Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting t...Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting the MIIP-stimulator of interferon genes(STING)pathway in colorectal cancer(CRC)therapy.Methods:MIIP expression was analyzed for associations with the STING pathway and M2 macrophage infiltration using public datasets and clinical CRC samples.CRC cells were genetically modified using lentiviral vectors to overexpress or silence MIIP and STING.The interactions of genetically modified CRC cells with macrophages were studied in co-culture systems.Techniques,including immunofluorescence staining,RT‒qPCR,western blot,ELISA,flow cytometry,and Transwell migration and invasion assays,were used to evaluate the crosstalk between CRC cells and macrophages.An orthotopic mouse CRC model was developed to study the effects of MIIP on M2 macrophage polarization and tumor metastasis through the STING-NFκB2-IL10 axis.The therapeutic significance of a STING antagonist was also assessed in vivo.Results:Analyses of The Cancer Genome Atlas(TCGA)cohort and our CRC cohort revealed low MIIP expression is associated with STING pathway activation,increased M2 macrophage infiltration,and poor clinical outcomes.The results of functional experiments demonstrated that MIIP inhibits IL10 production via the STING-TRAF3-NFκB2 axis in CRC cells,suppressing M2 macrophage polarization in co-culture systems.Conversely,M2 macrophages promoted CRC cell migration and invasion in an IL10-dependent manner.In vitro and in vivo studies confirmed that the MIIP-mediated feedback loop between CRC cells and macrophages depends on the STING-NFκB2-IL10 axis.Furthermore,inhibition of STING expression in a mouse model reduced M2 macrophage polarization and tumor metastasis.Conclusions:This study established MIIP as a crucial regulator of macrophage polarization in the CRC tumor microenvironment,providing new insights into the role in suppressing CRC progression and immune-tumor crosstalk.These findings highlight the potential of targeting the STING pathway as a therapeutic strategy for CRC patients who respond poorly to immune checkpoint inhibitors.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 Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic...BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.展开更多
Objective:Robotic colorectal surgery(RCS)provides a stable,magnifiedthree-dimensional visual field and enhanced ergonomics enabling precise dissection and tremor suppression.We postulate that this technique is associa...Objective:Robotic colorectal surgery(RCS)provides a stable,magnifiedthree-dimensional visual field and enhanced ergonomics enabling precise dissection and tremor suppression.We postulate that this technique is associated with less tissue trauma and improved postoperative outcomes than laparoscopic colorectal surgery(LCS).This study aimed to explore the inflammatoryresponse following RCS by measuring postoperative C-reactive protein(CRP)levels and compare them with LCS data reported in the literature.Methods:This single centre retrospective study included consecutive elective robotic colon and rectum resections via the da Vinci®Xi platform for benign and malignant colorectal tumours,performed by a single surgeon between January 2017 and December 2023 at the Sydney Adventist Hospital,Sydney.CRP values were measured on post-operative days(PODs)3 and 5.A narrative review of the literature was performed via EMBASE,MEDLINE via PubMed and Google Scholar from inception to December 2024 for comparative CRP values following LCS.Descriptive statistical comparisons were performed between the RCS and LCS.Results:One hundred ninety-three patients were identifiedin the RCS cohort.The median age was 73 y(range:62–83 y).Most colectomies were performed for adenocarcinoma(90.2%),with right hemicolectomy being the most common type of procedure(49.3%).The median CRP levels on PODs 3 and 5 were 83.10 mg/L(IQR:49.80–124.12 mg/L)and 26.20 mg/L(IQR:17.70–80.00 mg/L),respectively.The reported CRP after LCS was heterogeneous,with mean POD 3 values ranging from 69 mg/L to 99.5 mg/L,and mean POD 4–5 values ranging from 62.4 mg/L to 72.85 mg/L.Conclusions:There were similar,if not lower,POD 3 and 5 CRP values,suggesting that RCS was probably non-inferior to LCS regarding postoperative tissue trauma.In particular,there appeared to be a quicker recovery of the inflammatory response with RCS.展开更多
BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed...Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.展开更多
BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of pr...BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.展开更多
Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic re...Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.Methods:Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025,respectively.Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes.RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies,respectively.Data extracted was narratively analyzed.Results:Six studies involving a total of 361 individuals were included.Therapeutic interventions,either standard treatments and/or those targeting the gut microbiome,generally increased probiotic taxa and reduced pro-carcinogenic bacteria.However,no consistent pattern of improved clinical outcomes was observed,suggesting that treatment mechanisms,the tumor’s nature,and individual characteristics play critical roles in microbiome modulation.Conclusion:The gut microbiome holds significant potential in clinical settings.Nonetheless,further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms,the tumor’s nature,and individual characteristics as modulators,in order to optimize clinical outcomes.展开更多
BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning ofte...BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.展开更多
Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third ...Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third most common cancer worldwide and ranks second in mortality among all malignancies.Currently,it has become one of the most severe challenges faced by healthcare systems in many countries[2].A previous study has found that patients with psoriasis have a significantly increased risk of developing CRC[3].展开更多
Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which p...Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which peroxiredoxin 1(Prdx1)inhibits CRC progression through induction of pyroptosis,a pro-inflammatory form of programmed cell death.Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress,Prdx1 assu-mes a paradoxical immunogenic role when released extracellularly as a damageassociated molecular pattern.Using patient samples,recombinant protein assays,and murine xenograft models,the authors demonstrate that Prdx1 activates the NOD-,LRR-and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway,triggering membrane pore formation,tumor cell lysis,and release of interleukin-1β/interleukin-18.This cascade not only halts tumor proliferation,invasion,and migration but may also enhance anti-tumor immune surveillance.The study’s strengths include rigorous mechanistic validation,clinical cohort data,inhibitor-based causal proof,and in vivo confirmation.However,questions remain regarding the upstream receptor for Prdx1,heterogeneity across CRC subtypes,and the balance between therapeutic benefit and inflammatory toxicity.By establishing Prdx1-induced pyroptosis as a driver of tumor suppression,this work advances a promising paradigm in CRC therapy,linking cell death to immune activation and pointing toward future biomarker-driven,pyroptosis-based interventions.展开更多
Colorectal cancer(CRC)is the third most common malignancy worldwide and the second leading cause of cancer-related deaths,accounting for approximately 10%of all cancer cases.By 2050,CRC incidence is expected to rise s...Colorectal cancer(CRC)is the third most common malignancy worldwide and the second leading cause of cancer-related deaths,accounting for approximately 10%of all cancer cases.By 2050,CRC incidence is expected to rise substantially,driven by population aging and greater exposure to risk factors in developing countries.Despite advances in medicine and pharmacy,the effectiveness of available treatments remains limited,underscoring the urgent need for innovative therapeutic strategies.This review summarizes and critically evaluates currently available CRC therapies and explores new emerging directions.Particular attention is given to the role of immunotherapy,targeted therapies,nanotechnology-based approaches,metal-based compounds,PROTAC technology,and personalized medicine,with emphasis on their efficacy,safety,accessibility,and mechanisms of drug resistance.In conclusion,surgery and chemotherapy remain the backbone of CRC treatment,but novel therapeutic approaches are reshaping the treatment landscape.Emerging strategies may offer improved patient tolerability and survival outcomes by reducing the occurrence of burdensome adverse effects.Persistent challenges such as drug toxicity,the emergence of resistance mechanisms,and inequalities in access to innovative therapies underscore the need for further translational research.Integrating personalized therapeutic approaches will also be crucial to achieving more effective,safer,and accessible treatment strategies for CRC.展开更多
Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in...Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.展开更多
Objective:To investigate the expression of pyruvate kinase M2(PKM2)and RNA binding proteins 1(SERBP1)in colorectal cancer(CRC)and their clinical significance.Methods:A total of 101 cases of colorectal adenocarcinoma t...Objective:To investigate the expression of pyruvate kinase M2(PKM2)and RNA binding proteins 1(SERBP1)in colorectal cancer(CRC)and their clinical significance.Methods:A total of 101 cases of colorectal adenocarcinoma tissues and their corresponding adjacent tissues were collected from our hospital from December 2020 to December 2023.The immunohistochemical Elivision method was used to detect the expression of PKM2 and SERBP1 in CRC and corresponding adjacent tissues.The experimental data were analyzed using statistical software SPSS 27.0.Results:The expression rates of PKM2 and SERBP1 in CRC were higher than those in adjacent tissues.The expression of PKM2 was positively correlated with lymph node metastasis and TNM stage.The expression of SERBP1 was positively correlated with the degree of differentiation,lymph node metastasis,and TNM stage of CRC.Conclusion:PKM2 and SERBP1 may promote the occurrence and tumor progression of CRC,but further experimental research is still needed.展开更多
Background:The efficacy of standard 5-fluorouracil(5-FU)chemotherapy for colorectal cancer is limited by drug resistance and adverse effects,prompting research into esketamine,a potent ketamine variant with analgesic,...Background:The efficacy of standard 5-fluorouracil(5-FU)chemotherapy for colorectal cancer is limited by drug resistance and adverse effects,prompting research into esketamine,a potent ketamine variant with analgesic,antidepressant,and recently discovered anti-tumor properties,to determine if it can enhance 5-FU’s chemosensitivity.This study investigates whether esketamine synergizes with 5-FU to enhance therapeutic efficacy in colorectal adenocarcinoma cell models.Methods:We performed functional assays to evaluate proliferation(CCK-8),migration(wound healing),invasion(Transwell),and apoptosis(flow cytometry)in colorectal adenocarcinoma cell lines treated with 5-FU alone or in combination with esketamine.Transcriptomic profiling was conducted using RNA sequencing,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was employed to identify critical molecular targets and signaling networks.Protein-level validation of key pathway components was performed via western blotting.Results:Combination therapy with esketamine and 5-FU synergistically inhibited cellular proliferation,migration,and invasion while significantly inducing apoptosis compared to monotherapy.Mechanistically,esketamine potentiated 5-FU-driven AMP-activated protein kinase(AMPK)phosphorylation,leading to inhibition of both mammalian target of rapamycin(mTOR)and hyaluronan-mediated motility receptor(HMMR).Conclusion:Esketamine enhances 5-FU chemosensitivity in colorectal adenocarcinoma by activating the AMPK/mTOR/HMMR signaling axis,thereby suppressing tumor progression and metastatic potential.These findings position esketamine as a potential adjunctive therapy for 5-FU-based regimens,offering the dual benefit of enhancing chemotherapeutic efficacy while addressing cancer-associated comorbidities including pain and depression.展开更多
Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by ...Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.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
The colorectal cancer is one of the most common and lethal cancers,and colorectal polyps,as precancerous lesions,can lead to diagnostic oversight or misdiagnosis due to their varied shapes and sizes,thereby promoting ...The colorectal cancer is one of the most common and lethal cancers,and colorectal polyps,as precancerous lesions,can lead to diagnostic oversight or misdiagnosis due to their varied shapes and sizes,thereby promoting the irreversible progression of colorectal cancer.We propose a YOLO based model and name it EF-YOLO.It incorporates transformer to extract contextual information about the colorectal polyps.Simultaneously,leveraging the morphological characteristics of colorectal polyps,we design a brand-new module,namely advanced multi-scale aggregation(AMSA),to replace the traditional multi-scale module.The backbone adopts deformable convolutional network-maxpool(DCN-MP)to enhance feature extraction while adaptively sampling points to better match the shapes of colorectal polyps.By combining coordinate attention(CA),this model maximizes the use of positional and channel information,more effectively extracting features of colorectal polyps,directing the model’s attention toward the colorectal polyp region.EF-YOLO has made advancement on the merged Kvasir-SEG and CVC-ClinicDB dataset.Compared to the original model,the mean average precision(mAP)of EF-YOLO increases and reaches 96.60%,meeting automated colorectal polyp detection requirements.展开更多
Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains...Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.展开更多
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
文摘Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting the MIIP-stimulator of interferon genes(STING)pathway in colorectal cancer(CRC)therapy.Methods:MIIP expression was analyzed for associations with the STING pathway and M2 macrophage infiltration using public datasets and clinical CRC samples.CRC cells were genetically modified using lentiviral vectors to overexpress or silence MIIP and STING.The interactions of genetically modified CRC cells with macrophages were studied in co-culture systems.Techniques,including immunofluorescence staining,RT‒qPCR,western blot,ELISA,flow cytometry,and Transwell migration and invasion assays,were used to evaluate the crosstalk between CRC cells and macrophages.An orthotopic mouse CRC model was developed to study the effects of MIIP on M2 macrophage polarization and tumor metastasis through the STING-NFκB2-IL10 axis.The therapeutic significance of a STING antagonist was also assessed in vivo.Results:Analyses of The Cancer Genome Atlas(TCGA)cohort and our CRC cohort revealed low MIIP expression is associated with STING pathway activation,increased M2 macrophage infiltration,and poor clinical outcomes.The results of functional experiments demonstrated that MIIP inhibits IL10 production via the STING-TRAF3-NFκB2 axis in CRC cells,suppressing M2 macrophage polarization in co-culture systems.Conversely,M2 macrophages promoted CRC cell migration and invasion in an IL10-dependent manner.In vitro and in vivo studies confirmed that the MIIP-mediated feedback loop between CRC cells and macrophages depends on the STING-NFκB2-IL10 axis.Furthermore,inhibition of STING expression in a mouse model reduced M2 macrophage polarization and tumor metastasis.Conclusions:This study established MIIP as a crucial regulator of macrophage polarization in the CRC tumor microenvironment,providing new insights into the role in suppressing CRC progression and immune-tumor crosstalk.These findings highlight the potential of targeting the STING pathway as a therapeutic strategy for CRC patients who respond poorly to immune checkpoint inhibitors.
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 Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.
文摘Objective:Robotic colorectal surgery(RCS)provides a stable,magnifiedthree-dimensional visual field and enhanced ergonomics enabling precise dissection and tremor suppression.We postulate that this technique is associated with less tissue trauma and improved postoperative outcomes than laparoscopic colorectal surgery(LCS).This study aimed to explore the inflammatoryresponse following RCS by measuring postoperative C-reactive protein(CRP)levels and compare them with LCS data reported in the literature.Methods:This single centre retrospective study included consecutive elective robotic colon and rectum resections via the da Vinci®Xi platform for benign and malignant colorectal tumours,performed by a single surgeon between January 2017 and December 2023 at the Sydney Adventist Hospital,Sydney.CRP values were measured on post-operative days(PODs)3 and 5.A narrative review of the literature was performed via EMBASE,MEDLINE via PubMed and Google Scholar from inception to December 2024 for comparative CRP values following LCS.Descriptive statistical comparisons were performed between the RCS and LCS.Results:One hundred ninety-three patients were identifiedin the RCS cohort.The median age was 73 y(range:62–83 y).Most colectomies were performed for adenocarcinoma(90.2%),with right hemicolectomy being the most common type of procedure(49.3%).The median CRP levels on PODs 3 and 5 were 83.10 mg/L(IQR:49.80–124.12 mg/L)and 26.20 mg/L(IQR:17.70–80.00 mg/L),respectively.The reported CRP after LCS was heterogeneous,with mean POD 3 values ranging from 69 mg/L to 99.5 mg/L,and mean POD 4–5 values ranging from 62.4 mg/L to 72.85 mg/L.Conclusions:There were similar,if not lower,POD 3 and 5 CRP values,suggesting that RCS was probably non-inferior to LCS regarding postoperative tissue trauma.In particular,there appeared to be a quicker recovery of the inflammatory response with RCS.
