Words similar to alkylating
Example sentences for: alkylating
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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.
MGMT gene encodes O(6)-methylguanine-DNA methyltransferase and this enzyme effectively removes DNA adducts formed by alkylating agents [ 33 ] . Epigenetic gene silencing of MGMT confers enhanced sensitivity to alkylating-based chemotherapy, and lack of methylation associates with failure to respond to chemotherapy [ 34 35 ] . On the contrary, all patients that had MGMT promoter methylation were dead within 21 months of initial diagnosis, which predicts a poor prognosis.
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.
Seventeen ALDH genes have been identified in the human genome and have been classified into ten different families based on amino acid sequence identities [ 1 2 ] . High levels of ALDH1A1 activity can protect human and murine cells from the toxicity of the alkylating agent cyclophosphamide and its oxazaphosphorine analogs.
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