Gastric synovial sarcoma (GSS) is an exceptionally rare mesenchymal malignancy, with only 51 cases reported. We present a case of a man in his 50s with dyspeptic symptoms and epigastric pain. Gastroscopy revealed an ulcerous tumour below the gastro-oesophageal junction. Histology, immunohistochemistry and molecular analysis confirmed SS18::SSX1 fusion, diagnostic of synovial sarcoma. The patient underwent successful robot-assisted partial gastric resection with negative margins. No recurrence was noted at 6-month follow-up. This case underscores the diagnostic challenge of GSS, the critical role of molecular techniques and the efficacy of minimally invasive surgical management.

One of the most prevalent oral cancers, oral squamous cell carcinoma (OSCC), is distinguished by its rapid growth, invasiveness, and high metastatic potential. Green AgNPs are important because they can reduce systemic toxicity by inducing oxidative stress, cytotoxicity, and apoptosis in cancer cells. The goal of this study was to use saponins as natural stabilizers to create AgNPs, and the detrimental apoptotic effects on cancer cells were examined using high-content screening (HCS) assays such as TNI, CMP, and VCC.

HPV types 16 and 18 are associated with 70% of invasive cervical cancers. Between these two types of HPV, HPV type 16 is more commonly found in cervical cancer patients, whereas HPV type 18 is less frequently reported. Currently, the molecular mechanism underlying the increased cancer risk in HPV type 16, compared to HPV type 18, has not yet been fully elucidated.

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies worldwide. The long non-coding RNA MEG3 functions as a tumor suppressor in several cancers, potentially influencing gene expression through transcriptional, translational, and epigenetic mechanisms. let-7i plays a role in leukemia progression. This study aimed to evaluate MEG3 gene expression in adult ALL patients and investigate its possible regulatory interaction with let-7i-3p and let-7i-5p.

This study aimed to create a genetic and clinical roadmap for the TGF-β pathway in an Iraqi population, focusing on the TGF-β1 (+869 C/T) polymorphism.

Lymphoma is the most common hematologic malignancy in Thailand, with diffuse large B-cell lymphoma (DLBCL) being the predominant subtype. Early prognostic indicators are essential for guiding clinical decisions. Genetic alterations, particularly in regulatory regions, may serve as potential biomarkers. This study investigated sequence alterations upstream of exon 1 of the OSBPL10 gene and their clinical relevance in a Northern Thai DLBCL population.

A key element of computational drug discovery is the precise prediction of drug-gene interactions, particularly when working with intricate biological systems where relational dependencies are essential. Because biological networks are graph-structured, traditional machine learning techniques frequently fall short. Graph Neural Networks (GNNs) have emerged as a viable approach for learning meaningful representations from this data type in response to this challenge. In this study, three state-of-the-art GNN architectures Graph Convolutional Networks (GCN), Graph Attention Networks (GAT), and GraphSAGE are comprehensively compared using a bipartite graph constructed from drug-target biochemical activity data.

The present study was planned to examine the possible association of polymorphisms in the superoxide dismutase and catalase genes with adverse normal tissue effects or injury resulting from radiotherapy in HNC patients.

The aim of the study was to determine how the chemotherapeutic alkylating agent dacarbazine, together with the application of the miR-204-5p mimic in vivo, affects the presence of disseminated melanoma cells in distant organs - the lungs and liver.

Brain metastases arise from the spread of cancer cells from tumors residing outside the brain. Immunotherapy and molecularly targeted therapeutics have improved outcomes for some patients with brain metastases, but many patients are still faced with a dismal prognosis. The inability to effectively treat these tumors and improve patient survival highlights the dire need for improved therapeutic strategies that ultimately depend on developing a greater understanding of the molecular underpinnings and inner wiring of these tumors. In this Review, we discuss current and emerging insights into the genetics and cellular signaling pathways that contribute to the spread of tumors to the brain. We also discuss potential therapeutic targets in the metabolic vulnerabilities of cells that metastasize to the brain and in the interactions between metastases and the microenvironment.

Life-prolonging targeted therapies are available based on alterations detected on next-generation sequencing (NGS); however, clinical data on NGS adoption are limited.

