The morbidity rate of primary cardiac tumors(PCTs)is only 0.0138%.[1]Calcified amorphous tumors(CATs)are a particularly rare entity with only a few cases reported in the literature,and account for only 2.47%of PCTs.[2...The morbidity rate of primary cardiac tumors(PCTs)is only 0.0138%.[1]Calcified amorphous tumors(CATs)are a particularly rare entity with only a few cases reported in the literature,and account for only 2.47%of PCTs.[2]CATs can occur at any age and have been identified at various intracardiac locations.The clinical manifestations of patients are related to the location and size of the lesion.展开更多
Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune check...Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.展开更多
Gastric cancer,including stomach tumors,poses significant health challenges due to late-stage diagnosis and limited early detection methods.Accurate imaging and precise tumor margin demarcation are critical for effect...Gastric cancer,including stomach tumors,poses significant health challenges due to late-stage diagnosis and limited early detection methods.Accurate imaging and precise tumor margin demarcation are critical for effective treatment planning and improved patient outcomes.Conventional imaging techniques,such as endoscopy and histopathology,provide valuable diagnostic information but cannot offer real-time assessment.We aim to explore the application of optical coherence tomography(OCT),combined with statistical and machine learning methods,for rapid tumor margin demarcation in gastrointestinal(GI)cancer tissues in exvivo.GI tumor specimens from 17 patients were imaged intraoperatively with OCT.Quantitative features were extracted from the images,and statistical and machine learning analyses were applied to distinguish tissue types.Subsequent histopathological evaluation was used as the reference standard for validation.The combination of OCT imaging and data-driven analysis enables clear differentiation between healthy,marginal and tumor tissues in near real-time.The KNN model achieved the highest classification accuracy(0.921±0.040),with SVM(0.906±0.038)and Extra Trees(0.901±0.034)also demonstrating robust performance in discriminating tissue margins.OCT findings demonstrate strong agreement with histopathology.Integrated with statistical and machine learning techniques,OCT enables rapid assessment of GI tumor margins.This approach provides quantitative objectivity and real-time feedback,closely approximating histopathological analysis and supporting improved surgical decision-making.展开更多
This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 20...This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.展开更多
Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be d...Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be detected in bodily fluids.A PubMed search using the terms“ctHPV”or“circulating tumor DNA”and“cervical cancer”,limited to the past ten years,identified 104 articles,complemented by hand-searching for literature addressing medico-legal implications.Studies were evaluated for relevance and methodological quality.Detection and characterization of circulating tumor HPV DNA(ctHPV DNA)have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer.Detection techniques include polymerase chain reaction(PCR),digital droplet PCR(ddPCR),and next-generation sequencing(NGS).This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications,including management of discordant results,diagnostic errors,liability,and data protection compliance.展开更多
Background:Accurate classification of brain tumors from Magnetic Resonance Imaging(MRI)is essential for clinical decision-making but remains challenging due to tumor heterogeneity.Existing approaches often focus solel...Background:Accurate classification of brain tumors from Magnetic Resonance Imaging(MRI)is essential for clinical decision-making but remains challenging due to tumor heterogeneity.Existing approaches often focus solely on classification or treat segmentation and classification as separate tasks,limiting overall performance and interpretability.Methods:This study proposes an end-to-end automated framework that integrates optimized tumor localization with multiclass classification.An optimized segmentation model is first employed to generate tumor masks,which are then overlaid on MRI scans to produce attention-enhanced inputs.These inputs are subsequently used to train a convolutional neural network(CNN)classifier.Experiments were conducted on a public dataset comprising 4,237 MRI scans across four categories:normal,glioma,meningioma,and pituitary tumors.Results:Three widely used segmentation models were systematically evaluated,with an optimized U-Net achieving the best performance(accuracy=0.9939,Dice=0.8893).Segmentation-guided classification consistently improved performance across six CNN architectures,with the most notable gains observed in heterogeneous tumor types such as glioma and meningioma.Among the classifiers,EfficientNet-V2 achieved the highest performance,with an accuracy of 0.9835,precision of 0.9858,recall of 0.9804,and F1-score of 0.9828.The framework was further validated on an independent external dataset,demonstrating consistent performance and robustness across diverse MRI sources.Conclusion:The proposed framework demonstrates strong potential for multiclass brain tumor classification by effectively combining segmentation and classification.This segmentation-driven approach not only enhances predictive accuracy but also improves interpretability,making it more suitable for clinical applications.展开更多
Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches ...Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.展开更多
Objective:We investigated the clinical value of a novel circulating tumor cell(CTC)detection method—subtraction enrichment combined with immunostaining and fluorescence in situ hybridization(SEi FISH)—in ovarian can...Objective:We investigated the clinical value of a novel circulating tumor cell(CTC)detection method—subtraction enrichment combined with immunostaining and fluorescence in situ hybridization(SEi FISH)—in ovarian cancer(OC).This study evaluated the diagnostic and prognostic significance of chromosome 8aneuploidy in CTCs and circulating tumor endothelial cells(CTECs)for preoperative diagnosis,treatment efficacy assessment,and recurrence monitoring.Methods:A total of 331 patients were enrolled,including 56 with newly diagnosed primary OC,265 with benign ovarian tumors,and 10 with borderline tumors.Peripheral blood CTCs and CTECs were detected using SEi FISH;their quantity and ploidy characteristics were analyzed in relation to clinical indicators.To assess dynamic CTC changes during disease progression and treatment response,72 patients were followed longitudinally,of whom 19 experienced recurrence.Results:The CTC detection rate in OC patients was 92.9%,with significantly higher counts than that in the benign tumor group(median 5 vs.2).Receiver operating characteristic analysis demonstrated good diagnostic performance for total CTCs[area under the curve(AUC)=0.699],with triploid CTCs achieving the highest efficacy(AUC=0.792),surpassing carbohydrate antigen 125(CA125)(AUC=0.702).Postoperative follow-up showed that70%of patients exhibited concurrent decreases in CTCs and CA125 levels,indicating disease improvement.In30%of patients,CTC levels did not correlate with changes in CA125 levels.Individual case evidence suggests that CTC alterations may serve as an early indicator of recurrence or metastasis.Among the 19 recurrent cases,73.7%showed elevated CTCs at recurrence that decreased following treatment.In four patients,CTCs reflected disease progression earlier than CA125,indicating higher sensitivity for recurrence monitoring.Conclusions:CTCs with chromosome 8 aneuploidy demonstrate significant clinical value in the preoperative diagnosis,treatment efficacy evaluation,and recurrence monitoring of OC.Dynamic CTC changes may serve as a more sensitive indicator than CA125 for disease surveillance,supporting the translational potential of CTC-based biomarkers in OC.展开更多
Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—com...Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—comprised of interacting endothelial,stromal,and immune cells—plays a critical role in creating a supportive niche for tumor cell colonization and immune evasion and,thus,the establishment of metastases.The liver’s intrinsic nature further facilitates the development of immune tolerance,mediated by regulatory T cells,myeloid-derived suppressor cells,and soluble factors such as anti-inflammatory cytokines,which together dampen antitumor immune responses.This immunosuppressive milieu contributes significantly to resistance to immune checkpoint inhibitors,limiting the efficacy of immunotherapy in metastatic CRC.Deciphering the complex crosstalk between metastatic CRC cells and TME within the liver is essential for developing novel,effective immunotherapeutic approaches.Several strategies to overcome this lack of response are under research,including combination therapies,novel compounds,and approaches that target TME components.The scope of this review is to synthesize recent advances in the characterization of the hepatic metastatic microenvironment and emerging therapeutic approaches aimed at overcoming immune resistance in CRC liver metastases.展开更多
Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can si...Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.展开更多
Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulat...Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.展开更多
Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better appro...Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.展开更多
Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent...Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.展开更多
Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this com...Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.展开更多
AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital ...AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital IMT based on histopathological examination.The patients were followed up to assess their prognosis.Clinical data from patients,including age,gender,course of disease,past medical history,primary symptoms,ophthalmologic examination findings,general condition,as well as imaging,laboratory,histopathological,and immunohistochemical results from digital records were collected.Orbital magnetic resonance imaging(MRI)and(or)computed tomography(CT)scans were performed to assess bone destruction of the mass,invasion of surrounding tissues,and any inflammatory changes in periorbital areas.RESULTS:The mean age of patients with orbital IMT was 28.24±3.30y,with a male-to-female ratio of 1.2:1.Main clinical manifestations were proptosis,blurred vision,palpable mass,and pain.Bone destruction and surrounding tissue invasion occurred in 72.73%and 54.55%of cases,respectively.Inflammatory changes in the periorbital site were observed in 77.27%of the patients.Hematoxylin and eosin staining showed proliferation of fibroblasts and myofibroblasts,accompanied by infiltration of lymphocytes and plasma cells.Immunohistochemical staining revealed that smooth muscle actin(SMA)and vimentin were positive in 100%of cases,while anaplastic lymphoma kinase(ALK)showed positivity in 47.37%.The recurrence rate of orbital IMT was 27.27%,and sarcomatous degeneration could occur.There were no significant correlations between recurrence and factors such as age,gender,laterality,duration of the disease,periorbital tissue invasion,bone destruction,periorbital inflammation,tumor size,fever,leukocytosis,or treatment(P>0.05).However,lymphadenopathy and a Ki-67 index of 10%or higher may be risk factors for recurrence(P=0.046;P=0.023).CONCLUSION:Orbital IMT is a locally invasive disease that may recur or lead to sarcomatoid degeneration,primarily affecting young and middle-aged patients.The presence of lymphadenopathy and a Ki-67 index of 10%or higher may signify a poor prognosis.展开更多
Objective:Clinical use of stimulator of interferon genes(STING)agonists has challenges due to poor responsiveness and variable efficacy.Therefore,identifying tumor types that are sensitive to these agents and clarifyi...Objective:Clinical use of stimulator of interferon genes(STING)agonists has challenges due to poor responsiveness and variable efficacy.Therefore,identifying tumor types that are sensitive to these agents and clarifying the underlying mechanisms are essential.Methods:In vitro screening was performed to identify tumor types that are sensitive to STING agonists.The non-nucleotide agonist,SR-717,and the macrocyclic agonist,E7766,were compared for efficacy.Complementary in vivo and in vitro studies,including gene-knockout models,HMGN2-knockout Neuro-2A and CT-2A cells apoptosis assays,and murine tumor models,were then performed.These experiments focused on the mechanism by which SR-717 mediates antitumor effects and emphasized the role of STING signaling-induced high-mobility group nucleosome-binding protein 2(HMGN2).In addition,the potential of HMGN2 as a prognostic biomarker was assessed.Results:Neuroblastomas and glioblastomas,two nervous system tumors,were shown to be sensitive to STING agonists.SR-717 exhibited greater antitumor efficacy compared to E7766.Mechanistic studies indicated that STING agonists promote apoptosis through activation of the intrinsic STING-signal transducer and activator of transcription 1(STAT1)-HMGN2 axis within tumor cells.Ectopic expression of HMGN2 in melanoma cells,which naturally lack HMGN2,led to significant apoptosis.Furthermore,analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases revealed positive correlation between elevated HMGN2 expression and patient survival,supporting the utility of HMGN2 as a prognostic biomarker.Conclusions:This study clarified the mechanism underlying the potent antitumor activity of SR-717 in nervous system tumors through activation of the STING-STAT1-HMGN2 signaling pathway and demonstrated that SR-717 has superior efficacy compared to E7766.In addition,HMGN2 was shown to exhibit translational potential as a prognostic biomarker for patient survival.展开更多
Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and com...Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.展开更多
Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of ...BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.展开更多
Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological b...Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.展开更多
文摘The morbidity rate of primary cardiac tumors(PCTs)is only 0.0138%.[1]Calcified amorphous tumors(CATs)are a particularly rare entity with only a few cases reported in the literature,and account for only 2.47%of PCTs.[2]CATs can occur at any age and have been identified at various intracardiac locations.The clinical manifestations of patients are related to the location and size of the lesion.
基金supported by the National Natural Science Foundation of China(82472842 and 82473350)and Wuxi Double-Hundred Talent Fund Project(BJ2023075).
文摘Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.
