BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in ...BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.展开更多
Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reve...Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.展开更多
AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis(NF).METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of p...AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis(NF).METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of pathogenic mutations in RET protooncogene, von Hippel-Lindau(VHL) and succinate dehydrogenase complex subunits B(SDHB) genes were investigated. RET proto-oncogene mutation screening for exons 10, 11, 13, 14, 15, 16 were examined by polymerase chain reaction(PCR) and direct DNA sequencing in patient. Mutation screening for exons 1, 2, 3 of VHL gene was carried out. Both forward and reverse strandswere subjected to direct sequencing after PCR amplification. The entire coding sequence of SDHB gene was screened for the presence of pathogenic mutations by PCR-sequencing.RESULTS: A 45-year-old man presented with abdominal pain and hypertension over the previous year. The patient was a known case of neurofibromatosis type 1(NF1) who presented at the age of 15 years with hyperpigmented and hypopigmented lesions. After complete evaluation for hypertension, biochemical tests and imagings indicated a malignant pheochromocytoma of 120 mm × 70 mm in size. The patient underwent left adrenalectomy, nephrectomy and splenectomy. After surgery the symptoms improved and blood pressure was controlled. After 5 years he was admitted again for evaluation of hypertensive crisis. Biochemical tests were again consistent with pheochromocytoma and disease relapse. Imaging studies and liver biopsy confirmed metastatic pheochromocytoma to the liver and para-aortic area. 131 Iodine-metaiodobenzylguanidine therapy was carried out. Genetic screening of VHL(exons 1, 2, 3), RET proto-oncogene(exons 10, 11, 13, 14, 15, 16) and SDH complex subunits revealed no pathogenic mutation. CONCLUSION: We conclude that mutations in the NF1 gene are responsible for the patient's clinical findings. However, would be helpful to further examine somatic mutations for a more precise study of genotypephenotype correlation.展开更多
Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 ...Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.展开更多
Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectom...Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three展开更多
PDGF (platelet derived growth factor) has been shown to play animportant role in tumorigenesis, tumor growth, atherosclerosis and inflammation and other various pathologic settings. PDGF-B chain gene is 92% homologous...PDGF (platelet derived growth factor) has been shown to play animportant role in tumorigenesis, tumor growth, atherosclerosis and inflammation and other various pathologic settings. PDGF-B chain gene is 92% homologous to v-sis oncogene of the simian sarcoma virus. Thus PDGF-B gene is also called c-sis proto-oncogene. This report provides 3 TFOs (triplex-forming oligonucleotides) to inhibit the expression of c-sis/PDGF-B gene. The results from gel mobility shift analysis, in vitro transcription, DNase I footprinting and protein binding assays demonstrate that the TFOs we designed can form sequence-specific stable triplex with the target, and can effectively suppress the downstream gene transcription and inhibit transcription factors binding. They can be used for preparation of drugs to inhibit tumor growth and for the therapy of atherosclerosis, inflammation, etc.展开更多
BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LN...BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LNM)remains controversial. Different surgical strategies may bring a bias in demonsstrating the association between them.In order to delineate a risk stratification to guide a tailored initial approach to tumors that express BRAF^V600E mutation,we performed this meta-analysis by using the articles in which total or near-total thyroidectomy plus bilateral central lymph node dissection was routinely performed to avoid the bias from the surgical strategy.We searched the Medline,Embase and CNKI database for eligible studies from January 2003 to May 2018.Meta-analysis was performed using the STATA 12.0 software.Odds ratios (ORs)and 95% confidence intervals (CIs)were calculated under fixed-effects or random-effects models.Fifteen clinical studies were included with a total of 4909 PTC patients. Our meta-analysis results reported that BRAF^V600E mutation was associated with LNM (OR=1.34;95% CI:1.09-1.65;P=0.005),as well as central LNM (OR=1.59;95% CI: 1.35-1.88;P<0.00001).Moreover,in patients with papillary thyroid microcarcinoma, we also confirmed the predictive value of BRAF^V600E mutation for LNM (OR=3.49;95% CI:2.02-6.02;P<0.00001).This meta-analysis demonstrates that BRAF^V600E mutation is closely related to LNM in PTC patients.The results suggest that BRAF^V600E mutation can be considered as a risk factor for LNM in PTC.Moreover,combining BRAF^V600E mutation with other risk factors to determine the initial surgical treatment may bring benefits for PTC patients.展开更多
Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the inte...Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.展开更多
INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of t...INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of the gut ,it is defined as an unequivocal non-invasive epithelial change[2,3].The observation of gastric dysplasia as a cancerous lesion was recognized over a century ago ,but it is only after the advent of gastroscopy that its clinical significance has been stressed[4-7].展开更多
Objective: To elucidate the expression of the bcl-2 genein association with both biological characteristics of hu-man primary pancreatic carcinoma and patient’s prog-nosis.Methods: The s-p immunohistochemistry assay ...Objective: To elucidate the expression of the bcl-2 genein association with both biological characteristics of hu-man primary pancreatic carcinoma and patient’s prog-nosis.Methods: The s-p immunohistochemistry assay wasused to detect the expression of the bcl-2 gene on para-ffin-embedded sections from 97 cases of primary pan-creatic carcinoma, 32 cases of pancreatitis, and 21 ca-ses of normal pancreas.Results: Among the 97 cases of pancreatic carcinoma,70 (72.2%) showed positive staining for the bcl-2 pro-tein. In the 32 cases of pancreatitis, 3 (9.4%) showedpositive immunostaining for the bcl-2, and in the nor-mal pancreas cases, 1 (4.8%) showed positive immu-nostaining for the bcl-2. However, the positive stainingrates of the bcl-2 protein were lower in tumor tissuefrom the patients with metastases and tumor-node-me-tastasis (TNM) stages Ⅲ, Ⅳ than in those from thosewith non-metastases, well differentiation, non-invasionand TNM stages Ⅰ, Ⅱ. The patients with positive im-munostaining of bcl-2 have a longer postoperative sur-vival than those with negative staining.Conclusions: Pancreatic carcinoma expressed a highpositivity for bcl-2. Findings suggested that the overex-pression of bcl-2 is related to the carcinogenesis andprogression of human pancreatic carcinoma. Bcl-2might be one of the parameters in terms of biologicalcharacteristics and good prognosis in patients withpancreatic carcinoma.展开更多
Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods:...Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option a...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option and show a sustained objective response among patients with metastatic or unresectable GISTs.A wellknown higher risk of neoplasm has been described among renal transplant recipients(RTRs).Nevertheless,only few cases of GIST onset among transplant patients have been reported in the literature.CASE SUMMARY Here,we describe 2 cases of gastric GIST occurring during the follow-up of RTRs.We also review the existing literature concerning GIST occurrence in transplant patients.In total and in association with our 2 cases,16 patients have been reported.The median age was 59.5 years and 69%were male.With a median tumor size of 45 mm,no patient displayed metastatic dissemination at diagnosis.Time from transplantation to diagnosis was highly variable between 5 mo and 21 years.Histopathological data mostly revealed high risk of progression(43%).Death increased to 29%during follow-up.Surgical treatment was systematically performed when the tumor was operable(94%).The use of adjuvant therapy was uncommon(19%).CONCLUSION GISTs represent rare but potentially severe malignant complication among transplant patients.展开更多
Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid...Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid nodules are difficult to distinguish benign and malignant.BRAF gene mutation is a common human oncogenic mutation and the highest mutation frequency in papillary thyroid carcinoma.The combination of FNA and BRAF gene detection can significantly improve the diagnostic rate of benign and malignant thyroid nodules and make up for the deficiency of single diagnosis of cytology.Moreover,while the incidence of thyroid cancer is growing rapidly worldwide,its mortality remains stable.The problem of overdiagnosis and overtreatment of thyroid cancer is becoming more and more obvious.However,due to the limitations of current studies on BRAF genes,its prognostic value for papillary thyroid carcinoma remains controversial.Therefore,in order to reduce the adverse effects of overdiagnosis and treatment,the relationship between gene and tumor biological behavior needs further study in the future.展开更多
