The advent of tissue engineering and biomedical techniques has significantly advanced the development of three-dimensional (3D) cell culture systems, particularly tumor organoids. These self-assembled 3D cell clusters closely replicate the histopathological, genetic, and phenotypic characteristics of primary tissues, making them invaluable tools in cancer research and drug screening.

This review addresses the challenges in developing in vitro models that accurately reflect tumor heterogeneity and explores the application of tumor organoids in cancer research, with a specific focus on the screening of natural products for antitumor therapies.

This review synthesizes information from major databases, including Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, Google Scholar, Scopus, PubMed and Springer Link. Publications were selected without date restrictions, using terms such as 'organoid', 'natural product', 'pharmacological', 'extract', 'nanomaterial' and 'traditional uses'. Articles related to agriculture, ecology, synthetic work or published in languages other than English were excluded.

The review identifies key challenges related to the efficiency and variability of organoid generation and discusses ongoing efforts to enhance their predictive capabilities in drug screening and personalized medicine. Recent studies utilizing patient-derived organoid models for natural compound screening are highlighted, demonstrating the potential of these models in developing new classes of anticancer agents. The integration of natural products with patient-derived organoid models presents a promising approach for discovering novel anticancer compounds and elucidating their mechanisms of action.

Glioblastoma remain one of the deadliest malignant tumors in the central nervous system, largely due to their aggressiveness, high degree of heterogeneity, and the protective barrier of the blood-brain barrier (BBB). Conventional therapies including surgery, chemotherapy and radiotherapy often fail to improve patient prognosis due to limited drug penetration and non-specific toxicity. We then present recent advances in biomimetic nanodelivery systems, focusing on cell membrane coatings, nanoenzymes, and exosome-based carriers. By mimicking endogenous biological functions, these systems demonstrate improved immune evasion, enhanced BBB traversal, and selective drug release within the tumor microenvironment. Nevertheless, we acknowledge unresolved bottlenecks related to large-scale production, stability, and the intricacies of regulatory compliance. Looking forward, we propose an interdisciplinary roadmap that combines materials engineering, cellular biology, and clinical expertise. Through this collaborative approach, this work aims to optimize biomimetic nanodelivery for glioma therapy and ultimately improve patient outcomes.

Radioresistance presents a substantial obstacle to achieving optimal therapeutic outcomes for breast cancer treatment. In this study, we develop a cancer cell membrane (CM) - coated nanozyme system (MPPC@CM), specifically designed for radioimmunotherapy to address this issue. This innovative system involves the in situ reduction of platinum and palladium on mesoporous silica nanospheres, followed by functionalization with cinnamaldehyde via surface grafting. The CM coating endows the nanozyme with enhanced tumor-specific targeting capability due to its homing properties. Upon uptake by tumor cells, MPPC@CM catalytically generates O2 from H2O2, mitigating the hypoxic tumor microenvironment and reducing radioresistance.     The intracellular glutathione depletion mediated by Michael addition reactions concurrently disrupts endogenous antioxidant defenses against reactive oxygen species (ROS). This redox imbalance is synergistically amplified through nanozyme-mediated catalytic activities including both peroxidase-like and oxidase-like functions. The resultant massive ROS accumulation establishes a self-reinforcing oxidative cascade that ultimately induces functional inactivation of glutathione peroxidase 4. The immunosuppressive environment is remodeled by this disturbance in redox balance, which accelerates ferroptosis and increases CD8+ T-cell infiltration and dendritic cell maturation. Overall, this cell membrane-camouflaged nanozyme holds significant potential to enhance the efficacy of radioimmunotherapy.

Inflammatory mammary carcinoma (IMC) is the most aggressive variant of invasive mammary tumours in dogs and in women. Decorin is an extracellular matrix molecule whose expression can be reduced or absent in various human cancers, which is associated with a poor prognosis. E-cadherin is a cell adhesion protein whose expression is reduced in several neoplasms. However, it is overexpressed in inflammatory breast cancers of women. EGFR is also associated with cancer development and is commonly overexpressed in aggressive neoplasms. This study aimed to characterise the expressions of Decorin, E-cadherin, and EGFR in canine inflammatory and non-inflammatory mammary carcinomas (IMC and non-IMC) and to evaluate their expression levels as prognostic indicators for survival and occurrence of metastases. Thirty-three IMC and 43 non-IMC cases were analysed retrospectively and submitted to immunohistochemical analysis. The reactions were quantified in five high-power field images from areas of the highest intensity and frequency of immunostaining (hot spots). We found significantly lower expression of Decorin and higher of E-cadherin and EGFR in canine IMCs. Patients with tumours that exhibited Decorin expression in less than 26.35% of epithelial cells had shorter survival (p = 0.0410) and a higher occurrence of distant metastases (p = 0.0115). E-cadherin is overexpressed in canine IMCs (p < 0.0001), similar to what occurs in women, reinforcing that dogs can be used as a study model for human IMC. EGFR overexpression in canine IMCs (p = 0.0322) provides evidence for potential targeted therapy with tyrosine kinase inhibitors.

Cervical squamous cell carcinoma (CESC), one of the most common malignancies in women, imposes a significant burden on women's health worldwide. Despite extensive research, the molecular and pathogenic mechanisms of cervical squamous cell carcinoma and CESC remain unclear. This study aimed to explore the immune-related genes, immune microenvironment infiltration, and prognosis of CESC, providing a theoretical basis for guiding clinical treatment. Initially, by mining four gene sets and immune-related gene sets from public databases, 14 immune-related genes associated with CESC were identified. Through univariate and multivariate COX regression analyses, as well as lasso regression analysis, four CESC-independent prognostic genes were identified, and a prognostic model was constructed, dividing them into high and low-risk groups. The correlation between these genes and immune cells and immune functions were explored through ssGSEA enrichment analysis, revealing a close association between the high-risk group and processes such as angiogenesis and epithelial-mesenchymal transition. Furthermore, using public databases and qRT-PCR experiments, significant differences in CXCL8 expression between normal cervical cells and cervical cancer cells were discovered. Subsequently, a CXCL8 knockdown plasmid was constructed, and the efficiency of CXCL8 knockdown was validated in two CESC cell lines, MEG-01 and HCE-1. Through CCK-8, scratch, and Transwell assays, it was confirmed that CXCL8 knockdown could inhibit the proliferation, invasion, and migration abilities of CESC cells. Targeting CXCL8 holds promise for personalized therapy for CESC, providing a strong theoretical basis for achieving clinical translation.

