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Ginsenoside RD2 inhibits gastric cancer progression by suppressing TRIM46-mediated DUSP1 ubiquitination and modulating the ERK signaling pathway.2 weeks agoGinsenoside RD2, a bioactive compound derived from ginseng, has been shown to possess various biological activities, including potential anti-cancer effects. However, its therapeutic efficacy and molecular mechanisms, particularly in gastric cancer (GC), remain inadequately understood.
The impact of RD2 on GC cells' malignant behavior, epithelial-mesenchymal transition (EMT), and tumor growth in vivo were analyzed in vitro and in vivo. Hub genes were identified using bioinformatics analysis of the Cancer Genome Atlas (TCGA)-Stomach Adenocarcinoma (STAD) dataset and RNA sequencing (RNA-Seq) analysis of AGS cells treated with 80 μM RD2. After treating cells with RD2, cell viability, colony formation, and transwell assays were carried out to assess the functions of TRIM46 and DUSP1 in mediating the effects of RD2.
In a dose-dependent fashion, RD2 dramatically reduced the proliferation, migration, and invasion of GC cells. RD2 treatment reduced the expression of N-cadherin, Vimentin, and Snail and increased that of E-cadherin. Gene expression analysis showed that six key genes (MUC1, MMP9, COL18A1, GPC1, TRIM46, JUP) were downregulated by RD2. In addition, RD2 decreased TRIM46 expression and increased DUSP1 levels, suggesting a potential association with ERK signaling. TRIM46 overexpression reversed the inhibitory effect of RD2 on GC progression, while DUSP1 overexpression counteracted the effects of TRIM46 on EMT and cell viability.
Our results suggest RD2 inhibits GC progression through modulation of TRIM46 and DUSP1, with potential involvement of ERK signaling. TRIM46 promotes GC cell growth and EMT, while DUSP1 overexpression counteracts these effects, highlighting the potential therapeutic target of RD2 in GC treatment.CancerCare/Management -
A Potential miR-1246-5p-H3K27ac-NOL12 Regulatory Axis and Its Putative Tumour-Promoting Function in Hepatocellular Carcinoma.2 weeks agoHepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Although the nucleolar protein NOL12 has been implicated in HCC progression, its comprehensive expression patterns, clinical significance and regulation-particularly the potential involvement of miR-1246-5p and H3K27ac-are not fully understood, warranting further investigation. To analyse the expression pattern and clinical significance of NOL12, we integrated bulk RNA sequencing (bulk RNA-seq) data (4264 HCC cases vs. 3145 non-HCC cases), single-cell RNA sequencing (scRNA-seq) data (12 HCC samples) and spatial transcriptomics (ST) data from public databases including GEO, TCGA and GTEx. This integration was combined with in-house immunohistochemistry (IHC) data from 394 pairs of HCC tissues and adjacent non-tumour tissues. CRISPR screening was used to assess the effect of NOL12 depletion on HCC cell proliferation. Seven immune infiltration analysis methods (including CIBERSORT) were applied to the TCGA-GTEx dataset to explore the association between NOL12 and the tumour immune microenvironment (TME). Gene ontology (GO) enrichment, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway and Gene Set Enrichment Analysis (GSEA) were performed based on NOL12-associated genes involved in HCC initiation and progression. Additionally, chromatin immunoprecipitation sequencing (ChIP-seq) data from Cistrome DB were used to predict and construct the miR-1246-5p-enhancer-NOL12 regulatory network. Potential high-affinity drug molecules targeting NOL12 were screened via the Cancer Therapeutics Response Portal (CTRP) database and molecular docking. Multi-dimensional analysis revealed significant upregulation of NOL12 in HCC (SMD = 0.64, 95% CI: 0.42-0.85; sROC AUC = 0.79). IHC validation confirmed higher NOL12 expression in HCC tissues (p < 0.0001, ROC AUC = 0.665). CRISPR screening showed that NOL12 depletion inhibited HCC cell proliferation. Mechanistically, NOL12 was enriched in the spliceosome pathway. ChIP-seq identified an H3K27ac-modified enhancer in the NOL12 promoter overlapping with miR-1246-5p binding sites, and miR-1246-5p expression positively correlated with NOL12 (r = 0.43, p = 0.018). Drug sensitivity prediction analysis showed that NOL12 protein exhibited significant sensitivity to BRD-K71781559, MST-312, IU1, BRD9876 and PRL-3 inhibitor I, with favourable binding energies. NOL12 may be regulated by the putative miR-1246-5p/H3K27ac enhancer axis and promotes HCC progression through the spliceosome pathway, supporting its potential as a novel therapeutic target for HCC.CancerCare/ManagementPolicy
