Genes, myc ; Humans ; Lymphoma ; genetics

Cerebellar Neoplasms ; genetics ; Chromosome Aberrations ; Genes, myc ; Genes, p16 ; Genes, p53 ; Humans ; Medulloblastoma ; genetics ; Mutation ; Neuroectodermal Tumors, Primitive ; genetics ; Supratentorial Neoplasms ; genetics

A large number of data derived from molecular analyses support the hypothesis that human cancer is a genetic disease and a distinct subset of genes have been found to be genetically changed in most tumors. Molecular alterations in pancreatic cancer include: (1) oncogenes such as K-ras, c-myc, c-fos, and c-erbB-2; (2) tumor suppressor genes such as p53, p16, DPC4/SMAD4, and DCC; and (3) growth factors such as EGF, FGF, HGF, PDGF, VEGF, TGF-beta. Genetic alterations of K-ras and p53 are common in human pancreatic cancer, but the occurrence of pancreatic cancer is a multi-step phenomenon in which the accumulation of genetic changes is extremely important.
Epidermal Growth Factor ; genetics ; Fibroblast Growth Factors ; genetics ; Genes, Tumor Suppressor ; Genes, myc ; genetics ; Genes, p16 ; Genes, p53 ; genetics ; Genes, ras ; genetics ; Growth Substances ; genetics ; metabolism ; Humans ; Oncogenes ; genetics ; Pancreatic Neoplasms ; genetics

Animals ; Gene Amplification ; Genes, myc ; Humans ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Mutagenesis, Insertional ; Proto-Oncogene Proteins c-myc ; metabolism ; Translocation, Genetic

OBJECTIVE: To investigate the effect of small interfering RNA (siRNA) targeting c-myc gene in Hep-2 cells. METHOD: siRNA targeting c-myc mRNA was designed and synthesized. In vitro cultured Hep-2 cells were transfected with lipofectamine 2000 and the inhibitory effect was detected by MTT, morphology, real time PCR assay. RESULT: 1) The MTT result showed the c-myc siRNA to be able effectively to suppress the Hep-2 cell multiplication; 2) The real time PCR result showed c-myc at mRNA level inhibition ratio at 94% in group S3; 3) The morphology result showed the c-myc siRNA to be able effectively to suppress the Hep-2 cell multiplication, the cell heteromorphism was diminished. CONCLUSION siRNA targeting c-myc can remarkably suppress the Hep-2 cell growth and multiplication.
Apoptosis ; Cell Division ; Cell Line, Tumor ; Cell Proliferation ; Gene Targeting ; Genes, myc ; genetics ; Humans ; RNA, Small Interfering ; genetics ; Transfection

We examined the alteration and expression of c-myc protooncogene in 11 human intracranial meningiomas using Southern blot, Northern blot and immunohistochemical techniques. Southern blot showed neither amplification nor rearrangement but Northern blot and immunohistochemical study revealed enhanced expression of the c-myc gene. Immunohistochemically, c-myc product was found in all of the 11 cases and seven of these cases showed an above moderate degree of immunoreaction in semiquantitative analysis. Loss of heterozygosity at IGLC2 locus on chromosome 22 was detected in four of the 8 informative cases. But extent and intensity of immunoreactivity did not correlated with loss of heterozygosity on chromosome 22. These genetic changes may play important roles in the pathogenesis of human intracranial meningioma.
Adult ; Blotting, Southern ; Female ; *Gene Expression Regulation, Neoplastic ; *Genes, myc ; Humans ; Immunohistochemistry ; Male ; Meningeal Neoplasms/*genetics ; Meningioma/*genetics ; Middle Aged

