Search Results (1,527)

Classical Hodgkin lymphoma (cHL) is a biologically and clinically unique malignancy characterized by rare Hodgkin and Reed–Sternberg (HRS) cells surrounded by a dense and diverse inflammatory infiltrate. These malignant cells actively reshape the tumor microenvironment (TME) through metabolic reprogramming and immune evasion strategies. This review synthesizes current knowledge on how metabolic alterations contribute to tumor survival, immune dysfunction, and therapeutic resistance in cHL. We discuss novel therapeutic approaches aimed at disrupting these processes and examine the potential of combining metabolic interventions with immune-based strategies—such as immune checkpoint inhibitors (CPIs), epigenetic modulators, bispecific antibodies, and CAR-T/CAR-NK cell therapies—which may help overcome resistance and enhance anti-tumor responses. Several agents are currently under investigation for their ability to modulate immune cell metabolism and restore effective immune surveillance. Altogether, targeting metabolic vulnerabilities within both tumor and immune compartments offers a promising, multifaceted strategy to improve clinical outcomes in patients with relapsed or refractory cHL. Full article

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article

Cinnamic acid, an organic acid naturally occurring in plants of the Cinnamomum genus, has been highly valued for its medicinal properties in numerous ancient Chinese texts. This article reviews the chemical composition, pharmacological effects, and various applications of cinnamic acid and its derivatives reported in publications from 2016 to 2025, and anticipates their potential in medical and industrial fields. This review evaluates studies in major scientific databases, including Web of Science, PubMed, and ScienceDirect, to ensure a comprehensive analysis of the therapeutic potential of cinnamic acid. Through systematic integration of existing knowledge, it has been revealed that cinnamic acid has a wide range of pharmacological activities, including anti-tumor, antibacterial, anti-inflammatory, antidepressant and hypoglycemic effects. Additionally, it has been shown to be effective against a variety of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and foodborne Pseudomonas. Cinnamic acid acts by disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, thereby demonstrating its ability to act as a natural antimicrobial agent. Its anti-inflammatory properties are demonstrated by improving oxidative stress and reducing inflammatory cell infiltration. Furthermore, cinnamic acid enhances metabolic health by improving glucose uptake and insulin sensitivity, showing promising results in improving metabolic health in patients with diabetes and its complications. This systematic approach highlights the need for further investigation of the mechanisms and safety of cinnamic acid to substantiate its use as a basis for new drug development. Particularly in the context of increasing antibiotic resistance and the search for sustainable, effective medical treatments, the study of cinnamic acid is notably significant and innovative. Full article

Candida albicans is a clinically important fungal pathogen capable of causing both superficial and systemic infections, particularly in immunocompromised individuals. A key factor contributing to its pathogenicity is its ability to form biofilms, structured microbial communities that confer significant resistance to conventional antifungal therapies. Addressing this challenge, we explored the antivirulence potential of acridine derivatives, a class of heterocyclic aromatic compounds known for their diverse biological activities, including antimicrobial, antitumor, and antiparasitic properties. In this study, a series of acridine derivatives was screened against C. albicans biofilms, revealing notable inhibitory activity and highlighting their potential as scaffolds for the development of novel antifungal agents. Among the tested compounds, acridine-4-carboxylic acid demonstrated the most promising activity, significantly inhibiting the biofilm formation at 10 µg/mL without affecting planktonic cell growth, and with a minimum inhibitory concentration (MIC) of 60 µg/mL. Furthermore, it attenuated filamentation and cell aggregation in a fluconazole-resistant C. albicans strain. Toxicity assessments using Caenorhabditis elegans and plant models supported its low-toxicity profile. These findings highlight the potential of acridine-based scaffolds, particularly acridine-4-carboxylic acid, as lead structures for the development of therapeutics targeting both fungal growth and biofilm formation in Candida albicans infections. Full article

