Chordomas are low-grade but invasive tumors with limited therapies. Some conventional chordomas exhibit cartilage-like extracellular matrix (ECM). This study examined the expression and clinical significance of collagenases in chordomas.

Brachyury-positive primary chordoma tissues were analyzed by immunohistochemistry for matrix metalloproteinase (MMP)13, MMP9, and cathepsin K, and by immunofluorescence for MMP13 and MMP9. ECM phenotype was categorized using safranin-O staining, where safranin-O marks cartilage-like ECM. We compared MMP13 expression scores and progression-free survival (PFS) between safranin-O-negative and -positive groups. Collagenase gene expression and protein localization in JHC7 cells were analyzed by quantitative PCR and immunocytochemistry, respectively. Collagen digestion activity was evaluated using fluorescein isothiocyanate-labeled type II collagen (COL2) in the presence or absence of an MMP13-specific inhibitor. Cell growth was evaluated in the presence of type I collagen (COL1) or COL2.

Safranin-O negative chordomas had shorter PFS than safranin-O positive chordomas (p = 0.016). MMP13 was expressed in human chordoma tissues and JHC7 cells; the MMP13 expression score was higher in safranin-O-negative chordomas than in safranin-O-positive chordomas (p = 0.018). JHC7 cells digested COL2, and digestion was partially but significantly inhibited by an MMP13-specific inhibitor (p < 0.05). COL2 inhibited the growth of JHC7 cells more strongly than COL1 in a dose-dependent manner (p < 0.01).

MMP13 may promote aggressive behavior in chordoma by degrading growth-inhibitory COL2-rich ECM. These data support MMP13 as a potential unfavorable prognostic marker and therapeutic target in chordoma.

The pathogenesis of diffuse large B-cell lymphoma (DLBCL) remains unclear. Zinc finger protein 382 (ZNF382) expression is significantly downregulated in DLBCL, which is associated with poor prognosis. However, the underlying mechanisms remain unknown.

To investigate the association between DNA methylation of the promoter region of ZNF382 and ZNF382 expression with the occurrence and progression of DLBCL and to analyze the clinical significance of ZNF382 in DLBCL.

DLBCL cell lines and reactive hyperplastic lymph node tissues were used as the experimental subjects. Methylation-specific polymerase chain reaction and reverse-transcription polymerase chain reaction analyses revealed significantly higher methylation of the promoter region of ZNF382 (p < 0.0001), whereas ZNF382 mRNA expression was significantly lower (p < 0.01) in DLBCL cells compared with those in reactive hyperplastic lymph node tissues. Cells were treated with the demethylating agent decitabine (DAC), and the methylation status of the promoter and expression levels of ZNF382 were determined. ZNF382 promoter methylation was significantly reduced (p < 0.01) in DLBCL cells, whereas ZNF382 mRNA expression was significantly increased (p < 0.01) compared with those in the control cells. Furthermore, compared with that in the blank control group, the apoptosis rate of DLBCL cells was significantly increased following DAC intervention (p < 0.01). A cell model of ZNF382 overexpression was constructed, and its proliferation, migration, and clonogenic capacities were detected using CCK-8, Transwell, and soft agar assays, respectively. Compared with those of the vector control group, the cell proliferation, migration, and clone formation abilities of the ZNF382 overexpression group were significantly inhibited (p < 0.01).

DNA hypermethylation in the promoter region of ZNF382 and low ZNF382 mRNA expression are closely related to the occurrence and progression of DLBCL. Moreover, ZNF382 overexpression significantly increased apoptosis and inhibited cell proliferation, migration, and clone formation. Therefore, ZNF382 has potential as a therapeutic target in the treatment of DLBCL.

This review discusses neoplastic diseases in ferrets and rodents, highlighting common tumor types, clinical signs, diagnostics, and treatment options. It emphasizes the importance of imaging, cytology, and histopathology for accurate diagnosis, with surgery being the primary treatment. Chemotherapy and radiation are increasingly utilized, though the most recent research focuses on identifying new neoplasms rather than novel therapies. The article underscores ongoing progress in veterinary exotic companion mammal oncology, encouraging further research and reporting to improve diagnostic accuracy and treatment outcomes. Overall, the field is evolving, with future advancements expected in diagnostics and therapeutics for these popular exotic pets.

