Immunohistochemical expression of matrix metalloproteinase-9 and 13 in oral squamous cell carcinoma and their role in predicting lymph node metastasis

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.

Scapular metastasis from acinic cell carcinoma of parotid gland:A case report

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.

Coagulation indices and fibrinogen degradation products as predictive biomarkers for tumor-node-metastasis staging and metastasis in gastric cancer

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.

Solitary extraovarian primary peritoneal carcinoma with direct invasion into the liver,diaphragm and lung without peritoneal dissemination or distant metastasis

To the Editor:Extraovarian primary peritoneal carcinoma(EOPPC)is an uncommon malignancy with many similarities to epithelial ovarian carcinoma in histological,clinical,and etiological aspects[1].This phenomenon is explained by their common embryonal origin,in which both develop from the coelomic epithelium in the early embryological stage.Despite their similarities,the incidence of EOPPC is significantly lower than that of epithelial ovarian carcinoma(6.78 cases per million vs.120.5 cases per million)[1].

Important role of lymphovascular and perineural invasion in prognosis of colorectal cancer patients with N1c disease

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.

Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells

BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.

Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging,invasion,and metastasis

BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.

Risk factors for lymph node metastasis and invasion depth in early gastric cancer:Analysis of 210 cases

BACKGROUND Gastric cancer is the leading cause of cancer-related deaths worldwide.Early gastric cancer(EGC)is often associated with the risk of lymph node metastasis,which influences treatment decisions.Despite the use of enhanced computed tomography,the prediction of lymph node involvement remains challenging.AIM To investigate the risk factors for lymph node metastasis and invasion depth in patients with EGC.METHODS In total,210 patients with pathologically diagnosed EGC were included in this study.Univariate and multivariate statistical analyses were used to predict risk factors for lymph node metastasis and invasion depth in patients with EGC.RESULTS Among the 210 patients,27(12.9%)had lymph node metastases.Of the 117 patients with submucosal gastric cancer,24(20.5%)had lymph node metastases.Both univariate and multivariate analyses indicated that the depth of invasion in EGC was a risk factor for lymph node metastasis in these patients.Additionally,pathological type was identified as a risk factor for cancer cell invasion in patients with EGC.CONCLUSION EGC invasion depth,not tumor type,size,age,sex,or location,predicts lymph node spread.Tumor type,not size,age,sex,or location,predicts cancer cell invasion.

Predicting preoperative lymph node metastasis in esophageal cancer:Advancement and challenges

Accurate preoperative prediction of lymph node metastasis is crucial for developing clinical management strategies for patients with esophageal cancer.In this letter,we present our insights and opinions on a new nomogram proposed by Xu et al.Although this research has great potential,there are still concerns re-garding the small sample size,limited consideration of biological complexity,subjective image segmentation,incomplete image feature extraction and statistical analyses.Furthermore,we discuss how to achieve more robust and accurate predictive performance in future research.

LncRNA PCAT6 promotes progression and metastasis of colonic neuroendocrine carcinoma via MAPK pathway

BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6(PCAT6)in the progression of colonic NEC.METHODS Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction(RT-qPCR)of PCAT6 mRNA level.Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice.The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis.The expression of epithelial-mesenchymal transition(EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting.CD56 expression was assessed by immunofluorescence staining.The biological functions of PCAT6 were examined by cell counting kit-8,colony formation assays,Transwell assays and wound healing assays.The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays.RESULTS LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells,and its high expression was positively correlated with poor prognosis in patients with colonic NEC.Additionally,the expression of PCAT6 was positively associated with the proliferation,migration,invasion,and EMT of LCC-18 cells.Moreover,PCAT6 facilitated tumor growth,lung metastasis and EMT in xenografts.Mechanistically,PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326.CONCLUSION In conclusion,lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326.These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.

Differentiating between immune checkpoint inhibitor-induced myocarditis and cardiac metastasis in a cardio-oncology patient presenting with myocardial infarction: A case report

BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemotherapy or radiation therapy related complications and cardiac metastasis.CASE SUMMARY We present a case of a 47-year-old female with metastatic cancer on immuno-therapy presented with anterior ST elevation myocardial infarction followed by emergent percutaneous coronary intervention in the left anterior descending artery.Echocardiography after 72 hours showed thickening of inferior wall and cardiac magnetic resonance depicted inflammation and necrosis attributable to either cardiac metastasis or immunotherapy induced myocarditis.Biopsy was not performed because of treatment with antiplatelet drugs and a definite diagnosis was achieved after probationary administration of high-dose intravenous methyl-prednisolone that led to recovery.CONCLUSION In patients with malignancy,chemotherapy-induced cardiovascular complications and cardiac metastasis are common concerns and may coexist with common acute cardiovascular diseases including acute coronary syndromes.In such cases clinical suspicion aided by multimodality imaging is crucial for the diagnosis.A multidisciplinary team approach is required for prompt initiation of the appro-priate treatment.

