Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances withi...Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.展开更多
Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the ci...Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.展开更多
Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoct...Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoction in lung cancer treatment using network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction databases were used to screen the active ingredients of Baoyuan decoction and their relevant targets.Lung cancer-related targets were obtained from the GeneCards,Online Mendelian Inheritance in Man,and DrugBank databases.Protein-protein interaction network of the common targets was constructed using the STRING database and analyzed using Cytoscape software 3.10.1.Furthermore,Gene Ontology enrichment,Kyoto Encyclopedia of Genes and Genomes pathway analyses and visualization of common genes were performed using the R software.Finally,molecular docking of the selected key ingredients and targets was performed,and the results were verified using AutoDock Vina software.Results:We identified 142 potential active ingredients,3624 potential lung cancer-related targets,and 341 common drug targets.A total of 72 core targets were identified,of which AKT1,TP53,interleukin-6,epithelial growth factor receptor,and signal transducer and activator of transcription 3 were key.A total of 4116 items were obtained via Gene Ontology enrichment analyses.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 189 related signaling pathways,including the PI3K-Akt,AGE-RAGE signaling pathways in diabetic complications,FOXO,and TH signaling pathways,which are involved in cell proliferation,autophagy,metastasis,invasion,radiation resistance,and chemotherapy resistance in the lung cancer microenvironment.The molecular docking results suggested that the key ingredients had a strong affinity for key targets.Conclusion:This study demonstrates that Baoyuan decoction plays a key therapeutic role in a complex manner involving multiple ingredients,targets,and pathways in lung cancer.Our findings are anticipated to provide new ideas for follow-up experimental research and clinical application.展开更多
Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy people...Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.展开更多
Background:The ORAI family of proteins,comprising ORAI1,ORAI2,and ORAI3,plays a crucial role in the regulation of intracellular calcium signaling,which is essential for various cellular functions including proliferati...Background:The ORAI family of proteins,comprising ORAI1,ORAI2,and ORAI3,plays a crucial role in the regulation of intracellular calcium signaling,which is essential for various cellular functions including proliferation,differentiation,and apoptosis.Dysregulation of calcium signaling has been implicated in cancer pathogenesis,influencing tumor progression,metastasis,and resistance to therapy.This study aims to provide a comprehensive analysis of the ORAI family members across a broad spectrum of cancers.Methods:Publicly available datasets from The Cancer Genome Atlas and the Gene Expression Omnibus were utilized.RNA sequencing data,mutation profiles,copy number variation data,and methylation data across different cancer types were analyzed.Differential expression analysis,survival analysis,copy number variation analysis,mutation analysis,methylation analysis,immune cell infiltration analysis using the Cibersort algorithm,and gene set enrichment analysis were conducted using R software.Results:ORAI1 and ORAI3 were significantly upregulated in glioblastoma multiforme,whereas ORAI2 was notably downregulated in kidney chromophobe and pancreatic adenocarcinoma.ORAI2 exhibited higher mutation rates and copy number gains in multiple cancers compared to ORAI1 and ORAI3.The hypermethylation of ORAI2 in head and neck squamous cell carcinoma,esophageal carcinoma,and glioblastoma multiforme negatively correlated with its gene expression.ORAI1 and ORAI3 expression positively correlated with regulatory T cells infiltration,whereas ORAI2 showed a negative correlation with CD8^(+)T cell infiltration.Gene set enrichment analysis revealed that ORAI1 and ORAI2 are associated with immune-related pathways,while ORAI3 is linked to MYC targets and oxidative phosphorylation.Conclusion:Our pan-cancer analysis reveals significant differential expression,genomic alterations,and epigenetic regulation of ORAI family members across various cancers.ORAI1 and ORAI3 appear to promote an immunosuppressive environment,whereas ORAI2 may function as a tumor suppressor in certain contexts.These findings provide a foundation for future research targeting ORAI-mediated pathways in cancer therapy and highlight the therapeutic potential of ORAI proteins.展开更多
Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper pos...Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.展开更多
Background:The ORAI1 gene,central to store-operated calcium entry(SOCE),is increasingly recognized for its pivotal role in cancer progression and patient prognosis across a broad spectrum of malignancies.Despite its c...Background:The ORAI1 gene,central to store-operated calcium entry(SOCE),is increasingly recognized for its pivotal role in cancer progression and patient prognosis across a broad spectrum of malignancies.Despite its critical involvement in calcium signaling pathways that are essential for cellular functions such as proliferation,migration,and apoptosis,the comprehensive impacts of ORAI1 within the tumor microenvironment(TME)and its modulation across various cancers have not been fully elucidated.Methods:We conducted a pan-cancer analysis leveraging data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)to assess ORAI1 expression.Differential expression analyses were performed,complemented by correlative studies with tumor mutation burden(TMB),microsatellite instability(MSI),immune infiltration,and key biological processes and pathways.Results:Our results demonstrate that ORAI1 is consistently upregulated in a range of cancer types,associated with aggressive tumor characteristics and poor patient outcomes.Significantly,ORAI1 upregulation correlates with increased tumor mutation burden(TMB)and microsatellite instability(MSI),markers of genomic instability that are predictive of response to immunotherapy,underscoring its potential utility in clinical stratification and treatment decision-making.ORAI1's influence extended to the immune landscape,showing associations with immune cell infiltration and both immunosuppressive and immunostimulatory gene sets,thereby affecting the TME and possibly the efficacy of immunotherapeutic interventions.Conclusions:The multifaceted nature of ORAI1's involvement in cancer pathophysiology positions it as a prospective biomarker and therapeutic target.Its expression dynamics and correlative significance with prognostic and immune regulatory elements underscore its potential in guiding therapeutic strategies and improving clinical outcomes.This study lays a foundation for future research,aiming to leverage ORAI1's biological significance in cancer prognosis and therapy optimization.展开更多
Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing...Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.Methods:TFRC protein expression was obtained from Human Protein Altas(HPA).All datas were collected from TCGA and GTEx.In this study,we analyzed the expression of TFRC in cervical cancer and its clinical significance.Through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene set enrichment analyses(GSEA),investigated the related molecular pathways of TFRC.The relationship between TFRC and immune infiltration was then examined.The prognosis of different immune cell subsets was then analyzed after dividing cervical cancer patients into high and low expression of TFRC groups.Results:TFRC is highly expressed in various tumor tissues compared to control normal tissues,including cervical cancer.An increased expression of TFRC was associated with higher Tumor(T)and Node(N)stage,as well as a higher clinical stage.Kaplan–Meier(KM)survival analysis investigated that higher TFRC expression patients have a poor overall survival(OS),disease specific survival(DSS)and progress free interval(PFI).Both KEGG and GSEA enriched signaling pathway by high TFRC and low TFRC groups.There was a significant negative linear correlation between TFRC expression and immune infiltration.TFRC affects the prognosis of cervical cancer patients through immune pathway.Conclusions:Cervical cancer patients with TFRC expression may have a worse prognosis.展开更多
Background:The Fascin(FSCN)family,comprising actin-bundling proteins,plays vital roles in cytoskeletal reorganization and cell migration.FSCN1,FSCN2,and FSCN3 are implicated in cancer progression through cell motility...Background:The Fascin(FSCN)family,comprising actin-bundling proteins,plays vital roles in cytoskeletal reorganization and cell migration.FSCN1,FSCN2,and FSCN3 are implicated in cancer progression through cell motility,invasion,and metastasis.However,their specific contributions across different cancer types remain unclear.Methods:We conducted a pan-cancer bioinformatics analysis of FSCN genes using data from The Cancer Genome Atlas.This included differential expression patterns,copy number variations(CNVs),mutations,methylation status,and correlations with tumor mutational burden,microsatellite instability,and immune checkpoint molecule expression.Differential expression was analyzed using DESeq2,while CNV and mutation analyses utilized GISTIC2.0 and MuTect2.Methylation data were assessed using the Illumina Human Methylation 450K BeadChip.Results:FSCN1 and FSCN2 showed significant differential expression in multiple cancers,often correlating with poor prognosis.FSCN3 exhibited less variability but a protective role in certain contexts.CNV analysis indicated frequent gene gains in FSCN genes,correlating with increased expression.FSCN3 had a higher mutation rate,suggesting genetic instability.Methylation analysis showed hypomethylation of FSCN1 and FSCN2 in tumors compared to normal tissues,whereas FSCN3 had minor changes.Significant associations were found between FSCN gene expression and tumor mutational burden,microsatellite instability,and immune checkpoint molecules,suggesting their involvement in tumor immunogenicity and the immune microenvironment.Conclusions:This pan-cancer analysis highlights the multifaceted roles of FSCN genes in cancer biology,emphasizing their potential as biomarkers and therapeutic targets.FSCN1 and FSCN2 are associated with poor prognosis and aggressive phenotypes,while FSCN3 shows protective roles in specific contexts.These findings offer new avenues for cancer diagnosis and treatment,particularly in personalized medicine.Future studies should validate these findings and explore the underlying mechanisms to fully harness the clinical potential of FSCN family proteins in oncology.展开更多
Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is...Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.展开更多
Tumor immunotherapy has emerged as a promising method in cancer treatment,but patient responses vary,necessitating personalized strategies and prognostic biomarkers.This study aimed to identify prognostic factors and ...Tumor immunotherapy has emerged as a promising method in cancer treatment,but patient responses vary,necessitating personalized strategies and prognostic biomarkers.This study aimed to identify prognostic factors and construct a predictive model for patient survival outcomes and immunotherapy response.We curated six immunotherapy datasets representing diverse cancer types and treatment regimens.After data preprocessing,patients were stratified based on immunotherapy response.Differential gene expression analysis identified 22 genes consistently dysregulated across multiple datasets.Functional analysis provided critical insights,highlighting the enrichment of these dysregulated genes in immune response pathways and tumor microenvironment-related processes.To create a robust prognostic model,we meticulously employed a multistep approach.Initially,the identified 22 genes underwent rigorous univariate Cox regression analysis to evaluate their individual associations with patient survival outcomes.Genes showing statistical significance(p-values<0.05)at this stage advanced to the subsequent multivariate Cox regression analysis,which aimed to address potential confounding factors and collinearity among genes.From this analysis,we ultimately identified four key genes—ST6GALNAC2,SNORA65,MFAP2,and CDKN2B—that were significantly associated with patient survival outcomes.Incorporating these four key genes along with their corresponding coefficients,we constructed a predictive model.This model’s efficacy was validated through extensive Cox regression analyses,demonstrating its robustness in predicting patient survival outcomes.Furthermore,our model exhibited promising predictive capability for immunotherapy response,providing a potential tool for anticipating treatment efficacy.These findings provide insights into immunotherapy response mechanisms and suggest potential prognostic biomarkers for personalized treatment.Our study contributes to advancing cancer immunotherapy and personalized medicine.展开更多
Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC...Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.展开更多
