It has been reported recently that small undifferentiated intramucosal early gastric cancer(EGC) < 20 mm in size without any lymphovascular involvement or ulcerative findings had virtually no risk of lymph-node(LN)...It has been reported recently that small undifferentiated intramucosal early gastric cancer(EGC) < 20 mm in size without any lymphovascular involvement or ulcerative findings had virtually no risk of lymph-node(LN) metastasis.Consequently,the indications for endoscopic resection were expanded to include such undifferentiated EGC lesions.We describe herein a case of a small undifferentiated intramucosal EGC < 20 mm in size without lymphovascular involvement or ulcerative findings that involved lymph-node metastasis.A 57-year-old female underwent pylorus preserving gastrectomy as standard treatment for an undifferentiated EGC 15 mm in size without any ulcerative finding.The surgical specimen revealed a signet-ring cell carcinoma with a moderately to poorly differentiated adenocarcinoma limited to the mucosa that was 15 mm in size with no lymphovascular involvement or ulcerative findings.This case involved LN metastasis,however,and the lesion was diagnosed as pathological stage ⅡA(T1N2M0) according to the Japanese Classification of Gastric Carcinoma.展开更多
Background:The risk of lymph-node metastasis(LNM)in T1 colorectal cancer(CRC)has not been well documented in heterogeneous Western populations.This study investigated the predictors of LNM and the long-term outcomes o...Background:The risk of lymph-node metastasis(LNM)in T1 colorectal cancer(CRC)has not been well documented in heterogeneous Western populations.This study investigated the predictors of LNM and the long-term outcomes of patients by analysing T1 CRC surgical specimens and patients’demographic data.Methods:Patients with surgically resected T1 CRC between 2004 and 2014 were identified from the Surveillance,Epidemiology,and End Results(SEER)database.Patients with multiple primary cancers,with neoadjuvant therapy,or without a confirmed histopathological diagnosis were excluded.Multivariate logistic-regression analysis was used to identify the predictors of LNM.Results:Of the 22,319 patients,10.6%had a positive lymph-node status based on the final pathology(nodal category:N19.6%,N21.0%).Younger age,female sex,Asian or African-American ethnicity,poor differentiation,and tumor site outside the rectum were significantly associated with LNM.Subgroup analyses for patients stratified by tumor site suggested that the rate of positive lymph-node status was the lowest in the rectum(hazard ratio:0.74;95%confidence interval:0.63–0.86).Conclusion:The risk of LNM was potentially lower in Caucasian patients than in API or African-American patients with surgically resected T1 CRC.Regarding the T1 CRC site,the rectum was associated with a lower risk of LNM.展开更多
BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.A...BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.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
BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector compu...BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector computed tomography(MDCT)and gastrointestinal endoscopy for GC screening,preoperative staging,and lymph node metastasis detection,thereby providing a reference for clinical diagnosis and treatment.METHODS In this retrospective study clinical and imaging data of 134 patients with suspected GC who were admitted between January 2023 and October 2024 were initially reviewed.According to the inclusion and exclusion criteria,102 patients were finally enrolled in the analysis.All enrolled patients had undergone both MDCT and gastrointestinal endoscopy examinations prior to surgical intervention.Preoperative clinical staging and lymph node metastasis findings were compared with pathological results.RESULTS The combined use of MDCT and gastrointestinal endoscopy demonstrated a sensitivity of 98.53%,specificity of 97.06%,accuracy of 98.04%,positive predictive value of 98.53%,and negative predictive value of 97.06%for diagnosing GC.These factors were all significantly higher than those of MDCT or endoscopy alone(P<0.05).The accuracy rates of the combined approach for detecting clinical T and N stages were 97.06%and 92.65%,respectively,outperforming MDCT alone(86.76% and 79.41%)and endoscopy alone(85.29% and 70.59%)(P<0.05).Among 68 patients with confirmed GC,50(73.53%)were pathologically diagnosed with lymph node metastasis.The accuracy for detecting lymph node metastasis was 66.00%with endoscopy,76.00%with MDCT,and 92.00% with the combined approach,all with statistically significant differences(P<0.05).CONCLUSION The combined application of MDCT and gastrointestinal endoscopy enhanced diagnostic accuracy for GC,provided greater consistency in preoperative staging,and improved the detection of lymph node metastasis,thereby demonstrating significant clinical utility.展开更多
Background:In addition to the stepwise manner of lymph-node metastasis from the primary tumour,the skip lymph-node metastasis(SLNM)was identified as a low-incidence metastasis of gastric cancer(GC).So far,both the mec...Background:In addition to the stepwise manner of lymph-node metastasis from the primary tumour,the skip lymph-node metastasis(SLNM)was identified as a low-incidence metastasis of gastric cancer(GC).So far,both the mechanism and outcome of SLNM have not been elucidated completely.The purpose of this study was to analyse the clinical significance and the potential mechanism of SLNM in GC patients who had lymph-node metastasis.Methods:Clinicopathological data and follow-up information of 505 GC patients who had lymph-node metastasis were analysed to demonstrate the significance of SLNM in evaluating the prognostic outcome.According to the pathological results,all GC patients who had lymph-node metastasis were categorized into three groups:patients with the perigastric lymphnode metastasis,patients with the perigastric and extragastric lymph-node metastasis and patients with SLNM.Results:Among