Enhancing rectal cancer liver metastasis prediction:Magnetic resonance imaging-based radiomics,bias mitigation,and regulatory considerations

In this article,we comment on the article by Long et al published in the recent issue of the World Journal of Gastrointestinal Oncology.Rectal cancer patients are at risk for developing metachronous liver metastasis(MLM),yet early prediction remains challenging due to variations in tumor heterogeneity and the limitations of traditional diagnostic methods.Therefore,there is an urgent need for noninvasive techniques to improve patient outcomes.Long et al’s study introduces an innovative magnetic resonance imaging(MRI)-based radiomics model that integrates high-throughput imaging data with clinical variables to predict MLM.The study employed a 7:3 split to generate training and validation datasets.The MLM prediction model was constructed using the training set and subsequently validated on the validation set using area under the curve(AUC)and dollar-cost averaging metrics to assess performance,robustness,and generalizability.By employing advanced algorithms,the model provides a non-invasive solution to assess tumor heterogeneity for better metastasis prediction,enabling early intervention and personalized treatment planning.However,variations in MRI parameters,such as differences in scanning resolutions and protocols across facilities,patient heterogeneity(e.g.,age,comorbidities),and external factors like carcinoembryonic antigen levels introduce biases.Additionally,confounding factors such as diagnostic staging methods and patient comorbidities require further validation and adjustment to ensure accuracy and generalizability.With evolving Food and Drug Administration regulations on machine learning models in healthcare,compliance and careful consideration of these regulatory requirements are essential to ensuring safe and effective implementation of this approach in clinical practice.In the future,clinicians may be able to utilize datadriven,patient-centric artificial intelligence(AI)-enhanced imaging tools integrated with clinical data,which would help improve early detection of MLM and optimize personalized treatment strategies.Combining radiomics,genomics,histological data,and demographic information can significantly enhance the accuracy and precision of predictive models.

Research progress on the effect of pyroptosis on the occurrence,development,invasion and metastasis of colorectal cancer

Pyroptosis is a type of programmed cell death mediated by gasdermines(GSDMs).The N-terminal domain of GSDMs forms pores in the plasma membrane,causing cell membrane rupture and the release of cell contents,leading to an inflammatory response and mediating pyrodeath.Pyroptosis plays an important role in inflammatory diseases and malignant tumors.With the further study of pyroptosis,an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence,development,treatment and prognosis of colorectal cancer.This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence,development,treatment and prognosis of colorectal cancer(CRC)and to provide ideas for the clinical diagnosis and treatment of CRC.

Relationship between the Expression of MTA1 Gene and Invasion and Metastasis of Human Osteosarcoma Cells

Objective： To compare the expression level of metastasis associated-1 （MTA1） in the higher and lower metastasis sublines of human osteosarcoma cells （MG63）, and to investigate the relationship between the expression level of MTA1-EGFP and in vitro invasion and metastasis of human osteosarcoma cells. Methods： The expression level of MTA1 in two sublines of MG63 cells was detected by semi-quantitative RT-PCR, and cell invasion assay and cell proliferation assay were used to evaluate the invasive capacity in vitro in two sublines. The lower metastasis line of MG-63 cells were transfected with MTA1-EGFP full-length cDNA expression plasmid by lipofectamine. The changes of the MTA1-EGFP expression and in vitro invasion potential were measured after transfection. Results： M8 subline expressed significantly higher level of MTA1 than that of M6 subline by RT-PCR. The invasive potentials of low metastasis MG63 cell line were increased after MTA1 gene transfection. Conclusion： There may be a relationship between MTA1 and invasive potentials of human osteosarcoma cells, and MTA1 may play a role in the molecular mechanism of tumor metastases and be a potential target for gene therapy of osteosarcoma. Further studies of MTA1 in human ostersarcoma cell metastasis are needed.

miR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis

AIM: To profile expression of microRNAs (miRNAs) in gastric cancer cells and investigate the effect of miR-374b-5p on gastric cancer cell invasion and metastasis.