Background:Our previous work demonstrated that Gekko sulfated glycopeptide extracted from the Chinese gecko Shou gong(Gekko swinhonis Guenther)could inhibit tumor growth by regulating basic fibroblast growth factor.Ho...Background:Our previous work demonstrated that Gekko sulfated glycopeptide extracted from the Chinese gecko Shou gong(Gekko swinhonis Guenther)could inhibit tumor growth by regulating basic fibroblast growth factor.However,basic fibroblast growth factor has opposing effects on growth in breast and liver cancers.Direct effects and mechanisms of Gekko sulfated glycopeptide on tumor growth remain unclear and are ripe for further exploration.Methods:Differential regulation by Gekko sulfated glycopeptide and bFGF were studied in established human breast cancer MCF-7 cells and hepatocarcinoma HepG2 cells.Cell proliferation was evaluated with a Trypan blue exclusion assay.Cell cycle phases were measured by flow cytometry.Basic fibroblast growth factor,transforming growth factor-β1,and p21WAF1/CIP1 mRNA and protein expression levels were detected by real-time PCR(mRNA)and ELISA(protein).Changes in phosphorylated extracellular signal-regulated kinase levels were analyzed by Western blot.Results:Data indicated that Gekko sulfated glycopeptide inhibited the proliferation of HepG2 cells(P<0.001)and also blocked basic fibroblast growth factor-stimulated proliferation of these cells(P=0.001).Gekko sulfated glycopeptide was shown to increase transforming growth factor-β1 and p21WAF1/CiP1 expression(P<0.01)and partially compensate for reductions therein induced by basic fibroblast growth factor.Conversely,in MCF-7 cells,Gekko sulfated glycopeptide alone had no observable effect on transforming growth factor-β1 and p21WAF1/CiP1 expression.Gekko sulfated glycopeptide did,however,enhance basic fibroblast growth factor-induced inhibition of cell proliferation and transforming growth factor-β1 and p21WAF1/CiP1 expression in the MCF-7 cells(P=0.001,P<0.01,P<0.01,respectively).Gekko sulfated glycopeptide was shown to suppress basic fibroblast growth factor secretion in both HepG2 and MCF-7 cell lines(P<0.05 and P<0.01,respectively)and inhibited extracellular signal-regulated kinase 1/2 phosphorylation facilitated by basic fibroblast growth factor.Gekko sulfated glycopeptide alone decreased phosphorylated extracellular signal-regulated kinase in HepG2 cells but did not visibly affect phosphorylated extracellular signal-regulated kinase levels in MCF-7 cells.Conclusions:Gekko sulfated glycopeptide,a basic fibroblast growth factor inhibitor,differentially regulates growth in different cancer cell lines,and these differences may be determined by the opposing effects of basic fibroblast growth factor on transforming growth factor-β1 and p21WAF1/CiP1 levels in breast and liver cancer cells.展开更多
Background:According to World Health Organization,colorectal cancer is the third most common cancer in the world.The prognosis assessment and condition judgment of the colorectal cancer remains a challenge clinically....Background:According to World Health Organization,colorectal cancer is the third most common cancer in the world.The prognosis assessment and condition judgment of the colorectal cancer remains a challenge clinically.Therefore,identification of diagnostic markers to evaluate the prognosis of colorectal cancer clinically should be urgently developed.We have observed that a lot of cancer patients had thick tongue clinically,but what is the relationship between tongue coating and the tumor?Methods:Seventy-four patients with colorectal carcinoma were collected through the outpatients of Tianjin Medical University Cancer Institute and Hospital from May 2010 to September 2011,in which there were 49 patients confirmed with recurrence or metastasis.All photos of patients’tongue were taken with a SONY camera in the same room and under constant conditions such as brightness or distance.Regression equation predicting thickness of tongue coating was constructed using binary logistic regression analysis.The optimal cut off of probabilities to diagnosis thick tongue coating was determined by receiver operating curve analysis.χ2 test for paired data and kappa test were used to determine the diagnostic value for recurrence and/or metastasis in colorectal cancer patients.Kolmogorov-Smirnov test was used to determine the distribution of ALT,AST,ALP ALB,TP,GLO,TBIL,DBIL,GGT,LDH,GLU,UA,CA724,CA199,CA242 and CEA.Data with the skewed distribution were presented as median(quartile interval).The association between the thickness of tongue coating and clinical-pathological character was evaluated by chi square test and two-independent-sample test.The two-independent-samplesχ2 was used to determine whether there were significant differences in the thin coating and thick coating between patients with recurrence and/or metastasis and patients without recurrence and/or metastasis.Kaplan-Meier method was used to analyze survival time.Statistical analysis was performed by SPSS(version 16.0).Results:Through retrospective clinical study we found that overall survival of colorectal cancer patients with thick greasy tongue coating is less than the patients with less tongue coating.What’s more,the risk for recurrence or/and metastasis overall survival in thick coating group was higher than thin coating group.In addition,the histological staining of the tongue slices of rats showed that EGFR receptors in the tongue root were the most among whole tongue surface.Tongue thick coating may be due to tumor patients with high levels of serum EGF which results in significantly increasing tongue coating.This finding suggested that the tongue coating of cancer patients may reflect the level of serum EGF levels in patients which may be related to shorter survival time.In addition,another study showed that serum lactic dehydrogenase level in patients with thick tongue coating is higher than patients with thin tongue coating.Conclusions:These studies suggest that tongue coating is likely to reflect some of the growth factor and enzyme levels.By observing the tongue coating we could predict the prognosis of patients and the characteristics of tongue coating may be used as new diagnostic markers to patients with colorectal carcinoma.展开更多
Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancersubtype characterized by the absence of expression of estrogen receptor (ER), progesteronereceptor (PR), and human epidermal grow...Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancersubtype characterized by the absence of expression of estrogen receptor (ER), progesteronereceptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC exhibitsresistance to hormone and HER2-targeted therapy, along with a higher incidence ofrecurrence and poorer prognosis. Therefore, exploring the molecular features of TNBC andconstructing prognostic models are of significant importance for personalized treatmentstrategies. Methods: In this research, bioinformatics approaches were utilized to screendifferentially expressed genes in 405 TNBC cases and 128 normal tissue samples from 8 GEOdatasets. Key core genes and signaling pathways were further identified. Additionally, aprognostic model incorporating seven genes was established using clinical and pathologicalinformation from 169 TNBC cases in the TCGA dataset, and its predictive performance wasevaluated. Results: Functional analysis revealed dysregulated biological processes such asDNA replication, cell cycle, and mitotic chromosome separation in TNBC. Protein-proteininteraction network analysis identified ten core genes, including BUB1, BUB1B, CDK1,CDC20, CDCA8, CCNB1, CCNB2, KIF2C, NDC80, and CENPF. A prognostic model consistingof seven genes (EXO1, SHCBP1, ABRACL, DMD, THRB, DCDC2, and APOD) was establishedusing a step-wise Cox regression analysis. The model demonstrated good predictiveperformance in distinguishing patients' risk. Conclusion: This research provides importantinsights into the molecular characteristics of TNBC and establishes a reliable prognosticmodel for understanding its pathogenesis and predicting prognosis. These findingscontribute to the advancement of personalized treatment for TNBC.展开更多