We have analyzed paired samples of genomic DNA from peripheral leukocyte and primary tumor tissue from nine patients with retinoblastoma (RB) and from two RB cell lines, WERI-Rb-1 and Y79, to detect the molecular alterations of the retinoblastoma susceptibility gene (RB-1) and N-myc gene. In Southern analysis, RB-1 deletions in tumor tissues were detected in five patients (56%), one of these revealed a total loss of RB-1. N-myc amplification was found only in one (11.1%) out of nine patients. We also observed a total loss of RB-1 in WERI-Rb-1, and a more than 100-fold amplification of N-myc in Y79. The analysis of the relationship between molecular events and clinical characteristics such as age, sex, tumor laterality did not reveal any specific correlation. These results suggest that genetic backgrounds of RB in Korean patients are quite similar to those of reported cases elsewhere. The high sensitivity of our method in detecting the RB-1 loss indicates that this method can be a useful tool for initially screening a large number of tumors.
Child ; Child, Preschool ; Eye Neoplasms/*genetics ; Female ; *Gene Amplification ; *Gene Deletion ; *Genes, Retinoblastoma ; *Genes, myc ; Humans ; Infant ; Male ; Retinoblastoma/*genetics ; Tumor Cells, Cultured

This study was purposed to analyze the relation of N-myc gene copy number with clinical staging, pathological types and tumor biological factors in children with neuroblastoma (NB), and to investigate the influence of chemotherapy on N-myc gene expression and explore the relationship of N-myc gene copies with prognosis of NB children. The newly diagnosed children with NB from 1 March 2007 to 31 January 2011 were enrolled in this study. The treatment was carried out by BCH-NB-2007 based on Hongkong NB-07 protocol, and the patients were follow up to 31 January 2012. The N-myc gene in NB children was detected by FISH. According to number of N-myc gene copies, the NB children were divided into 3 groups. A group (N-myc gene negative) had less than 2 copies, B group (N-myc gene gains) had 3 to 9 copies, and C group (N-myc amplification) had more than 10 copies. The results showed that the N-myc gene expression in 58 cases of NB was observed. There were 36 males and 22 females. NB children aged from 6.5 to 138 months (median age 47.5 months), all patients were followed up for 11 - 57 months with an average of 31.5 months. INSS stages I-IV were 1, 5, 8 and 44 cases, respectively. Twenty-five cases had primary post mediastinal tumor, thirty-three cases had retroperitoneal and pelvic tumor, three of which also companied with post mediastinal tumor. Thirty-five cases had bone metastasis (60.3%), thirty-two cases had bone marrow metastasis (55%). Of the 54 patients with fully known biologic features, seventeen cases had ganglioneuroblastoma, thirty-seven cases had neuroblastoma (15 displayed differentiated, 7 poorly differentiated or undifferentiated, 15 with pathological changes after chemotherapy), four cases had bone marrow metastasis only detected by bone marrow biopsy. Eleven cases had N-myc gene negative, forty-three had N-myc gains, four had N-myc amplification. The average copy number of N-myc gene copies in 58 cases was 5.96 ± 7.81 in which 28 children were non chemotherapy cases, their average copy number was 4.00 ± 1.88, thirty cases out of 58 cases received preoperation chemotherapy (chemotherapy group), and their average copy number was 7.80 ± 10.46, the difference is significant (P = 0.064). The clinic stage, the location of primary tumor, pathological classification, urine VMA and serum neurogenic specific enolase had no effects on the N-myc gene expression, but the serum LDH level had influence (P < 0.01). Single factor Kaplan-Meier analysis showed that the number of N-myc gene copies in NB patients were closely related with the poor prognosis. The more copies of N-myc gene, the more poor prognosis, the difference is statistically significant (P < 0.05). It is concluded that the number of N-myc gene copies correlates with the rapid growth of NB and its poor prognosis, detecting the N-myc amplification can help to estimate the prognosis and decide the program of treatment. Serum LDH, which correlated with the rapid growth of NB, had effect on the N-myc gene expression and is closely related with the poor prognosis of NB.
Child ; Child, Preschool ; Female ; Gene Amplification ; Genes, myc ; Humans ; Infant ; Male ; Neoplasm Staging ; Neuroblastoma ; diagnosis ; genetics ; pathology ; Prognosis

OBJECTIVETo construct the recombinant adenovirus encoding antisense c-myc fragment and to investigate its effect on the chemotherapy sensitivity of osteosarcoma MG-63 cells to cisplatin.