基金supported by the financial support received from the Indian Council of Medical Research-Department of Health Research(ICMRDHR-CoE-5/3/8/5/2019/I-MDMS)Medical Device and Diagnostics Mission Secretariat(MDMS)and Foundation for Centre for Healthcare Entrepreneurship(CfHE).
文摘Gastric cancer,including stomach tumors,poses significant health challenges due to late-stage diagnosis and limited early detection methods.Accurate imaging and precise tumor margin demarcation are critical for effective treatment planning and improved patient outcomes.Conventional imaging techniques,such as endoscopy and histopathology,provide valuable diagnostic information but cannot offer real-time assessment.We aim to explore the application of optical coherence tomography(OCT),combined with statistical and machine learning methods,for rapid tumor margin demarcation in gastrointestinal(GI)cancer tissues in exvivo.GI tumor specimens from 17 patients were imaged intraoperatively with OCT.Quantitative features were extracted from the images,and statistical and machine learning analyses were applied to distinguish tissue types.Subsequent histopathological evaluation was used as the reference standard for validation.The combination of OCT imaging and data-driven analysis enables clear differentiation between healthy,marginal and tumor tissues in near real-time.The KNN model achieved the highest classification accuracy(0.921±0.040),with SVM(0.906±0.038)and Extra Trees(0.901±0.034)also demonstrating robust performance in discriminating tissue margins.OCT findings demonstrate strong agreement with histopathology.Integrated with statistical and machine learning techniques,OCT enables rapid assessment of GI tumor margins.This approach provides quantitative objectivity and real-time feedback,closely approximating histopathological analysis and supporting improved surgical decision-making.
文摘This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.
文摘Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be detected in bodily fluids.A PubMed search using the terms“ctHPV”or“circulating tumor DNA”and“cervical cancer”,limited to the past ten years,identified 104 articles,complemented by hand-searching for literature addressing medico-legal implications.Studies were evaluated for relevance and methodological quality.Detection and characterization of circulating tumor HPV DNA(ctHPV DNA)have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer.Detection techniques include polymerase chain reaction(PCR),digital droplet PCR(ddPCR),and next-generation sequencing(NGS).This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications,including management of discordant results,diagnostic errors,liability,and data protection compliance.
文摘Background:Accurate classification of brain tumors from Magnetic Resonance Imaging(MRI)is essential for clinical decision-making but remains challenging due to tumor heterogeneity.Existing approaches often focus solely on classification or treat segmentation and classification as separate tasks,limiting overall performance and interpretability.Methods:This study proposes an end-to-end automated framework that integrates optimized tumor localization with multiclass classification.An optimized segmentation model is first employed to generate tumor masks,which are then overlaid on MRI scans to produce attention-enhanced inputs.These inputs are subsequently used to train a convolutional neural network(CNN)classifier.Experiments were conducted on a public dataset comprising 4,237 MRI scans across four categories:normal,glioma,meningioma,and pituitary tumors.Results:Three widely used segmentation models were systematically evaluated,with an optimized U-Net achieving the best performance(accuracy=0.9939,Dice=0.8893).Segmentation-guided classification consistently improved performance across six CNN architectures,with the most notable gains observed in heterogeneous tumor types such as glioma and meningioma.Among the classifiers,EfficientNet-V2 achieved the highest performance,with an accuracy of 0.9835,precision of 0.9858,recall of 0.9804,and F1-score of 0.9828.The framework was further validated on an independent external dataset,demonstrating consistent performance and robustness across diverse MRI sources.Conclusion:The proposed framework demonstrates strong potential for multiclass brain tumor classification by effectively combining segmentation and classification.This segmentation-driven approach not only enhances predictive accuracy but also improves interpretability,making it more suitable for clinical applications.
基金Supported by National Natural Science Foundation of China,No.82170638Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality,No.23ZR1458300+1 种基金Key Discipline Project of Shanghai Municipal Health System,No.2024ZDXK0004and Pujiang Project of Shanghai Magnolia Talent Plan,No.24PJD098.
文摘Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.