Mounting evidence underscores the prevalent hierarchical organization of cancer tissues. At the foundation of this hierarchy reside cancer stem cells, a subset of cells endowed with the pivotal role of engendering the entire cancer tissue through cell differentiation. In recent times, substantial attention has been directed toward the phenomenon of cancer cell plasticity, where the dynamic interconversion between cancer stem cells and nonstem cancer cells has garnered significant interest. Since the task of detecting cancer cell plasticity from empirical data remains a formidable challenge, we propose a Bayesian statistical framework designed to infer phenotypic plasticity within cancer cells, utilizing temporal data on cancer stem cell proportions. Our approach is grounded in a stochastic model, adept at capturing the dynamic behaviors of cells. Leveraging Bayesian analysis, we scrutinize the moment equation governing cancer stem cell proportions, derived from the Kolmogorov forward equation of our stochastic model. Our methodology introduces an improved Euler method for parameter estimation within nonlinear ordinary differential equation models, also extending insights to compositional data. Extensive simulations robustly validate the efficacy of our proposed method. To further corroborate our findings, we apply our approach to analyze published data from SW620 colon cancer cell lines. Our results harmonize with in situ experiments, thereby reinforcing the utility of our method in discerning and quantifying phenotypic plasticity within cancer cells.

Bacterial extracellular vesicles (BEVs) have emerged as pivotal mediators of host-microbe interactions, profoundly influencing cancer biology. These nanoscale vesicles, produced by both Gram-positive and Gram-negative bacteria, carry diverse biomolecular cargo such as proteins, lipids, nucleic acids, and metabolites. BEVs play dualistic roles in tumor promotion and suppression by modulating the tumor microenvironment, immune responses, and genetic regulation. This review synthesizes the current understanding of BEVs in various cancers, including gastrointestinal, ovarian, breast, lung, brain, and renal malignancies. BEVs are highlighted for their potential as diagnostic biomarkers, prognostic indicators, and therapeutic agents, including their applications in immunotherapy and advanced engineering for precision medicine. Challenges such as heterogeneity, standardization, and clinical scalability are critically analyzed, with case examples providing actionable insights. Future directions emphasize interdisciplinary collaborations, emerging technologies, and the integration of BEV-based tools into clinical workflows. This review underscores the transformative potential of BEVs in advancing cancer diagnostics and therapeutics, paving the way for innovations in precision oncology.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with poor response to conventional treatments such as surgery, chemotherapy and radiotherapy. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of HNSCC, but many patients still exhibit poor responses due to insufficient T cell infiltration and impaired dendritic cell (DC) function within the tumor microenvironment. DCs are crucial for initiating anti-tumor immune responses, but their dysfunction in HNSCC leads to inadequate T cell activation and immune evasion. DC-based immunotherapy offers a promising approach to enhance ICIs therapy efficacy by improving DC function and enhancing T cell-mediated anti-tumor immune response. This review discusses the mechanisms underlying DC dysfunction in HNSCC, recent advances in DC-based immunotherapy, and the potential for combination therapies to overcome resistance to ICIs. Future strategies should focus on optimizing DC vaccines and developing personalized treatments to improve outcomes for HNSCC patients.

Prostate cancer (PCa) is a leading cause of cancer-related mortality among men worldwide. Despite progress in the understanding of tumor biology, the prognosis for advanced prostate cancer remains poor, necessitating the identification of novel diagnostic, prognostic, and therapeutic biomarkers. Methuosis, a recently identified form of programmed cell death (PCD), is characterized by cytoplasmic vacuole accumulation and subsequent cell rupture, distinct from classical apoptosis and necrosis. The key regulatory gene in Methuosis, ARF6 (ADP-ribosylation factor 6), has emerged as a potential marker for cancer diagnosis and treatment. However, its role in prostate cancer and other malignancies remains insufficiently understood.

In this study, we performed a comprehensive pan-cancer multi-omics analysis to investigate the role of ARF6 in Methuosis across multiple cancer types, with a specific focus on PCa as the primary context. Using data from public databases, including RNA sequencing, gene expression profiling, and clinical outcomes, we assessed the association between ARF6 expression and patient prognosis in PCa within this broader pan-cancer framework. Additionally, we employed functional enrichment analyses and survival analysis to explore the potential of ARF6 as a diagnostic and prognostic marker for prostate cancer. Immunotherapy-related gene expression signatures were also evaluated to determine the therapeutic relevance of ARF6.

ARF6 was significantly overexpressed in PCa tissues compared to normal tissues and was associated with poor prognosis (p < 0.05), particularly in advanced and metastatic stages. Receiver operating characteristic (ROC) analysis revealed a diagnostic AUC of 0.792 for ARF6. Functional analyses indicated that ARF6 regulates pathways critical to cell migration, invasion, and drug resistance. Moreover, ARF6 expression showed a strong negative correlation with immune checkpoint markers, such as PD-L1 (r = - 0.74), suggesting its potential as an immunotherapy target. These findings underscore ARF6's pivotal role in Methuosis and its promise as a biomarker in PCa.

ARF6 is a key regulator of Methuosis in prostate cancer, contributing to tumor progression, metastasis, and resistance to treatment. Our findings support the potential of ARF6 as a diagnostic, prognostic, and immunotherapeutic target in prostate cancer. Further experimental validation is needed to confirm these observations and to explore the therapeutic implications of targeting ARF6 in cancer treatment.

Basal cell carcinoma (BCC) is the most common type of malignant skin tumour, and its incidence is increasing worldwide. While it grows slowly, BCC is locally invasive, causing significant tissue damage. This study investigated the role of mRNAs in BCC through bioinformatics and experimental validation to elucidate the molecular mechanisms involved.

Differentially expressed genes (DEGs) were identified from the transcriptome data of 30 BCC patients and 16 controls from the GSE7553, GSE103439, and GSE42109 datasets. Gene Ontology and KEGG analyses were performed to explore gene expression and pathways. A protein‒protein interaction (PPI) network was constructed to identify hub genes, and immune cell infiltration was analysed to study the tumour microenvironment. The diagnostic potential of target genes (LEF1, LGR5, and SOX4) was assessed using ROC curves. Gene expression was validated with qPCR and Western blotting.