Role of environmental fungi and Aspergillus fumigatus in respiratory diseases remains evident; however, its contribution to directly influencing lung cancer progression remains obscure. In this study, we investigated the effect of Aspergillus fumigatus extract (AFE) on the development of tumor-promoting characteristics in human lung cancer cell lines. The organism was distinguished based on Lactophenol Cotton Blue staining and further distinguished with protein expression patterns via SDS-PAGE and BCA analysis. A549 and H1299 lung adenocarcinoma human cell lines were challenged with AFE, and various cellular responses were monitored simultaneously for cell viability, proliferative activity, inflammatory gene expression, DNA damage expression, and migratory responses. AFE caused increased cell viability and exhibited cellular characteristics of highly proliferating cells with significant expression of Cyclin D1 and c-MYC. Highly inflammatory gene expression responses and protein expressions of AKT, ERK1/2, and NF-κB signaling pathways were noticed at both the gene and protein expression levels with NF-κB nuclear translocation verified with confocal microscopy studies. DNA damage expression markers like γ-H2AX, p-ATM, and p53 significantly contributed with observable genomic DNA cleavage. Additionally, AFE-exposed cells exhibited faster wound closure and expression of Epithelial-mesenchymal transition-associated factors contributing to cell migration and therapeutic efficacy of this combined approach needs further investigation and development into a targeting therapeutic agent against lung cancer.

CD8+ T cell-mediated immune escape is a key mechanism in tumor progression. GPC3 has an impact on the progression of various tumors. However, its potential function and regulatory mechanism in the immune escape of gastric cancer (GC) are still unclear. GC clinical samples were collected to assess the expression of GPC3. The impact of GPC3 on GC prognosis was analyzed by bioinformatics analysis. CCK-8, colony formation, flow cytometry, and Transwell were utilized to detect changes in GC cell viability, proliferation, antiapoptosis, migration, and invasion ability. According to bioinformatics analysis, the linkage between N6 m6A modification, protein interactions, ubiquitination, and transcriptional regulation was revealed. The m6A modification effect of YTHDF1 on GPC3 was verified through MeRIP, RIP, RNA-pull-down assays, and multiribosome experiments. CO-IP and immunofluorescence were undertaken to validate the interaction between GPC3 and MUL1. The effect of GPC3 and MUL1 on HSF1 ubiquitination was assessed by the in vitro ubiquitination assay. Moreover, the transcriptional activation effect of HSF1 on CD276 was examined through ChIP and dual luciferase experiments. We constructed a co-culture system of tumor cells and CD8+T cells, detected CD8+T cell proliferation using CFSE, assessed cell toxicity using LDH, and evaluated the cytotoxicity of CD8+T cells by detecting the secretion of killing factors using ELISA. Finally, an allograft mouse model was constructed to validate the therapeutic effect of targeting GPC3 and CD276 monoclonal antibodies. Combining bioinformatics analysis, clinical sample testing, and cell experiments, it was confirmed that GPC3 was highly upregulated in GC, boosting malignant progression such as GC cell viability, proliferation, and antiapoptosis, and affecting the poor prognosis of GC. Mechanistically, YTHDF1 mediated m6A methylation to reinforce GPC3 translation. GPC3 interacted with MUL1 to repress ubiquitination degradation of HSF1, and HSF1 enhanced transcriptional activation of the immune checkpoint CD276. GPC3 depressed the antitumor activity of CD8+T cells through the MUL1/HSF1/CD276 axis, mediating GC tumor immune escape. YTHDF1 upregulates the expression of GPC3 in GC in an m6A-dependent manner. GPC3 interacts with MUL1 to depress the ubiquitination degradation of HSF1, thereby upregulating the immune checkpoint CD276 and affecting GC immune escape.

