Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its ...Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its roles in embryonic development,regulates growth,proliferation and cancer stem cell(CSC)self-renewal.The glioma-associated oncogene homolog(GLI)transcription factors play crucial roles in melanoma.However,oncogenic B-Raf proto-oncogene,serine/threonine kinase(BRAF)steals the spotlight by driving the aberrant activation of HH-GLI1/2 signaling.Oncogenic BRAF-driven HH-GLI1/2 signaling imparts invasive phenotype to melanoma cells and sustains CSC self-renewal.Interestingly,the transcriptional activities of GLI1 and GLI2 are suppressed by acetylation,a process that is counteracted by the deacetylating actions of histone deacetylase(HDAC)1/2.Therefore,inhibiting HDAC1/2 might keep GLI proteins in inactive acetylated form,thus representing an attractive druggable target.Notably,both HDAC1 and HDAC2 are induced by HH signaling,creating a positive feedback loop where HH signaling upregulates the expression of both HDAC1 and HDAC2.Selective inhibition of BRAF/HH/HDAC/GLI signaling axis is likely to unravel new therapeutic opportunities in melanoma.However,the precise contribution of oncogenic BRAF-driven HH signaling to therapy resistance and CSC renewal remains unclear and requires thorough investigation.In this article,we endeavored to explore the crosstalk between oncogenic BRAF and HH signaling,and the pivotal role this interaction plays in the self-renewal of melanoma stem cells.A better understanding of the molecular mechanisms governing these interactions is essential for improving melanoma treatment strategies and identifying new therapeutic targets.展开更多
Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed ...Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.展开更多
Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 1...Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 15 cases of non-tumor nasopharyngeal (NP), 55 cases of NPC. Results: The positive rates of c-Met mRNA in NP and NPC cells were 13.3% (2/15) and 61.8% (34/55) respectively. The expression of c-Met mRNA was significantly correlated with lymph node metastasis, local invasion (skull base erosion), and clinical stage. In cases with cervical lymph node metastasis, local invasion, and clinical stage III and IV (UICC), the positive rates of expression of c-Met mRNA were significantly higher than that in those without the conditions mentioned above (P < 0.05 or P < 0.01). But it was not significantly correlated with age, gender, histo- logic grade, and cranial nerve palsy (P > 0.05). Conclusion: The abnormal expression of c-Met gene was well correlated with the biological behavior of metastasis and invasion. To detection the expression of c-Met mRNA could serve as an important index to estimate the prognosis of NPC. C-Met may be a new diagnostic/therapeutic target of NPC.展开更多
Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/...Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.展开更多
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 effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of su...Objective:To investigate the effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of subtoxic concentrations of arecoline on the expression of viral oncoproteins and transcriptional factors was examined in CaSki and SiHa cells.HPV16 promoter activity was evaluated in a plasmid containing HPV16 long control region(pGL3-HPV16LCR)-transfected cells.Cell proliferation,cell migration,and number of colonies were assessed by MTT,wound healing assay,and colony-forming assay,respectively.Results:Arecoline at 0.01μg/mL significantly upregulated HPV16 E6 and E7 oncoproteins in both CaSki and SiHa cells.It also upregulated the expression level of c-Fos and c-Jun mRNAs,and c-Myc protein in CaSki and SiHa cells.In addition,arecoline at subtoxic concentrations(0.0025 and 0.01μg/mL)significantly induced HPV16 promoter activity in pGL3-16LCR-transfected cells.It also promoted SiHa and CaSki cell proliferation,migration,and colony formation.Conclusions:Arecoline at subtoxic concentrations promotes the proliferation,migration,and colony formation of CaSki and SiHa cells via upregulation of c-Fos,c-Jun,c-Myc,and HPV16 E6 and E7 expressions.展开更多
In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10....In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10.32604/or.2023.030771,https://www.techscience.com/or/v32n7/57163),an inadvertent error occurred during the compilation of Fig.3H.This needed corrections to ensure the accuracy and integrity of the data presented.展开更多
Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybri...Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybridization and immunohistochemistry techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Results: Expression of c-fos and c-myc mRNA could not be detected or detected at very low level in the control group. There were greatly increased expression of c-fos and c-myc mRNA after guinea pigs were challenged by ovoglobulin. Thirty minutes after the challenge, the expression of c-fos and c-myc mRNA reached to the peak and returned to normal level 4 h after the challenge. Immunohistochemistry studies showed that Fos, Myc, Jun and Sis expressed at low level in control group and increased after ovoglobulin stimulation. Immunohistochemically positive cells laid in the plasma of airway epithelium, in cell nucleus of bronchial epithelium and in the inflammatory cells. Pathologic studies showed there were smooth muscle thicken around bronchia and lymphocytes infiltration under mucosa or around bronchia smooth muscle. Conclusion: Proto-oncogenes expressed in airway of asthma in a guinea pig model, proto-oncogenes may have roles in the process of airway remodeling.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 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
AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic...AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic specimens of 83 cases of gastric cancer and 101 metastatic lymph nodes.RESULTS C-erbB-2 amplification was found in 28.9% (24/ 83) surgical specimens and 20.5% (17/ 83) endoscopic ones of gastric cancer patients. The amplification was significant in both types of specimens of advanced cancer cases (P＜0.05) and surgical specimens with lymph node metastasis (P＜0.01). The incidence of C-erbB-2 amplification in lymph nodes with metastasis was higher than in primary sites (surgical specimens, P＜0.05). The patients with amplification tumors had poorer 5-year survival rates than those with unamplification ones in the early cancers and well to moderately differentiated adenocarcinomas (P＜0.05). The same surgical samples were tested again by Southern blot hybridization to ascertain C-erbB-2 amplification, and the positive rate of C-erbB-2 amplification (15.7%) was lower than that of dPCR (28.9%, P＜0.05).CONCLUSION Examining C-erbB-2 amplification by dPCR is a quick, simple, reliable and independent method, and is helpful in predicting prognosis and metastatic potential of gastric cancer.展开更多
BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in...BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.展开更多
AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expressio...AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma.展开更多
Summary: To investigate the significance of hepatocyte apoptosis, proliferation and oncogene c fos expression in carbon tetrachloride (CCl 4) induced cirrhotic rat liver. Rat cirrhosis was induced by subcutaneous i...Summary: To investigate the significance of hepatocyte apoptosis, proliferation and oncogene c fos expression in carbon tetrachloride (CCl 4) induced cirrhotic rat liver. Rat cirrhosis was induced by subcutaneous injection of 50 % (v∶v 1∶1) CCl 4. Hepatocyte apoptosis, proliferation and oncogene c fos expression were examined with TUNEL, PCNA and c fos immunohistochemical methods in control group and treatment group 72 h, 5, 7, 11 and 15 weeks after CCl 4 induction. Hepatocyte apoptosis was rarely seen in control rat liver. The hepatocyte apoptosis was obviously increased 72 h after treatment. Fifteen weeks after treatment, the apoptosis was still more obvious in treatment group than that in controls. PCNA was constantly expressed in CCl 4 group, with highest level at middle phase. C fos was positive 7 and 11 weeks after CCl 4 treatment. The results suggest that: 1) apoptosis is involved in rat liver damage at the early phase in CCl 4 induced injury, and the process can alleviate nodule reconstruction or eradicate potentially mutational hepatocytes at the later phase; 2) hepatocytes constantly proliferate in CCl 4 induced rat liver cirrhosis, especially at the middle phase; 3) c fos might modulate hepatocyte proliferation in CCl 4 induced rat liver cirrhosis.展开更多
BACKGROUND: Recent research found abnormal expres- sion of the c-fms oncogene, which encodes the macro- phage colony-stimulating factor receptor (CSF-1R), in several human carcinomas including hepatocellular carcino- ...BACKGROUND: Recent research found abnormal expres- sion of the c-fms oncogene, which encodes the macro- phage colony-stimulating factor receptor (CSF-1R), in several human carcinomas including hepatocellular carcino- ma (HCC). But the relationship between the point muta- tion and abnormal expressing of c-fms oncogene in HCC was not clear. This study is to investigate the relationship between point mutation and abnormal expression of c-fms oncogene in hepatocellular carcinoma (HCC) and to clari- fy the mechanism of HCC. METHODS: The expression of c-fms oncogene at different levels of cell, protein and transcription was observed using immune histological ABC, Western blot and Northern blot. PCR-single strand conformation polymorphism and gene sequencing were used to detect the mutation of c-fms in HCC tissues and their surrounding tissues of 30 patients. RESULTS: The expression of c-fms was significantly higher in HCC tissues than in their surrounding tissues (P <0.01). Point mutation of Leu (TTG)—>Ser (TCG) at codon 301 of c-fms amino acids was observed in 21.4% (3/14) HCC tissues. No mutation of c-fms oncogene was detected in the surrounding cancerous tissues. CONCLUSION: Point mutation at codon 301 of c-fms on- cogene is one of the mechanisms of abnormal over-expres- sion in HCC.展开更多