BACKGROUND Schwannoma is a benign tumor originating from the peripheral nerve sheath.The clinical symptoms of tracheal schwannoma depend on the location of the tumor,and the most common clinical symptoms are cough and...BACKGROUND Schwannoma is a benign tumor originating from the peripheral nerve sheath.The clinical symptoms of tracheal schwannoma depend on the location of the tumor,and the most common clinical symptoms are cough and hemoptysis.The most effective treatment for benign tumors is complete resection of the primary lesion at an early stage.Our experience has demonstrated that primary tracheal schwannoma can be safely excised with a high-frequency electric knife in a minimally invasive manner.CASE SUMMARY We report a 61-year-old asymptomatic woman who underwent chest computed tomography(CT),which accidentally found an intraluminal tracheal mass without enlarged lymph nodes.Then,the patient underwent bronchoscopy,which found that the tracheal mass originated from the left wall of the upper trachea,was less than 1.5 cm in size,immovable,smooth and 4 cm away from the vocal cord,resulting in partial upper respiratory tract obstruction.Treatment was performed using an endoscopic resection for en bloc removal of the tracheal mass.The diagnosis was primary tracheal schwannoma.A follow-up was performed after endoscopic surgery,and bronchoscopy and thoracic CT were used to monitor whether there was a recurrence.At present,there is no evidence of recurrence,and the patient had a good quality of life.Endoscopic resection may be effective and safe in the treatment of primary tracheal schwannoma.CONCLUSION Primary tracheal schwannoma is a very rare benign tumor.In this case,we cured it by complete endoscopic resection.展开更多
The Chaihu herbal injection was the first herbal injection to be developed and used in China,which has been used in clinic for more than 70 years.This injection is widely used to treat fever caused by influenza or com...The Chaihu herbal injection was the first herbal injection to be developed and used in China,which has been used in clinic for more than 70 years.This injection is widely used to treat fever caused by influenza or common cold and malaria.However,there is an ongoing debate about the safety of the clinical use of Chaihu herbal injection in view of the large number of adverse drug reaction reports and literature in China.On May 29,2018,the China Food and Drug Administration issued a notice requiring to revise the instruction manual of Chaihu herbal injection,list"prohibit for children"under the taboo item,and add the warning"adverse reactions of this product include anaphylactic shock".The purpose of this review is to provide updated,comprehensive information on the pharmacology and adverse drug reaction of Chaihu herbal injection based on scientific literatures in the past few decades.展开更多
Neuroblastoma is the most prevalent solid tumor seen outside of the brain in children.Despite multimodal therapy,high-risk neuroblastoma has a 5-year survival rate of less than 50%.Necroptosis,an inflammatory form of ...Neuroblastoma is the most prevalent solid tumor seen outside of the brain in children.Despite multimodal therapy,high-risk neuroblastoma has a 5-year survival rate of less than 50%.Necroptosis,an inflammatory form of controlled cell death,has either anti-tumor or pro-tumor functions in several types of adult malignancies.However,the genes related to necroptosis and their association with prognosis in neuroblastoma are unclear.This study sought to determine the role of necroptosis-related genes in neuroblastoma a comprehensive bioinformatics analysis.Based on the expression of genes associated with necroptosis,the neuroblastoma samples were classified into three groups.We found that neuroblastoma with high necroptosis displayed promising outcomes and increased infiltration of immune cells.On the basis of the findings of the Cox regression analysis,we developed a four-gene prediction model consisting of PGAM family member 5(PGAM5),tumor necrosis factor(TNF),baculoviral IAP repeat containing 2(BIRC2),and fas associated via death domain(FADD)that is strongly linked with overall survival.The model exhibited superior performance,both internally and externally.Our data demonstrate that a high necroptosis rate correlates with favorable outcome and immune infiltration.These four necroptosis-related genes may serve as therapeutic targets,encouraging research on necroptosis in high-risk neuroblastoma therapy.展开更多
Objective:To explore the expression and clinical significance of RACGAP1 gene in hepatocellular carcinoma.Methods:Data about RACGAP1 gene and clinic pathological data in liver cancer were retrieved from The Cancer Gen...Objective:To explore the expression and clinical significance of RACGAP1 gene in hepatocellular carcinoma.Methods:Data about RACGAP1 gene and clinic pathological data in liver cancer were retrieved from The Cancer Genome Atlas(TCGA).The relationship between the expression of RACGAP1 gene and clinic pathological parameters,and prognosis were analyzed by R 2.15.3 software.The association between RACGAP1 gene expression and prognosis of liver cancer patients was analyzed by Kaplan-Meier survival function analysis and Cox regression analysis.Results:TCGA database was used to collect 235 cases of liver cancer with clinical pathological parameters and their corresponding RACGAP1 expression levels.After the incomplete cases and those with no detailed pathological parameters were excluded,and it was found that RACGAP1 was highly expressed in liver cancer tissues.Meanwhile,the expression of RACGAP1 in patients with liver cancer in the TCGA tumor database was further analyzed with the matching clinical data parameters.The expression level of RACGAP1 was significantly correlated with the pathological grade and T stage of liver cancer patients(all P<0.05),but was not significantly correlated with American Joint Committee on Cancer(AJCC)pathological stage and gender(P>0.05).There was a significant correlation between RACGAP1 expression level and overall survival(OS)in patients with liver cancer(P<0.05),and the overall survival time of patients with low expression was better than that of patients with high expression(P<0.05).Cox regression was used to analyze the correlation between T stage,M stage,N stage and RACGAP1 expression in patients with hepatocellular carcinoma(HCC),and RACGAP1 became an independent prognostic factor in patients with HCC(P<0.05).Conclusion:Based on the tumor-related gene information in the public database TCGA,RACGAP1 gene is highly expressed in liver cancer tissues and becomes an independent prognostic factor of liver cancer,which is expected to become an important therapeutic target of drug therapy for liver cancer.展开更多
基金supported by grants from the National Clinical Research Center Cancer Fundthe Haihe Laboratory of Synthetic Biology(22HHSWSS00004)。
文摘Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.