Background: Gastric cancer (GC) is a malignant tumor of the gastrointestinal tract, characterized by high mortality rates and responsible for about one million new cases each year globally. Surgery is the main treatment, but achieving radical resection remains a relevant intraoperative challenge. Fluorescence-guided surgery offers clinicians greater capabilities for real-time detection of tumor nodules and visualization of tumor margins. In this field, the main challenge remains the development of fluorescent dyes that can selectively target tumor tissues. Methods: we examined the expression of the most suitable GC markers, including carcinoembryonic antigen cell adhesion molecule-5 (CEACAM5) and Claudin-4 (CLDN4), in GC cell lines. To further evaluate their expression, we performed immunohistochemistry (IHC) on tumor and healthy tissue samples from 30 GC patients who underwent partial gastrectomy at the Digestive System Surgery Unit, AOU Careggi, Florence. Additionally, we validated anti-CEACAM5 expression on patient-derived organoids. Furthermore, we developed a fluorescent molecule targeting CEACAM5 on the surface of GC cells and assessed its binding properties on patient tissue slices and fragments. Results: in this work, we first identified CEACAM5 as an optimal GC biomarker, and then we developed a fluorescent antibody specific for CEACAM5. We also evaluated its binding specificity for GC cell lines and patient-derived tumor tissue, achieving an optimal ability to discriminate tumor tissue from healthy mucosa. Conclusions: Overall, our results support the development of our fluorescent antibody as a promising tumor-specific imaging agent that, after further in vivo validation, could improve the accuracy of complete tumor resection. Full article

Hepatocellular carcinoma (HCC) remains a therapeutic challenge due to metabolic plasticity and drug resistance. Oncolytic viruses (OVs), such as thymidine kinase-deleted vaccinia virus (oncoVV), selectively lyse tumors while stimulating antitumor immunity, however, their metabolic interplay with cancer cells is poorly understood. Here, we engineered an oncoVV-expressing Aphrocallistes vastus lectin (oncoVV-AVL) and uncovered its unique ability to exploit the ACSS2/TFEB axis, driving metabolic competition in HCC. In vitro, oncoVV-AVL triggered cell autophagy and lipid accumulation (3.4–5.7-fold upregulation of FASN and ACC1) while suppressing glucose uptake (41–63% higher extracellular glucose and 33–34% reduced lactate). Mechanistically, oncoVV-AVL upregulated acetyl-CoA synthetase 2 (ACSS2), promoting its nuclear translocation and interaction with transcription factor EB (TFEB) to concurrently activate lipogenesis and autophagic flux. The pharmacological inhibition of ACSS2 abolished these effects, confirming its central role. In vivo, oncoVV-AVL suppressed tumor growth while inducing lipid deposition (2-fold triglyceride increase), systemic hypoglycemia (42% glucose reduction), and autophagy activation (elevated LC3B-II/I ratios). This study establishes ACSS2 as a metabolic checkpoint in OV therapy, providing a rationale for combining oncolytic virotherapy with metabolic modulators in HCC. Full article

Background: Mesenchymal stem cells (MSCs) possess an intrinsic tumor-tropic ability, and therefore, MSCs may potentially be used as biomimetic carriers for active drug delivery systems targeting tumors. We previously developed a method to efficiently load liposomes onto the surface of MSCs via electrostatic interactions. The prepared liposome-loaded MSCs (Lip-MSCs) spontaneously accumulated in solid melanoma tumors with low vascular permeability while stably carrying liposomes. Methods: To explore Lip-MSC applications in cancer chemotherapy, doxorubicin (DOX)-encapsulated liposomes (DOX-Lip) were prepared and loaded onto MSCs. The cell viability, DOX-releasing properties, tumor-homing capacity, and anti-tumor efficacy of DOX-Lip-MSCs were analyzed. Results: Small liposomes (100 nm) retained DOX, whereas significant leakage of DOX was observed from 600 nm-sized liposomes. Based on this result, we used 100 nm DOX-Lip for the preparation of DOX-Lip-MSCs. Compared with MSCs loaded with DOX by incubation with DOX solution, DOX-Lip-MSCs could load a larger amount of DOX with minimal cytotoxicity. DOX-Lip-MSCs also showed sustained DOX release. DOX-Lip-MSCs efficiently migrated toward the conditioned medium of B16/BL6 melanoma cells in vitro and accumulated in B16/BL6 tumors in vivo, leading to a significant inhibitory effect on tumor growth. Conclusions: Lip-MSCs can serve as an efficient carrier to deliver anti-cancer drugs into solid tumors. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