the 505 GC patients who had lymph-node metastasis,24(4.8%)had pathologically identified SLNM.The location of lymph-node metastasis was not significantly associated with 5-year survival rate and overall survival(OS)(P=0.194).The stratified survival analysis results showed that the status of SLNM was significantly associated with the OS in patients with pN1 GC(P=0.001).The median OS was significantly shorter in 19 pN1 GC patients with SLNM than in 100 patients with perigastric lymph-node metastasis(P<0.001).The case–control matched logistic regression analysis results showed that tumour size(P=0.002)was the only clinicopathological factor that may predict SLNM in pN1 GC patients undergoing curative surgery.Among the 19 pN1 GC patients with SLNM,17(89.5%)had metastatic lymph nodes along the common hepatic artery,around the celiac artery or in the hepatoduodenal ligament.Conclusions:SLNM may be considered a potentially practicable indicator for prognosis among various subgroups of pN1 GC patients.展开更多
Background and objective:Biomarkers are important tools for prompt diagnosis of cancer.This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node(LN)me...Background and objective:Biomarkers are important tools for prompt diagnosis of cancer.This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node(LN)metastasis.Methods:Between 1 December 2014 and 31 December 2015,we prospectively collected samples of gastric-cancer tissues,corresponding matched-pair normal gastric mucosa,and their peri-gastric metastatic and non-metastatic LNs to identify quantitatively reliable genes using quantitative real-time polymerase chain reaction.Relative quantity(RQ)was used to calculate the mRNA expression levels of our target genes.Statistics were calculated using one-way analysis of variance(ANOVA)and Tukey’s multiple comparison test.Analytical graphs were plotted using GraphPad Prism.Results:Of nine assessed genes,the mRNA levels of inhibin beta A(INHBA)and secreted phosphoprotein 1(SPP1)were most consistently highly expressed in tumor tissues by 15.4-and 15.6-fold,respectively,as compared with normal tissues(P<0.001),with 91.3%sensitivity and 95.7%specificity(receiver operating characteristic[ROC]curve area=0.974)for the former and 82.6%sensitivity and 87.0%specificity(ROC curve area=0.924)for the latter.Further analysis revealed no differentiating significance of SPP1 mRNA expression between metastatic and non-metastatic LNs(P=0.470).In contrast,the INHBA mRNA level was up-regulated 4.1-fold in metastatic LNs(P<0.001),with 80.0%sensitivity and 81.5%specificity(ROC curve area=0.857),and was also able to successfully differentiate between more severe disease conditions,T3 and T4(P=0.003),M0 and M1(P=0.043)and different histological variants(intestinal type vs diffuse type,P=0.019).Conclusions:Our results showed that INHBA was the most optimally reliable biomarker for diagnosing gastric cancer and LN metastasis.展开更多
BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notabl...BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notably China,reports disproportionately high GC incidences.The disease often progresses asymptoma-tically in the early stages,leading to delayed diagnosis and compromised out-comes.Thus,it is crucial to identify early diagnostic biomarkers and enhance treatment strategies to improve patient outcomes and reduce mortality.METHODS Retrospectively analyzed the clinical data of 148 patients with GC treated at the Civil Aviation Shanghai Hospital between December 2022 and December 2023.The associations of coagulation indices-partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen,fibrinogen degradation products(FDP),fasting blood glucose,and D-dimer(D-D)with TNM stage and distant metastasis were examined.RESULTS Prolongation of APTT,PT,and TT was significantly correlated with the GC TNM stage.Hence,abnormal coagulation system activation was closely related to disease progression.Elevated FDP and D-D were significantly associated with distant metastasis in GC(P<0.05),suggesting that increased fibrinolytic activity contributes to increased metastatic risk.CONCLUSION Our Results reveal coagulation indices,FDPs as GC biomarkers,reflecting abnormal coagulation/fibrinolysis,aiding disease progression,metastasis prediction,and helping clinicians assess thrombotic risk for early intervention and personalized treatment plans.展开更多
BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors...BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.展开更多
Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surge...Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.展开更多
Bone metastasis is the primary cause of mortality in breast cancer(BC)patients.The present study elucidates the functional role of the differentiated embryonic chondrocyte-expressed gene 1(DEC1)in promoting BC-related...Bone metastasis is the primary cause of mortality in breast cancer(BC)patients.The present study elucidates the functional role of the differentiated embryonic chondrocyte-expressed gene 1(DEC1)in promoting BC-related bone metastasis.Analysis of patient-derived samples and public databases revealed a significant upregulation of DEC1 and CXCR4 in breast tumors compared with adjacent normal tissues,with elevated levels correlating with increased metastatic potential,suggesting their synergistic involvement in BC progression.Intracardiac injection experiments demonstrated that Dec1-WT 4T1 cells induced more severe osteolysis and larger metastatic lesions than Dec1-KD 4T1 cells.In MDA-MB-231 cells,DEC1 overexpression(OE)upregulated CXCR4 and proliferation/migration-related genes,whereas DEC1 knockdown reversed these effects.Notably,AMD3100,a specific CXCR4 antagonist,partially reversed the DEC1-OE-induced upregulation of CXCR4 and associated pro-metastatic genes.Mechanistically,DEC1 bound to the CXCR4 promoter region(-230 to-326)and activated its transcription,corroborated by ChIP-seq data.Furthermore,pharmacological inhibition of AKT(LY294002)or JAK2(AZD1480),but not ERK(PD98059),attenuated DEC1-mediated CXCR4 upregulation,although all three inhibitors mitigated DEC1-driven migration-related gene expression.Additionally,DEC1 enhanced CXCL12 secretion from mesenchymal stromal cells and osteoblasts,amplifying the CXCR4/CXCL12 axis within the bone microenvironment.Collectively,our findings demonstrate that DEC1 promotes BC bone metastasis by directly transactivating CXCR4 expression,providing a molecular basis for targeting DEC1 to prevent and treat BC bone metastasis.展开更多