Objective: This study was designed to explore whether inhibition of the extracellular-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways can inhibit the growth of xenografts of endometr...Objective: This study was designed to explore whether inhibition of the extracellular-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways can inhibit the growth of xenografts of endometrial cancer cell lines with different estrogen receptors (ER) profiles in vivo and to provide preliminary laboratory basis for the probability of endometrial adenocarcinoma treatment with blockage of the two pathways, especially to endometrial cancer with low ER status. Methods: Human endometrial cancer Ishikawa bearing ER and HEC-1Awith low ER status cells were subcutaneously injected into BALB/c nude mice to establish endometrial cancer xenograft tumor models. The effects of PI3K/Akt inhibitor LY294002, MAPK/ERK1/2 inhibitor PD-98059 and their combinations on the growth of the xenograft tumors and apoptotic state of Ishikawa and HEC-1Acells were tested in vivo using the inhibitory rate, the terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, H/E-stain. Western blot analysis was used to detect the alterations of activated ERK (P-ERK) and AKT (P-AKT) during this process. Results: LY294002, a PI3K/Akt pathway inhibitor, induced significant suppression in the growth of both Ishikawa and HEC-1Acell xenograft tumors, concomitant with increased apoptosis in xenografts as evidenced by TUNEL. A similar effect was also observed when the MAPK/ERK1/2 signaling pathway was inhibited by PD98059. Concurrent inhibition of the PI3K/Akt and MAPK/ERK1/2 pathways showed enhanced anti-tumor effects in vivo as indicated by increased apoptosis. At the same time, the levels of P-ERK and P-AKT in both xenograft tumors decreased, and their levels in combination group was the lowest. Conclusions: PD98059, LY294002 and their combinations showed remarkable inhibitory effects on xenograft tumors of endometrial carcinoma cell lines with different expression status of ER in vivo through blockage of PI3K/Akt and MAPK/ERK1/2 signaling pathways. This suggests that targeting these pathways may be an effective therapeutic strategy against endometrial carcinomas, especially for ER-negative cancers which show poor response to endocrinal therapy.展开更多
Objective:To study the correlation of serum Exosome and Dickkopf-1 content with pathological process and gene expression in patients with gastric cancer.Methods:A total of 480 patients diagnosed with gastric cancer in...Objective:To study the correlation of serum Exosome and Dickkopf-1 content with pathological process and gene expression in patients with gastric cancer.Methods:A total of 480 patients diagnosed with gastric cancer in our hospital between May 2015 and July 2016 were selected as the gastric cancer group and 220 healthy volunteers receiving physical examination during the same period were selected as control group. Serum was collected to detect Exosome and Dickkopf-1 content, and gastric cancer tissue and para-carcinoma tissue were collected to detect the expression of pro-proliferation and pro-invasion molecules as well as tumor suppressor genes.Results:Serum Exosome and Dickkopf-1 content of gastric cancer group were significantly higher than those of control group and the deeper the infiltration and the worse the differentiation, the higher the serum Exosome and Dickkopf-1 content, and serum Exosome and Dickkopf-1 content in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis;UHRF1, SIRT1 and LOXL2 expression in gastric cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with serum Exosome and Dickkopf-1 content while RASAL2, ING5, Period1 and Period2 expression were significantly lower than those in para-carcinoma tissue and negatively correlated with serum Exosome and Dickkopf-1 content. Conclusion:The elevated serum Exosome and Dickkopf-1 in patients with gastric cancer are closely related to the high expression of pro-proliferation and pro-invasion molecules as well as the low expression of proto-oncogene.展开更多