Physalis Alkekengi L. var. franchetii (Mast.) Makino (PAF), which is used in both food and medicine, has a long history of about 1800 years of application in China. There are many active constituents in the calyx of PAF. Physalins and physalins with a single oxygen bridge are the unique components of the PAF calyx. Physalins with multiple biological activities, including anticancer activity, antimicrobial activity, anti-inflammatory activity, etc., have been found. As such, physalins deserve to be studied further. In this study, we aimed to extract, separate, and identify the effective components of physalins from the calyx of PAF and investigate ability to inhibit the proliferation of tumor cell lines. Three new physalins, physalin VIII (1), 3α-hydroxy-2,3,25,27-tetrahydro-4,7-didehydro-7-deoxyneophysalin A (2), and physalin IX (3), along with three known compounds, physalin L (4), physalin D (5), and alkekengilin A (6) were isolated from PAF calyxes. Physalin D was superior to the positive control drug cisplatin in inhibiting the proliferation of five tumor cell lines. The physalin compounds exhibited potential antitumor activity, being deemed worthy of further research in the fields of antitumor drug development and the application in health foods. Full article

A young adult patient presented to the gastrointestinal outpatient department with a suspected hepatic tumor. The patient was in a traffic accident ten years ago and underwent splenectomy and distal pancreatectomy at another medical institution. The physical examination was unremarkable. The liver function tests and tumor markers were within normal limits, with the alpha-fetoprotein level at 1.38 ng/mL. Both hepatitis B surface antigen and anti-HCV were negative. Based on the clinical history, intrahepatic splenosis was suspected first. Dynamic computed tomography revealed a 2.3 cm lesion exhibiting suspicious early wash-in and early wash-out enhancement patterns. As previous studies have reported, this finding makes hepatocellular carcinoma and metastatic lesions the major differential diagnoses. For further evaluation, dynamic magnetic resonance imaging was performed, and similar enhancing features were observed, along with restricted diffusion. As hepatocellular carcinoma still could not be confidently ruled out, the patient underwent an ultrasound-guided biopsy. The diagnosis of intrahepatic splenosis was confirmed by the pathologic examination. Intrahepatic splenosis is a rare condition defined as an acquired autoimplantation of splenic tissue within the hepatic parenchyma. Diagnosis can be challenging due to its ability to mimic liver tumors in imaging studies. Therefore, in patients with a history of splenic trauma and/or splenectomy, a high index of suspicion and awareness is crucial for accurate diagnosis and for prevention of unnecessary surgeries or interventions. Full article

Despite significant advances in cancer therapy, the prognosis for patients with advanced, disseminated disease remains poor. This underscores the urgent need for novel treatments that not only eliminate tumor cells effectively but also stimulate a strong, durable anti-cancer immune response. Among emerging strategies, oncolytic viruses have shown exceptional promise due to their selective cytotoxicity and their ability to activate T cell-mediated immune responses. In this review, we focus on the vaccinia virus (VACV), a member of the Poxviridae family, which has emerged as a leading candidate in modern oncolytic immunotherapy. We examine the virus’s properties that enable it to evade antiviral defenses and serve as a versatile, potent oncolytic agent. Furthermore, we explore its interactions with various components of the immune system and how these contribute to the induction of a robust T cell-driven response. Finally, we assess current efforts to harness VACV for the treatment of various cancer types and highlight future directions where its application is most likely to succeed. Overall, our goal is to present VACV as a powerful and broadly applicable platform with the potential to transform the landscape of oncology. Full article