BACKGROUND Acinic cell carcinoma(ACC)is a malignant epithelial neoplasm that commonly occurs in the parotid gland.It is known to have a high recurrence rate and the potential to metastasize to the lung or cervical lym...BACKGROUND Acinic cell carcinoma(ACC)is a malignant epithelial neoplasm that commonly occurs in the parotid gland.It is known to have a high recurrence rate and the potential to metastasize to the lung or cervical lymph nodes.However,few cases of ACC with bone metastasis have been reported in the medical literature.CASE SUMMARY The clinical significance of this case report lies in the unique site of occurrence of the metastasis:To the best of our knowledge,this report is the only literature documenting ACC arising in a shoulder mass.CONCLUSION Unusual presentations of uncommon malignancies can present diagnostic challenges for both surgeons and histopathologists.It is important to be aware of these rare occurrences in order to provide the best possible treatment for patients.展开更多
BACKGROUND Gastric cancer is the fifth most common cancer and the fourth leading cause of death worldwide.Most cases of newly diagnosed gastric cancer involve not only locally advanced tumor growth and regional lymph ...BACKGROUND Gastric cancer is the fifth most common cancer and the fourth leading cause of death worldwide.Most cases of newly diagnosed gastric cancer involve not only locally advanced tumor growth and regional lymph node metastases but also distant metastases.We report a rare case finding of a mass in the right inguinal area which is derived from gastric cancer.CASE SUMMARY A 68-year-old male initially diagnosed with an inguinal hernia presented with a 2 cm mass in the right inguinal area.Gastrointestinal symptoms led to the discovery of a stomach tumor.Biopsy confirmed gastrointestinal adenocarcinoma.The diagnosis was advanced gastric cancer with peritoneal dissemination,and the inguinal mass was due to direct infiltration.Due to gastrointestinal bleeding,the patient underwent palliative gastrectomy and lymph node dissection.Postoperatively,the patient received hyperthermic intraperitoneal chemotherapy and localized radiation therapy.CONCLUSION This case indicates that a systematic evaluation should be conducted during the initial consultation to explore the potential connection between unrecognized distant masses and the primary tumor.展开更多
Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-...Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].展开更多
BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicat...BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicator,typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes.Contralateral axillary metastasis(CAM)without ipsilateral involvement is exceedingly rare,particularly in early-stage breast cancer.This report presents a case of CAM in a patient with triple-negative breast cancer(TNBC),underscoring diagnostic and therapeutic complexities.CASE SUMMARY A 73-year-old female presented with left-sided early-stage IDC in February 2023.Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes,a postoperative positron emission tomography(PET)scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla.Biopsy confirmed metastatic ductal carcinoma with triple-negative status,resulting in an upstaged diagnosis of metastatic breast cancer,stage IV,M1.The patient underwent six cycles of adjuvant chemotherapy,with follow-up PET imaging showing regression of the contralateral lesion.This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.CONCLUSION This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.展开更多
Osteocytes are the main cells in mineralized bone tissue.Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma.However,their precise contribution to bone metastasis rem...Osteocytes are the main cells in mineralized bone tissue.Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma.However,their precise contribution to bone metastasis remains unclear.Here,we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death.Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death.We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone metastasis.HMOX1 was identified as a crucial regulatory factor in this process,directly involved in inducing ferroptosis and affecting osteocyte viability.We uncover a non-canonical pathway that involves excessive autophagy-mediated ferritin degradation,highlighting the complex relationship between autophagy and ferroptosis in melanoma-induced osteocyte death.In addition,HIF1αpathway was shown as an upstream regulator,providing a potential target for modulating HMOX1 expression and influencing autophagy-dependent ferroptosis.In conclusion,our study provides insight into the pathogenic mechanisms of osteocyte death induced by melanoma bone metastasis,with a specific focus on ferroptosis and its regulation.This would enhance our comprehension of melanoma-induced osteocyte death.展开更多
BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is...BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is even less common.CASE SUMMARY A 58-year-old male with known history of RCC presented with a recurrence that was diagnosed through imaging and biopsies.Mucosa abnormalities of small bowel noted during endoscopy were biopsied as well as lesion in the psoas muscle that was noted.CONCLUSION This case report emphasizes that RCC can not only recur but can do so even decades later and present as metastatic foci at atypical sites.展开更多