Objective: To study the clinical significance and relationship between c-fms oncogene and hepatocellular carcinogenesis, to further clarify the occurring mechanism of hepatocellular carcinoma (HCC). Methods: PCR-SSCP ...Objective: To study the clinical significance and relationship between c-fms oncogene and hepatocellular carcinogenesis, to further clarify the occurring mechanism of hepatocellular carcinoma (HCC). Methods: PCR-SSCP technique was used to analyse mutation of c-fms oncogene in 30 cases of HCC tissues. Sequencing the PCR products after cloning to prove the mutations, meanwhile the relationship between c-fms mutations and clinical pathology of HCC was investigated. Results: Two abnormal single strands were observed in 10% (3/30) HCC tissues from c-fms DNA corresponding to 301st codon of c-fms amino acids. PCR products of abnormal single strands were sequenced after cloning, it demonstrated that there was transition of T→C at nucleic acid 14855 of c-fms DNA, which corresponded to transition of Leu (TTG)→Ser (TCG) at 301st codon of c-fms amino acids. The mutation was related to malignant degree and type of HCC tissues as well as patient’s age. Conclusion: Mutation of c-fms codon at site 301 implied a molecular mechanism contributing to hepatocellular carcinogenesis.展开更多
Objective: To study the distribution of c fos oncogene expression within central nervous system (CNS) of the rat during halothane anesthesia. Methods: c-fos oncogene immunohistochemical technique (ABC method) was empl...Objective: To study the distribution of c fos oncogene expression within central nervous system (CNS) of the rat during halothane anesthesia. Methods: c-fos oncogene immunohistochemical technique (ABC method) was employed. Results: When halothane concentration was 0.75%,1.5%or2.0%, most of the Fos-like immunore- active neurons (FLNs) appeared in telencephalon, diencephalon and brain stem, including cerebral cortex, amygaloid nucleus, accumbens nucleus, lateral keptal nucleus. bed nucleus of the stria terminalis, field CA1 of Ammon’s horn, islands of Calleja, paraventricular thalamic nucleus, central medial thalamic nucleus, reuniens thalamic nucleus, rhomboid thalamic nucleus. ventral posterolateral thalamic nucleus, paraventricular hypothalamic nucleus(ventral part). periventricular hypothalamic nucleus, median preoptic nucleus, supraoptic nucleus, suprachiasmatic nucleus. medial and lateral habenular nucleus. midbrain periaqueductal gray and Edinger-Westphal nucleus.In the present stude. we have also found that the number of FLN registered stable increase along with the increaseof the concentration of halothane. Conclusion: It has been indicated that FLNs participate in the process ofhalothane anesthesia. which should necessitate and pave the way for a further study of the patterns of linkage andthe mechanism of interaction between functional nuclei.展开更多
The expression of three protooncogenes (c-myc, c-fos, N-ras) in.the primary cells from 53 cases of leukemia as well as peripheral WBC from 8 normal individuals was studied. Semiquantitative analysis of mRNA levels of ...The expression of three protooncogenes (c-myc, c-fos, N-ras) in.the primary cells from 53 cases of leukemia as well as peripheral WBC from 8 normal individuals was studied. Semiquantitative analysis of mRNA levels of the protooncogenes was carried out by Quick-blot. The results showed that (1) c-myc oncogene was slightly expressed and Nras was marginally expressed, whereas the expression of the c-fos was undetectable in the peripheral leucocytes of 8 normal individuals; (2) the c-myc was obviously expressed in almost all leukemic cells irrespective of the cell types, while N-ras and c-fos were variable expressed; (3) the c-fos was expressed in all 4 cases of M4; (4) the c-myc transcript was detected but the N-ras and c-fos were not in 4 chronic leukemic cases; (5) the relationship between protooncogene expression and state of leukemia or after chemotherapy was also analysed.展开更多
During oncogenesis,the hyper-activation of proto-oncogenes and defection of tumor suppressor genes（Zhao et al.,2012,2016a）can regulate cell proliferation,differentiation,apoptosis,and cell-to-cell communication（Bal...During oncogenesis,the hyper-activation of proto-oncogenes and defection of tumor suppressor genes（Zhao et al.,2012,2016a）can regulate cell proliferation,differentiation,apoptosis,and cell-to-cell communication（Balmain et al.,2003;Haber and Settleman,2007）.Recent evidence has shown that non-coding RNAs, such as microRNAs （miRNAs） （Chen, 2005）, and long non- coding RNAs （lncRNAs）, can also act as oncogenes to initiate and promote cancer progression.展开更多
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expr...PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.展开更多
基金Supported by the Science and Engineering Research Board,No.PDF/2016/002730.
