Font Size: a A A

Treatment Of Endometrial Cancer Cells In Vitro And In Vivo With Antisense Oligodeoxynucleotides Of Human Telomerase Reverse Transcriptase Gene

Posted on:2004-01-21Degree:MasterType:Thesis
Country:ChinaCandidate:X J ChenFull Text:PDF
GTID:2144360092490779Subject:Gynecological oncology
Abstract/Summary:PDF Full Text Request
Endometrial cancer is the second most common gynecologic malignancy, accounting for 20%~30% of all gynecologic cancers. Endometrial carcinoma usually presents as early-stage disease and can generally be managed with surgery or radiotherapy, and survival of early stage disease was about 85% at 5 years. But advanced or recurrent disease still have a poor survival, about 10%~13% of all endometrial cancers have clinical evidence of disease spread outside of uterine body, and about one fourth of patients treated for early endometrial cancer develop recurrent disease. Treatment of advanced or recurrent disease involves surgery, radiation therapy and systemic hormonal or chemotherapy. As the complicated complications and poor performance status, many patientscannot be tolerant with surgery or radiation therapy. Hormonal therapy or cytotic agents are capable of inducing objective response, but response and survival times are short, so far systemic agents therapy just provide adjuvant or relief therapy of disease. Although there are many studies about advanced endometrial cancer, the survival of diseases has not improved significantly for decades.Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the end of eukaryotic chromosomes, called telomeres, which appear to be associated with senescence, replication, and cell cycle clock. Telomerase is composed of an RNA molecule and protein. The RNA component of human telomerase (hTER) functions as a template the extension reaction of the telomere repeats. Human telomerase reverse transcriptase (hTERT), the key protein component of the telomerase, is a catalytic subunit of telomerase, and studies have shown that hTERT is a rate-limiting determinant of telomerase activity. Thus, it has proposed that the specific inhibition of telomerase activity in tumors might have significant and beneficial therapeutic effects.In most human somatic cells, telomerase expression is repressed, and telomeres shorten progressively with each cell division. In contrast, most human tumors express telomerase , resulting in stabilized telomere length. These observations indicate that telomerase maintenance is essential to the proliferation of tumor cells, and telomerase activation is therefore a crucial step in cellar immortalization and carcinogenesis. Previous studies have reported that approximately 95% of denometrial cancer telomerase positive.High telomerase activity was significantly correlated with advanced surgical stage and with pelvic lymph node metastasis. In recently reported studies, the treatment of various tumor derived cell lines with telomerase inhibitorresulted in cellular senescence.Antisense technology is a new strategy, and plays an important role in gene therapy. A synthetic antisense molecule recognizes complementary mRNA or DNA by sequence-specific base paring, and hence prevents translation or transcription, resulting in a selective inhibition of protein synthesis. Antisense oligonucleotides offer the potetial for blocking the expression of targeted gene and acting as new therapeutic agents in human disease, such as malignant tumor, vascular disease, inflammatory, viral infection. Designed to specifically inhibit the expression of disease -related genes, antisense compounds have shown efficacy in numerous preclinical studies.Studies have shown that inhibition of telomerase activity leads to inhibition of cell growth, and therefore, telomerase can be considered as an attractive target for therapy of cancer or other pathogenically proliferating cells. Recent data have demonstrated inhibition of cell division in cancer cells and inducing apoptosis in presence of telomerase antisense oligodeoxyonucleotides (AODN), and also AODN was demonstrated to be effective in animal tumor model, all of which provided a proof of concept for the use of telomerase inhibitors as candidate cancer drugs.In this study, we synthesized a 20 bases antisense oligonucleotide against human telomerase reverse transcriptase and investigated itsantit...
Keywords/Search Tags:Endometrial, neoplasm, telomerase, antisense, oligonucleotide, nude mice, transplantation, cisplatin, model
PDF Full Text Request
Related items