NEAT1 (Nuclear-Enriched Abundant Transcript1) is a long non-coding RNA (lncRNA) that critically regulates tumorigenesis, with growing recognition of its potential as a therapeutic target. However, most functional in vitro studies of lncRNAs rely on 2D cell culture systems, which lack the architectural and physiological complexity of tumors. Here, we demonstrate that 3D tumor architecture reshapes lncRNA-driven oncogenic programs. In 3D tumoroids, microenvironmental features such as mechanical cues, cell-cell interactions, and metabolic gradients modulate NEAT1 expression, and function. Using GBM as a proof-of-concept, we show that these context-dependent changes influence stemness, invasion, and EMT pathways. NEAT1 expression was significantly elevated in 3D tumoroids and positively correlated with stemness, invasion, glucose transporter expression, and epithelial-mesenchymal transition (EMT), both at the mRNA and functional levels. siRNA-mediated NEAT1 downregulation in 3D tumoroids to levels comparable to 2D culture, reduced the expression of these cancer-associated markers and suppressed proliferation, migration, and invasion, establishing a causal relationship. To establish broader relevance, we further examined NEAT1 and another oncogenic lncRNA, MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript (1) expression levels across breast, cervical, GBM, liver, and lung cancer models observing consistent expression differences. Collectively, our findings highlight the importance of evaluating the role of lncRNAs in physiologically relevant 3D systems.

IntroductionCurrent cervical cancer screening guidelines recommend colposcopy referral for women co-positive for high-risk human papillomavirus (hrHPV) and abnormal cytology (≥ASC-US). However, cytology exhibits suboptimal sensitivity, and this strategy leads to high colposcopy burdens, especially in populations where non-HPV16/18 genotypes predominate. We evaluated a novel triage strategy using HPV16/18 genotyping and PAX1 methylation to optimize resource allocation.MethodsThis was a retrospective cohort study. In a cohort of 3,233 hrHPV-positive women who underwent HPV genotyping, liquid-based cytology (TCT), PAX1 methylation testing, colposcopy, and histopathological confirmation, we compared two strategies: (A) standard referral (hrHPV+ & TCT ≥ ASC-US); (B) novel referral (HPV16/18+ → immediate colposcopy; non-16/18 hrHPV+ → colposcopy if PAX1 methylation ΔCt ≤ 8.79). CIN3+ (CIN3 or cancer) served as the clinical endpoint.ResultsNon-16/18 hrHPV types (especially HPV52/58) accounted for over 30% of infections and 60% of CIN2+ lesions. PAX1 methylation was strongly associated with lesion severity (median ΔCt: chronic cervicitis 17.92 vs. CIN3 7.36 vs. cancer 5.97; P < 0.001) and predicted CIN3+ with high accuracy (AUC = 0.82 in non-16/18 group). Strategy B detected 40 additional CIN3+ cases (+30.5%), reduced colposcopy referrals by 853 cases (absolute -25%, relative -46%), and increased the positive predictive value (PPV) from 6.6% to 14.6% (2.2-fold improvement) compared to Strategy A.ConclusionA triage algorithm combining HPV16/18 genotyping with PAX1 methylation significantly enhances CIN3+ detection while substantially reducing immediate colposcopies. This strategy is particularly well-suited for Chinese and other Asian populations where non-16/18 hrHPV types are prevalent, offering a more precise, cost-effective approach toward WHO's 2030 cervical cancer elimination goals.

Although cisplatin (CDDP) is widely employed in combination immunotherapy, no CDDP-based regimen has shown a survival benefit when treating the ovarian cancers. This is mainly because the impact of CDDP on immunotherapy is not fully understood. A critical gap concerns how CDDP reshape the tumour microenvironment, especially through extracellular vesicles (EVs)-mediated communication. In this work, using human and murine ovarian cancer cells as a model, we demonstrate that CDDP boosts the secretion of EVs from cancer cells, while exerting no such effect on non-cancerous cells. These CDDP-induced tumour-derived EVs, in turn, drive the differentiation of CD4+ T cells towards immunosuppressive regulatory T cells (Treg cells), which are known to limit the efficacy of immunotherapy. Based on next-generation sequencing, a significant enrichment of miR-181a-5p was identified in CDDP-induced tumour-derived EVs, and further functional studies confirmed that this microRNA promoted Treg cell differentiation via suppressing sirtuin 1 (SIRT1), a key regulator of the transcription factor forkhead box protein P3 (FOXP3). Importantly, inhibition of miR-181a-5p abrogated the Treg-promoting effect of CDDP-induced tumour-derived EVs, a finding further validated in vivo, where blockade of miR-181a-5p not only impaired Treg differentiation but also restored T-cell-mediated antitumour immunity and restrained tumour growth. Together, these findings uncover a previously unrecognised mechanism by which CDDP exacerbates immunosuppression via miR-181a-5p-enriched EVs and suggest that targeting this pathway could improve the therapeutic efficacy of combination immunotherapy in ovarian cancer.