基金sponsored by the Peking University People’s Hospital Research and Development Fund(No.RDZH2024-06)the National Key Research and Development Program of China(No.2022YFC2704204)。
文摘Objective:We investigated the clinical value of a novel circulating tumor cell(CTC)detection method—subtraction enrichment combined with immunostaining and fluorescence in situ hybridization(SEi FISH)—in ovarian cancer(OC).This study evaluated the diagnostic and prognostic significance of chromosome 8aneuploidy in CTCs and circulating tumor endothelial cells(CTECs)for preoperative diagnosis,treatment efficacy assessment,and recurrence monitoring.Methods:A total of 331 patients were enrolled,including 56 with newly diagnosed primary OC,265 with benign ovarian tumors,and 10 with borderline tumors.Peripheral blood CTCs and CTECs were detected using SEi FISH;their quantity and ploidy characteristics were analyzed in relation to clinical indicators.To assess dynamic CTC changes during disease progression and treatment response,72 patients were followed longitudinally,of whom 19 experienced recurrence.Results:The CTC detection rate in OC patients was 92.9%,with significantly higher counts than that in the benign tumor group(median 5 vs.2).Receiver operating characteristic analysis demonstrated good diagnostic performance for total CTCs[area under the curve(AUC)=0.699],with triploid CTCs achieving the highest efficacy(AUC=0.792),surpassing carbohydrate antigen 125(CA125)(AUC=0.702).Postoperative follow-up showed that70%of patients exhibited concurrent decreases in CTCs and CA125 levels,indicating disease improvement.In30%of patients,CTC levels did not correlate with changes in CA125 levels.Individual case evidence suggests that CTC alterations may serve as an early indicator of recurrence or metastasis.Among the 19 recurrent cases,73.7%showed elevated CTCs at recurrence that decreased following treatment.In four patients,CTCs reflected disease progression earlier than CA125,indicating higher sensitivity for recurrence monitoring.Conclusions:CTCs with chromosome 8 aneuploidy demonstrate significant clinical value in the preoperative diagnosis,treatment efficacy evaluation,and recurrence monitoring of OC.Dynamic CTC changes may serve as a more sensitive indicator than CA125 for disease surveillance,supporting the translational potential of CTC-based biomarkers in OC.
基金funded by the Italian Ministry of Health through the grant“PRIN 2022 PNRR”entitled“Landscape ANalyses of immune CEll signatures associated with early Liver metastatic cOlorecTal cancer”(LANCELOT),P2022N3NC4,which has received funding from European Commission—NextGeneration for the salary of the researcher Candela Cives-Losada.
文摘Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—comprised of interacting endothelial,stromal,and immune cells—plays a critical role in creating a supportive niche for tumor cell colonization and immune evasion and,thus,the establishment of metastases.The liver’s intrinsic nature further facilitates the development of immune tolerance,mediated by regulatory T cells,myeloid-derived suppressor cells,and soluble factors such as anti-inflammatory cytokines,which together dampen antitumor immune responses.This immunosuppressive milieu contributes significantly to resistance to immune checkpoint inhibitors,limiting the efficacy of immunotherapy in metastatic CRC.Deciphering the complex crosstalk between metastatic CRC cells and TME within the liver is essential for developing novel,effective immunotherapeutic approaches.Several strategies to overcome this lack of response are under research,including combination therapies,novel compounds,and approaches that target TME components.The scope of this review is to synthesize recent advances in the characterization of the hepatic metastatic microenvironment and emerging therapeutic approaches aimed at overcoming immune resistance in CRC liver metastases.
基金supported by the National Natural Science Foundation of China (No. 82373809 to Y.L., No. 825B2116 to J.L., No. 82373805 to N.Z., No. 82204295 to W.M)the Shandong Excellent Youth Fund and Provincial Natural Science Foundation (ZR2022YQ76 to Y.L., ZR2022QH224 to W.M.)。
文摘Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.
文摘Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.
文摘Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.
基金supported by the National Natural Science Foundation of China(Nos.82302373,81903846)Natural Science Foundation of Sichuan Province(No.2022NSFSC1925)+1 种基金Chengdu Technology Innovation Research and Development Project(No.2022-YF05-01546-SN)the Introduction of Talents Research Project of Chengdu University(No.2081921049)。
文摘Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.