基金supported by the National Natural Science Foundation of China(Grant Nos.82073276 and 82273100)Science and Technology Project of Tianjin Binhai New Area Health Commission(Grant No.2022BWKY016)the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058).
文摘Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.
文摘Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoction in lung cancer treatment using network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction databases were used to screen the active ingredients of Baoyuan decoction and their relevant targets.Lung cancer-related targets were obtained from the GeneCards,Online Mendelian Inheritance in Man,and DrugBank databases.Protein-protein interaction network of the common targets was constructed using the STRING database and analyzed using Cytoscape software 3.10.1.Furthermore,Gene Ontology enrichment,Kyoto Encyclopedia of Genes and Genomes pathway analyses and visualization of common genes were performed using the R software.Finally,molecular docking of the selected key ingredients and targets was performed,and the results were verified using AutoDock Vina software.Results:We identified 142 potential active ingredients,3624 potential lung cancer-related targets,and 341 common drug targets.A total of 72 core targets were identified,of which AKT1,TP53,interleukin-6,epithelial growth factor receptor,and signal transducer and activator of transcription 3 were key.A total of 4116 items were obtained via Gene Ontology enrichment analyses.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 189 related signaling pathways,including the PI3K-Akt,AGE-RAGE signaling pathways in diabetic complications,FOXO,and TH signaling pathways,which are involved in cell proliferation,autophagy,metastasis,invasion,radiation resistance,and chemotherapy resistance in the lung cancer microenvironment.The molecular docking results suggested that the key ingredients had a strong affinity for key targets.Conclusion:This study demonstrates that Baoyuan decoction plays a key therapeutic role in a complex manner involving multiple ingredients,targets,and pathways in lung cancer.Our findings are anticipated to provide new ideas for follow-up experimental research and clinical application.
基金supported by the National Natural Science Foundation of China(No.81602020).
文摘Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:The ORAI family of proteins,comprising ORAI1,ORAI2,and ORAI3,plays a crucial role in the regulation of intracellular calcium signaling,which is essential for various cellular functions including proliferation,differentiation,and apoptosis.Dysregulation of calcium signaling has been implicated in cancer pathogenesis,influencing tumor progression,metastasis,and resistance to therapy.This study aims to provide a comprehensive analysis of the ORAI family members across a broad spectrum of cancers.Methods:Publicly available datasets from The Cancer Genome Atlas and the Gene Expression Omnibus were utilized.RNA sequencing data,mutation profiles,copy number variation data,and methylation data across different cancer types were analyzed.Differential expression analysis,survival analysis,copy number variation analysis,mutation analysis,methylation analysis,immune cell infiltration analysis using the Cibersort algorithm,and gene set enrichment analysis were conducted using R software.Results:ORAI1 and ORAI3 were significantly upregulated in glioblastoma multiforme,whereas ORAI2 was notably downregulated in kidney chromophobe and pancreatic adenocarcinoma.ORAI2 exhibited higher mutation rates and copy number gains in multiple cancers compared to ORAI1 and ORAI3.The hypermethylation of ORAI2 in head and neck squamous cell carcinoma,esophageal carcinoma,and glioblastoma multiforme negatively correlated with its gene expression.ORAI1 and ORAI3 expression positively correlated with regulatory T cells infiltration,whereas ORAI2 showed a negative correlation with CD8^(+)T cell infiltration.Gene set enrichment analysis revealed that ORAI1 and ORAI2 are associated with immune-related pathways,while ORAI3 is linked to MYC targets and oxidative phosphorylation.Conclusion:Our pan-cancer analysis reveals significant differential expression,genomic alterations,and epigenetic regulation of ORAI family members across various cancers.ORAI1 and ORAI3 appear to promote an immunosuppressive environment,whereas ORAI2 may function as a tumor suppressor in certain contexts.These findings provide a foundation for future research targeting ORAI-mediated pathways in cancer therapy and highlight the therapeutic potential of ORAI proteins.
基金Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.
基金grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:The ORAI1 gene,central to store-operated calcium entry(SOCE),is increasingly recognized for its pivotal role in cancer progression and patient prognosis across a broad spectrum of malignancies.Despite its critical involvement in calcium signaling pathways that are essential for cellular functions such as proliferation,migration,and apoptosis,the comprehensive impacts of ORAI1 within the tumor microenvironment(TME)and its modulation across various cancers have not been fully elucidated.Methods:We conducted a pan-cancer analysis leveraging data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)to assess ORAI1 expression.Differential expression analyses were performed,complemented by correlative studies with tumor mutation burden(TMB),microsatellite instability(MSI),immune infiltration,and key biological processes and pathways.Results:Our results demonstrate that ORAI1 is consistently upregulated in a range of cancer types,associated with aggressive tumor characteristics and poor patient outcomes.Significantly,ORAI1 upregulation correlates with increased tumor mutation burden(TMB)and microsatellite instability(MSI),markers of genomic instability that are predictive of response to immunotherapy,underscoring its potential utility in clinical stratification and treatment decision-making.ORAI1's influence extended to the immune landscape,showing associations with immune cell infiltration and both immunosuppressive and immunostimulatory gene sets,thereby affecting the TME and possibly the efficacy of immunotherapeutic interventions.Conclusions:The multifaceted nature of ORAI1's involvement in cancer pathophysiology positions it as a prospective biomarker and therapeutic target.Its expression dynamics and correlative significance with prognostic and immune regulatory elements underscore its potential in guiding therapeutic strategies and improving clinical outcomes.This study lays a foundation for future research,aiming to leverage ORAI1's biological significance in cancer prognosis and therapy optimization.