To elucidate how ALX Homeobox 4 (ALX4) modulates cisplatin sensitivity via DNA damage regulation in breast cancer (BC), this study explored the established role of mRNA-mediated DNA repair in driving chemoresistance.

Spatial transcriptomics allows for the investigation of complex cellular ecosystems directly in their native tissues and enables the dissection of immune niches as spatially organized and functionally diverse microenvironments across homeostatic, inflammatory, and malignant settings. In this review, we examine how spatial transcriptomics tools have been applied to interrogate the cellular and molecular architecture of immune niches, including the emerging studies of B and T cell clonal niches. We focus on immune niches in intestinal and tumor tissues due to their importance to both health and pathology, discuss pressing immunological questions these technologies may help to address, and highlight future developments in the field.

Hepatocellular carcinoma (HCC) remains a major global health burden with limited therapeutic options and poor prognosis. PDRG1 is upregulated in several malignancies, yet its clinical relevance and mechanistic role in HCC are not fully understood. Here, we investigated the contribution of PDRG1 to HCC progression and delineated the underlying molecular mechanism. Using public datasets, patient specimens, in vitro functional assays, and subcutaneous xenograft models, we evaluated PDRG1 expression, biological functions, and downstream pathways. Transcriptome profiling, pathway enrichment analysis, rescue experiments, co-immunoprecipitation, and ChIP-qPCR were performed to define the PDRG1-EZH2-p21 axis. PDRG1 was significantly upregulated in HCC tumor tissues compared with adjacent non-tumor liver tissues and was associated with worse patient survival. Functionally, PDRG1 enhanced HCC cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. RNA-seq and enrichment analyses identified cellular senescence as a prominent downstream program regulated by PDRG1. Mechanistically, PDRG1 directly interacted with EZH2, increased H3K27me3 enrichment at the p21 promoter, and suppressed p21 transcription. Restoration of p21 expression attenuated the oncogenic effects of PDRG1, whereas EZH2 overexpression rescued the impaired malignant phenotypes caused by PDRG1 knockdown. Domain-mapping further indicated that the N-terminal residues 36-70 of PDRG1 contribute to its interaction with EZH2. Collectively, our findings identify PDRG1 as a clinically relevant oncogene in HCC and reveal an epigenetic mechanism by which PDRG1 cooperates with EZH2 to repress p21 and bypass senescence. The PDRG1-EZH2-p21 axis may represent a potential biomarker and therapeutic target for HCC.

Triple-negative breast cancer (TNBC), a distinct breast cancer subtype, poses significant challenges to conventional therapeutic approaches, and effective targeted therapies are limited. CRISPR/Cas9 library screening has demonstrated unprecedented efficiency and revolutionary potential in the identification of therapeutic targets. In this study, we performed In vivo CRISPR/Cas9 library screening and identified the E2 ubiquitin-conjugating enzyme UBE2L3 as a critical regulatory factor in the progression of TNBC. Loss of UBE2L3 restricted tumor cell growth by modulating autophagy in TNBC cells. Mechanistically, UBE2L3 downregulation led to increased tuberous sclerosis complex 2 (TSC2) expression, suppressing mTOR activity and altering autophagic processes in tumor cells. This regulation was mediated through the interaction between UBE2L3 and the E3 ubiquitin ligase SMURF2, which together control TSC2 protein ubiquitination and degradation. Autophagy and the tumor microenvironment are closely associated, and we observed that UBE2L3 knockdown in TNBC tumors significantly increased CD8+ T lymphocyte infiltration and enhanced tumor sensitivity to anti-PD-1 therapy. Collectively, our findings provide a theoretical foundation for considering UBE2L3 as a potential therapeutic target in TNBC.