Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coil protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical stai...Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coil protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P〈0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P〈0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P〈0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P〈0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.展开更多
Objective: To study the effect of active compound 6F and A from Pteris semipinnata L.(PsL) on the activities of DNA topoisomerase (TOPO) I and II, activities of cytosolic and membrane TPK, and expression of oncogene c...Objective: To study the effect of active compound 6F and A from Pteris semipinnata L.(PsL) on the activities of DNA topoisomerase (TOPO) I and II, activities of cytosolic and membrane TPK, and expression of oncogene c-myc in lung adenocarcinoma cells. Methods: The effect of compound 6F and A on activities of cytosolic and membrane TPK was measured by scintillation counting; the effect of compound A on expression of oncogene c-myc was determined by flow cytometry indirect fluorimetry. Results: compound 6F and A could inhibit the activities of TOPO I, and they strongly inhibited the TOPO II in 0.01 mg/L and 10.0 mg/L respectively. Compound A slightly inhibited the activities of membrane TPK, but not the cytosolic one. Compound A could inhibit the expression of oncogene c-myc. Conclusion: Topoisomerases are target of compound 6F and A. Compound A could slightly inhibit the activities of TPK, and showed an inhibitory effect on the expression of oncogene c-myc.展开更多
BACKGROUND The Hippo signaling pathway regulates organ size by regulating cell proliferation and apoptosis with terminal effectors including Yes-associated protein-1(YAP-1).Dysregulation in Hippo pathway has been prop...BACKGROUND The Hippo signaling pathway regulates organ size by regulating cell proliferation and apoptosis with terminal effectors including Yes-associated protein-1(YAP-1).Dysregulation in Hippo pathway has been proposed as one of the therapeutic targets in hepatocarcinogenesis.The levels of reactive oxygen species(ROS)increase during the progression from early to advanced hepatocellular carcinoma(HCC).AIM To study the activation of YAP-1 by ROS-induced damage in HCC and the involved signaling pathway.METHODS The expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761)was quantified using real-time polymerase chain reaction and immunoblotting.Human HCC cells were treated with H2O2,which is a major component of ROS in living organisms,and with either YAP-1 small interfering RNA(siRNA)or control siRNA.To investigate the role of YAP-1 in HCC cells under oxidative stress,MTS assays were performed.Immunoblotting was performed to evaluate the signaling pathway responsible for the activation of YAP-1.Eighty-eight surgically resected frozen HCC tissue samples and 88 nontumor liver tissue samples were used for gene expression analyses.RESULTS H2O2 treatment increased the mRNA and protein expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761).Suppression of YAP-1 using siRNA transfection resulted in a significant decrease in tumor proliferation during H2O2 treatment both in vitro and in vivo(both P<0.05).The oncogenic action of YAP-1 occurred via the activation of the c-Myc pathway,leading to the upregulation of components of the unfolded protein response(UPR),including 78-kDa glucoseregulated protein and activating transcription factor-6(ATF-6).The YAP-1 mRNA levels in human HCC tissues were upregulated by 2.6-fold compared with those in nontumor tissues(P<0.05)and were positively correlated with the ATF-6 Levels(Pearson’s coefficient=0.299;P<0.05).CONCLUSION This study shows a novel connection between YAP-1 and the UPR through the c-Myc pathway during oxidative stress in HCC.The ROS-induced activation of YAP-1 via the c-Myc pathway,which leads to the activation of the UPR pathway,might be a therapeutic target in HCC.展开更多
Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expression on the model of rat cardiac volu...Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expression on the model of rat cardiac volume-overload hypertrophy was examined by immunohistochemical study. Results The immunohistochemical study indicated the expression of c-myc protein was increased obviously at 4-6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-overload, then decreased gradually along with development of volume-overload hypertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on,c-myc gene and the product of it do not act anymore;While it may be that c-myc gene and the product of it increased following with myocardial hypertrophy, and have not direct relation to the occurrence and development of myocardial hypertrophy.展开更多
Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the ...Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.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
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 examine the effect of recombinant human transforming growth factor β1 (rhTGF β1) alone or recombinant human interleukin 6 (rhIL 6) alone or in combination on proliferation inhibition of the hum...Objective To examine the effect of recombinant human transforming growth factor β1 (rhTGF β1) alone or recombinant human interleukin 6 (rhIL 6) alone or in combination on proliferation inhibition of the human leukaemia cell line. Methods In the present study, using the human monoblastic cell line (U 937 ) and human promyelocytic cell line (HL 60 ) as an in vitro model, we analyzed the effect of two cytokins on proliferation inhibition with rate of 3H TdR incorporation, the cellular content of DNA, DNA indices, the cell cycle and the expression of c myc mRNA. Results With administration of rhTGF β 1 and rhIL 6, U 937 cell growth was inhibited and the rate of 3H TdR incorporation inhibition was increased. There was a decrease in the cellular content of DNA and DNA indices. And no change in the cell cycle was observed after administration of rhTGF β 1 or rhIL 6. However, there was an increase in G 0/G 1 phase cells and a decrease in G 2M+S phase cells after administration of combination of rhTGF β 1 and rhIL 6. It was also found that rhIL 6 could inhibit proliferative responses of HL 60 cells, meanwhile the inhibition could be enhanced by rhTGF β 1. The rate of 3H TdR incorporation inhibition rose up to 39.89%, and DNA index fell to 1.00 following induction by rhIL 6 plus rhTGF β 1. Furthermore, G 0/G 1 phase cells increased while G 2M+S cells decreased. Conclusions These results suggest that combination of rhTGF β 1 and rhIL 6 acted in synergy to inhibit proliferation of both U 937 and HL 60 cell lines. Molecular hybridization test show that rhTGF β 1 alone, rhIL 6 alone or rhTGF β 1 and rhIL 6 in combination can inhibit U 937 and HL 60 cells expression of c myc mRNA in a time and dose dependent manner. rhTGF β 1 and rhIL 6 in combination synergistically inhibited c myc expression, which may be one of the machanisms for the actions of the two cytokines.展开更多
蛋白磷酸酶2A(protein phosphatase 2A,PP2A)的癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A),又名KIAA1524或p90,是最近被鉴别出的一种人类癌蛋白,多项研究表明,CIP2A能够直接与癌转录因子c-Myc蛋白相互作用...蛋白磷酸酶2A(protein phosphatase 2A,PP2A)的癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A),又名KIAA1524或p90,是最近被鉴别出的一种人类癌蛋白,多项研究表明,CIP2A能够直接与癌转录因子c-Myc蛋白相互作用,抑制PP2A对其丝氨酸62位(S62)的去磷酸化作用,从而抑制了细胞内c-Myc蛋白的水解,稳定了其蛋白表达水平。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
Isolation and characteriation of functional nudear matrix proteins involved in DNA anchoring and gene expression is one of the major subjects of current nudear matrix research. Southwestern blotting (DNA-protein hybri...Isolation and characteriation of functional nudear matrix proteins involved in DNA anchoring and gene expression is one of the major subjects of current nudear matrix research. Southwestern blotting (DNA-protein hybridization) was applied to studying the anchoring of c-myc on the nudear matrix proteins in mouse thymic T lymphocytes. The results showed that c-myc bound to the lamin, p34 and p36 nudear matrix proteins specifically. In the process of mouse thymic PNA T lymphocytes proliferation induced by ConA, the anchoring of c-myc on p34 and p36 nudear matrix proteins changed dynamically.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
The recombinant plasmid PGC was constructed for transcription unit of c-myc gene with diorientation in vitro, to make RNA probes for detection of c-myc mRNA and antisence RNA expression of tranfectant HL-9,which was o...The recombinant plasmid PGC was constructed for transcription unit of c-myc gene with diorientation in vitro, to make RNA probes for detection of c-myc mRNA and antisence RNA expression of tranfectant HL-9,which was obtained from HL60 cells transfected with inducible c-myc antisense RNA expression plasmid. The results from HL-9 cells induced by Cd2+ indicated that expression of c-myc antisense RNA increased with Cd2+ concentration and exposure time, while c-myc mRNA expression progressively reduced. Using immunohistochemical technique no c-myc P62 protein expression was detected. The incorporation of 3H-TdR, 3H-UR and 3H-Leu revealed significant suppression of DNA, RNA and protein biosynthesis. It is suggested that the reversion changes previously reported in malignant Phenotypes of HL-9 cells and the inhibition of macromolecular biosynthesis mentioned above were associated with the blockade of c-myc gene expression by its antisense RNA.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