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
基金funded by The Tunisian Ministry of Research and Higher Education.
文摘Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.
文摘BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.
基金supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020).
文摘Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.Methods:Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025,respectively.Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes.RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies,respectively.Data extracted was narratively analyzed.Results:Six studies involving a total of 361 individuals were included.Therapeutic interventions,either standard treatments and/or those targeting the gut microbiome,generally increased probiotic taxa and reduced pro-carcinogenic bacteria.However,no consistent pattern of improved clinical outcomes was observed,suggesting that treatment mechanisms,the tumor’s nature,and individual characteristics play critical roles in microbiome modulation.Conclusion:The gut microbiome holds significant potential in clinical settings.Nonetheless,further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms,the tumor’s nature,and individual characteristics as modulators,in order to optimize clinical outcomes.
基金Supported by Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2023MSXM060.
文摘BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.
基金supported by the National Natural Science Foundation of China(Grant No.82373475).
文摘Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third most common cancer worldwide and ranks second in mortality among all malignancies.Currently,it has become one of the most severe challenges faced by healthcare systems in many countries[2].A previous study has found that patients with psoriasis have a significantly increased risk of developing CRC[3].
文摘Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which peroxiredoxin 1(Prdx1)inhibits CRC progression through induction of pyroptosis,a pro-inflammatory form of programmed cell death.Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress,Prdx1 assu-mes a paradoxical immunogenic role when released extracellularly as a damageassociated molecular pattern.Using patient samples,recombinant protein assays,and murine xenograft models,the authors demonstrate that Prdx1 activates the NOD-,LRR-and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway,triggering membrane pore formation,tumor cell lysis,and release of interleukin-1β/interleukin-18.This cascade not only halts tumor proliferation,invasion,and migration but may also enhance anti-tumor immune surveillance.The study’s strengths include rigorous mechanistic validation,clinical cohort data,inhibitor-based causal proof,and in vivo confirmation.However,questions remain regarding the upstream receptor for Prdx1,heterogeneity across CRC subtypes,and the balance between therapeutic benefit and inflammatory toxicity.By establishing Prdx1-induced pyroptosis as a driver of tumor suppression,this work advances a promising paradigm in CRC therapy,linking cell death to immune activation and pointing toward future biomarker-driven,pyroptosis-based interventions.
文摘Colorectal cancer(CRC)is the third most common malignancy worldwide and the second leading cause of cancer-related deaths,accounting for approximately 10%of all cancer cases.By 2050,CRC incidence is expected to rise substantially,driven by population aging and greater exposure to risk factors in developing countries.Despite advances in medicine and pharmacy,the effectiveness of available treatments remains limited,underscoring the urgent need for innovative therapeutic strategies.This review summarizes and critically evaluates currently available CRC therapies and explores new emerging directions.Particular attention is given to the role of immunotherapy,targeted therapies,nanotechnology-based approaches,metal-based compounds,PROTAC technology,and personalized medicine,with emphasis on their efficacy,safety,accessibility,and mechanisms of drug resistance.In conclusion,surgery and chemotherapy remain the backbone of CRC treatment,but novel therapeutic approaches are reshaping the treatment landscape.Emerging strategies may offer improved patient tolerability and survival outcomes by reducing the occurrence of burdensome adverse effects.Persistent challenges such as drug toxicity,the emergence of resistance mechanisms,and inequalities in access to innovative therapies underscore the need for further translational research.Integrating personalized therapeutic approaches will also be crucial to achieving more effective,safer,and accessible treatment strategies for CRC.
文摘Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.