At present, malignant tumor is a serious threat to human health. Its pathogenesis is complicated and caused by the interaction of various carcinogenic factors in human body. Human sal-like protein 4 (SALL4) is a newly...At present, malignant tumor is a serious threat to human health. Its pathogenesis is complicated and caused by the interaction of various carcinogenic factors in human body. Human sal-like protein 4 (SALL4) is a newly discovered gene. It can play an important role in the function of embryonic stem cells since it is with protein transcription factor of C2H2 zinc fingers. Studies have found that mutations of the gene often lead to the occurrence of malignant tumors. This article reviews the molecular mechanism of SALL4 in the occurrence and development of malignant tumors and its role in the diagnosis and treatment of malignant tumors.展开更多
Background:Clear cell renal carcinoma(ccRCC)is notorious for its highly unfavorable prognosis,closely related to immune cell infiltration(ICI).MYB Proto-Oncogene Like 2(MYBL2)is elevated in multiple types of human can...Background:Clear cell renal carcinoma(ccRCC)is notorious for its highly unfavorable prognosis,closely related to immune cell infiltration(ICI).MYB Proto-Oncogene Like 2(MYBL2)is elevated in multiple types of human cancer and is recognized as a crucial role in tumorigenesis.In the present study,we aimed to determine the roles of MYBL2 in the prognostic outcomes of ccRCC.Methods:We analyzed the GSE100666 dataset from the Gene Expression Omnibus(GEO)database and found that the expression of MYBL2 was significantly higher in ccRCC subjects than in normal controls.Next,RNA sequencing data related to ccRCC were retrieved from The Cancer Genome Atlas(TCGA)database and the levels of MYBL2 were compared between tumor and peri-tumor tissues.The correlation between MYBL2 and clinicopathological parameters was assessed by logistic analysis.The Kaplan-Meier method,Cox-regression analysis,and nomograms,were applied to investigate the potential clinical benefits of MYBL2 in ccRCC.We also evaluated the correlation between MYBL2 and immune cell infiltration with a single-sample gene set enrichment analysis(ssGSEA).The association between MYBL2 and immune checkpoints was determined via the TIMER and TISIDB databases.Finally,correlation analysis was conducted to predict upstream non-coding RNAs(ncRNAs)regulating MYBL2,and a completing endogenous RNA(ceRNA)network was constructed to visualize the long non-coding RNAs(lncRNAs)-microRNAs(miRNAs)-MYBL2 axis in ccRCC.Finally,further analysis of upstream lncRNAs was carried out to validate the accuracy of the network.Results:MYBL2 was significantly over-expressed in ccRCC(P<0.001).High levels of MYBL2 expression in ccRCC correlated with a worse T stage,a more advanced N stage,a higher M stage,a more deleterious pathological stage,and higher histological grades.MYBL2 was identified as a risk factor for disease-specific survival(hazard ratio(HR)=2.73,P<0.001),overall survival(HR=1.91,P<0.001),and progression-free interval(HR=2.03,P<0.001).MYBL2 also positively associated with multiple types of immune cells and checkpoints.Finally,two ceRNA axes,PVT1-miR-30e-5p-MYBL2 and LINC00511-miR-29c-3p-MYBL2 were detected as the most promising upstream ncRNAs regulating MYBL2 in ccRCC,and we also validated the expression of MYBL2 and PVT1 by launching qRT-PCR.We found that the expression of MYBL2 was significantly higher in 786-O than in human kidney-2 cell line HK-2(P<0.001)and the expression of PVT1 was significantly higher in Caki-1 than in HK-2(P<0.001).Conclusion:Our study revealed that ncRNAs might upregulated the expression of MYBL2 in ccRCC and that this was associated with an unfavorable prognosis and immune infiltration.展开更多
OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved fro...OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Protein-Protein interaction network,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD.Then,the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG.The levels of interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot,respectively.RESULTS:Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD.Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD.Further experiments showed that the significantly decreased alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total cholesterol,triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment,as well as the expression levels of IL-6 and TNF-αin the liver.Furthermore,drug intervention increased the protein expression levels of phosphorylated-PI3K(P-PI3K)and P-AKT in the liver of the model group mice,and decreased the protein expression level of sterol regulatory element-binding protein 1.CONCLUSION:We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.展开更多
文摘BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
文摘Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.