The incidence of gastric cancer is currently increasing,with gastrectomy and D2 Lymphadenectomy being the primary treatments for resectable gastric cancer.For advanced or unresectable metastatic gastric cancer,systemi...The incidence of gastric cancer is currently increasing,with gastrectomy and D2 Lymphadenectomy being the primary treatments for resectable gastric cancer.For advanced or unresectable metastatic gastric cancer,systemic treatment options include chemotherapy,targeted therapy,or immunotherapy.Krukenberg tumours are types of metastatic tumours in the ovaries that exclusively occur in female patients and that originate from the stomach.Previously deemed an incurable stage of advanced disease,the prognosis of patients with ovarian metastases from gastric cancer depends on multiple factors,including tumour biology and treatment response.With the development of comprehensive cancer treatment options,the combination of surgery and chemotherapy has gradually become the primary treatment for patients with ovarian metastasis from gastric cancer.Individualised comprehensive treatment regimens are crucial for improving patient outcomes.This review summarises the comprehensive treatment strategies for ovarian metastasis from gastric cancer.展开更多
Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance me...Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism.We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib.Method:A 53-year-old,never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer(NSCLC)developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg.Salvage therapy with zorifertinib(200 mg BID)plus firmonertinib(80 mg qd)was initiated.Results:Within 14 days,the coma resolved.Karnofsky Performance Status improved from 20 to 70.Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1.Only grade 1-2 diarrhea,rash,and transaminitis occurred and resolved with symptomatic care.Conclusion:The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure.Prospective validation is warranted.展开更多
Background:The prognosis of stage IV non-small cell lung cancer(NSCLC)with pleural metastasis is poor,with a 5-year survival rate of only 2%to 4%for patients,with the median survival was 9.5-11.5 months.According to ...Background:The prognosis of stage IV non-small cell lung cancer(NSCLC)with pleural metastasis is poor,with a 5-year survival rate of only 2%to 4%for patients,with the median survival was 9.5-11.5 months.According to the“NCCN Lung Cancer Guidelines,”stage IV NSCLC lung cancer is a contraindication for surgery.It is recommended to adopt a standard treatment plan mainly based on chemotherapy or targeted therapy with EGFR-TKIs.However,Neoadjuvant therapy with alectinib for non-small cell lung cancer with pleural metastasis is rarely reported.Case presentation:A 41-year-old Asian male patient presented with a persistent cough for one month.A chest computed tomography(CT)scan conducted two years prior revealed that a nodular radiative anomalous concentrated shadow was observed in the inferior tongue segment of the upper lobe of the left lung,approximately 2.2×1.6×1.2 cm in size,with a SUVmax of about 5.5.Two small nodular shadows were seen beside the disease in the inferior lingual segment of the upper lobe of the left lung,with the larger one having a diameter of approximately 0.6 cm.Multiple lymph node metastases in the left hilum and mediastinum;Multiple metastases of the left pleura and a small amount of pleural effusion on the left side.The patient began to receive 2 courses of chemotherapy and targeted therapy(pemetrexed+carboplatin+crizotinib)and 1 course of chemotherapy and other targeted therapy(pemetrexed+carboplatin+alectinib).The result of re-examination of CT demonstrated that peripheral lung cancer in the lower lingual segment of the left upper lung is approximately 0.8×0.9 cm in size,slightly smaller than before.A thoracoscopic lobectomy was performed,and the pulmonary bulla was removed concurrently.Pathological examination confirmed non-small cell lung carcinoma(NSCLC)in the mass.Patient discharged on the 7th day after the operation and received 2 courses of chemotherapy(pemetrexed+carboplatin)and had been receiving alectinib targeted drug treatment all along for over 5 years.However,the patient stopped taking the medicine on his own for half a year.Though in the recent CT examination,the result demonstrated no recurrence and metastasis and the patient has been clinically cured.Unfortunately,the results of brain magnetic resonance imaging suggested that multiple brain metastases of lung cancer occurred,and the patient began taking the third-generation ALK-targeted drug lorlatinib.Conclusions:The patient with stage IV non-small cell lung cancer(NSCLC)presenting with pleural metastasis received neoadjuvant alectinib therapy and underwent thoracoscopic lobectomy,which resulted in significant therapeutic effects and fulfilled the criteria for clinical cure.This case highlights the potential for improved preventative strategies and treatment approaches in similar patients.展开更多
文摘It has been reported recently that small undifferentiated intramucosal early gastric cancer(EGC) < 20 mm in size without any lymphovascular involvement or ulcerative findings had virtually no risk of lymph-node(LN) metastasis.Consequently,the indications for endoscopic resection were expanded to include such undifferentiated EGC lesions.We describe herein a case of a small undifferentiated intramucosal EGC < 20 mm in size without lymphovascular involvement or ulcerative findings that involved lymph-node metastasis.A 57-year-old female underwent pylorus preserving gastrectomy as standard treatment for an undifferentiated EGC 15 mm in size without any ulcerative finding.The surgical specimen revealed a signet-ring cell carcinoma with a moderately to poorly differentiated adenocarcinoma limited to the mucosa that was 15 mm in size with no lymphovascular involvement or ulcerative findings.This case involved LN metastasis,however,and the lesion was diagnosed as pathological stage ⅡA(T1N2M0) according to the Japanese Classification of Gastric Carcinoma.