A total of 135 DEGs were identified, with 9 hub genes selected. LEF1, LGR5, and SOX4 showed strong diagnostic potential, with AUC values of 0.888, 0.955, and 0.996, respectively. The immune cell analysis revealed increased numbers of B cells, NK cells, and T cells in BCC, whereas the numbers of DCs, pDCs, and Treg cells were reduced. qPCR and Western blotting confirmed increased LEF1 and LGR5 expression in BCC. SOX4 expression was increased according to the qPCR results but was not significantly elevated according to the Western blot results, warranting further validation.

LEF1, LGR5, and SOX4 may play roles in BCC pathogenesis and could serve as diagnostic biomarkers. These findings provide insights into BCC development and support future research for improved detection and treatment.

Breast cancer ranks as the foremost cause of cancer-related mortality among women globally. Timely diagnosis stands as the most effective approach in mitigating breast cancer mortality rates. There exists a close relationship between immune processes and tumorigenesis. This study aims to elucidate the immune mechanisms and potential biomarkers associated with breast cancer using bioinformatics techniques.

Initially, differentially expressed genes were identified through consensus analysis of invasive breast cancer (BRCA) samples sourced from The Cancer Genome Atlas (TCGA) database, focusing on immunotherapy response. Subsequently, protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to refine the selection of potential genes. Lastly, expression and prognostic analyses of hub genes were conducted to identify reliable key genes, with a focus on CCL19. Immunohistochemistry (IHC) was employed to assess the differential expression of CCL19 in both tumor and adjacent breast tissue samples. Additionally, protein correlation analysis, signaling pathway analysis, immune infiltration analysis, gene co-expression analysis, and drug sensitivity analysis of CCL19 were conducted to investigate its pathological clinical features and potential biological functions.

CCL19 expression exhibited a significant increase in breast cancer. Elevated CCL19 expression correlates with advanced tumor stage and indicates a favorable prognosis in breast cancer. CCL19 expression correlates with the abundance of diverse tumor-infiltrating immune cells (TIICs). CCL19 exhibits a positive correlation with the expression of the majority of immune-related genes. Enrichment analysis revealed the involvement of CCL19 in immune-related pathways and the PI3K-Akt signaling pathway. These findings suggest that CCL19 may influence breast cancer prognosis through immune infiltration. Patients exhibiting high CCL19 expression demonstrated more favorable responses to immunotherapy.

Breast cancer demonstrates overexpression of CCL19. CCL19 holds promise as a biomarker for forecasting breast cancer prognosis and as a potential therapeutic target.

Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant brain tumor, characterized by its heterogeneity and the presence of glioblastoma stem cells (GSCs). GSCs are a subpopulation of cells within the tumor that possess self-renewal and differentiation capabilities, contributing to tumor initiation, progression, and recurrence. This review explores the unique biological properties of GSCs, including their molecular markers, signalling pathways, and interactions with the tumor microenvironment. We discuss the mechanisms by which GSCs evade conventional therapies, such as enhanced DNA repair and metabolic plasticity, which complicate treatment outcomes. Furthermore, we highlight recent advancements in identifying novel biomarkers and therapeutic targets that may improve the efficacy of treatments aimed at GSCs. The potential of targeted therapies, including immunotherapy and combination strategies, is also examined to overcome the challenges posed by GSCs. Ultimately, a deeper understanding of GSC biology is essential for developing personalized treatment approaches that can enhance patient outcomes in glioblastoma.

Cuproptosis represents a novel mechanism of cellular demise characterized by the intracellular buildup of copper ions. Unlike other cell death mechanisms, its distinct process has drawn considerable interest for its promising applications in managing inflammatory bowel disease (IBD) and colorectal cancer (CRC). Emerging evidence indicates that copper metabolism and cuproptosis may exert dual regulatory effects within pathological cellular environments, specifically modulating oxidative stress responses, metabolic reprogramming, and immunotherapeutic efficacy. An appropriate level of copper may promote disease progression and exert synergistic effects, but exceeding a certain threshold, copper can inhibit disease development by inducing cuproptosis in pathological cells. This makes abnormal copper levels a potential new therapeutic target for IBD and CRC. This review emphasizes the dual function of copper metabolism and cuproptosis in the progression of IBD and CRC, while also exploring the potential application of copper-based therapies in disease treatment. The analysis further delineates the modulatory influence of tumor immune microenvironment on cuproptosis dynamics, while establishing the therapeutic potential of cuproptosis-targeted strategies in circumventing resistance to both conventional chemotherapeutic agents and emerging immunotherapies. This provides new research directions for the development of future cuproptosis inducers. Finally, this article discusses the latest advances in potential molecular targets of cuproptosis and their related genes in the treatment of IBD and CRC, highlighting future research priorities and unresolved issues.

The discovery of biomarkers for malignant tumors is driving the development of new radiopharmaceuticals in nuclear medicine. The development and optimization of novel radiopharmaceuticals to occupy an increasingly important role in tumor diagnosis and treatment. In recent years, fibroblast activation protein (FAP) has gained attention as a promising tumor target due to its widespread expression across various tumors. FAP inhibitor (FAPI) radiopharmaceuticals are considered to be the most promising to be developed for targeting FAP due to their rapid and specific tumor targeting. This review briefly outlines the developmental history of FAP-targeted small-molecule enzyme activity inhibitors, highlighting the effective role of targeting molecules, linkers, and certain functional groups in the delivery of radioisotopes to cancerous tissues. These development strategies will serve as a reference for the further development and application of relevant radiopharmaceuticals. This review also delineates the progress on clinical FAPI as a radioisotope delivery vehicle for the targeted radioligand therapy of tumors and introduces the latest combination therapy involving FAPI radiopharmaceutical for tumor treatment. The findings provide novel therapeutic insights into the targeted radioligand therapy of tumors.

T cells and their T cell receptors (TCRs) play crucial roles in the adaptive immune system's response against pathogens and tumors. However, immunosenescence, characterized by declining T cell function and quantity with age, significantly impairs antitumor immunity. Recent years have witnessed remarkable progress in T cell-based cancer treatments, driven by a deeper understanding of T cell biology and innovative screening technologies. This review comprehensively examines T cell maturation mechanisms, T cell-mediated antitumor responses, and the implications of thymic involution on T cell diversity and cancer prognosis. We discuss recent advances in adoptive T cell therapies, including tumor-infiltrating lymphocyte (TIL) therapy, engineered T cell receptor (TCR-T) therapy, and chimeric antigen receptor T cell (CAR-T) therapy. Notably, we highlight emerging DNA-encoded library technologies in mammalian cells for high-throughput screening of TCR-antigen interactions, which are revolutionizing the discovery of novel tumor antigens and optimization of TCR affinity. The review also explores strategies to overcome challenges in the solid tumor microenvironment and emerging approaches to enhance the efficacy of T cell therapy. As our understanding of T cell biology deepens and screening technologies advances, T cell-based immunotherapies show increasing promise for delivering durable clinical benefits to a broader patient population.