基金Research Project of Xi’an Health Commission(Project No.:2023yb11)。
文摘Objective:To investigate the expression of pyruvate kinase M2(PKM2)and RNA binding proteins 1(SERBP1)in colorectal cancer(CRC)and their clinical significance.Methods:A total of 101 cases of colorectal adenocarcinoma tissues and their corresponding adjacent tissues were collected from our hospital from December 2020 to December 2023.The immunohistochemical Elivision method was used to detect the expression of PKM2 and SERBP1 in CRC and corresponding adjacent tissues.The experimental data were analyzed using statistical software SPSS 27.0.Results:The expression rates of PKM2 and SERBP1 in CRC were higher than those in adjacent tissues.The expression of PKM2 was positively correlated with lymph node metastasis and TNM stage.The expression of SERBP1 was positively correlated with the degree of differentiation,lymph node metastasis,and TNM stage of CRC.Conclusion:PKM2 and SERBP1 may promote the occurrence and tumor progression of CRC,but further experimental research is still needed.
基金funded by the Natural Science Foundation of Guangdong Provice(2022A1515012543).
文摘Background:The efficacy of standard 5-fluorouracil(5-FU)chemotherapy for colorectal cancer is limited by drug resistance and adverse effects,prompting research into esketamine,a potent ketamine variant with analgesic,antidepressant,and recently discovered anti-tumor properties,to determine if it can enhance 5-FU’s chemosensitivity.This study investigates whether esketamine synergizes with 5-FU to enhance therapeutic efficacy in colorectal adenocarcinoma cell models.Methods:We performed functional assays to evaluate proliferation(CCK-8),migration(wound healing),invasion(Transwell),and apoptosis(flow cytometry)in colorectal adenocarcinoma cell lines treated with 5-FU alone or in combination with esketamine.Transcriptomic profiling was conducted using RNA sequencing,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was employed to identify critical molecular targets and signaling networks.Protein-level validation of key pathway components was performed via western blotting.Results:Combination therapy with esketamine and 5-FU synergistically inhibited cellular proliferation,migration,and invasion while significantly inducing apoptosis compared to monotherapy.Mechanistically,esketamine potentiated 5-FU-driven AMP-activated protein kinase(AMPK)phosphorylation,leading to inhibition of both mammalian target of rapamycin(mTOR)and hyaluronan-mediated motility receptor(HMMR).Conclusion:Esketamine enhances 5-FU chemosensitivity in colorectal adenocarcinoma by activating the AMPK/mTOR/HMMR signaling axis,thereby suppressing tumor progression and metastatic potential.These findings position esketamine as a potential adjunctive therapy for 5-FU-based regimens,offering the dual benefit of enhancing chemotherapeutic efficacy while addressing cancer-associated comorbidities including pain and depression.
文摘Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.
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.
文摘The colorectal cancer is one of the most common and lethal cancers,and colorectal polyps,as precancerous lesions,can lead to diagnostic oversight or misdiagnosis due to their varied shapes and sizes,thereby promoting the irreversible progression of colorectal cancer.We propose a YOLO based model and name it EF-YOLO.It incorporates transformer to extract contextual information about the colorectal polyps.Simultaneously,leveraging the morphological characteristics of colorectal polyps,we design a brand-new module,namely advanced multi-scale aggregation(AMSA),to replace the traditional multi-scale module.The backbone adopts deformable convolutional network-maxpool(DCN-MP)to enhance feature extraction while adaptively sampling points to better match the shapes of colorectal polyps.By combining coordinate attention(CA),this model maximizes the use of positional and channel information,more effectively extracting features of colorectal polyps,directing the model’s attention toward the colorectal polyp region.EF-YOLO has made advancement on the merged Kvasir-SEG and CVC-ClinicDB dataset.Compared to the original model,the mean average precision(mAP)of EF-YOLO increases and reaches 96.60%,meeting automated colorectal polyp detection requirements.
基金supported by the Joint Project of the Chongqing Science and Technology Commission(2025MSXM040).
文摘Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
