Example sentences for: alkylating

How can you use “alkylating” in a sentence? Here are some example sentences to help you improve your vocabulary:

  • The prodrug TLK286 [γ-glutamyl-α-amino-β(2-ethyl-N,N,N,N-tetrakis(2-chloroethyl)phosphorodiamidate)-sulfonyl-propionyl-(R)-(-)phenylglycine] is activated by glutathione S-transferase (GST) P1-1 and to a lesser degree A1-1 and generates tetrakis chloroethyl alkylating moieties that can react with cellular nucleophiles.

  • 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.

  • Our current observation that undetectable levels of MGMT gene expression in >95% of GCTs appears to suggest that the lack of the O(6)-methylguanine-DNA methyltransferase enzyme may direct cells to undergo apoptosis due to failure of repair of DNA adducts formed by alkylating agents.

  • 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.

  • 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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