文摘Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its roles in embryonic development,regulates growth,proliferation and cancer stem cell(CSC)self-renewal.The glioma-associated oncogene homolog(GLI)transcription factors play crucial roles in melanoma.However,oncogenic B-Raf proto-oncogene,serine/threonine kinase(BRAF)steals the spotlight by driving the aberrant activation of HH-GLI1/2 signaling.Oncogenic BRAF-driven HH-GLI1/2 signaling imparts invasive phenotype to melanoma cells and sustains CSC self-renewal.Interestingly,the transcriptional activities of GLI1 and GLI2 are suppressed by acetylation,a process that is counteracted by the deacetylating actions of histone deacetylase(HDAC)1/2.Therefore,inhibiting HDAC1/2 might keep GLI proteins in inactive acetylated form,thus representing an attractive druggable target.Notably,both HDAC1 and HDAC2 are induced by HH signaling,creating a positive feedback loop where HH signaling upregulates the expression of both HDAC1 and HDAC2.Selective inhibition of BRAF/HH/HDAC/GLI signaling axis is likely to unravel new therapeutic opportunities in melanoma.However,the precise contribution of oncogenic BRAF-driven HH signaling to therapy resistance and CSC renewal remains unclear and requires thorough investigation.In this article,we endeavored to explore the crosstalk between oncogenic BRAF and HH signaling,and the pivotal role this interaction plays in the self-renewal of melanoma stem cells.A better understanding of the molecular mechanisms governing these interactions is essential for improving melanoma treatment strategies and identifying new therapeutic targets.
文摘Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.
文摘Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 15 cases of non-tumor nasopharyngeal (NP), 55 cases of NPC. Results: The positive rates of c-Met mRNA in NP and NPC cells were 13.3% (2/15) and 61.8% (34/55) respectively. The expression of c-Met mRNA was significantly correlated with lymph node metastasis, local invasion (skull base erosion), and clinical stage. In cases with cervical lymph node metastasis, local invasion, and clinical stage III and IV (UICC), the positive rates of expression of c-Met mRNA were significantly higher than that in those without the conditions mentioned above (P < 0.05 or P < 0.01). But it was not significantly correlated with age, gender, histo- logic grade, and cranial nerve palsy (P > 0.05). Conclusion: The abnormal expression of c-Met gene was well correlated with the biological behavior of metastasis and invasion. To detection the expression of c-Met mRNA could serve as an important index to estimate the prognosis of NPC. C-Met may be a new diagnostic/therapeutic target of NPC.
基金This work was supported by the National Natural Science Foundation of China (No. 30271110).
文摘Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.
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 effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of subtoxic concentrations of arecoline on the expression of viral oncoproteins and transcriptional factors was examined in CaSki and SiHa cells.HPV16 promoter activity was evaluated in a plasmid containing HPV16 long control region(pGL3-HPV16LCR)-transfected cells.Cell proliferation,cell migration,and number of colonies were assessed by MTT,wound healing assay,and colony-forming assay,respectively.Results:Arecoline at 0.01μg/mL significantly upregulated HPV16 E6 and E7 oncoproteins in both CaSki and SiHa cells.It also upregulated the expression level of c-Fos and c-Jun mRNAs,and c-Myc protein in CaSki and SiHa cells.In addition,arecoline at subtoxic concentrations(0.0025 and 0.01μg/mL)significantly induced HPV16 promoter activity in pGL3-16LCR-transfected cells.It also promoted SiHa and CaSki cell proliferation,migration,and colony formation.Conclusions:Arecoline at subtoxic concentrations promotes the proliferation,migration,and colony formation of CaSki and SiHa cells via upregulation of c-Fos,c-Jun,c-Myc,and HPV16 E6 and E7 expressions.
文摘In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10.32604/or.2023.030771,https://www.techscience.com/or/v32n7/57163),an inadvertent error occurred during the compilation of Fig.3H.This needed corrections to ensure the accuracy and integrity of the data presented.