基金supported by the National Natural Science Foundation of China[grant numbers 81860433,81860466]the Guangdong Provincial Science and Technology Plan and Jiangxi Provincial Science and Technology Plan[grant numbers 2017A020215036,20192BAB215036]+3 种基金the National Natural Science Foundation of China[Grant Number:81860433]Training Plan for Academic and Technical Young Leaders of Major Disciplines in Jiangxi Province[Grant Number:20204BCJ23021]the Key Technology Research and Development Program of Jiangxi Province[Grant Number:20202BBG73024]the Foundation for Fostering Young Scholar of Nanchang Universiy[Grant Number:PY201822].
文摘Background:The risk of lymph-node metastasis(LNM)in T1 colorectal cancer(CRC)has not been well documented in heterogeneous Western populations.This study investigated the predictors of LNM and the long-term outcomes of patients by analysing T1 CRC surgical specimens and patients’demographic data.Methods:Patients with surgically resected T1 CRC between 2004 and 2014 were identified from the Surveillance,Epidemiology,and End Results(SEER)database.Patients with multiple primary cancers,with neoadjuvant therapy,or without a confirmed histopathological diagnosis were excluded.Multivariate logistic-regression analysis was used to identify the predictors of LNM.Results:Of the 22,319 patients,10.6%had a positive lymph-node status based on the final pathology(nodal category:N19.6%,N21.0%).Younger age,female sex,Asian or African-American ethnicity,poor differentiation,and tumor site outside the rectum were significantly associated with LNM.Subgroup analyses for patients stratified by tumor site suggested that the rate of positive lymph-node status was the lowest in the rectum(hazard ratio:0.74;95%confidence interval:0.63–0.86).Conclusion:The risk of LNM was potentially lower in Caucasian patients than in API or African-American patients with surgically resected T1 CRC.Regarding the T1 CRC site,the rectum was associated with a lower risk of LNM.
文摘BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.
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.
文摘BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector computed tomography(MDCT)and gastrointestinal endoscopy for GC screening,preoperative staging,and lymph node metastasis detection,thereby providing a reference for clinical diagnosis and treatment.METHODS In this retrospective study clinical and imaging data of 134 patients with suspected GC who were admitted between January 2023 and October 2024 were initially reviewed.According to the inclusion and exclusion criteria,102 patients were finally enrolled in the analysis.All enrolled patients had undergone both MDCT and gastrointestinal endoscopy examinations prior to surgical intervention.Preoperative clinical staging and lymph node metastasis findings were compared with pathological results.RESULTS The combined use of MDCT and gastrointestinal endoscopy demonstrated a sensitivity of 98.53%,specificity of 97.06%,accuracy of 98.04%,positive predictive value of 98.53%,and negative predictive value of 97.06%for diagnosing GC.These factors were all significantly higher than those of MDCT or endoscopy alone(P<0.05).The accuracy rates of the combined approach for detecting clinical T and N stages were 97.06%and 92.65%,respectively,outperforming MDCT alone(86.76% and 79.41%)and endoscopy alone(85.29% and 70.59%)(P<0.05).Among 68 patients with confirmed GC,50(73.53%)were pathologically diagnosed with lymph node metastasis.The accuracy for detecting lymph node metastasis was 66.00%with endoscopy,76.00%with MDCT,and 92.00% with the combined approach,all with statistically significant differences(P<0.05).CONCLUSION The combined application of MDCT and gastrointestinal endoscopy enhanced diagnostic accuracy for GC,provided greater consistency in preoperative staging,and improved the detection of lymph node metastasis,thereby demonstrating significant clinical utility.
基金supported in part by grants from the Programs of National Natural Science Foundation of China(No.81572372)the National Key Research and Development Program‘Major Chronic Non-Infectious Disease Research’of China(No.2016YFC1303202)the National Key Research and Development Program‘Precision Medicine Research’of China(No.2017YFC0908304).