文摘AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis(NF).METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of pathogenic mutations in RET protooncogene, von Hippel-Lindau(VHL) and succinate dehydrogenase complex subunits B(SDHB) genes were investigated. RET proto-oncogene mutation screening for exons 10, 11, 13, 14, 15, 16 were examined by polymerase chain reaction(PCR) and direct DNA sequencing in patient. Mutation screening for exons 1, 2, 3 of VHL gene was carried out. Both forward and reverse strandswere subjected to direct sequencing after PCR amplification. The entire coding sequence of SDHB gene was screened for the presence of pathogenic mutations by PCR-sequencing.RESULTS: A 45-year-old man presented with abdominal pain and hypertension over the previous year. The patient was a known case of neurofibromatosis type 1(NF1) who presented at the age of 15 years with hyperpigmented and hypopigmented lesions. After complete evaluation for hypertension, biochemical tests and imagings indicated a malignant pheochromocytoma of 120 mm × 70 mm in size. The patient underwent left adrenalectomy, nephrectomy and splenectomy. After surgery the symptoms improved and blood pressure was controlled. After 5 years he was admitted again for evaluation of hypertensive crisis. Biochemical tests were again consistent with pheochromocytoma and disease relapse. Imaging studies and liver biopsy confirmed metastatic pheochromocytoma to the liver and para-aortic area. 131 Iodine-metaiodobenzylguanidine therapy was carried out. Genetic screening of VHL(exons 1, 2, 3), RET proto-oncogene(exons 10, 11, 13, 14, 15, 16) and SDH complex subunits revealed no pathogenic mutation. CONCLUSION: We conclude that mutations in the NF1 gene are responsible for the patient's clinical findings. However, would be helpful to further examine somatic mutations for a more precise study of genotypephenotype correlation.
文摘Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.
文摘Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three
基金the State Key Programs Basic Research of China (Grant No. G1998051103) and National High Technology Programs of China (Grant No. 863-102-08-8).
文摘PDGF (platelet derived growth factor) has been shown to play animportant role in tumorigenesis, tumor growth, atherosclerosis and inflammation and other various pathologic settings. PDGF-B chain gene is 92% homologous to v-sis oncogene of the simian sarcoma virus. Thus PDGF-B gene is also called c-sis proto-oncogene. This report provides 3 TFOs (triplex-forming oligonucleotides) to inhibit the expression of c-sis/PDGF-B gene. The results from gel mobility shift analysis, in vitro transcription, DNase I footprinting and protein binding assays demonstrate that the TFOs we designed can form sequence-specific stable triplex with the target, and can effectively suppress the downstream gene transcription and inhibit transcription factors binding. They can be used for preparation of drugs to inhibit tumor growth and for the therapy of atherosclerosis, inflammation, etc.
基金This study was supported by National Natural Science Foundation of China (No.81702650),Natural Science Foundation of Hubei Province (No.2016CFB323)and Innovation Foundation of Huazhong University of Science and Technology (No.2016YXMS229).