The prognostic significance of platelet-to-lymphocyte ratio (PLR) in non-muscle invasive bladder cancer (NMIBC) remains controversial despite numerous investigations. This study aimed to systematically evaluate the prognostic value of PLR in NMIBC.

An extensive systematic search was executed utilizing four major electronic databases: Embase, PubMed, Web of Science, and Cochrane Library. The prognostic significance of PLR was assessed using pooled hazard ratios (HRs) with 95% CIs. Forest plots were used to present data visualization and statistical summaries, illustrating the effects of individual studies and the reliability of the pooled results. Funnel plot analysis and Egger's test were employed to evaluate the potential presence of publication bias. Sensitivity analysis was performed to assess the robustness of the pooled findings. Subgroup analysis and meta-regression were used to identify sources of heterogeneity.

Eleven retrospective studies encomprising 3,566 patients met the inclusion criteria. Elevated PLR notably correlated with inferior progression-free survival (PFS) (HR=2.132, 95% CI: 1.146-3.967, p=0.017) and relapse-free survival (RFS) (HR=1.732, 95% CI: 1.174-2.554, p=0.006). No statistically meaningful correlation emerged in cancer-specific survival (CSS) (HR=1.218, 95% CI: 0.800-1.854, p=0.358) or overall survival (OS) (HR=1.350, 95% CI: 0.611-2.983, p=0.459). Publication bias was detected in RFS analyses (Egger's test, P=0.010). Sensitivity analysis demonstrated that the pooled results were robust. Subgroup analysis and meta-regression identified geographic differences and patient characteristics as key sources of heterogeneity in RFS outcomes. Subgroup analysis indicated that geographic differences and sample size were potential sources of heterogeneity in PFS results.

This study comprehensively analyzed 11 studies and 3,566 NMIBC cases and found that elevated PLR was significantly associated with poorer RFS and PFS, suggesting that PLR can be used as a prognostic biomarker for the management of NMIBC. The prognostic value of PLR may be related to immune regulation and inflammatory response in the tumor microenvironment; nevertheless, further studies are needed to elucidate its mechanism and establish its clinical application.

This study demonstrates that elevated PLR serves as an independent predictor of poor PFS and RFS in NMIBC patients. As a cost-effective biomarker, PLR shows promise in risk stratification and treatment planning. However, large-scale prospective studies are warranted to validate these findings and establish standardized cut-off values.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024621307 , identifier CRD42024621307.

Cancer is one of the leading causes of mortality worldwide. Nanomedicines have significantly improved life expectancy and survival rates for cancer patients in current standard care. However, recurrence of cancer due to metastasis remains a significant challenge. Vaccines can provide long-term protection and are ideal for preventing bacterial and viral infections. Cancer vaccines, however, have shown limited therapeutic efficacy and raised safety concerns despite extensive research. Cancer vaccines target and stimulate responses against tumor-specific antigens and have demonstrated great potential for cancer treatment in preclinical studies. However, tumor-associated immunosuppression and immune tolerance driven by immunoediting pose significant challenges for vaccine design. In situ vaccination represents an alternative approach to traditional cancer vaccines. This strategy involves the intratumoral administration of immunostimulants to modulate the growth and differentiation of innate immune cells, such as dendritic cells, macrophages, and neutrophils, and restore T-cell activity. Currently approved in situ vaccines, such as T-VEC, have demonstrated clinical promise, while ongoing clinical trials continue to explore novel strategies for broader efficacy. Despite these advancements, failures in vaccine research highlight the need to address tumor-associated immune suppression and immune escape mechanisms. In situ vaccination strategies combine innate and adaptive immune stimulation, leveraging tumor-associated antigens to activate dendritic cells and cross-prime CD8+ T cells. Various vaccine modalities, such as nucleotide-based vaccines (e.g., RNA and DNA vaccines), peptide-based vaccines, and cell-based vaccines (including dendritic, T-cell, and B-cell approaches), show significant potential. Plant-based viral approaches, including cowpea mosaic virus and Newcastle disease virus, further expand the toolkit for in situ vaccination. Therapeutic modalities such as chemotherapy, radiation, photodynamic therapy, photothermal therapy, and Checkpoint blockade inhibitors contribute to enhanced antigen presentation and immune activation. Adjuvants like CpG-ODN and PRR agonists further enhance immune modulation and vaccine efficacy. The advantages of in situ vaccination include patient specificity, personalization, minimized antigen immune escape, and reduced logistical costs. However, significant barriers such as tumor heterogeneity, immune evasion, and logistical challenges remain. This review explores strategies for developing potent cancer vaccines, examines ongoing clinical trials, evaluates immune stimulation methods, and discusses prospects for advancing in situ cancer vaccination.

Precise modulation of the cell cycle via electromagnetic (EM) control presents a groundbreaking approach for cancer therapy, especially in the development of personalized treatment strategies. EM fields can precisely regulate key cellular homeostatic mechanisms such as proliferation, apoptosis, and repair by finely tuning parameters like frequency, intensity, and duration. This review summarizes the mechanisms through which EM fields influence cancer cell dynamics, highlighting recent developments in high-throughput electromagnetic modulation platforms that facilitate precise cell cycle regulation. Additionally, the integration of electromagnetic modulation with emerging technologies such as artificial intelligence, immunotherapy, and nanotechnology is explored, collectively enhancing targeting precision, immune activation, and therapeutic efficacy. A systematic analysis of existing clinical studies indicates that EM modulation technology significantly overcomes key challenges such as tumor heterogeneity, microenvironment complexity, and treatment-related adverse effects. This review summarizes the prospects of electromagnetic modulation in clinical translation and future research directions, emphasizing its critical potential as a core element in individualized and multimodal cancer treatment strategies.

