy. To address challenge in cancer treatment, light-activated prodrugs have emerged as a promising strategy to achieve precise drug release and activation through light control in terms of time and location. This review explores the classification and mechanisms of light-activated prodrugs, with a focus on covalent and non-covalent photosensitizer-drug conjugates. These approaches enhance targeting, precisely control drug release, and achieve synergistic effects between PDT and chemotherapy. By analyzing these strategies, we highlight their potential in improving PDT efficacy and advancing targeted cancer therapy. Finally, we discuss future directions for designing advanced light-activated prodrug systems, providing new insights for the development of more effective and targeted cancer treatments.