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Niclosamide ethanolamine induces malignant phyllodes tumor cell death via mTOR-TFEB axis-mediated lysosomal biogenesis and functional uncoupling.2 weeks agoBreast malignant phyllodes tumor (MPT) is a fibroepithelial neoplasm characterized by high recurrence rates. Currently, no effective therapeutic agents are available, and surgery remains the mainstay of treatment for MPT. Niclosamide ethanolamine (NEN), an antiparasitic agent, has recently demonstrated broad-spectrum antitumor activity against various solid malignancies. This study aimed to evaluate the antitumor efficacy of NEN against MPT and elucidate the underlying molecular mechanisms. The effects of NEN on MPT cell proliferation and migration were assessed using CCK-8, wound healing, and Transwell migration assays. Ultrastructural alterations following NEN treatment were examined by transmission electron microscopy. Bioinformatics analyses, quantitative real-time PCR (qPCR), Western blotting, and immunofluorescence staining were employed to investigate the molecular mechanisms underlying NEN-mediated modulation of autophagy and lysosomal function. NEN significantly inhibited MPT cell proliferation and migration. Transmission electron microscopy revealed the accumulation of numerous autolysosomal structures in NEN-treated cells. Mechanistically, NEN suppressed mTOR phosphorylation, promoted nuclear translocation of transcription factor EB (TFEB), and induced lysosomal biogenesis. However, lysosomal function was compromised, as evidenced by elevated luminal pH, impaired cathepsin D maturation, and lysosomal membrane permeabilization, ultimately resulting in autophagic flux blockade at the degradation stage. Furthermore, lysosomal cathepsin leakage activated the mitochondrial apoptotic pathway, culminating in caspase-3-dependent apoptosis. NEN effectively kills MPT cells by inducing "lysosomal biogenesis-function uncoupling." This study is the first to reveal a novel anti-MPT mechanism that targets the mTOR-TFEB-lysosome axis and disrupts lysosomal homeostasis, providing a potential drug candidate for the treatment of MPT.CancerCare/Management
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Menopause and Endometriosis - Symptoms and Risk of Malignant Transformation: A Systematic Review of the Literature.2 weeks agoTo review the evidence concerning the clinical presentation of endometriosis in postmenopausal women and the associated risk of malignant transformation.
This systematic review was conducted following the PRISMA 2020 guidelines and prospectively registered with PROSPERO (CRD420251025035). The study research was conducted across three databases: MEDLINE/PubMed, Scopus, and the Cochrane Library. Only studies published in English were considered, and publications prior to 2000 were excluded from the review.
Two authors independently screened all records. Studies were selected if they included postmenopausal women with endometriosis and reported data on clinical symptoms or malignant transformation of endometriotic lesions. We included 32 articles, comprising case-control studies, cohort studies, case series, and cross-sectional studies, encompassing 30 895 women with histologically confirmed endometriosis.
Six studies provided information on the clinical manifestations, with 55.7% of women experiencing no symptoms. Among symptomatic women, pelvic or abdominal pain was the most common. Malignant transformation of endometrioma into ovarian cancer was reported in 29 articles, with 821 ovarian cancer cases identified. Ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) were the most common histological subtypes related to endometriosis. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) Critical Appraisal Tools.