Given the rapid advancements in high-throughput technology, multi-omics data have become essential for identifying cancer subtypes and providing accurate medical treatments for patients. However, integrating multi-omics data and collecting patient information pose complex and challenging tasks. Although numerous integration techniques have emerged in recent years to address the challenges posed by heterogeneity and noise in omics data, most of these algorithms are based on unsupervised methods due to the lack of labeled data. This indicates there is still potential for enhancing the extraction of valuable information from omics data. This study introduces a novel framework, namely Deep Subspace Fusion based on Integrated Self-supervision (DSFIS), for the recognition of cancer subtypes. DSFIS is built on the autoencoder with a self-representation layer and guides the autoencoder to generate the most representative sample subspace structure by integrating self-supervision. This framework can not only create a comprehensive representation of the differences and similarities among patients but also more fully uncover the potential information from omics data. The DSFIS was compared to eight cutting-edge approaches for integrating multi-omics data. The experimental findings demonstrated that DSFIS effectively identified cancer subtypes according to the omics data. It achieved significant results superior to other algorithms in survival prognosis analysis and clinical correlation analysis, demonstrating that DSFIS has great potential in identifying cancer subtypes through multi-omics data.

Leptomeningeal metastasis (LM) is a fatal complication of advanced cancer with limited therapeutic options and poor prognosis. Immune checkpoint inhibitors (ICIs) have shown promise in systemic disease, but intrathecal ICIs efficacy and immunological impact in LM remain unclear. Cerebrospinal fluid (CSF) proteomics may provide a unique window into the CNS immune microenvironment and enable response prediction.

We enrolled 62 patients with LM who received intrathecal pemetrexed (InPe) with or without ICIs (InPe+programmed cell death protein-1 (PD-1), InPe+PD-1+cytotoxic T-lymphocyte associated protein 4 (CTLA-4), InPe+PD-1+vascular endothelial growth factor (VEGF)). Matched CSF (pretreatment and post-treatment) and pretreatment serum samples were collected for high-content proteomic profiling using the Olink platform. Differential expression, pathway enrichment, and machine learning-based modeling were applied to identify treatment-induced changes and predictive biomarkers.

Nearly half of the patients achieved clinical response. Post-treatment CSF showed enrichment of cytokine and chemokine signaling pathways, with a marked decrease in EGF. Adding PD-1 inhibitor restored immune cell function and upregulated interferon-γ. Compared with serum, CSF proteomic profiles provided superior predictive performance (area under the curve (AUC) 0.884 vs 0.780). A five-protein CSF signature (ADGRG1, CD28, CCL23, DCN, IL-15) achieved robust prediction (AUC 0.968 in InPe+PD-1 training cohort, 0.917 in InPe+PD-1+CTLA-4 validation cohort, and 1 in InPe+PD-1 subsequent validation cohort). ADGRG1 was significantly higher in non-responders at baseline (p=0.031) and decreased after treatment, and specific enrichment in dura-derived LM-associated macrophages, suggesting a macrophage-derived source and potential role in LM progression.

This study provides the first high-content proteomic atlas of intrathecal ICI therapy in LM, identifies intrathecal ICI therapy-specific immune remodeling in LM, and establishes a CSF-based predictive model with high accuracy. ADGRG1 represents a promising biomarker of treatment responsiveness and a potential mechanistic link between macrophage biology and LM progression.

Cancer poses a global challenge in diagnostics and therapeutics. Treatments like chemotherapy, radiotherapy, surgery, and immunotherapy have significantly decreased the fatality rate, but drug resistance, therapy side effects, and relapse remain as major concerns. Live biotherapeutics are microorganisms that can be developed as therapeutic agents to modulate cancer pathophysiology and aid in disease management. Live biotherapeutic products (LBPs) have the potential to suppress tumour growth, enhance the effectiveness of conventional therapies, and reduce treatment-related side effects. Dysbiosis in the gut and cancer-specific tissues is linked to cancers of the colon, stomach, pancreas, and liver. Live biotherapeutics aim either to re-establish microbial balance or to employ microbes directly as anticancer tools. Both native and engineered LBPs (bacteria and viruses) represent promising interventions that may form part of next-generation cancer treatment strategies. Their clinical application draws on the integration of microbiology, immunology, synthetic biology, and oncology. LBPs can be used to target cancer cells by delivering antitumour payloads such as immune modulators, toxins, exposing cancer antigens, and molecules for targeted killing. LBPs offer advantages such as reduced systemic toxicity, overcoming drug resistance, and synergy with chemo-, radio-, and immunotherapies. Despite challenges in safety, manufacturing, regulation, and personalization, advances in synthetic biology and omics are enabling precision approaches. Future innovations such as bacteriobots, biocontainment systems, and patient-specific microbiome integration highlight their potential as next-generation cancer therapeutics.