Head and neck cancer (HNC) is the sixth most prevalent malignancy worldwide and includes a variety of upper gastrointestinal abnormalities. HNC includes oral, throat, voice box, nasal cavity, paranasal sinuses, and salivary gland cancers. Squamous cells in the mouth, nose, and throat cause HNC. Drugs, alcohol, poor diets, smoking, and genetics all contribute to this condition. Cancer research has focused on three-dimensional (3D) models in HNC biology in recent decades. An adequate microenvironmental system and cancer cell culture are the initial steps to understanding cancer cells' complicated interactions with their surroundings. New 3D models claim to bridge in vivo and in vitro investigations and erase the gap. Interdisciplinary cell biology and tissue engineering researchers are creating 3D cancer tissue models to better understand the illness and develop more accurate cancer medicines. Tissue engineering researchers, who are always exploring novel approaches to treat cancer, have been able to include the third dimension into laboratory settings and mimic cell-to-cell and cell-to-matrix interactions by recreating the tumor microenvironment using 3D models and so make research on cancer easier. This review addresses recent developments in tissue engineering with an emphasis on 3D models in HNC.

The occurrence and death rates of primary hepatocellular carcinoma (HCC) are increasing, and there remains a shortage of effective oral medications with minimal side effects. We aim to identify potential biomarkers and compounds from Radix Astragali (RA) and Pueraria Mirifica (PM) to treat liver cancer and improve prognosis. Differentially expressed genes (DEGs) associated with HCC were identified by bioinformatics analysis of three datasets, GSE112791, GSE101685, and GSE45114. Using public databases to predict the bioactive components and possible targets of RA and PM. Target crossover from Gene Expression Omnibus (GEO) and public databases were used to identify potential biomarkers for HCC. Subsequently, validation and prognostic value analyses were performed using the Gene Expression Profile Interaction Analysis (GEPIA) platform. The Cytoscape software created a network of "compound targets" to pinpoint compounds linked to the biomarkers. Molecular docking techniques were utilized to validate the connection between these compounds and the identified biomarkers. Ultimately, the HepG2 liver cancer cell line was chosen to assess the inhibitory effect of Hederagenin (HDG) and to confirm the expression of ADH1B through Western blot analysis. In this study, four key biomarkers (NR1I2, ADH1B, NQO1, GHR) were identified. Molecular docking showed that these four core targets could form stable conformations with the corresponding compounds. As the drug concentration decreases, the inhibitory effect on HepG2 diminishes, and the survival rate of HepG2 cells significantly declines following the administration of 100 µmol/L HDG. Compared to the control, the expression of ADH1B protein is significantly increased in HepG2 cells treated with 100 µmol/L HDG. The study identified four key biomarkers (ADH1B, GHR, NQO1, NR1I2) that have prognostic ability for HCC. This study provides biomarkers and potential targeted monomeric medicines for treating HCC.

Traditional tumor treatments (surgery, radiotherapy, chemotherapy, etc.) have certain limitations and can have serious negative effects, such as difficulty in cutting out tumors, damage to normal tissues, and complications. Ordinary nanozymes have low catalytic activity and require higher doses for treatment, which can increase in vivo toxicity and side effects. To address these limitations, we developed a Ti3C2 MXene-based nanocomposite (Ti3C2/Cu(2- x )Se) integrating Cu(2- x )Se nanozymes with dual enzyme-mimicking activities (catalase and peroxidase) and MXene's photothermal properties. The Cu(2- x )Se component catalyzes the decomposition of tumor-overexpressed H2O2 into O2 and cytotoxic ·OH, alleviating hypoxia while inducing oxidative stress. Simultaneously, MXene's high surface area and photothermal capability enhance nanozyme stability, biocompatibility, and catalytic efficiency under near-infrared irradiation. Notably, the photothermal effect amplifies enzymatic activity, enabling synergistic nanocatalytic-photothermal therapy. This synergy not only degrades glutathione to suppress tumor antioxidant defenses but also achieves targeted tumor ablation with reduced dosage requirements. Our work highlights a rational design of MXene-based nanozymes for enhanced multimodal tumor therapy, offering a paradigm for nanocomposite-driven disease treatment.

SARIFA (Stroma AReactive Invasion Front Areas), defined as the direct contact between a tumour cell cluster and adipose cells at the invasion margin, has been proposed as a prognostic marker in gastrointestinal cancers. We hypothesized that SARIFA is associated with an immunosuppressive tumour microenvironment.

SARIFA status was evaluated in two large colorectal cancer cohorts (N = 1876). Survival analyses were performed using multivariable Cox regression. Immune cell densities were analysed utilizing multiplex and conventional immunohistochemistry combined with digital image analysis.

SARIFA-positivity was independently associated with a shorter cancer-specific survival in both cohorts [Cohort 1: hazard ratio (HR) for SARIFA-positive (vs. negative) 1.75 (95% CI 1.35-2.25), P < 0.0001; Cohort 2: HR for SARIFA-positive (vs. negative) 2.09 (95% CI 1.43-3.05), P = 0.0001]. SARIFA-positivity was associated with lower densities of CD3+ T cells, CD66b+ granulocytes, M1-like macrophages, and CD14+HLA-DR+ mature monocytic cells, but higher densities of M2-like macrophages and CD14+HLA-DR- immature monocytic cells. Mean Cohen's kappa for SARIFA evaluation between eight investigators was 0.80.

SARIFA status is a highly reproducible, independent prognostic factor in colorectal cancer. SARIFA-positivity is associated with lower densities of antitumourigenic immune cells and the polarisation of macrophages towards a protumourigenic M2-like phenotype.

Metastasis is one of the major challenges in the treatment of colorectal cancer (CRC), during which cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critically involved.

In this study, we aim to explore the regulatory role of extracellular nicotinamide phosphoribosyltransferase Visfatin and its impact on CRC metastasis.

To examine the effect of visfatin on CAFs, human CRC tissue-derived CAFs were exposed to visfatin, and the expression of inflammatory factors, activation of JAK-STAT pathway and production of ROS in CAFs were assessed. To examine the effect of visfatin-treated CAFs on CRC metastasis, human CRC cell line SW480 or SW620 were cultured with the conditioned medium derived from visfatin-treated CAFs, and the invasion and migration ability of SW480 or SW620 cells were evaluated by transwell migration and matrigel invasion assays.