METHODSThe recombinant adenovirus (Ad-Asc-myc) encoding antisense c-myc fragment was constructed by cloning c-myc cDNA of about 720 base pairs in a reverse direction into adenovirus vector, then undergoing recombination, amplifying and being complemented in vivo. The osteosarcoma MG-63 cells were transfected by the Ad-Asc-myc in vitro, and Wright staining, Acridine Orange staining, Western Blot, MTT, Flow Cytometry (FCM) were used to study cell morphology, expression of c-myc protein, tumor cell proliferation in vitro, apoptosis and cell cycle change.

RESULTSAd-Asc-myc encoding antisense c-myc fragment was obtained with the titer of 2 x 10(9) pfu/ml. Ad-Asc-myc down-regulated the expression of c-myc protein after transfected MG-63 cells for 48 h, combined with the treatment of 2.0, 5.0 microg/ml cisplatin for 2 h could inhibit tumor cells proliferation in vitro by 33.4% and 54.2% respectively, which were significantly difference compared with control recombinant adenovirus (Ad-LacZ) groups (P < 0.05). Acridine Orange staining and FCM analysis showed that Ad-Asc-myc could induce apoptosis of transfected cells, which was enhanced by the treatment of cisplatin cell. Cycle analysis showed that obvious G2/M phase arrested in transfected cells.

CONCLUSIONAd-Asc-myc increases the chemotherapy sensitivity of osteosarcoma MG-63 cells to cisplatin as well as induced apoptosis.

Adenoviruses, Human ; genetics ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Cisplatin ; pharmacology ; DNA, Antisense ; genetics ; Genes, myc ; Genetic Vectors ; Humans ; Osteosarcoma ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Recombination, Genetic ; Transfection ; Tumor Cells, Cultured

OBJECTIVETo explore the hematopoietic pathophysiology of myelodysplastic syndrome (MDS) at stem/progenitor cell level by analyzing the gene expression profiles associated with hematopoiesis.

METHODSThe differentially expressed genes which were involved in the hematopoiesis were screened by microarray using CD34(+) cells from MDS patients firstly. RQ-PCR was then applied to validate the screened genes using CD34(+) cells from MDS-RA patients who had normal karyotype. The linkages with hematopoiesis among these validated genes were analyzed.

RESULTSAmong the differentially expressed genes in CD34(+) cells of MDS-RA patients, Rap1GAP was up-regulated significantly (P < 0.01). Cadherins, which can interplay with Rap1, including N-cadherin and E-cadherin, were down-regulated significantly (P < 0.01). β-catenin, a downstream effector of cadherins, was highly expressed in MDS-RA patients (P < 0.01). c-myc binding protein was down-regulated (P < 0.01), and c-myc promoter binding protein was up-regulated (P < 0.01). Rac1, Rac2 and Cdc42, which belong to RhoGTPases family and are associated with the cell morphology and hematopoiesis, were all expressed highly in MDS-RA patients (P < 0.01).

CONCLUSIONThe abnormal expression of cadherin, β-catenin and c-myc associated genes were closely related to the dysplastic hematopoiesis of MDS. The down regulation of cadherin was associated with the positive feedback mechanism between Rap1 and cadherin. The aberrant expression of Rac1, Rac2 and Cdc42 may contribute to the morphological dysplasia of MDS.

Cadherins ; genetics ; metabolism ; Gene Expression ; Gene Expression Profiling ; Genes, myc ; Humans ; Myelodysplastic Syndromes ; genetics ; metabolism ; beta Catenin ; genetics ; rap1 GTP-Binding Proteins ; genetics ; metabolism