文摘BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LNM)remains controversial. Different surgical strategies may bring a bias in demonsstrating the association between them.In order to delineate a risk stratification to guide a tailored initial approach to tumors that express BRAF^V600E mutation,we performed this meta-analysis by using the articles in which total or near-total thyroidectomy plus bilateral central lymph node dissection was routinely performed to avoid the bias from the surgical strategy.We searched the Medline,Embase and CNKI database for eligible studies from January 2003 to May 2018.Meta-analysis was performed using the STATA 12.0 software.Odds ratios (ORs)and 95% confidence intervals (CIs)were calculated under fixed-effects or random-effects models.Fifteen clinical studies were included with a total of 4909 PTC patients. Our meta-analysis results reported that BRAF^V600E mutation was associated with LNM (OR=1.34;95% CI:1.09-1.65;P=0.005),as well as central LNM (OR=1.59;95% CI: 1.35-1.88;P<0.00001).Moreover,in patients with papillary thyroid microcarcinoma, we also confirmed the predictive value of BRAF^V600E mutation for LNM (OR=3.49;95% CI:2.02-6.02;P<0.00001).This meta-analysis demonstrates that BRAF^V600E mutation is closely related to LNM in PTC patients.The results suggest that BRAF^V600E mutation can be considered as a risk factor for LNM in PTC.Moreover,combining BRAF^V600E mutation with other risk factors to determine the initial surgical treatment may bring benefits for PTC patients.
文摘Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.
基金Supported by the Science Fund of Health Department,No.95A2141.and the Science Fund of Health Bureau of Shanghai.No.982019
文摘INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of the gut ,it is defined as an unequivocal non-invasive epithelial change[2,3].The observation of gastric dysplasia as a cancerous lesion was recognized over a century ago ,but it is only after the advent of gastroscopy that its clinical significance has been stressed[4-7].
文摘Objective: To elucidate the expression of the bcl-2 genein association with both biological characteristics of hu-man primary pancreatic carcinoma and patient’s prog-nosis.Methods: The s-p immunohistochemistry assay wasused to detect the expression of the bcl-2 gene on para-ffin-embedded sections from 97 cases of primary pan-creatic carcinoma, 32 cases of pancreatitis, and 21 ca-ses of normal pancreas.Results: Among the 97 cases of pancreatic carcinoma,70 (72.2%) showed positive staining for the bcl-2 pro-tein. In the 32 cases of pancreatitis, 3 (9.4%) showedpositive immunostaining for the bcl-2, and in the nor-mal pancreas cases, 1 (4.8%) showed positive immu-nostaining for the bcl-2. However, the positive stainingrates of the bcl-2 protein were lower in tumor tissuefrom the patients with metastases and tumor-node-me-tastasis (TNM) stages Ⅲ, Ⅳ than in those from thosewith non-metastases, well differentiation, non-invasionand TNM stages Ⅰ, Ⅱ. The patients with positive im-munostaining of bcl-2 have a longer postoperative sur-vival than those with negative staining.Conclusions: Pancreatic carcinoma expressed a highpositivity for bcl-2. Findings suggested that the overex-pression of bcl-2 is related to the carcinogenesis andprogression of human pancreatic carcinoma. Bcl-2might be one of the parameters in terms of biologicalcharacteristics and good prognosis in patients withpancreatic carcinoma.
文摘Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option and show a sustained objective response among patients with metastatic or unresectable GISTs.A wellknown higher risk of neoplasm has been described among renal transplant recipients(RTRs).Nevertheless,only few cases of GIST onset among transplant patients have been reported in the literature.CASE SUMMARY Here,we describe 2 cases of gastric GIST occurring during the follow-up of RTRs.We also review the existing literature concerning GIST occurrence in transplant patients.In total and in association with our 2 cases,16 patients have been reported.The median age was 59.5 years and 69%were male.With a median tumor size of 45 mm,no patient displayed metastatic dissemination at diagnosis.Time from transplantation to diagnosis was highly variable between 5 mo and 21 years.Histopathological data mostly revealed high risk of progression(43%).Death increased to 29%during follow-up.Surgical treatment was systematically performed when the tumor was operable(94%).The use of adjuvant therapy was uncommon(19%).CONCLUSION GISTs represent rare but potentially severe malignant complication among transplant patients.