基金supported by the National Natural Science Foundation of China[No.81602020]the Tianjin Medical University Cancer Institute&Hospital Research Project[No.1805].
文摘Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.Methods:TFRC protein expression was obtained from Human Protein Altas(HPA).All datas were collected from TCGA and GTEx.In this study,we analyzed the expression of TFRC in cervical cancer and its clinical significance.Through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene set enrichment analyses(GSEA),investigated the related molecular pathways of TFRC.The relationship between TFRC and immune infiltration was then examined.The prognosis of different immune cell subsets was then analyzed after dividing cervical cancer patients into high and low expression of TFRC groups.Results:TFRC is highly expressed in various tumor tissues compared to control normal tissues,including cervical cancer.An increased expression of TFRC was associated with higher Tumor(T)and Node(N)stage,as well as a higher clinical stage.Kaplan–Meier(KM)survival analysis investigated that higher TFRC expression patients have a poor overall survival(OS),disease specific survival(DSS)and progress free interval(PFI).Both KEGG and GSEA enriched signaling pathway by high TFRC and low TFRC groups.There was a significant negative linear correlation between TFRC expression and immune infiltration.TFRC affects the prognosis of cervical cancer patients through immune pathway.Conclusions:Cervical cancer patients with TFRC expression may have a worse prognosis.
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:The Fascin(FSCN)family,comprising actin-bundling proteins,plays vital roles in cytoskeletal reorganization and cell migration.FSCN1,FSCN2,and FSCN3 are implicated in cancer progression through cell motility,invasion,and metastasis.However,their specific contributions across different cancer types remain unclear.Methods:We conducted a pan-cancer bioinformatics analysis of FSCN genes using data from The Cancer Genome Atlas.This included differential expression patterns,copy number variations(CNVs),mutations,methylation status,and correlations with tumor mutational burden,microsatellite instability,and immune checkpoint molecule expression.Differential expression was analyzed using DESeq2,while CNV and mutation analyses utilized GISTIC2.0 and MuTect2.Methylation data were assessed using the Illumina Human Methylation 450K BeadChip.Results:FSCN1 and FSCN2 showed significant differential expression in multiple cancers,often correlating with poor prognosis.FSCN3 exhibited less variability but a protective role in certain contexts.CNV analysis indicated frequent gene gains in FSCN genes,correlating with increased expression.FSCN3 had a higher mutation rate,suggesting genetic instability.Methylation analysis showed hypomethylation of FSCN1 and FSCN2 in tumors compared to normal tissues,whereas FSCN3 had minor changes.Significant associations were found between FSCN gene expression and tumor mutational burden,microsatellite instability,and immune checkpoint molecules,suggesting their involvement in tumor immunogenicity and the immune microenvironment.Conclusions:This pan-cancer analysis highlights the multifaceted roles of FSCN genes in cancer biology,emphasizing their potential as biomarkers and therapeutic targets.FSCN1 and FSCN2 are associated with poor prognosis and aggressive phenotypes,while FSCN3 shows protective roles in specific contexts.These findings offer new avenues for cancer diagnosis and treatment,particularly in personalized medicine.Future studies should validate these findings and explore the underlying mechanisms to fully harness the clinical potential of FSCN family proteins in oncology.
文摘Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.
文摘Tumor immunotherapy has emerged as a promising method in cancer treatment,but patient responses vary,necessitating personalized strategies and prognostic biomarkers.This study aimed to identify prognostic factors and construct a predictive model for patient survival outcomes and immunotherapy response.We curated six immunotherapy datasets representing diverse cancer types and treatment regimens.After data preprocessing,patients were stratified based on immunotherapy response.Differential gene expression analysis identified 22 genes consistently dysregulated across multiple datasets.Functional analysis provided critical insights,highlighting the enrichment of these dysregulated genes in immune response pathways and tumor microenvironment-related processes.To create a robust prognostic model,we meticulously employed a multistep approach.Initially,the identified 22 genes underwent rigorous univariate Cox regression analysis to evaluate their individual associations with patient survival outcomes.Genes showing statistical significance(p-values<0.05)at this stage advanced to the subsequent multivariate Cox regression analysis,which aimed to address potential confounding factors and collinearity among genes.From this analysis,we ultimately identified four key genes—ST6GALNAC2,SNORA65,MFAP2,and CDKN2B—that were significantly associated with patient survival outcomes.Incorporating these four key genes along with their corresponding coefficients,we constructed a predictive model.This model’s efficacy was validated through extensive Cox regression analyses,demonstrating its robustness in predicting patient survival outcomes.Furthermore,our model exhibited promising predictive capability for immunotherapy response,providing a potential tool for anticipating treatment efficacy.These findings provide insights into immunotherapy response mechanisms and suggest potential prognostic biomarkers for personalized treatment.Our study contributes to advancing cancer immunotherapy and personalized medicine.
基金supported by the Science and Technology Support Plan Key Projects of Tianjin(Grant No.20YFZCSY00070)the National Natural Science Foundation of China(Grant Nos.82073276,82273100)+1 种基金the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058)Science and Technology project of Health Commission of Tianjin Binhai New Area(Grant No.2022BWKY016).
文摘Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.
基金This work was supported by grants from the New Century Excellent Talent(NCET-11-1068)and National Science Foundation of China(No.81173376).