Background: The mechanisms underlying the metastasis of non-small-cell lung cancer (NSCLC) have long been a focal point of medical research. The anti-tumor effects of chelerythrine (CHE) have been confirmed; however, its ability to inhibit tumor metastasis and the underlying mechanisms remain unknown. The aim of this study was to investigate the inhibitory effects and molecular mechanisms of CHE on transforming growth factor-beta (TGF-β)-induced epithelial–mesenchymal transition (EMT). Methods: Wound healing and Transwell assays were employed to evaluate TGF-β-induced migration in A549 cells and the inhibitory effects of CHE. Ribonucleotide reductase subunit M2 (RRM2) expression levels were detected via Western blot and immunofluorescence staining. Western blot and RT-qPCR were used to examine the expression levels of EMT-related markers. Animal experiments were conducted to analyze the role of RRM2 in the CHE inhibition of TGF-β-induced lung cancer metastasis. Results: This study found that TGF-β treatment enhanced the metastasis of A549 cells, while CHE inhibited the expression of TGF-β-induced EMT-related transcription factors by RRM2, thereby suppressing tumor cell migration (p < 0.05). Furthermore, the oral administration of CHE inhibited the metastasis of A549 cells to the lungs from the tail vein in mice, consistent with in vitro findings. Despite the high doses of CHE used, there was no evidence of toxicity. Conclusions: Our data reveal the mechanism of the anti-metastatic effects of CHE on TGF-β-induced EMT and indicate that CHE can be used as an effective anti-tumor treatment. Full article

Salmonella therapies are a promising tool for the treatment of solid tumors. Salmonella can be engineered to increase their tumor infiltration, cell killing abilities, and immunostimulatory properties. However, bacterial therapies have often failed in clinical trials due to poor characterization. Mathematical models are useful for predicting the immune response to cancer treatments and characterizing the properties of bacterial invasion. Herein we develop an ordinary differential equation-based model that combines bacterial therapies with classical anti-tumor immunotherapies. Our modeling results suggest that increasing bacterial localization to the tumor is key for therapeutic efficacy; however, increased intracellular invasion and direct bacterial mediated cytotoxicity does not reduce tumor growth. Further, the model suggests that enhancing T cell-mediated cell death by both bacterial stimulation of pro-inflammatory cytokines and activation of T cells via antigen cascade is critical for therapeutic efficacy. A balance of intracellular and extracellular Salmonella leads to more effective therapeutic response, which suggests a strategy for strain design to be tested in vivo. Overall, this model provides a system to predict which engineered features of Salmonella therapies lead to effective treatment outcomes. Full article

Glioblastoma (GBM) is the most common malignant brain tumor, with a poor prognosis and low survival. Its treatment includes complete surgical resection followed by radiotherapy combined with temozolomide (TMZ). GBM contains glial stem cells (GSCs), which contribute to tumor progression, invasiveness, and drug resistance. The histone deacetylase (HDAC) inhibitor valproic acid (VA) has been shown to be a potent antitumor and cytostatic agent. In this study, we tested the effects of VA on glioma cell proliferation, migration, and apoptosis using T98G monolayer and spheroid cells. T98G and U-87MG glioblastoma cell viability was determined by MTT. Cell cycle and ROS levels were analyzed by flow cytometry, and gene and protein levels were detected, respectively, by RT-PCR and immunoblotting. VA reduces cell viability in 2D and 3D T98G and U-87MG cells and blocks the cell cycle at the G0/G1 with decreased levels of cyclin D1. VA addresses apoptosis and ROS production. In addition, VA significantly decreases the mRNA levels of the mesenchymal markers, and it counteracts cell migration, also decreasing MMP2. The results confirm the inhibitory effect of VA on the growth of the T98G and U-87MG cell lines and its ability to counteract migration in both 2D and 3D cellular models. Full article