Objectiv:To observe the effects ofRadix Salviae Miltiorrhizae (SM) on humanfibroblast in culture of kidney with lupus nephritis (LN ). Methods: Fibroblasts wereisolated from culture of kidney biopsy of LN patients, an...Objectiv:To observe the effects ofRadix Salviae Miltiorrhizae (SM) on humanfibroblast in culture of kidney with lupus nephritis (LN ). Methods: Fibroblasts wereisolated from culture of kidney biopsy of LN patients, and effect of SM on 3H-TdR incorporated rate of fibroblasts was observed. Theapoptosis and c-myc expression were detectedin the same time by flow cytometry.Results:SM could inhibit the proliferation of fibrolast,and promote the programmed cell deaththrough upregulate c-myc protein expression inhuman renal fibroblasts. Conclusions: Longterm administration of SM in large dosagecould be effective on interstial fibrosis of LN,so that to prevent or reduce the scar tissue for-mation and teatrd the occurrence of uremia.展开更多
泛素蛋白酶体途径成员的异常表达或突变可导致包括恶性肿瘤在内的多种疾病的发生[1].作为泛素蛋白酶体途径的重要识别因子之一,F框/WD40域蛋白7(F-box and WD-40 domain protein 7,FBXW7)作用的许多底物都是癌基因,如c-mye、细胞周期...泛素蛋白酶体途径成员的异常表达或突变可导致包括恶性肿瘤在内的多种疾病的发生[1].作为泛素蛋白酶体途径的重要识别因子之一,F框/WD40域蛋白7(F-box and WD-40 domain protein 7,FBXW7)作用的许多底物都是癌基因,如c-mye、细胞周期素E、c-jun和Notch等都是通过FBXW7介导的泛素蛋白酶体途径进行降解的[2-5].近年研究发现,FBXW7在多种肿瘤中的表达均有不同程度的缺失.展开更多
Background:Adamantinomatous craniopharyngioma(ACP)is the commonest pediatric sellar tumor.No effective drug is available and interpatient heterogeneity is prominent.This study aimed to identify distinct molecular subg...Background:Adamantinomatous craniopharyngioma(ACP)is the commonest pediatric sellar tumor.No effective drug is available and interpatient heterogeneity is prominent.This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles,imaging findings,and histological features,in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods:Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled,including 119 ACPs and 23 papillary craniopharyngiomas.Whole-exome sequencing(151 tumors,including recurrent ones),RNA sequencing(84 tumors),and DNA methylome profiling(95 tumors)were performed.Consensus clustering and non-negative matrix factorization were used for subgrouping,and Cox regression were utilized for prognostic evaluation,respectively.Results:Three distinct molecular subgroups were identified:WNT,ImA,and ImB.The WNT subgroup showed higher Wnt/β-catenin pathway activity,with a greater number of epithelial cells and more predominantly solid tumors.The ImA and ImB subgroups had activated inflammatory and interferon response pathways,with enhanced immune cell infiltration and more predominantly cystic tumors.Mitogen-activated protein kinases(MEK/MAPK)signaling was activated only in ImA samples,while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group,mostly consisting of children.The degree of astrogliosis was significantly elevated in the ImA group,with severe finger-like protrusions at the invasive front of the tumor.The molecular subgrouping was an independent prognostic factor,with the WNT group having longer event-free survival than ImB(Cox,P=0.04).ImA/ImB cases were more likely to respond to immune checkpoint blockade(ICB)therapy than the WNT group(P<0.01).In the preliminary screening of subtyping markers,CD38 was significantly downregulated in WNT compared with ImA and ImB(P=0.01).Conclusions:ACP comprises three molecular subtypes with distinct imaging and histological features.The prognosis of the WNT type is better than that of the ImB group,which is more likely to benefit from the ICB treatment.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
基金the Scientific Research Start Found of Chongqing Medical University(QD 200201) project of Chongqing Science and Technology Committee (No. 040307)
文摘Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coil protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P〈0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P〈0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P〈0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P〈0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.