Radiation-induced salivary gland dysfunction (RSGD) is a common complication of radiotherapy in patients with head and neck cancers that leads to xerostomia and related oral complications. It reduces treatment tolerance and quality of life, while current clinical interventions only alleviate superficial symptoms and fail to restore salivary gland function. This highlights the necessity to explore the pathogenesis of RSGD and to identify targets; existing studies have focused on DNA damage, oxidative stress, and fibrosis, but lack insights into emerging mechanisms such as ferroptosis, and therapies require improvement.

Based on models of radiation-induced salivary gland injury, this review had two core tasks: 1) to systematically explore multi-dimensional injury mechanisms, including existing and latest findings, and 2) to summarize current RSGD-related clinical drug regimens and stem cell/exosome-mediated therapies. The aims were to clarify core molecular mechanisms and potential targets, provide theoretical/practical references for novel effective therapies, overcome limitations in symptomatic treatment, and provide insights into how to improve outcomes and quality of life for patients with RSGD.

Conventional tumor chemotherapy faces limitations including drug resistance, high toxicity, non-selectivity, and side effects. Nano-drug delivery systems (DDSs) demonstrate stronger efficacy via enhanced permeability and retention (EPR) effect in tumor vasculature. This review provides a comprehensive analysis of a promising solution: redox-responsive drug delivery systems engineered from biocompatible polysaccharides. It exclusively details how the distinct reductive (glutathione, GSH) and oxidative (reactive oxygen species, ROS) species within the tumor microenvironment (TME) can be exploited for triggered drug release. We systematically evaluate a wide range of responsive groups - from established and emerging linkages such as disulfides, diselenides, thioketals, arylboronates, Pt (IV)- and ferrocene-based structures - integrated with versatile polysaccharide carriers. This review critically examines how these designs not only facilitate selective drug release and activation within tumor site but also enable active targeting (for instance via CD44 receptors) and synergistic combination therapies including photodynamic therapy (PDT) and immunotherapy. Furthermore, we discuss the key challenges in clinical translation and offer a perspective on integrating artificial intelligence for the design of personalized nanomedicines. This review by combining design approaches, their efficacy, and limitations assist scientists to select the optimal polysaccharide and most effective redox-responsive group to maximize anticancer effect and minimize off-target effects.

Castleman's disease is a rare lymphoproliferative disorder with a variable presentation ranging from no clinical symptoms to fever and fatigue. We report a case of a male in his 30s who presented to the emergency department with non-specific symptoms, including fever, cough, diarrhoea, abdominal pain and findings of bloody mucus in his stool. Preoperative imaging using CT showed a hypervascular mass in the abdomen measuring 3.9 cm. Positron emission tomography with Gallium-68 DOTA-Tyr³-octreotate (DOTATATE) showed moderate radiotracer uptake, raising suspicion for a neuroendocrine tumour. Preoperative endoscopic ultrasound biopsy results showed a benign reactive lymph node. The patient's case was discussed at a multidisciplinary tumour board, where diagnostic/therapeutic resection was advised. Following resection of the mass, it was found to be an enlarged lymph node with histopathological features consistent with hyaline vascular Castleman's disease. The patient did not experience any complications, postoperative imaging was unremarkable, and he is being monitored closely for recurrence.

This case describes a presentation of a patient with clinical features of acromegaly, elevated growth hormone (GH) concentrations, a pituitary adenoma but with normal insulin-like growth factor-1 (IGF-1) concentrations in the context of previously undiagnosed liver cirrhosis. In this case, a diagnosis of acromegaly was made based on clinical grounds and failure of GH to suppress during oral glucose tolerance testing despite a normal IGF-1 screening test. Following liver transplantation, the patient's IGF-1 concentrations rose significantly in keeping with a diagnosis of active acromegaly. This case demonstrates the importance of history, physical examination and clinical judgement in the diagnosis of this rare disease. It also highlights the vital role played by the liver in the GH/IGF-1 axis.