基金It was supported by Lanzhou Science and Technology Plan Project(2018-3-58)。
文摘Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid nodules are difficult to distinguish benign and malignant.BRAF gene mutation is a common human oncogenic mutation and the highest mutation frequency in papillary thyroid carcinoma.The combination of FNA and BRAF gene detection can significantly improve the diagnostic rate of benign and malignant thyroid nodules and make up for the deficiency of single diagnosis of cytology.Moreover,while the incidence of thyroid cancer is growing rapidly worldwide,its mortality remains stable.The problem of overdiagnosis and overtreatment of thyroid cancer is becoming more and more obvious.However,due to the limitations of current studies on BRAF genes,its prognostic value for papillary thyroid carcinoma remains controversial.Therefore,in order to reduce the adverse effects of overdiagnosis and treatment,the relationship between gene and tumor biological behavior needs further study in the future.
文摘Objective: This study was designed to explore whether inhibition of the extracellular-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways can inhibit the growth of xenografts of endometrial cancer cell lines with different estrogen receptors (ER) profiles in vivo and to provide preliminary laboratory basis for the probability of endometrial adenocarcinoma treatment with blockage of the two pathways, especially to endometrial cancer with low ER status. Methods: Human endometrial cancer Ishikawa bearing ER and HEC-1Awith low ER status cells were subcutaneously injected into BALB/c nude mice to establish endometrial cancer xenograft tumor models. The effects of PI3K/Akt inhibitor LY294002, MAPK/ERK1/2 inhibitor PD-98059 and their combinations on the growth of the xenograft tumors and apoptotic state of Ishikawa and HEC-1Acells were tested in vivo using the inhibitory rate, the terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, H/E-stain. Western blot analysis was used to detect the alterations of activated ERK (P-ERK) and AKT (P-AKT) during this process. Results: LY294002, a PI3K/Akt pathway inhibitor, induced significant suppression in the growth of both Ishikawa and HEC-1Acell xenograft tumors, concomitant with increased apoptosis in xenografts as evidenced by TUNEL. A similar effect was also observed when the MAPK/ERK1/2 signaling pathway was inhibited by PD98059. Concurrent inhibition of the PI3K/Akt and MAPK/ERK1/2 pathways showed enhanced anti-tumor effects in vivo as indicated by increased apoptosis. At the same time, the levels of P-ERK and P-AKT in both xenograft tumors decreased, and their levels in combination group was the lowest. Conclusions: PD98059, LY294002 and their combinations showed remarkable inhibitory effects on xenograft tumors of endometrial carcinoma cell lines with different expression status of ER in vivo through blockage of PI3K/Akt and MAPK/ERK1/2 signaling pathways. This suggests that targeting these pathways may be an effective therapeutic strategy against endometrial carcinomas, especially for ER-negative cancers which show poor response to endocrinal therapy.
文摘Objective:To study the correlation of serum Exosome and Dickkopf-1 content with pathological process and gene expression in patients with gastric cancer.Methods:A total of 480 patients diagnosed with gastric cancer in our hospital between May 2015 and July 2016 were selected as the gastric cancer group and 220 healthy volunteers receiving physical examination during the same period were selected as control group. Serum was collected to detect Exosome and Dickkopf-1 content, and gastric cancer tissue and para-carcinoma tissue were collected to detect the expression of pro-proliferation and pro-invasion molecules as well as tumor suppressor genes.Results:Serum Exosome and Dickkopf-1 content of gastric cancer group were significantly higher than those of control group and the deeper the infiltration and the worse the differentiation, the higher the serum Exosome and Dickkopf-1 content, and serum Exosome and Dickkopf-1 content in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis;UHRF1, SIRT1 and LOXL2 expression in gastric cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with serum Exosome and Dickkopf-1 content while RASAL2, ING5, Period1 and Period2 expression were significantly lower than those in para-carcinoma tissue and negatively correlated with serum Exosome and Dickkopf-1 content. Conclusion:The elevated serum Exosome and Dickkopf-1 in patients with gastric cancer are closely related to the high expression of pro-proliferation and pro-invasion molecules as well as the low expression of proto-oncogene.
