Words similar to gcts
Example sentences for: gcts
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It has been shown that engineered over-expression of wild-type p53 in vitro causes inhibition of MGMT transcription in human tumor cells [ 29 ] . Abundant over-expression of wild-type p53, owing to their stage of origin, is a characteristic feature of GCTs [ 30 ] . A possibility also exists that the MGMT expression may, in general, be down regulated in tumors arising from embryonic-type cells.
Lack of MGMT expression in the majority of GCTs suggests a potential role for this protein in lack of repair of cisplatin-induced DNA damage that may result in exquisite sensitivity in this tumor.
Given the importance of the MGMT protein in treatment response to alkylating agents, this molecular switch may play a critical role in sensitivity to cisplatin-based therapy in GCTs.
3 region to which RASSF1A maps undergoes deletions in many solid tumor types, including GCTs [ 9 ] . RASSF1A encodes a splice variant of human RAS effector homologue, which interacts with the XPA protein and functions as a negative regulator of cell growth [ 16 17 ] . RASSF1A has been shown to be inactivated by promoter methylation in a variety of tumor types [ 16 17 18 19 ] . The 17q21 and 17p13 regions, to which BRCA1 and HIC1 map, respectively, also have been characterized by high frequency of LOH in GCT [ 9 ] . The BRCA 1 gene plays critical roles in DNA repair and recombination, cell cycle checkpoint control, and transcription and has been shown to be hypermethylated in breast-ovarian cancer [ 4 ] . The HIC1 gene is also often hypermethylated in many human cancers [ 20 21 22 ] . The DNA repair gene MGMT encodes O(6)-methylguanine-DNA methyltransferase and this enzyme effectively removes DNA adducts formed by alkylating agents [ 23 ] . Epigenetic inactivation of the MGMT gene was reported in a wide variety of cancers [ 24 25 ] . Also, a low frequency of methylation of the APC , RARB , and FHIT genes was detected in NSGCTs.
Epigenetic gene silencing of the MGMT confers enhanced sensitivity to alkylating agents in cancer [ 24 25 ] . Lack of methylation, on the other hand, associates with high-risk of death [ 25 26 ] . It has been suggested that the high-levels of MGMT proteins contribute to a drug-resistant phenotype [ 27 ] . More than 90% of newly diagnosed GCTs and 70-80% of patients who present metastatic disease are cured with cisplatin-based chemotherapy [ 28 ] . However, 20-30% of the patients with metastatic disease exhibit resistance to the cisplatin curative regimen leading to high mortality in this group.
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