文摘Background:In addition to the stepwise manner of lymph-node metastasis from the primary tumour,the skip lymph-node metastasis(SLNM)was identified as a low-incidence metastasis of gastric cancer(GC).So far,both the mechanism and outcome of SLNM have not been elucidated completely.The purpose of this study was to analyse the clinical significance and the potential mechanism of SLNM in GC patients who had lymph-node metastasis.Methods:Clinicopathological data and follow-up information of 505 GC patients who had lymph-node metastasis were analysed to demonstrate the significance of SLNM in evaluating the prognostic outcome.According to the pathological results,all GC patients who had lymph-node metastasis were categorized into three groups:patients with the perigastric lymphnode metastasis,patients with the perigastric and extragastric lymph-node metastasis and patients with SLNM.Results:Among the 505 GC patients who had lymph-node metastasis,24(4.8%)had pathologically identified SLNM.The location of lymph-node metastasis was not significantly associated with 5-year survival rate and overall survival(OS)(P=0.194).The stratified survival analysis results showed that the status of SLNM was significantly associated with the OS in patients with pN1 GC(P=0.001).The median OS was significantly shorter in 19 pN1 GC patients with SLNM than in 100 patients with perigastric lymph-node metastasis(P<0.001).The case–control matched logistic regression analysis results showed that tumour size(P=0.002)was the only clinicopathological factor that may predict SLNM in pN1 GC patients undergoing curative surgery.Among the 19 pN1 GC patients with SLNM,17(89.5%)had metastatic lymph nodes along the common hepatic artery,around the celiac artery or in the hepatoduodenal ligament.Conclusions:SLNM may be considered a potentially practicable indicator for prognosis among various subgroups of pN1 GC patients.
基金This work was supported by the Natural Science Foundation of Guangdong Province(Grant number 2015A030313089,2018A030313631)Guangzhou University-Institute-Industry Collaborative Innovation Major Projects(Grant number 201508030042,201604020038)+1 种基金Center for Nasopharyngeal Carcinoma Research,Hong Kong(Grant number AoE/M-06/08)Shenzhen Dept.of Science and Information(Grant number JCYJ20130329110752138).
文摘Background and objective:Biomarkers are important tools for prompt diagnosis of cancer.This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node(LN)metastasis.Methods:Between 1 December 2014 and 31 December 2015,we prospectively collected samples of gastric-cancer tissues,corresponding matched-pair normal gastric mucosa,and their peri-gastric metastatic and non-metastatic LNs to identify quantitatively reliable genes using quantitative real-time polymerase chain reaction.Relative quantity(RQ)was used to calculate the mRNA expression levels of our target genes.Statistics were calculated using one-way analysis of variance(ANOVA)and Tukey’s multiple comparison test.Analytical graphs were plotted using GraphPad Prism.Results:Of nine assessed genes,the mRNA levels of inhibin beta A(INHBA)and secreted phosphoprotein 1(SPP1)were most consistently highly expressed in tumor tissues by 15.4-and 15.6-fold,respectively,as compared with normal tissues(P<0.001),with 91.3%sensitivity and 95.7%specificity(receiver operating characteristic[ROC]curve area=0.974)for the former and 82.6%sensitivity and 87.0%specificity(ROC curve area=0.924)for the latter.Further analysis revealed no differentiating significance of SPP1 mRNA expression between metastatic and non-metastatic LNs(P=0.470).In contrast,the INHBA mRNA level was up-regulated 4.1-fold in metastatic LNs(P<0.001),with 80.0%sensitivity and 81.5%specificity(ROC curve area=0.857),and was also able to successfully differentiate between more severe disease conditions,T3 and T4(P=0.003),M0 and M1(P=0.043)and different histological variants(intestinal type vs diffuse type,P=0.019).Conclusions:Our results showed that INHBA was the most optimally reliable biomarker for diagnosing gastric cancer and LN metastasis.
文摘BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notably China,reports disproportionately high GC incidences.The disease often progresses asymptoma-tically in the early stages,leading to delayed diagnosis and compromised out-comes.Thus,it is crucial to identify early diagnostic biomarkers and enhance treatment strategies to improve patient outcomes and reduce mortality.METHODS Retrospectively analyzed the clinical data of 148 patients with GC treated at the Civil Aviation Shanghai Hospital between December 2022 and December 2023.The associations of coagulation indices-partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen,fibrinogen degradation products(FDP),fasting blood glucose,and D-dimer(D-D)with TNM stage and distant metastasis were examined.RESULTS Prolongation of APTT,PT,and TT was significantly correlated with the GC TNM stage.Hence,abnormal coagulation system activation was closely related to disease progression.Elevated FDP and D-D were significantly associated with distant metastasis in GC(P<0.05),suggesting that increased fibrinolytic activity contributes to increased metastatic risk.CONCLUSION Our Results reveal coagulation indices,FDPs as GC biomarkers,reflecting abnormal coagulation/fibrinolysis,aiding disease progression,metastasis prediction,and helping clinicians assess thrombotic risk for early intervention and personalized treatment plans.
文摘BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.
基金supported by the National Natural Science Foundation of China(No.82272845)the Natural Science Foundation of Shandong(No.ZR2023ZD26).
文摘Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.
基金supported by the Natural Science Foundation of China(Grant Nos.82073934,81872937)Office of Jiangsu Provincial Academic Degrees Committee(Grant No.JX10114120).
