Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic alterations of various cancers have been clarified by recent development of molecular biology. Multiple genetic alterations occur through the development of cancer. Both activation of proto-oncogenes and inactivation of tumor suppressor genes are important for the development of cancer. Alterations of oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor suppressor genes such as p53, RB and DCC have been reported in ovarian cancer. Allelic losses of the specific chromosomes, which suggest the existence of tumor suppressor genes on those chromosomes, also have been reported in ovarian cancer. Further studies on genetic alterations of ovarian cancer will clarify the mechanisms for the development of ovarian cancer and also will develop new methods for prevention, diagnosis and treatment in clinical.
 ...
PMID:[Genetic alterations in the genesis and development of ovarian cancer]. 135 31

Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.
 ...
PMID:Oncogenesis in ovarian cancer. 150 89

Expression of the c-myc gene was analyzed in 56 human primary ovarian cancer tissues, including 51 common epithelial and 5 non-epithelial tumours to determine molecular events in the carcinogenic process in ovaries. Over-expression of the c-myc gene was found in 37.3% of all ovarian tumour tissues, and in 63.5% of serous adenocarcinoma tissues. Significant over-expression of the c-myc gene at Stage III compared with other stages, and one remarkable case of over-expression in a serous tumour of low malignant potential suggest that c-myc expression is temporarily activated at some stage(s) during tumorigenesis of ovarian cancer, especially of serous tumours.
 ...
PMID:c-myc over-expression in human primary ovarian tumours: its relevance to tumour progression. 154 16

Amplification of the c-erbB-2 protooncogene has been associated with a poor prognosis in human breast and ovarian cancers. Our study was undertaken to examine whether amplification, rearrangement, or overexpression of c-erbB-2 and other protooncogenes was frequently observed in epithelial ovarian cancers. c-erbB-2 was expressed in 87% of 22 ovarian cancers analyzed, but expression was significantly increased in only one of the 22 tumor specimens. In this case elevated c-erbB-2 expression was associated with dramatic amplification of the gene. In another tumor a 3.8 kb EcoRI fragment was found, in addition to the usual 4.4 and 6.0 kb fragments; this is consistent with a possible gene rearrangement or a restriction fragment length polymorphism. To place these results in perspective, expression of several other protooncogenes has been examined in ovarian carcinomas. The c-fos, c-myc, n-myc, c-fms, and c-Ha-ras protooncogenes were expressed in different fractions of tumors, but expression of l-myc, c-erbB, c-myb, c-sis, and c-mos was not detectable. Aside from c-erbB-2, neither amplification nor rearrangement was observed among the other protooncogenes studied. Expression of c-erbB-2, c-fms, c-myc, n-myc, c-fos, and c-Ha-ras deserves further evaluation as a prognostic factor in ovarian cancer.
 ...
PMID:Expression and amplification of the HER-2/neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines. 167 63

We isolated clonogenic cells from differentiated HOC-7 ovarian cancer cells. Both cell subsets were characterised in respect to morphology, growth behaviour, DNA content and expression of tumour-associated antigens and nuclear oncogenes. Ten cell fractions (Fr) were separated by centrifugation in a discontinuous density gradient (Fr 1 less than 1.037 g/ml to Fr 10 greater than 1.069 g/ml, steps 0.004 g/ml). Large adenoid cells containing vacuoles filled with neutral polysaccharides were concentrated in Fr 1-4. These cells were non-clonogenic in soft agar. The growth on solid substrate was highest in Fr 6 and 7, intermediate in Fr 2-5 and Fr 8-10 and lowest in Fr 1. The mean cloning efficiencies of the fractions in soft agar were highest in Fr 6 (8.1%) and lowest in Fr 2 and 3 (0.1%). Diploid and near tetraploid cell subsets were found with similar frequency in all fractions. Immunocytochemistry revealed 4-7% Ki-67 positive cells in Fr 1-6 and 12-20% in Fr 7-10. In Fr 3-10 greater than or equal to 79% of the cells expressed CA 125. Positivity for c-myc, c-myb and c-fos (greater than or equal to 74%) was not correlated with clonogenicity. In conclusion, differentiated cells (Fr 1-4) were separated from cells with higher growth rates (Fr 5-10). Clonogenic cells were enriched in Fr 6. These data indicate that discontinuous density gradient fractionation represents a useful method for separation of cells with different degrees of differentiation, growth potential and clonogenicity.
 ...
PMID:Separation of clonogenic and differentiated cell phenotypes of ovarian cancer cells (HOC-7) by discontinuous density gradient centrifugation. 204 85

The c-myc oncogene codes for a DNA binding protein that appears to play an important role in the regulation of cell growth. c-myc gene amplification has been documented to occur in both hematopoietic and solid neoplasms and often indicates more biologically aggressive tumors. Southern hybridization analysis was performed on high-molecular-weight DNA isolated from primary ovarian carcinomas. Major structural rearrangements of c-myc were not detected. Five of seventeen (29.4%) tumor samples demonstrated amplification of the myc oncogene. The 5 patients with ovarian carcinomas associated with c-myc amplification exhibited a median survival of 17 months. Of the 12 patients without evidence of tumor-associated c-myc amplification, 5 have exhibited disease-free survival for an average of 36.8 months and are currently alive. The remaining 7 patients, the majority of whom had advanced-stage, poorly differentiated lesions with a normal c-myc copy number, exhibited a median survival of 9 months. There was no apparent relationship between c-myc amplification, grade of tumor differentiation, and response to platinol-based chemotherapy. These data do not suggest a prognostic role for c-myc amplification in primary ovarian cancer. However, c-myc amplification is a common finding in advanced-stage ovarian cancer.
 ...
PMID:c-myc amplification in ovarian cancer. 222 45