Most postmenopausal women with endometriosis are asymptomatic; however, a small subset may have ectopic implants that remain biologically active and progress to malignant precursor forms. Postmenopausal endometriosis appears to confer an increased risk of ovarian carcinoma, particularly OCCC and OEC. Therefore, clinicians should consider this diagnosis and ensure an appropriate assessment for malignancy.CancerCare/Management -
Decoding osteosarcoma pathogenesis: the pivotal influence of m6A modification.2 weeks agoOsteosarcoma (OS) is the predominant primary malignant bone tumor in children and adolescents. Current treatments mainly include surgical resection combined with chemotherapy, but they still cannot effectively control tumor metastasis and recurrence, and may pose a risk of long-term complications. N6-methyladenosine (m6A) is the most widespread internal modification. It orchestrates various biological and disease-related events via the reversible m6A machinery comprising writers, erasers and readers. As a key epigenetic regulatory mechanism, m6A modification opens new avenues for deeper exploration of OS mechanisms and for developing new therapeutic targets and biomarkers. In this manuscript, we systematically explore the critical roles of m6A in OS cell proliferation, metastasis, metabolic reprogramming, programmed cell death, and tumor microenvironment regulation. Our aim is to provide a robust theoretical framework to underpin future basic studies and clinical applications in this field.CancerCare/ManagementPolicy
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Pearls & Oy-sters: Acute Cerebral Occlusion due to Parosteal Osteosarcoma Embolus.2 weeks agoTumor embolism is a rare cause of acute ischemic stroke. We present a case of a 46-year-old man with a history of distal femoral amputation 11 years prior due to parosteal osteosarcoma who developed acute onset left-sided weakness. Computed tomography (CT) angiography revealed occlusion of the right middle cerebral artery (MCA). Mechanical thrombectomy achieved recanalization and retrieved a white, gelatinous embolus. Histopathologic examination revealed atypical pleomorphic tumor cells. Immunohistochemistry demonstrated strong positivity for SATB2 and SOX9, positivity for CDK4, and a Ki-67 proliferation index of approximately 10%-20%. Fluorescence in situ hybridization (FISH) confirmed amplification of the MDM2 gene, supporting the diagnosis of metastatic dedifferentiated parosteal osteosarcoma. Postoperative MRI revealed infarcts in the right basal ganglia and temporal lobe, while chest CT showed bilateral pulmonary metastases. Transthoracic echocardiography identified a mass on the cardiac valve. This case illustrates an exceptionally rare clinical course in which a low-grade bone tumor underwent dedifferentiation after long-term survival and subsequently developed cardiopulmonary metastases. Tumor fragments arising from the valvular lesion likely entered the systemic circulation and embolized to the cerebral arteries, resulting in right MCA occlusion. Mechanical thrombectomy was pivotal not only for restoring cerebral perfusion but also for obtaining tissue for definitive histopathologic diagnosis.CancerCardiovascular diseasesCare/Management
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LC-MS/MS-Based Phytochemical Characterization of Cakile maritima Methanol Extract and Its Photodynamic Anticancer Activity in Gastric Cancer Cells.2 weeks agoIn this study, the phytochemical composition, in vitro anticancer activity, photodynamic therapy (PDT) activity, and molecular interaction potential with carbonic anhydrase IX (CA IX) of Cakile maritima methanol extract were evaluated.
LC-MS/MS analysis identified 11 compounds among 35 screened phytochemicals, with fumaric acid (13797.19 ppb), ferulic acid (771.37 ppb) and p-coumaric acid (601.95 ppb) accounting for approximately 97% of the total content. Molecular docking results demonstrated that sinapic acid (-6.13 kcal/mol) and quinic acid (-6.11 kcal/mol) exhibited the highest binding affinities toward CA IX. Cell culture studies revealed that LogIC50 values differed significantly among cell lines (p < 0.0001). PDT applied to the MKN-28 gastric cancer cell line significantly enhanced cytotoxicity compared with the control group, with the highest photodynamic efficacy observed under green-light irradiation (p < 0.0001).
These findings indicate that C. maritima methanol extract exhibits light-enhanced cytotoxicity in MKN-28 gastric cancer cells and warrant further investigation regarding its potential photosensitising properties.CancerCare/Management -
Multiturn Large Language Model-Based Conversational Agents for Patients With Cancer and Caregivers: Scoping Review.2 weeks agoLarge language model (LLM)-based conversational agents are increasingly used in health care, yet their capacity to support genuine multiturn dialogue remains underexplored. In oncology, where patients and caregivers experience complex informational and emotional needs throughout the disease trajectory, conversational agents may support information provision, symptom consultation, and emotional assistance. However, research specifically examining multiturn conversational agents designed for patients with cancer and informal caregivers remains limited.
This scoping review aimed to map the research landscape of LLM-based multiturn conversational chatbots developed for patients with cancer and informal caregivers, focusing on system design, intervention purposes, evaluation approaches, safety considerations, and transparency of LLM-related components.
This scoping review followed the Joanna Briggs Institute methodology and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Six databases-PubMed, Embase, Scopus, Web of Science, CINAHL, and PsycINFO-were searched for studies published between January 2022 and January 2026, with supplementary searches conducted in IEEE Xplore Digital Library and ACM Digital Library in May 2026. Studies were included if they described LLM-based chatbots designed for patients with cancer or informal caregivers that supported multiturn conversational interaction. Two reviewers independently conducted the study selection and data extraction.
Eight studies met the inclusion criteria. Most studies focused on prototype development, with limited research evaluating clinical outcomes. ChatGPT-based models were the most commonly used LLMs, and retrieval-augmented generation techniques were applied in several studies. Chatbots were primarily designed for emotional support or information provision. Evaluation approaches varied widely, including response quality, psychological outcomes, and user experience. However, no studies evaluated interaction-level characteristics such as conversational continuity or context retention, and only 2 studies reported any conversational memory mechanism. Reporting on safety risks, mitigation strategies, prompt design, model parameters, and adherence to LLM reporting guidelines was often limited or absent.