文摘Bone metastasis is the primary cause of mortality in breast cancer(BC)patients.The present study elucidates the functional role of the differentiated embryonic chondrocyte-expressed gene 1(DEC1)in promoting BC-related bone metastasis.Analysis of patient-derived samples and public databases revealed a significant upregulation of DEC1 and CXCR4 in breast tumors compared with adjacent normal tissues,with elevated levels correlating with increased metastatic potential,suggesting their synergistic involvement in BC progression.Intracardiac injection experiments demonstrated that Dec1-WT 4T1 cells induced more severe osteolysis and larger metastatic lesions than Dec1-KD 4T1 cells.In MDA-MB-231 cells,DEC1 overexpression(OE)upregulated CXCR4 and proliferation/migration-related genes,whereas DEC1 knockdown reversed these effects.Notably,AMD3100,a specific CXCR4 antagonist,partially reversed the DEC1-OE-induced upregulation of CXCR4 and associated pro-metastatic genes.Mechanistically,DEC1 bound to the CXCR4 promoter region(-230 to-326)and activated its transcription,corroborated by ChIP-seq data.Furthermore,pharmacological inhibition of AKT(LY294002)or JAK2(AZD1480),but not ERK(PD98059),attenuated DEC1-mediated CXCR4 upregulation,although all three inhibitors mitigated DEC1-driven migration-related gene expression.Additionally,DEC1 enhanced CXCL12 secretion from mesenchymal stromal cells and osteoblasts,amplifying the CXCR4/CXCL12 axis within the bone microenvironment.Collectively,our findings demonstrate that DEC1 promotes BC bone metastasis by directly transactivating CXCR4 expression,providing a molecular basis for targeting DEC1 to prevent and treat BC bone metastasis.
文摘BACKGROUND Acinic cell carcinoma(ACC)is a malignant epithelial neoplasm that commonly occurs in the parotid gland.It is known to have a high recurrence rate and the potential to metastasize to the lung or cervical lymph nodes.However,few cases of ACC with bone metastasis have been reported in the medical literature.CASE SUMMARY The clinical significance of this case report lies in the unique site of occurrence of the metastasis:To the best of our knowledge,this report is the only literature documenting ACC arising in a shoulder mass.CONCLUSION Unusual presentations of uncommon malignancies can present diagnostic challenges for both surgeons and histopathologists.It is important to be aware of these rare occurrences in order to provide the best possible treatment for patients.
文摘BACKGROUND Gastric cancer is the fifth most common cancer and the fourth leading cause of death worldwide.Most cases of newly diagnosed gastric cancer involve not only locally advanced tumor growth and regional lymph node metastases but also distant metastases.We report a rare case finding of a mass in the right inguinal area which is derived from gastric cancer.CASE SUMMARY A 68-year-old male initially diagnosed with an inguinal hernia presented with a 2 cm mass in the right inguinal area.Gastrointestinal symptoms led to the discovery of a stomach tumor.Biopsy confirmed gastrointestinal adenocarcinoma.The diagnosis was advanced gastric cancer with peritoneal dissemination,and the inguinal mass was due to direct infiltration.Due to gastrointestinal bleeding,the patient underwent palliative gastrectomy and lymph node dissection.Postoperatively,the patient received hyperthermic intraperitoneal chemotherapy and localized radiation therapy.CONCLUSION This case indicates that a systematic evaluation should be conducted during the initial consultation to explore the potential connection between unrecognized distant masses and the primary tumor.
文摘Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].
文摘BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicator,typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes.Contralateral axillary metastasis(CAM)without ipsilateral involvement is exceedingly rare,particularly in early-stage breast cancer.This report presents a case of CAM in a patient with triple-negative breast cancer(TNBC),underscoring diagnostic and therapeutic complexities.CASE SUMMARY A 73-year-old female presented with left-sided early-stage IDC in February 2023.Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes,a postoperative positron emission tomography(PET)scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla.Biopsy confirmed metastatic ductal carcinoma with triple-negative status,resulting in an upstaged diagnosis of metastatic breast cancer,stage IV,M1.The patient underwent six cycles of adjuvant chemotherapy,with follow-up PET imaging showing regression of the contralateral lesion.This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.CONCLUSION This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.
基金funding from the European Research Council(ERC)under the european union Horizon 2020 research and innovation program(grant agreement ERC co-LS4 ODE(AB)and ERC Synergy Grant 4D Nanoscope(GS))Deutsche Forschungsgemeinschaft DFG-Project number 501752319-TRR369-DIONE-Project No A02 and B05,FOR 2886(TP02),CRC1181(TPA01)DFG funding(450993414)Thunder Imager and the Leibniz Award(GS)。
文摘Osteocytes are the main cells in mineralized bone tissue.Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma.However,their precise contribution to bone metastasis remains unclear.Here,we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death.Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death.We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone metastasis.HMOX1 was identified as a crucial regulatory factor in this process,directly involved in inducing ferroptosis and affecting osteocyte viability.We uncover a non-canonical pathway that involves excessive autophagy-mediated ferritin degradation,highlighting the complex relationship between autophagy and ferroptosis in melanoma-induced osteocyte death.In addition,HIF1αpathway was shown as an upstream regulator,providing a potential target for modulating HMOX1 expression and influencing autophagy-dependent ferroptosis.In conclusion,our study provides insight into the pathogenic mechanisms of osteocyte death induced by melanoma bone metastasis,with a specific focus on ferroptosis and its regulation.This would enhance our comprehension of melanoma-induced osteocyte death.