文摘Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybridization and immunohistochemistry techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Results: Expression of c-fos and c-myc mRNA could not be detected or detected at very low level in the control group. There were greatly increased expression of c-fos and c-myc mRNA after guinea pigs were challenged by ovoglobulin. Thirty minutes after the challenge, the expression of c-fos and c-myc mRNA reached to the peak and returned to normal level 4 h after the challenge. Immunohistochemistry studies showed that Fos, Myc, Jun and Sis expressed at low level in control group and increased after ovoglobulin stimulation. Immunohistochemically positive cells laid in the plasma of airway epithelium, in cell nucleus of bronchial epithelium and in the inflammatory cells. Pathologic studies showed there were smooth muscle thicken around bronchia and lymphocytes infiltration under mucosa or around bronchia smooth muscle. Conclusion: Proto-oncogenes expressed in airway of asthma in a guinea pig model, proto-oncogenes may have roles in the process of airway remodeling.
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.
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.
基金Project supported by the zhejiang Natural Scierce Fundation No.925006.
文摘AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic specimens of 83 cases of gastric cancer and 101 metastatic lymph nodes.RESULTS C-erbB-2 amplification was found in 28.9% (24/ 83) surgical specimens and 20.5% (17/ 83) endoscopic ones of gastric cancer patients. The amplification was significant in both types of specimens of advanced cancer cases (P＜0.05) and surgical specimens with lymph node metastasis (P＜0.01). The incidence of C-erbB-2 amplification in lymph nodes with metastasis was higher than in primary sites (surgical specimens, P＜0.05). The patients with amplification tumors had poorer 5-year survival rates than those with unamplification ones in the early cancers and well to moderately differentiated adenocarcinomas (P＜0.05). The same surgical samples were tested again by Southern blot hybridization to ascertain C-erbB-2 amplification, and the positive rate of C-erbB-2 amplification (15.7%) was lower than that of dPCR (28.9%, P＜0.05).CONCLUSION Examining C-erbB-2 amplification by dPCR is a quick, simple, reliable and independent method, and is helpful in predicting prognosis and metastatic potential of gastric cancer.
基金This study was supported by grants from the National Outstanding YouthFoundation of China (type B, No. 3982511 ) and the Provincial NaturalScience Foundation of Guangdong, China (No. 980107)
文摘BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.
基金Supported by The General Research Fund, offered by Research Grant Council of Hong Kong to Tang JCO and Lam AKY, PolyU5627/08MGriffith Health Institute Project Grant
文摘AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma.
文摘Summary: To investigate the significance of hepatocyte apoptosis, proliferation and oncogene c fos expression in carbon tetrachloride (CCl 4) induced cirrhotic rat liver. Rat cirrhosis was induced by subcutaneous injection of 50 % (v∶v 1∶1) CCl 4. Hepatocyte apoptosis, proliferation and oncogene c fos expression were examined with TUNEL, PCNA and c fos immunohistochemical methods in control group and treatment group 72 h, 5, 7, 11 and 15 weeks after CCl 4 induction. Hepatocyte apoptosis was rarely seen in control rat liver. The hepatocyte apoptosis was obviously increased 72 h after treatment. Fifteen weeks after treatment, the apoptosis was still more obvious in treatment group than that in controls. PCNA was constantly expressed in CCl 4 group, with highest level at middle phase. C fos was positive 7 and 11 weeks after CCl 4 treatment. The results suggest that: 1) apoptosis is involved in rat liver damage at the early phase in CCl 4 induced injury, and the process can alleviate nodule reconstruction or eradicate potentially mutational hepatocytes at the later phase; 2) hepatocytes constantly proliferate in CCl 4 induced rat liver cirrhosis, especially at the middle phase; 3) c fos might modulate hepatocyte proliferation in CCl 4 induced rat liver cirrhosis.
基金This study was supported by the National Science Foundation of China( No 30070853 ) and the Science Foundation of Guangdong Province,China (No. 990422)
文摘BACKGROUND: Recent research found abnormal expres- sion of the c-fms oncogene, which encodes the macro- phage colony-stimulating factor receptor (CSF-1R), in several human carcinomas including hepatocellular carcino- ma (HCC). But the relationship between the point muta- tion and abnormal expressing of c-fms oncogene in HCC was not clear. This study is to investigate the relationship between point mutation and abnormal expression of c-fms oncogene in hepatocellular carcinoma (HCC) and to clari- fy the mechanism of HCC. METHODS: The expression of c-fms oncogene at different levels of cell, protein and transcription was observed using immune histological ABC, Western blot and Northern blot. PCR-single strand conformation polymorphism and gene sequencing were used to detect the mutation of c-fms in HCC tissues and their surrounding tissues of 30 patients. RESULTS: The expression of c-fms was significantly higher in HCC tissues than in their surrounding tissues (P <0.01). Point mutation of Leu (TTG)—>Ser (TCG) at codon 301 of c-fms amino acids was observed in 21.4% (3/14) HCC tissues. No mutation of c-fms oncogene was detected in the surrounding cancerous tissues. CONCLUSION: Point mutation at codon 301 of c-fms on- cogene is one of the mechanisms of abnormal over-expres- sion in HCC.