基金the National Natural Science Foundation of China (No. 39870900) and the key project grant from Guangdong Province Science and Te
文摘Objective: To study the effect of active compound 6F and A from Pteris semipinnata L.(PsL) on the activities of DNA topoisomerase (TOPO) I and II, activities of cytosolic and membrane TPK, and expression of oncogene c-myc in lung adenocarcinoma cells. Methods: The effect of compound 6F and A on activities of cytosolic and membrane TPK was measured by scintillation counting; the effect of compound A on expression of oncogene c-myc was determined by flow cytometry indirect fluorimetry. Results: compound 6F and A could inhibit the activities of TOPO I, and they strongly inhibited the TOPO II in 0.01 mg/L and 10.0 mg/L respectively. Compound A slightly inhibited the activities of membrane TPK, but not the cytosolic one. Compound A could inhibit the expression of oncogene c-myc. Conclusion: Topoisomerases are target of compound 6F and A. Compound A could slightly inhibit the activities of TPK, and showed an inhibitory effect on the expression of oncogene c-myc.
文摘BACKGROUND The Hippo signaling pathway regulates organ size by regulating cell proliferation and apoptosis with terminal effectors including Yes-associated protein-1(YAP-1).Dysregulation in Hippo pathway has been proposed as one of the therapeutic targets in hepatocarcinogenesis.The levels of reactive oxygen species(ROS)increase during the progression from early to advanced hepatocellular carcinoma(HCC).AIM To study the activation of YAP-1 by ROS-induced damage in HCC and the involved signaling pathway.METHODS The expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761)was quantified using real-time polymerase chain reaction and immunoblotting.Human HCC cells were treated with H2O2,which is a major component of ROS in living organisms,and with either YAP-1 small interfering RNA(siRNA)or control siRNA.To investigate the role of YAP-1 in HCC cells under oxidative stress,MTS assays were performed.Immunoblotting was performed to evaluate the signaling pathway responsible for the activation of YAP-1.Eighty-eight surgically resected frozen HCC tissue samples and 88 nontumor liver tissue samples were used for gene expression analyses.RESULTS H2O2 treatment increased the mRNA and protein expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761).Suppression of YAP-1 using siRNA transfection resulted in a significant decrease in tumor proliferation during H2O2 treatment both in vitro and in vivo(both P<0.05).The oncogenic action of YAP-1 occurred via the activation of the c-Myc pathway,leading to the upregulation of components of the unfolded protein response(UPR),including 78-kDa glucoseregulated protein and activating transcription factor-6(ATF-6).The YAP-1 mRNA levels in human HCC tissues were upregulated by 2.6-fold compared with those in nontumor tissues(P<0.05)and were positively correlated with the ATF-6 Levels(Pearson’s coefficient=0.299;P<0.05).CONCLUSION This study shows a novel connection between YAP-1 and the UPR through the c-Myc pathway during oxidative stress in HCC.The ROS-induced activation of YAP-1 via the c-Myc pathway,which leads to the activation of the UPR pathway,might be a therapeutic target in HCC.