文摘At present, malignant tumor is a serious threat to human health. Its pathogenesis is complicated and caused by the interaction of various carcinogenic factors in human body. Human sal-like protein 4 (SALL4) is a newly discovered gene. It can play an important role in the function of embryonic stem cells since it is with protein transcription factor of C2H2 zinc fingers. Studies have found that mutations of the gene often lead to the occurrence of malignant tumors. This article reviews the molecular mechanism of SALL4 in the occurrence and development of malignant tumors and its role in the diagnosis and treatment of malignant tumors.
基金supported by the Key Medical Research Projects of Jiangsu Commission of Health(ID:2022013).
文摘Background:Clear cell renal carcinoma(ccRCC)is notorious for its highly unfavorable prognosis,closely related to immune cell infiltration(ICI).MYB Proto-Oncogene Like 2(MYBL2)is elevated in multiple types of human cancer and is recognized as a crucial role in tumorigenesis.In the present study,we aimed to determine the roles of MYBL2 in the prognostic outcomes of ccRCC.Methods:We analyzed the GSE100666 dataset from the Gene Expression Omnibus(GEO)database and found that the expression of MYBL2 was significantly higher in ccRCC subjects than in normal controls.Next,RNA sequencing data related to ccRCC were retrieved from The Cancer Genome Atlas(TCGA)database and the levels of MYBL2 were compared between tumor and peri-tumor tissues.The correlation between MYBL2 and clinicopathological parameters was assessed by logistic analysis.The Kaplan-Meier method,Cox-regression analysis,and nomograms,were applied to investigate the potential clinical benefits of MYBL2 in ccRCC.We also evaluated the correlation between MYBL2 and immune cell infiltration with a single-sample gene set enrichment analysis(ssGSEA).The association between MYBL2 and immune checkpoints was determined via the TIMER and TISIDB databases.Finally,correlation analysis was conducted to predict upstream non-coding RNAs(ncRNAs)regulating MYBL2,and a completing endogenous RNA(ceRNA)network was constructed to visualize the long non-coding RNAs(lncRNAs)-microRNAs(miRNAs)-MYBL2 axis in ccRCC.Finally,further analysis of upstream lncRNAs was carried out to validate the accuracy of the network.Results:MYBL2 was significantly over-expressed in ccRCC(P<0.001).High levels of MYBL2 expression in ccRCC correlated with a worse T stage,a more advanced N stage,a higher M stage,a more deleterious pathological stage,and higher histological grades.MYBL2 was identified as a risk factor for disease-specific survival(hazard ratio(HR)=2.73,P<0.001),overall survival(HR=1.91,P<0.001),and progression-free interval(HR=2.03,P<0.001).MYBL2 also positively associated with multiple types of immune cells and checkpoints.Finally,two ceRNA axes,PVT1-miR-30e-5p-MYBL2 and LINC00511-miR-29c-3p-MYBL2 were detected as the most promising upstream ncRNAs regulating MYBL2 in ccRCC,and we also validated the expression of MYBL2 and PVT1 by launching qRT-PCR.We found that the expression of MYBL2 was significantly higher in 786-O than in human kidney-2 cell line HK-2(P<0.001)and the expression of PVT1 was significantly higher in Caki-1 than in HK-2(P<0.001).Conclusion:Our study revealed that ncRNAs might upregulated the expression of MYBL2 in ccRCC and that this was associated with an unfavorable prognosis and immune infiltration.
基金the Chengdu University of Traditional Chinese Medicine:Application of A Mouse Model to Explore the Mechanism of Therapeutic Action of Safranin in Type 2 Diabetes Mellitus(No.YXRC2018003)。
文摘OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Protein-Protein interaction network,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD.Then,the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG.The levels of interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot,respectively.RESULTS:Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD.Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD.Further experiments showed that the significantly decreased alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total cholesterol,triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment,as well as the expression levels of IL-6 and TNF-αin the liver.Furthermore,drug intervention increased the protein expression levels of phosphorylated-PI3K(P-PI3K)and P-AKT in the liver of the model group mice,and decreased the protein expression level of sterol regulatory element-binding protein 1.CONCLUSION:We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.