Our previous study found that visfatin, a secreted form of nicotinamide phosphoribosyltransferase that governs the rate-limiting step of NAD synthesis, promoted CRC metastasis. However, little is known about the effect of visfatin on CAFs. The conditioned medium derived from visfatin- treated CAFs promotes the migratory and invasive capability of CRC cells, and enhance lung metastasis in mouse model. Visfatin treatment stimulated the expression of a couple of inflammatory factors in CAFs, which was mediated by visfatin-induced activation of JAK- STAT pathway and accumulation of ROS. Inhibition of JAK-STAT pathway or neutralization of cellular ROS attenuated visfatin-mediated migration and invasion of CRC cells.

The present work highlights a critical role of visfatin in the crosstalk between CRC cells and CAFs, which moonlight as a non-metabolic extracellular signal molecule to hijacks JAK-STAT pathway in CAFs to promote CRC metastasis.

Ion channels are proteins that regulate the flow of ions across cell membranes, playing a vital role in cervical cancer development and progression. These channels serve as both potential diagnostic markers and therapeutic targets, offering new opportunities for cancer treatment. Moreover, ion channels are crucial molecular indicators and possible therapeutic targets due to their role in the development of cervical cancer. Our review focuses on the various types of ion channels which are associated with cervical cancer (CCa), including sodium, calcium, and potassium channels. In our review, we clarify their diagnostic and prognostic value, as well as their relationship to the prognosis and stage of the disease. We also examine how ion channels contribute to the metastasis of cervical cancer, specifically in relation to their influence on cell motility, invasion, and interaction with the tumor microenvironment. By examining preclinical and clinical research involving ion channel blockers and modulators, we also highlight the therapeutic potential of targeting ion channels. We have demonstrated the available assays and imaging methods based on ion channel activity as examples of emerging diagnostic breakthroughs that show promise for enhancing the early detection of cervical cancer. Additionally, the possibility that ion channel modulator-based combination therapy could improve the efficacy of traditional treatments is investigated. To demonstrate the potential of ion channels in cervical cancer diagnosis and treatment, our review highlights the current challenges and the promising role in cervical cancer diagnostics and therapy.

As an important component in preventing the progression of endometrial cancer, CD8 T cells play a crucial role in this process and are important targets for immunotherapy. However, the status of CD8+ T cells in endometrial cancer and the key genes influencing their activation still remain to be elucidated.

Genes associated with the activation of CD8+ T cells were identified through differential analysis and weighted gene co-expression network analysis (WGCNA). A risk score model was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. The clinical characteristics and differences between the high-risk group and the low-risk group were explored, and the applicability of the model to chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors, and immune checkpoint inhibitors was evaluated. The characteristics of the model at the single-cell level were studied, and the tumor-suppressive effect of ASB2 was verified through experiments on endometrial cancer cells.

A risk model based on genes related to the activation of CD8+ T cells was constructed, and the prognostic differences were verified using the Kaplan-Meier curve. A nomogram was designed to predict the survival probability. Pathway analysis showed that it was related to metabolism and DNA repair. There were significant differences between the high-risk and low-risk groups in terms of tumor mutational burden (TMB), checkpoint molecules, and major histocompatibility complex (MHC) class I molecules, and they had different sensitivities to different therapies. The tumor-suppressive effect of ASB2 was confirmed in experiments on cell proliferation, invasion, and migration.

This study provides a predictive tool for endometrial cancer. The classification based on the status of CD8+ T cells can distinguish the prognosis and treatment response, highlighting the potential of this model in personalized treatment.

Background/Objectives: Colon adenocarcinoma (COAD), the most prevalent form of colorectal cancer, remains a leading cause of cancer-related mortality. Advances in various treatments for COAD have significantly improved treatment outcomes. However, therapeutic limitations persist, highlighting the need for personalized strategies driven by novel biomarkers. The aim was to identify key hub genes that could be potential biomarkers of COAD using comprehensive bioinformatic analyses. Methods: Differentially expressed genes (DEGs) and co-DEGs were identified from COAD gene expression datasets. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Hub genes were extracted from protein-protein interaction (PPI) networks and validated epigenetically using microRNA (miRNA) and DNA methylation datasets. Their expression patterns were further examined via single-cell RNA sequencing (scRNA-seq) and immune cell infiltration analysis. Prognostic relevance was assessed based on tumor metastasis and survival outcomes. Results: Gene expression profiling identified 118 co-DEGs, with GO and KEGG pathway analyses revealing significant pathway enrichment. PPI network analysis pinpointed 27 key co-DEGs. Epigenetic profiling indicated that both miRNA interference and DNA methylation regulate CLDN1, INHBA, and CXCL12 expression levels. scRNA-seq analysis showed elevated CLDN1 expression in epithelial cells and INHBA in myeloid cells, and reduced CXCL12 expression in stromal cells. Prognostic analysis further demonstrated that CLDN1 and INHBA are significantly associated with poor COAD outcomes. Conclusions: We identified some potential prognostic biomarkers for patients with COAD. Further experimental validation is required to translate these findings into precision medicine for COAD.

Lung adenocarcinoma (LUAD) is a prevalent and aggressive form of lung cancer with poor prognosis, largely due to late-stage diagnosis and limited therapeutic options. Recent studies suggest that long noncoding RNAs (lncRNAs) play critical roles in cancer progression and immune modulation, emerging as potential therapeutic targets. In this study, we investigated the expression and functional role of LINC00892 in LUAD using RNA sequencing data from The Cancer Genome Atlas (TCGA) and functional assays in vitro and in vivo. We found that LINC00892 is significantly downregulated in LUAD tissues compared to normal tissues, and lower LINC00892 expression correlates with poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI), particularly in younger patients and those with early-stage disease. Bioinformatic analyses revealed that LINC00892 expression is positively correlated with immune cell infiltration, including CD4+ and CD8+ T cells, and negatively correlated with tumor-promoting Th2 cells, suggesting its role in shaping the tumor immune microenvironment. In vitro functional assays showed that LINC00892 overexpression inhibits LUAD cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, LINC00892 upregulation was found to suppress epithelial-mesenchymal transition (EMT) by increasing E-cadherin expression and decreasing levels of N-cadherin, vimentin, and slug. Additionally, in an in vivo mouse xenograft model, LINC00892 overexpression suppressed tumor growth and metastasis, accompanied by enhanced immune cell infiltration such as CD4+ and CD8+ T cells. Collectively, these findings suggest that LINC00892 acts as a tumor suppressor in LUAD by modulating immune infiltration and EMT, highlighting its potential as a prognostic biomarker and therapeutic target.