This scoping review identified only 8 studies on LLM-based multiturn conversational chatbots for patients with cancer and informal caregivers. The field remains at an early stage, characterized by prototype-oriented development, heterogeneous design and evaluation approaches, and inconsistent safety and transparency reporting. Future development should prioritize genuine conversational capability, safety management, and transparent reporting.CancerCare/Management -
A Supervised Fine-Tuned Large Language Model for Lifestyle Management in Patients With Prostate Cancer: Development and Evaluation Study.2 weeks agoLifestyle interventions for patients with prostate cancer have been shown to improve treatment adherence and quality of life. However, there remains a lack of large language models (LLMs) capable of delivering individualized and professional lifestyle recommendations under clearly defined medical safety boundaries and controlled evidence sources.
This study aimed to develop and evaluate a supervised fine-tuned LLM-PCaPLMM_SFT (Prostate Cancer Patient Lifestyle Management Model via Supervised Fine-Tuning)-to support health literacy improvement and lifestyle self-management among patients with prostate cancer.
We searched English-language literature primarily from PubMed (February 2015 to February 2025) to build a structured lifestyle management knowledge base covering diet, physical activity, weight management, medication adherence, and psychological support. We used a retrieval-augmented generation pipeline to generate patient-style question-answer (QA) pairs from retrieved knowledge slices. Bilingual English-Chinese QA data were generated from English-language source evidence through patient-oriented reformulation and retrieval-augmented generation-based answer generation, and independent English and Chinese test sets were constructed to assess bilingual QA performance. We trained Baichuan2-7B-Chat using a 2-stage strategy, consisting of continued pretraining, followed by supervised fine-tuning with low-rank adaptation. Model outputs were evaluated in 2 double-blind rounds by referee LLMs (Qwen3-Max and DeepSeek-R1) and compared with GPT-3.5-Turbo and the base Baichuan2-7B-Chat using 2500 queries across 5 lifestyle scenarios. Additionally, 3 domain experts conducted a blinded review of 50 QA samples (10 per scenario). We used the Mann-Whitney U test with effect size r, and Benjamini-Hochberg false discovery rate correction, and examined consistency using intraclass correlation coefficients.
Based on 2211 included publications, we constructed the PCaPLMM_SFT-Train dataset. The knowledge base yielded >150,000 structured knowledge slices. After 2 rounds of review, we obtained 42,330 single-turn QA pairs and 3008 multiturn dialogues, and the supervised fine-tuning phase used 45,338 structured QA samples. In the dual-round referee LLM assessment, PCaPLMM_SFT consistently outperformed Baichuan2-7B-Chat across dimensions and showed comparable or superior performance to GPT-3.5-Turbo across 5 lifestyle scenarios. Consistency analyses indicated moderate to good agreement between referee models across rounds, supporting the robustness of the comparative evaluation.
PCaPLMM_SFT demonstrates the feasibility of constructing a medical lifestyle-focused LLM by integrating structured medical knowledge, QA-style training data, and a multilayer evaluation system. This framework provides a reproducible methodological foundation for evidence-based health education and lifestyle management and establishes groundwork for future evaluation in real-world health management settings.CancerCare/ManagementAdvocacyEducation -
Pediatric Uveal Melanoma Masquerading as Vitreous Hemorrhage: A Case Report.2 weeks agoThis case is among the first reported instances of pediatric uveal melanoma masquerading as vitreous hemorrhage on ophthalmologic examination as well as on computed tomography and magnetic resonance imaging, illustrating how reliance on imaging alone can delay diagnosis when fundus visualization is obscured. A 10-year-old girl presented with unilateral vision loss; initial imaging suggested serous retinal detachment with vitreous hemorrhage, but persistent clinical suspicion for melanoma versus retinoblastoma prompted referral to a tertiary ocular oncology service, where magnetic resonance imaging revealed a gadolinium-enhancing intraocular mass. Enucleation was performed, and pathology confirmed spindle cell uveal melanoma (pT4aNxM0). Genetic and molecular testing showed low baseline metastatic risk despite large tumor size. The key takeaway is that persistent clinical suspicion, even when contradicted by initial radiologic interpretation, is essential in atypical pediatric presentations of intraocular hemorrhage, and multidisciplinary reevaluation can be diagnostic.CancerCare/Management