基金Institutional Research Grant,MD Anderson Cancer CenterUPWARDS Training Program(Undergraduate Students Working Towards Research in Science),Grant/Award Number:1R25CA240137-01A1the CPRIT Research Training Award CPRIT Training Program,Grant/Award Number:RP210028。
文摘Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.
基金Supported by the National Key R&D Program of China(No.2023YFC2410203)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202503).
文摘AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital IMT based on histopathological examination.The patients were followed up to assess their prognosis.Clinical data from patients,including age,gender,course of disease,past medical history,primary symptoms,ophthalmologic examination findings,general condition,as well as imaging,laboratory,histopathological,and immunohistochemical results from digital records were collected.Orbital magnetic resonance imaging(MRI)and(or)computed tomography(CT)scans were performed to assess bone destruction of the mass,invasion of surrounding tissues,and any inflammatory changes in periorbital areas.RESULTS:The mean age of patients with orbital IMT was 28.24±3.30y,with a male-to-female ratio of 1.2:1.Main clinical manifestations were proptosis,blurred vision,palpable mass,and pain.Bone destruction and surrounding tissue invasion occurred in 72.73%and 54.55%of cases,respectively.Inflammatory changes in the periorbital site were observed in 77.27%of the patients.Hematoxylin and eosin staining showed proliferation of fibroblasts and myofibroblasts,accompanied by infiltration of lymphocytes and plasma cells.Immunohistochemical staining revealed that smooth muscle actin(SMA)and vimentin were positive in 100%of cases,while anaplastic lymphoma kinase(ALK)showed positivity in 47.37%.The recurrence rate of orbital IMT was 27.27%,and sarcomatous degeneration could occur.There were no significant correlations between recurrence and factors such as age,gender,laterality,duration of the disease,periorbital tissue invasion,bone destruction,periorbital inflammation,tumor size,fever,leukocytosis,or treatment(P>0.05).However,lymphadenopathy and a Ki-67 index of 10%or higher may be risk factors for recurrence(P=0.046;P=0.023).CONCLUSION:Orbital IMT is a locally invasive disease that may recur or lead to sarcomatoid degeneration,primarily affecting young and middle-aged patients.The presence of lymphadenopathy and a Ki-67 index of 10%or higher may signify a poor prognosis.
文摘Objective:Clinical use of stimulator of interferon genes(STING)agonists has challenges due to poor responsiveness and variable efficacy.Therefore,identifying tumor types that are sensitive to these agents and clarifying the underlying mechanisms are essential.Methods:In vitro screening was performed to identify tumor types that are sensitive to STING agonists.The non-nucleotide agonist,SR-717,and the macrocyclic agonist,E7766,were compared for efficacy.Complementary in vivo and in vitro studies,including gene-knockout models,HMGN2-knockout Neuro-2A and CT-2A cells apoptosis assays,and murine tumor models,were then performed.These experiments focused on the mechanism by which SR-717 mediates antitumor effects and emphasized the role of STING signaling-induced high-mobility group nucleosome-binding protein 2(HMGN2).In addition,the potential of HMGN2 as a prognostic biomarker was assessed.Results:Neuroblastomas and glioblastomas,two nervous system tumors,were shown to be sensitive to STING agonists.SR-717 exhibited greater antitumor efficacy compared to E7766.Mechanistic studies indicated that STING agonists promote apoptosis through activation of the intrinsic STING-signal transducer and activator of transcription 1(STAT1)-HMGN2 axis within tumor cells.Ectopic expression of HMGN2 in melanoma cells,which naturally lack HMGN2,led to significant apoptosis.Furthermore,analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases revealed positive correlation between elevated HMGN2 expression and patient survival,supporting the utility of HMGN2 as a prognostic biomarker.Conclusions:This study clarified the mechanism underlying the potent antitumor activity of SR-717 in nervous system tumors through activation of the STING-STAT1-HMGN2 signaling pathway and demonstrated that SR-717 has superior efficacy compared to E7766.In addition,HMGN2 was shown to exhibit translational potential as a prognostic biomarker for patient survival.
文摘Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.
文摘Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.