Expression of MAPK1 in cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition,invasion and metastasis

Objective:To discuss the expression of mitogen-activated protein kinase 1(MAPK1) in the cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition and invasion and metastasis.Methods:Immunohistoehemistry,western blot and RT-PCR method were employed to detect the expression of MAPKl protein and mRNA in cervical cancer tissue and adjacent normal tissue.The constructed siRNA-MAPKI was transferred into human cervical cancer HeLa cells using Lipofectamine^(?)2000.MTT method was used to detect the cell vitality,transwell method to detect the cell invasion,and western blot to detect the expression of matrix metalloproteinases(MMP)-2,MMP-9,tissue inhibitor of metalloproteinase(TIMP)-1,TIMP-2,zinc finger transcription factor(Snail),epithelialmesenchymal transition related protein(EMT) E-cadherin and vimentin in cells.Results:The expression of MAPKl protein and mRNA in the cervical cancer tissue was significantly higher than the one in the adjacent normal tissue(P<0.01):after transfecting the siRNA-MAPKI into the human cervical cancer HeLa cells through liposome,compared with the control group,its cell vitality was significantly decreased(P<0.01),cell invasion was significantly decreased(P<0.01);expressed of MMP2.MMP-9,Snail and vimentin was significantly decreased(P<0.01),and expression of TIMP-1,TIMP-2 and E-cadherin was significantly increased(/J<0.01).Conclusions:Because of the high expression of MAPKl in the cervical cancer tissue,the interference in the expression of MAPK1 can significantly inhibit the invasion and metastasis of cervical cancer HeLa cells,which is related to the interference in the expression of MMPs/TIMP and Snail-mediated generation of EMT.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were independent influencing factors.The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824,respectively,which were slightly greater than those of CT-T and CT-EMVI(AUC=0.793,0.762).The nomogram combining CT-T stage,CT-EMVI,VP-70 keV and EP-NIC yielded AUCs of 0.918(0.866-0.954)and 0.874(0.784-0.936)in the training and validation cohorts,which are significantly higher than using each of single independent factors(P<0.05).CONCLUSION The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC,with accuracy boosted by integrating clinical markers.

Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFβ2/NF-κB/Kindlin-2 axis

Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.

Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

AIM To detect the expression of CD44v6 mRNA and nm23-H1 mRNA in hepatocellular carcinoma (HCC) by in situ hybridization, and to evaluate the relationship between their expression and also relationship between their expressions and tumor invasion and metastasis.METHODS CD44v6 cDNA probe was synthesized with PCR technique and the nm23-H1 cRNA probe by in vitro transcription. The expression of CD44v6 mRNA and nm23-H1 mRNA was detected by in situ hybridization.RESULTS In group with high invasion and metastasis potential, the positive rates of CD44v6 mRNA and nm23-H1 mRNA were 80% (8/10) and 40% (4/10), in group with poor invasion and metastasis potential, they were 21.7% (5/23) and 91.3% (21/23). There was a positive correlation between the expression of CD44v6 mRNA and tumor invasion and metastasis potential in HCC (P＜0.01), and a reverse correlation between the expression of nm23-H1 mRNA and tumor invasion and metastasis potential (P＜0.01) and a reverse correlation in the expression between CD44v6 mRNA and nm23-H1 mRNA in HCC (P＜0.01).CONCLUSION Detection of CD44v6 mRNA and nm23-H1 mRNA may be useful for tumor invasion and metastasis in HCC.INTRODUCTIONCD44 is a cell surface transmembrane glycoprotein. As a kind of adhesive molecule, it participates in cell-cell and cell-matrix adhesion and interactions. Many studies revealed a correlation between high-level expression of CD44, especially CD44v and tumor invasion, metastasis and prognosis. The exon 6v containing isoforms may be an independent diagnostic parameter[1,2]. Some other studies, however, had different results[3,4]. Some researches showed a reverse correlation between the expression of nm23-H1 mRNA and tumor metastasis[5,6]. In order to evaluate the relationship between the expression of CD44v6 mRNA and nm23-H1 mRNA and tumor invasive and metastatic potential in HCC and to evaluate the relationship in the expression between CD44v6 mRNA and nm23-H1 mRNA, we detected their expression in HCC by in situ hybridization.

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.