文摘Objective: To study the clinical significance and relationship between c-fms oncogene and hepatocellular carcinogenesis, to further clarify the occurring mechanism of hepatocellular carcinoma (HCC). Methods: PCR-SSCP technique was used to analyse mutation of c-fms oncogene in 30 cases of HCC tissues. Sequencing the PCR products after cloning to prove the mutations, meanwhile the relationship between c-fms mutations and clinical pathology of HCC was investigated. Results: Two abnormal single strands were observed in 10% (3/30) HCC tissues from c-fms DNA corresponding to 301st codon of c-fms amino acids. PCR products of abnormal single strands were sequenced after cloning, it demonstrated that there was transition of T→C at nucleic acid 14855 of c-fms DNA, which corresponded to transition of Leu (TTG)→Ser (TCG) at 301st codon of c-fms amino acids. The mutation was related to malignant degree and type of HCC tissues as well as patient’s age. Conclusion: Mutation of c-fms codon at site 301 implied a molecular mechanism contributing to hepatocellular carcinogenesis.
文摘Objective: To study the distribution of c fos oncogene expression within central nervous system (CNS) of the rat during halothane anesthesia. Methods: c-fos oncogene immunohistochemical technique (ABC method) was employed. Results: When halothane concentration was 0.75%,1.5%or2.0%, most of the Fos-like immunore- active neurons (FLNs) appeared in telencephalon, diencephalon and brain stem, including cerebral cortex, amygaloid nucleus, accumbens nucleus, lateral keptal nucleus. bed nucleus of the stria terminalis, field CA1 of Ammon’s horn, islands of Calleja, paraventricular thalamic nucleus, central medial thalamic nucleus, reuniens thalamic nucleus, rhomboid thalamic nucleus. ventral posterolateral thalamic nucleus, paraventricular hypothalamic nucleus(ventral part). periventricular hypothalamic nucleus, median preoptic nucleus, supraoptic nucleus, suprachiasmatic nucleus. medial and lateral habenular nucleus. midbrain periaqueductal gray and Edinger-Westphal nucleus.In the present stude. we have also found that the number of FLN registered stable increase along with the increaseof the concentration of halothane. Conclusion: It has been indicated that FLNs participate in the process ofhalothane anesthesia. which should necessitate and pave the way for a further study of the patterns of linkage andthe mechanism of interaction between functional nuclei.
文摘The expression of three protooncogenes (c-myc, c-fos, N-ras) in.the primary cells from 53 cases of leukemia as well as peripheral WBC from 8 normal individuals was studied. Semiquantitative analysis of mRNA levels of the protooncogenes was carried out by Quick-blot. The results showed that (1) c-myc oncogene was slightly expressed and Nras was marginally expressed, whereas the expression of the c-fos was undetectable in the peripheral leucocytes of 8 normal individuals; (2) the c-myc was obviously expressed in almost all leukemic cells irrespective of the cell types, while N-ras and c-fos were variable expressed; (3) the c-fos was expressed in all 4 cases of M4; (4) the c-myc transcript was detected but the N-ras and c-fos were not in 4 chronic leukemic cases; (5) the relationship between protooncogene expression and state of leukemia or after chemotherapy was also analysed.
文摘During oncogenesis,the hyper-activation of proto-oncogenes and defection of tumor suppressor genes（Zhao et al.,2012,2016a）can regulate cell proliferation,differentiation,apoptosis,and cell-to-cell communication（Balmain et al.,2003;Haber and Settleman,2007）.Recent evidence has shown that non-coding RNAs, such as microRNAs （miRNAs） （Chen, 2005）, and long non- coding RNAs （lncRNAs）, can also act as oncogenes to initiate and promote cancer progression.
基金support by the Ministerio Educación y CienciaMinisterio de Economía y Competitividad of Spain(until June 2013)
文摘PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.