文摘Background:Our previous work demonstrated that Gekko sulfated glycopeptide extracted from the Chinese gecko Shou gong(Gekko swinhonis Guenther)could inhibit tumor growth by regulating basic fibroblast growth factor.However,basic fibroblast growth factor has opposing effects on growth in breast and liver cancers.Direct effects and mechanisms of Gekko sulfated glycopeptide on tumor growth remain unclear and are ripe for further exploration.Methods:Differential regulation by Gekko sulfated glycopeptide and bFGF were studied in established human breast cancer MCF-7 cells and hepatocarcinoma HepG2 cells.Cell proliferation was evaluated with a Trypan blue exclusion assay.Cell cycle phases were measured by flow cytometry.Basic fibroblast growth factor,transforming growth factor-β1,and p21WAF1/CIP1 mRNA and protein expression levels were detected by real-time PCR(mRNA)and ELISA(protein).Changes in phosphorylated extracellular signal-regulated kinase levels were analyzed by Western blot.Results:Data indicated that Gekko sulfated glycopeptide inhibited the proliferation of HepG2 cells(P<0.001)and also blocked basic fibroblast growth factor-stimulated proliferation of these cells(P=0.001).Gekko sulfated glycopeptide was shown to increase transforming growth factor-β1 and p21WAF1/CiP1 expression(P<0.01)and partially compensate for reductions therein induced by basic fibroblast growth factor.Conversely,in MCF-7 cells,Gekko sulfated glycopeptide alone had no observable effect on transforming growth factor-β1 and p21WAF1/CiP1 expression.Gekko sulfated glycopeptide did,however,enhance basic fibroblast growth factor-induced inhibition of cell proliferation and transforming growth factor-β1 and p21WAF1/CiP1 expression in the MCF-7 cells(P=0.001,P<0.01,P<0.01,respectively).Gekko sulfated glycopeptide was shown to suppress basic fibroblast growth factor secretion in both HepG2 and MCF-7 cell lines(P<0.05 and P<0.01,respectively)and inhibited extracellular signal-regulated kinase 1/2 phosphorylation facilitated by basic fibroblast growth factor.Gekko sulfated glycopeptide alone decreased phosphorylated extracellular signal-regulated kinase in HepG2 cells but did not visibly affect phosphorylated extracellular signal-regulated kinase levels in MCF-7 cells.Conclusions:Gekko sulfated glycopeptide,a basic fibroblast growth factor inhibitor,differentially regulates growth in different cancer cell lines,and these differences may be determined by the opposing effects of basic fibroblast growth factor on transforming growth factor-β1 and p21WAF1/CiP1 levels in breast and liver cancer cells.
文摘Background:According to World Health Organization,colorectal cancer is the third most common cancer in the world.The prognosis assessment and condition judgment of the colorectal cancer remains a challenge clinically.Therefore,identification of diagnostic markers to evaluate the prognosis of colorectal cancer clinically should be urgently developed.We have observed that a lot of cancer patients had thick tongue clinically,but what is the relationship between tongue coating and the tumor?Methods:Seventy-four patients with colorectal carcinoma were collected through the outpatients of Tianjin Medical University Cancer Institute and Hospital from May 2010 to September 2011,in which there were 49 patients confirmed with recurrence or metastasis.All photos of patients’tongue were taken with a SONY camera in the same room and under constant conditions such as brightness or distance.Regression equation predicting thickness of tongue coating was constructed using binary logistic regression analysis.The optimal cut off of probabilities to diagnosis thick tongue coating was determined by receiver operating curve analysis.χ2 test for paired data and kappa test were used to determine the diagnostic value for recurrence and/or metastasis in colorectal cancer patients.Kolmogorov-Smirnov test was used to determine the distribution of ALT,AST,ALP ALB,TP,GLO,TBIL,DBIL,GGT,LDH,GLU,UA,CA724,CA199,CA242 and CEA.Data with the skewed distribution were presented as median(quartile interval).The association between the thickness of tongue coating and clinical-pathological character was evaluated by chi square test and two-independent-sample test.The two-independent-samplesχ2 was used to determine whether there were significant differences in the thin coating and thick coating between patients with recurrence and/or metastasis and patients without recurrence and/or metastasis.Kaplan-Meier method was used to analyze survival time.Statistical analysis was performed by SPSS(version 16.0).Results:Through retrospective clinical study we found that overall survival of colorectal cancer patients with thick greasy tongue coating is less than the patients with less tongue coating.What’s more,the risk for recurrence or/and metastasis overall survival in thick coating group was higher than thin coating group.In addition,the histological staining of the tongue slices of rats showed that EGFR receptors in the tongue root were the most among whole tongue surface.Tongue thick coating may be due to tumor patients with high levels of serum EGF which results in significantly increasing tongue coating.This finding suggested that the tongue coating of cancer patients may reflect the level of serum EGF levels in patients which may be related to shorter survival time.In addition,another study showed that serum lactic dehydrogenase level in patients with thick tongue coating is higher than patients with thin tongue coating.Conclusions:These studies suggest that tongue coating is likely to reflect some of the growth factor and enzyme levels.By observing the tongue coating we could predict the prognosis of patients and the characteristics of tongue coating may be used as new diagnostic markers to patients with colorectal carcinoma.