Laryngeal cancer (LC) is a prevalent head and neck carcinoma. Extensive research has established a link between immune cells in the tumor microenvironment (TME) and cancer progression, as well as responses to immunotherapy. This study aims to develop a prognostic model based on immune cell-related genes and examine the TME in LC.

RNA-seq data for LC were sourced from The Cancer Genome Atlas (TCGA), and GSE27020 and GSE51985 datasets were retrieved from the Gene Expression Omnibus (GEO) database. Key genes were identified through the intersection of differentially expressed genes (DEGs) between normal and LC samples and module genes derived from weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. The prognostic risk model was constructed using univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Gene Set Variation Analysis (GSVA) was subsequently performed for hallmark and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses in high- and low-risk groups. Immune infiltration analysis between risk groups was conducted via Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and single sample gene set enrichment analysis (ssGSEA). Finally, the relationship between the risk model and immunotherapy response was explored.

A total of 124 key genes were identified through the overlap analysis, predominantly enriched in GO terms such as defense response to viruses and regulation of response to biotic stimuli, as well as KEGG pathways related to phagosome and Epstein-Barr virus infection. Machine learning indicated that the optimal prognostic model was constructed from two biomarkers, RENBP and OLR1. GSVA revealed that in the high-risk group, epithelial-mesenchymal transition and ECM-receptor interaction were the most significantly enriched pathways, while autoimmune thyroid disease, ribosome, and oxidative phosphorylation predominated in the low-risk group. Additionally, the stromal score was significantly higher in the high-risk group, while CD8+ T cells, cytolytic activity, inflammation promotion, and T cell co-stimulation were elevated in the low-risk group. Tumor Immune Dysfunction and Exclusion (TIDE) analysis showed higher TIDE and exclusion scores in the high-risk group, whereas the CD8 score was higher in the low-risk group. Finally, CD274 (PD-L1) expression was significantly elevated in the low-risk group.

This study identified two key prognostic biomarkers, RENBP and OLR1, and characterized TME differences across risk groups, offering novel insights into the diagnosis and treatment of LC.

Colorectal cancer (CRC), the third leading cause of cancer globally, with high mortality, necessitates more effective treatments and adjunct therapies. MicroRNAs (miRNAs), short non-coding RNAs, regulate gene expression. Food-derived active components have the potential to modulate CRC cellular processes, aiding in the prevention and management of CRC. This review explores the role of miRNAs in CRC and summarizes the anti-inflammatory, antioxidant, and pro-apoptotic effects of typical food bioactive components by modulating specific miRNAs. We investigate the potential and scientific basis of regulating miRNA expression through dietary therapy and preventive approaches, providing new directions for CRC treatment. Collectively, miRNAs regulate gene expression, impacting the onset, progression, metastasis, and treatment response of CRC. Food components such as curcumin and resveratrol modulate specific miRNAs, affecting CRC cell behavior. Bioactive food components influence CRC cell proliferation, apoptosis, and drug sensitivity by regulating key proteins and pathways.

Cancer, an important global health problem, is defined by aberrant cell proliferation and continues to be the main cause of death globally. The tumor microenvironment (TME) plays an essential role in the development of cancer, resistance to therapy, and regulation of the immune response. Some immune cells in the TME, like T cells, B cells, macrophages, dendritic cells, and natural killer cells, can either stop or help tumor growth, depending on how metabolic and cytokine changes happen. Cytokines function as essential signaling molecules that modulate immune cell metabolism, altering their functionality. This review focuses on how cytokine-mediated metabolic reprogramming affects the activity of immune cells inside the TME, which can either make the immune response stronger or weaker. New ways of treating cancer that focus on metabolic pathways and cytokine signaling, such as using IL (Interleukin) - 15, IL- 10, and IL- 4, show promise in boosting immune cell activity and making cancer treatments more effective. Finding these pathways could lead to new ways to treat cancer with immunotherapy that focus on metabolic competition and immune resistance in the TME.

Tumor metastasis involves the spread of tumor cells from the primary site to distant organs via the lymphatic system, blood vessels, and other pathways. It stands as a major contributor to cancer incidence and mortality. Laminin α5 (LMα5) is a member of the laminin family, which is widely expressed in various tumor tissues and is significantly associated with poor cancer prognosis. Laminin α5 plays an important role in cancer metastasis, serving as a key regulator in this process. LMα5 facilitates tumor metastasis through its interactions with various receptors, including integrins and Lutheran/basal cell adhesion molecules (Lu/BCAM). Moreover, it modulates the epithelial-mesenchymal transition (EMT) by influencing the Notch signaling pathway, thus regulating the invasive capabilities of tumor cells. By mediating the interplay between tumors and their microenvironment, LMα5 disrupts the adhesion of tumor cells to vascular endothelial cells, consequently reducing metastatic tumor growth. In this review, we have discussed the core mechanisms of action underlying the role of LMα5 in tumor metastasis and its therapeutic potential. By shedding light on novel therapeutic targets and treatment strategies, the aim is to combat cancer metastasis and improve the efficacy of cancer treatments.

Tumor metastasis is a significant contributor to increased cancer mortality. Transfer RNA-derived small RNAs (tsRNAs), a class of endogenous non-coding RNA molecules, play crucial functional roles in various physiological processes, including the regulation of transcription and reverse transcription, the modulation of translation processes, the modification of epigenetic inheritance, the regulation of the cell cycle, etc. Dysregulated tsRNAs are closely related to the occurrence and progression of human malignancies. Accumulating evidence indicates that the abnormal expression of tsRNAs is associated with tumor metastasis through a variety of mechanisms. Hence, we summarize the fundamental structure and biological functions of tsRNAs, with a focus on how tsRNAs influence the tumor metastasis process through downstream targets or the regulation of interactions between upstream and downstream molecules, thereby providing a novel perspective for targeted therapy for tumor metastasis.