文摘Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expression on the model of rat cardiac volume-overload hypertrophy was examined by immunohistochemical study. Results The immunohistochemical study indicated the expression of c-myc protein was increased obviously at 4-6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-overload, then decreased gradually along with development of volume-overload hypertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on,c-myc gene and the product of it do not act anymore;While it may be that c-myc gene and the product of it increased following with myocardial hypertrophy, and have not direct relation to the occurrence and development of myocardial hypertrophy.
基金Supported by Natural Science Foundation of Shaanxi Province(Grant No.2018722)
文摘Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.
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 examine the effect of recombinant human transforming growth factor β1 (rhTGF β1) alone or recombinant human interleukin 6 (rhIL 6) alone or in combination on proliferation inhibition of the human leukaemia cell line. Methods In the present study, using the human monoblastic cell line (U 937 ) and human promyelocytic cell line (HL 60 ) as an in vitro model, we analyzed the effect of two cytokins on proliferation inhibition with rate of 3H TdR incorporation, the cellular content of DNA, DNA indices, the cell cycle and the expression of c myc mRNA. Results With administration of rhTGF β 1 and rhIL 6, U 937 cell growth was inhibited and the rate of 3H TdR incorporation inhibition was increased. There was a decrease in the cellular content of DNA and DNA indices. And no change in the cell cycle was observed after administration of rhTGF β 1 or rhIL 6. However, there was an increase in G 0/G 1 phase cells and a decrease in G 2M+S phase cells after administration of combination of rhTGF β 1 and rhIL 6. It was also found that rhIL 6 could inhibit proliferative responses of HL 60 cells, meanwhile the inhibition could be enhanced by rhTGF β 1. The rate of 3H TdR incorporation inhibition rose up to 39.89%, and DNA index fell to 1.00 following induction by rhIL 6 plus rhTGF β 1. Furthermore, G 0/G 1 phase cells increased while G 2M+S cells decreased. Conclusions These results suggest that combination of rhTGF β 1 and rhIL 6 acted in synergy to inhibit proliferation of both U 937 and HL 60 cell lines. Molecular hybridization test show that rhTGF β 1 alone, rhIL 6 alone or rhTGF β 1 and rhIL 6 in combination can inhibit U 937 and HL 60 cells expression of c myc mRNA in a time and dose dependent manner. rhTGF β 1 and rhIL 6 in combination synergistically inhibited c myc expression, which may be one of the machanisms for the actions of the two cytokines.
文摘蛋白磷酸酶2A(protein phosphatase 2A,PP2A)的癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A),又名KIAA1524或p90,是最近被鉴别出的一种人类癌蛋白,多项研究表明,CIP2A能够直接与癌转录因子c-Myc蛋白相互作用,抑制PP2A对其丝氨酸62位(S62)的去磷酸化作用,从而抑制了细胞内c-Myc蛋白的水解,稳定了其蛋白表达水平。
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].
基金Project supported by the National Natural Science Foundation of China and Institute of Biophysics, Chinese Academy of Sciences.
文摘Isolation and characteriation of functional nudear matrix proteins involved in DNA anchoring and gene expression is one of the major subjects of current nudear matrix research. Southwestern blotting (DNA-protein hybridization) was applied to studying the anchoring of c-myc on the nudear matrix proteins in mouse thymic T lymphocytes. The results showed that c-myc bound to the lamin, p34 and p36 nudear matrix proteins specifically. In the process of mouse thymic PNA T lymphocytes proliferation induced by ConA, the anchoring of c-myc on p34 and p36 nudear matrix proteins changed dynamically.
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.