文摘Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancersubtype characterized by the absence of expression of estrogen receptor (ER), progesteronereceptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC exhibitsresistance to hormone and HER2-targeted therapy, along with a higher incidence ofrecurrence and poorer prognosis. Therefore, exploring the molecular features of TNBC andconstructing prognostic models are of significant importance for personalized treatmentstrategies. Methods: In this research, bioinformatics approaches were utilized to screendifferentially expressed genes in 405 TNBC cases and 128 normal tissue samples from 8 GEOdatasets. Key core genes and signaling pathways were further identified. Additionally, aprognostic model incorporating seven genes was established using clinical and pathologicalinformation from 169 TNBC cases in the TCGA dataset, and its predictive performance wasevaluated. Results: Functional analysis revealed dysregulated biological processes such asDNA replication, cell cycle, and mitotic chromosome separation in TNBC. Protein-proteininteraction network analysis identified ten core genes, including BUB1, BUB1B, CDK1,CDC20, CDCA8, CCNB1, CCNB2, KIF2C, NDC80, and CENPF. A prognostic model consistingof seven genes (EXO1, SHCBP1, ABRACL, DMD, THRB, DCDC2, and APOD) was establishedusing a step-wise Cox regression analysis. The model demonstrated good predictiveperformance in distinguishing patients' risk. Conclusion: This research provides importantinsights into the molecular characteristics of TNBC and establishes a reliable prognosticmodel for understanding its pathogenesis and predicting prognosis. These findingscontribute to the advancement of personalized treatment for TNBC.
文摘BACKGROUND Schwannoma is a benign tumor originating from the peripheral nerve sheath.The clinical symptoms of tracheal schwannoma depend on the location of the tumor,and the most common clinical symptoms are cough and hemoptysis.The most effective treatment for benign tumors is complete resection of the primary lesion at an early stage.Our experience has demonstrated that primary tracheal schwannoma can be safely excised with a high-frequency electric knife in a minimally invasive manner.CASE SUMMARY We report a 61-year-old asymptomatic woman who underwent chest computed tomography(CT),which accidentally found an intraluminal tracheal mass without enlarged lymph nodes.Then,the patient underwent bronchoscopy,which found that the tracheal mass originated from the left wall of the upper trachea,was less than 1.5 cm in size,immovable,smooth and 4 cm away from the vocal cord,resulting in partial upper respiratory tract obstruction.Treatment was performed using an endoscopic resection for en bloc removal of the tracheal mass.The diagnosis was primary tracheal schwannoma.A follow-up was performed after endoscopic surgery,and bronchoscopy and thoracic CT were used to monitor whether there was a recurrence.At present,there is no evidence of recurrence,and the patient had a good quality of life.Endoscopic resection may be effective and safe in the treatment of primary tracheal schwannoma.CONCLUSION Primary tracheal schwannoma is a very rare benign tumor.In this case,we cured it by complete endoscopic resection.
文摘The Chaihu herbal injection was the first herbal injection to be developed and used in China,which has been used in clinic for more than 70 years.This injection is widely used to treat fever caused by influenza or common cold and malaria.However,there is an ongoing debate about the safety of the clinical use of Chaihu herbal injection in view of the large number of adverse drug reaction reports and literature in China.On May 29,2018,the China Food and Drug Administration issued a notice requiring to revise the instruction manual of Chaihu herbal injection,list"prohibit for children"under the taboo item,and add the warning"adverse reactions of this product include anaphylactic shock".The purpose of this review is to provide updated,comprehensive information on the pharmacology and adverse drug reaction of Chaihu herbal injection based on scientific literatures in the past few decades.
文摘Neuroblastoma is the most prevalent solid tumor seen outside of the brain in children.Despite multimodal therapy,high-risk neuroblastoma has a 5-year survival rate of less than 50%.Necroptosis,an inflammatory form of controlled cell death,has either anti-tumor or pro-tumor functions in several types of adult malignancies.However,the genes related to necroptosis and their association with prognosis in neuroblastoma are unclear.This study sought to determine the role of necroptosis-related genes in neuroblastoma a comprehensive bioinformatics analysis.Based on the expression of genes associated with necroptosis,the neuroblastoma samples were classified into three groups.We found that neuroblastoma with high necroptosis displayed promising outcomes and increased infiltration of immune cells.On the basis of the findings of the Cox regression analysis,we developed a four-gene prediction model consisting of PGAM family member 5(PGAM5),tumor necrosis factor(TNF),baculoviral IAP repeat containing 2(BIRC2),and fas associated via death domain(FADD)that is strongly linked with overall survival.The model exhibited superior performance,both internally and externally.Our data demonstrate that a high necroptosis rate correlates with favorable outcome and immune infiltration.These four necroptosis-related genes may serve as therapeutic targets,encouraging research on necroptosis in high-risk neuroblastoma therapy.
文摘Objective:To explore the expression and clinical significance of RACGAP1 gene in hepatocellular carcinoma.Methods:Data about RACGAP1 gene and clinic pathological data in liver cancer were retrieved from The Cancer Genome Atlas(TCGA).The relationship between the expression of RACGAP1 gene and clinic pathological parameters,and prognosis were analyzed by R 2.15.3 software.The association between RACGAP1 gene expression and prognosis of liver cancer patients was analyzed by Kaplan-Meier survival function analysis and Cox regression analysis.Results:TCGA database was used to collect 235 cases of liver cancer with clinical pathological parameters and their corresponding RACGAP1 expression levels.After the incomplete cases and those with no detailed pathological parameters were excluded,and it was found that RACGAP1 was highly expressed in liver cancer tissues.Meanwhile,the expression of RACGAP1 in patients with liver cancer in the TCGA tumor database was further analyzed with the matching clinical data parameters.The expression level of RACGAP1 was significantly correlated with the pathological grade and T stage of liver cancer patients(all P<0.05),but was not significantly correlated with American Joint Committee on Cancer(AJCC)pathological stage and gender(P>0.05).There was a significant correlation between RACGAP1 expression level and overall survival(OS)in patients with liver cancer(P<0.05),and the overall survival time of patients with low expression was better than that of patients with high expression(P<0.05).Cox regression was used to analyze the correlation between T stage,M stage,N stage and RACGAP1 expression in patients with hepatocellular carcinoma(HCC),and RACGAP1 became an independent prognostic factor in patients with HCC(P<0.05).Conclusion:Based on the tumor-related gene information in the public database TCGA,RACGAP1 gene is highly expressed in liver cancer tissues and becomes an independent prognostic factor of liver cancer,which is expected to become an important therapeutic target of drug therapy for liver cancer.