Mitochondrial dysfunction has emerged as a critical factor in the progression and prognosis of low-grade glioma (LGG). In this study, we explored the role of mitochondrial-related genes through consensus clustering analysis using multi-omics data from the TCGA, CGGA, and other independent datasets. Patients were categorized into three clusters (Cluster A, B, and C), with Cluster B consistently associated with poorer prognosis. Mutation landscape analysis revealed distinct genetic alterations and copy number variations among clusters, particularly in Cluster B, which exhibited unique genetic signatures. Immune infiltration analysis showed that Cluster B had higher expression levels of immune checkpoint genes, stronger immune evasion activity, and greater immune cell infiltration, suggesting an immunosuppressive tumor microenvironment. Furthermore, we identified mitochondrial-related prognostic markers and developed a MITscore based on gene expression patterns, which stratified patients into high- and low-risk groups. High MITscore groups displayed stronger stemness characteristics, poorer survival outcomes, and differential responses to chemotherapy and immunotherapy. Cross-validation with drug sensitivity and immunotherapy cohorts indicated that high MITscore patients were more sensitive to certain chemotherapeutic agents and responded better to immunotherapy. Finally, using the SRGA method, we identified novel biomarkers (KDR, LRRK2, SQSTM1) closely associated with mitochondrial function, which may serve as potential targets for therapeutic intervention. These findings highlight the critical role of mitochondrial dysfunction in LGG prognosis, tumor microenvironment regulation, and treatment response, providing new avenues for precision oncology.

The tumor microenvironment (TME) is a highly complex and continuous evolving ecosystem, consisting of a diverse array of cellular and non-cellular components. Among these, benign non-immune cells, including cancer-associated fibroblasts (CAFs), adipocytes, endothelial cells (ECs), pericytes (PCs), Schwann cells (SCs) and others, are crucial factors for tumor development. Benign non-immune cells within the TME interact with both tumor cells and immune cells. These interactions contribute to tumor progression through both direct contact and indirect communication. Numerous studies have highlighted the role that benign non-immune cells exert on tumor progression and potential tumor-promoting mechanisms via multiple signaling pathways and factors. However, these benign non-immune cells may play different roles across cancer types. Therefore, it is important to understand the potential roles of benign non-immune cells within the TME based on tumor heterogeneity. A deep understanding allows us to develop novel cancer therapies by targeting these cells. In this review, we will introduce several types of benign non-immune cells that exert on different cancer types according to tumor heterogeneity and their roles in the TME.

This review delves into the pivotal role and intricate mechanisms of aerobic glycolysis in nasopharyngeal carcinoma (NPC). NPC, a malignancy originating from the nasopharyngeal epithelium, displays distinct geographical and clinical features. The article emphasizes the significance of aerobic glycolysis, a pivotal metabolic alteration in cancer cells, in NPC progression. Key enzymes such as hexokinase 2, lactate dehydrogenase A, phosphofructokinase 1, and pyruvate kinase M2 are discussed for their regulatory functions in NPC glycolysis through signaling pathways like PI3K/Akt and mTOR. Further, the article explores how oncogenic signaling pathways and transcription factors like c-Myc and HIF-1α modulate aerobic glycolysis, thereby affecting NPC's proliferation, invasion, metastasis, angiogenesis, and immune evasion. By elucidating these mechanisms, the review aims to advance research and clinical practice in NPC, informing the development of targeted therapeutic strategies that enhance treatment precision and reduce side effects. Overall, this review offers a broad understanding of the multifaceted role of aerobic glycolysis in NPC and its potential impact on therapeutic outcomes.

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivity to insulin. In many cases, it also inhibits the growth of cancer cell lines, like breast, gastric, lung, and prostate cancer. In melanoma, PPAR-γ regulates cell proliferation, differentiation, apoptosis, and survival. During tumorigenesis, it controls metabolic changes and the immunogenicity of stromal cells. PPAR-γ agonists can target hypoxia-induced angiogenesis in tumor therapy, but their effects on tumors can be suppressive or promotional, depending on the tumor environment. Published data show that PPAR-γ-targeting agents can be effective in specific groups of patients, but further studies are needed to understand lesser-known biological effects of PPAR-γ and address the existing safety concerns. This review provides a summary of the current understanding of PPAR-γ and its involvement in melanoma.

Regression is an immunological phenomenon described in cutaneous melanoma whereby tumor is replaced with tumor-infiltrating lymphocytes, granulation tissue, and mature fibroblasts often accompanied by pigment incontinence (accumulation of melanin in the upper dermis). Pigment incontinence results in grossly pigmented lesions that may be mistaken for viable tumor and has not been described in sinonasal mucosal melanoma (SNMM). This study investigates the presence of regression and pigment incontinence in patients with SNMM.

A retrospective chart review was conducted on SNMM patients from 2007 to 2023. Pathology slides from surgical resection were examined by two pathologists blinded to treatment information for the presence and extent of pigment-laden macrophages and other histopathologic features of regression.

Seventeen patients with SNMM were included in this study who underwent surgical resection. Three patients received neoadjuvant therapy followed by surgical resection. Regression was present in 94% of patients and pigment incontinence was present in 65% of patients and occurred in both neoadjuvant treated patients and treatment naïve patients. All three patients with neoadjuvant treatment had evidence of pigment incontinence.

This study highlights that SNMM often displays characteristics of regression. This study is one of the first to describe the presence of pigment incontinence in patients with SNMM. Pigment incontinence can be a part of the natural tumor life cycle and grossly pigmented lesions could easily be confused for melanoma especially after neoadjuvant therapy. Developing an understanding of regression and pigment incontinence within SNMM is important for diagnosis and clinical management.

4 Laryngoscope, 135:1321-1325, 2025.

Cancer, one of the world's deadliest diseases, is expected to claim an estimated 16 million lives by 2040. Three-dimensional (3D) models of cancer have become invaluable tools for the study of tumor biology and the development of new therapies. The tumor microenvironment (TME) is a determinant of tumor progression and has implications for clinical therapies. Cancer-associated fibroblasts (CAFs) are one of the most important components of the TME. Modeling the interactions between cancer cells and CAFs in vitro can help to create biomimetic tumor equivalents for elucidating the causes of cancer growth and assessing the effectiveness of therapies. Here, we are investigated the effect of the mutual arrangement of tumor cells and fibroblasts on the formation of tumor models and their biomimetic properties. Pancreatic tumor models of three different designs were formed by the bioprinting method. Gelatin-alginate hydrogels with and without PANC-1 (pancreatic cancer) and NIH/3 T3 (mouse fibroblasts) cells, as well as their homo- and heterospheroids, were used as bioink. To enable bioprinting, we have chosen the most suitable compositions of alginate and gelatin that provide both good printability and cell proliferation activity. We also have investigated the kinetics of spheroid formation to identify the optimal cultivation parameters for achieving spheroid sizes suitable for bioprinting. All tumor models remained viable for 3-4 weeks. At the same time, the patterns of model development in the cultivation process and the biomimetic properties of the final tissue-engineered structures depended on the model design.