文摘The recombinant plasmid PGC was constructed for transcription unit of c-myc gene with diorientation in vitro, to make RNA probes for detection of c-myc mRNA and antisence RNA expression of tranfectant HL-9,which was obtained from HL60 cells transfected with inducible c-myc antisense RNA expression plasmid. The results from HL-9 cells induced by Cd2+ indicated that expression of c-myc antisense RNA increased with Cd2+ concentration and exposure time, while c-myc mRNA expression progressively reduced. Using immunohistochemical technique no c-myc P62 protein expression was detected. The incorporation of 3H-TdR, 3H-UR and 3H-Leu revealed significant suppression of DNA, RNA and protein biosynthesis. It is suggested that the reversion changes previously reported in malignant Phenotypes of HL-9 cells and the inhibition of macromolecular biosynthesis mentioned above were associated with the blockade of c-myc gene expression by its antisense RNA.
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Objectiv:To observe the effects ofRadix Salviae Miltiorrhizae (SM) on humanfibroblast in culture of kidney with lupus nephritis (LN ). Methods: Fibroblasts wereisolated from culture of kidney biopsy of LN patients, and effect of SM on 3H-TdR incorporated rate of fibroblasts was observed. Theapoptosis and c-myc expression were detectedin the same time by flow cytometry.Results:SM could inhibit the proliferation of fibrolast,and promote the programmed cell deaththrough upregulate c-myc protein expression inhuman renal fibroblasts. Conclusions: Longterm administration of SM in large dosagecould be effective on interstial fibrosis of LN,so that to prevent or reduce the scar tissue for-mation and teatrd the occurrence of uremia.
文摘泛素蛋白酶体途径成员的异常表达或突变可导致包括恶性肿瘤在内的多种疾病的发生[1].作为泛素蛋白酶体途径的重要识别因子之一,F框/WD40域蛋白7(F-box and WD-40 domain protein 7,FBXW7)作用的许多底物都是癌基因,如c-mye、细胞周期素E、c-jun和Notch等都是通过FBXW7介导的泛素蛋白酶体途径进行降解的[2-5].近年研究发现,FBXW7在多种肿瘤中的表达均有不同程度的缺失.
基金Fujian Medical University(No.XRCZX2017001 to XW)Natural Science Foundation of Fujian Province(No.2019J01294 to XW)+1 种基金Sanbo Brain Hospital Management Group(No.SBJT-KY-2020-002 to ZL)Capital Health Research and Development Special Fund(No.2022-2-8013 to ZL)
文摘Background:Adamantinomatous craniopharyngioma(ACP)is the commonest pediatric sellar tumor.No effective drug is available and interpatient heterogeneity is prominent.This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles,imaging findings,and histological features,in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods:Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled,including 119 ACPs and 23 papillary craniopharyngiomas.Whole-exome sequencing(151 tumors,including recurrent ones),RNA sequencing(84 tumors),and DNA methylome profiling(95 tumors)were performed.Consensus clustering and non-negative matrix factorization were used for subgrouping,and Cox regression were utilized for prognostic evaluation,respectively.Results:Three distinct molecular subgroups were identified:WNT,ImA,and ImB.The WNT subgroup showed higher Wnt/β-catenin pathway activity,with a greater number of epithelial cells and more predominantly solid tumors.The ImA and ImB subgroups had activated inflammatory and interferon response pathways,with enhanced immune cell infiltration and more predominantly cystic tumors.Mitogen-activated protein kinases(MEK/MAPK)signaling was activated only in ImA samples,while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group,mostly consisting of children.The degree of astrogliosis was significantly elevated in the ImA group,with severe finger-like protrusions at the invasive front of the tumor.The molecular subgrouping was an independent prognostic factor,with the WNT group having longer event-free survival than ImB(Cox,P=0.04).ImA/ImB cases were more likely to respond to immune checkpoint blockade(ICB)therapy than the WNT group(P<0.01).In the preliminary screening of subtyping markers,CD38 was significantly downregulated in WNT compared with ImA and ImB(P=0.01).Conclusions:ACP comprises three molecular subtypes with distinct imaging and histological features.The prognosis of the WNT type is better than that of the ImB group,which is more likely to benefit from the ICB treatment.
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.