文摘BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is even less common.CASE SUMMARY A 58-year-old male with known history of RCC presented with a recurrence that was diagnosed through imaging and biopsies.Mucosa abnormalities of small bowel noted during endoscopy were biopsied as well as lesion in the psoas muscle that was noted.CONCLUSION This case report emphasizes that RCC can not only recur but can do so even decades later and present as metastatic foci at atypical sites.
基金Supported by Quanzhou Science and Technology Plan Projects,No.2024NY033Fujian Provincial Health and Youth Research Project,No.2022QNA066.
文摘The incidence of gastric cancer is currently increasing,with gastrectomy and D2 Lymphadenectomy being the primary treatments for resectable gastric cancer.For advanced or unresectable metastatic gastric cancer,systemic treatment options include chemotherapy,targeted therapy,or immunotherapy.Krukenberg tumours are types of metastatic tumours in the ovaries that exclusively occur in female patients and that originate from the stomach.Previously deemed an incurable stage of advanced disease,the prognosis of patients with ovarian metastases from gastric cancer depends on multiple factors,including tumour biology and treatment response.With the development of comprehensive cancer treatment options,the combination of surgery and chemotherapy has gradually become the primary treatment for patients with ovarian metastasis from gastric cancer.Individualised comprehensive treatment regimens are crucial for improving patient outcomes.This review summarises the comprehensive treatment strategies for ovarian metastasis from gastric cancer.
文摘Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism.We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib.Method:A 53-year-old,never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer(NSCLC)developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg.Salvage therapy with zorifertinib(200 mg BID)plus firmonertinib(80 mg qd)was initiated.Results:Within 14 days,the coma resolved.Karnofsky Performance Status improved from 20 to 70.Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1.Only grade 1-2 diarrhea,rash,and transaminitis occurred and resolved with symptomatic care.Conclusion:The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure.Prospective validation is warranted.
基金Guangzhou Municipal Health Commission Project(Project No.:2023C-TS17)。
文摘Background:The prognosis of stage IV non-small cell lung cancer(NSCLC)with pleural metastasis is poor,with a 5-year survival rate of only 2%to 4%for patients,with the median survival was 9.5-11.5 months.According to the“NCCN Lung Cancer Guidelines,”stage IV NSCLC lung cancer is a contraindication for surgery.It is recommended to adopt a standard treatment plan mainly based on chemotherapy or targeted therapy with EGFR-TKIs.However,Neoadjuvant therapy with alectinib for non-small cell lung cancer with pleural metastasis is rarely reported.Case presentation:A 41-year-old Asian male patient presented with a persistent cough for one month.A chest computed tomography(CT)scan conducted two years prior revealed that a nodular radiative anomalous concentrated shadow was observed in the inferior tongue segment of the upper lobe of the left lung,approximately 2.2×1.6×1.2 cm in size,with a SUVmax of about 5.5.Two small nodular shadows were seen beside the disease in the inferior lingual segment of the upper lobe of the left lung,with the larger one having a diameter of approximately 0.6 cm.Multiple lymph node metastases in the left hilum and mediastinum;Multiple metastases of the left pleura and a small amount of pleural effusion on the left side.The patient began to receive 2 courses of chemotherapy and targeted therapy(pemetrexed+carboplatin+crizotinib)and 1 course of chemotherapy and other targeted therapy(pemetrexed+carboplatin+alectinib).The result of re-examination of CT demonstrated that peripheral lung cancer in the lower lingual segment of the left upper lung is approximately 0.8×0.9 cm in size,slightly smaller than before.A thoracoscopic lobectomy was performed,and the pulmonary bulla was removed concurrently.Pathological examination confirmed non-small cell lung carcinoma(NSCLC)in the mass.Patient discharged on the 7th day after the operation and received 2 courses of chemotherapy(pemetrexed+carboplatin)and had been receiving alectinib targeted drug treatment all along for over 5 years.However,the patient stopped taking the medicine on his own for half a year.Though in the recent CT examination,the result demonstrated no recurrence and metastasis and the patient has been clinically cured.Unfortunately,the results of brain magnetic resonance imaging suggested that multiple brain metastases of lung cancer occurred,and the patient began taking the third-generation ALK-targeted drug lorlatinib.Conclusions:The patient with stage IV non-small cell lung cancer(NSCLC)presenting with pleural metastasis received neoadjuvant alectinib therapy and underwent thoracoscopic lobectomy,which resulted in significant therapeutic effects and fulfilled the criteria for clinical cure.This case highlights the potential for improved preventative strategies and treatment approaches in similar patients.