The structure of DNA sequences homologous to the viral myc oncogene from ovarian tumours, intact tissues and the same patients peripheral blood leukocytes has been studied. The Southern blot analysis of malignant tumour DNA reveals amplification of c-myc protooncogene of 3 from 11 patients. Metastases DNAs of two from those patients also contain multiple copies of c-myc. No myc gene amplification has been detected in 6 examined benign ovarian tumours. The presence of extra copies of myc-related sequences has been shown in two from three DNA samples from peripheral blood leukocytes of patients with ovarian cancer.
 ...
PMID:[Amplification of c-myc proto-oncogene in primary tumors, metastases and blood leukocytes of patients with ovarian cancer]. 302 56

Gene therapy clinical trials targeting p53 and other genes are underway in nongynecologic cancer systems. To explore the potential for antigene therapy in gynecologic oncology, we examined the in vitro effects of oligonucleotides targeting c-myc and p53 in the ovarian cancer cell lines CAOV-3, SKOV-3, and BG-1. The ATP cell viability assay was used to measure growth effects after 6-day treatments with 27-mer antisense phosphorothioate oligodeoxyribonucleotides (oligos) targeting the Puf/nm23 binding region of c-myc and promoter/ATG region of p53. A random sequence of the p53 27-mer was used as a control, and an untransformed fibroblast cell line was used for comparison. IC50 was defined as the oligo concentration required for 50% growth reduction compared to untreated controls. Synergistic vs antagonistic effects of oligo combinations were quantitated by combination indexes (CI) as calculated from median effect parameters by the methods of Chou and Talalay. Mean +/- SE IC50's of c-myc and p53 antisense oligos in CAOV-3 and SKOV-3 ranged from 1.0 +/- 0.2 to 9.7 +/- 1.3 microM. The IC50's of c-myc oligos were consistently lower than corresponding p53 oligos in all cell lines (P < 0.034, t test). The fibroblast cell line was sensitive to anti-c-myc and combination anti-c-myc/p53 oligos (IC50 = 1.5 +/- 0.6 and 1.4 +/- 0.2 microM, respectively), but not to anti-p53 oligos alone (IC50 > 16 microM). Nonspecific toxicity was observed at concentrations of 16 microM for all cell lines except in BG-1, where maximal growth stimulation occurred at this concentration with anti-p53 oligos. Growth stimulation was also observed in BG-1 with anti-c-myc and anti-c-myc/p53 combinations at intermediate doses, with inhibition at higher doses. While c-myc/p53 combinations in CAOV-3 were synergistic (CI < 0.8), they were antagonistic in SKOV-3 (CI > 3.2). Phosphorothioate oligos directed against c-myc and p53 in different cell lines were shown to have both antiproliferative and stimulatory activity, as single agents and in combination, at concentrations that are achievable in vivo. Because of the complex patterns of effects, further in vitro studies are warranted before considering clinical trials with these agents in gynecologic cancers.
 ...
PMID:Combination anti-gene therapy targeting c-myc and p53 in ovarian cancer cell lines. 755 22

Apoptosis can be regulated in a number of different systems by the actions of cytokines. Rapamycin has been shown to exert its effects on growth factor-induced cell proliferation, at least in part, by blocking the activation of the p70 S6 kinase and thus preventing the downstream signaling process, such as the activation of the members of the cdk family. To determine whether this pathway plays a role in the regulation of apoptosis, we assessed the effect of rapamycin on apoptosis induced by interleukin 2 deprivation in murine T-cell lines, by T-cell receptor ligation in a murine T-cell hybridoma, by enforced c-myc expression in murine fibroblasts, and by corticosteroids in murine T-lymphoma cell lines. Although rapamycin did not induce apoptosis on its own, rapamycin augmented apoptosis in each of the cell lines used as indicated by increased genomic DNA fragmentation, decreased cell viability, and characteristic apoptotic changes in morphology. These results suggest that a signal transduction pathway(s) inhibited by rapamycin plays an important role in the susceptibility of cells to apoptosis. Many chemotherapeutic agents kill cancer cells through the induction of apoptosis. Strikingly, rapamycin increased the ability of the alkylating agent, cisplatin, to induce apoptosis in the human promyelocytic leukemia cell line HL-60 and the human ovarian cancer cell line SKOV3. These data suggest that a signal transduction pathway, likely related to p70 S6 kinase, inhibited by rapamycin may be an important component of the pathway which prevents cell death in many cell lineages and also indicate that rapamycin has the potential to augment the efficacy of selected anticancer therapies.
 ...
PMID:Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro. 772 69

Nineteen paraffin-embedded breast cancer tissue samples selected for long survival (more than 5 years) were analysed for detecting the amplification of the c-erbB-2 (Her-2/neu) oncogene by Polymerase Chain Reaction (PCR). Strong correlation was elucidated between c-erbB-2 amplification and survival; such correlation was also observed with histopathologic types and nuclear grading. Because of the similarity of the breast and ovarian cancer in the etiology of the diseases, amplification of c-erbB-2, c-myc and Ki-ras genes was examined in 32 ovarian carcinoma samples (stage I-IV). In ovarian carcinomas c-erbB-2 amplification occurred in 34% (11/32) of the fresh tumour samples, and correlation between amplification and clinical staging at P < 0.05 significance level was observed. Amplification of c-myc was detected in 9% (3/32) and none of the tumours showed amplification of Ki-ras.
 ...
PMID:Oncogene patterns in breast and ovarian carcinomas. 790 45


1 2 3 4 5 6 7 Next >>