These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Synergistic cytotoxicity of buthionine sulfoximine (BSO) and intensive melphalan (L-PAM) for neuroblastoma cell lines established at relapse after myeloablative therapy.
    Author: Anderson CP, Reynolds CP.
    Journal: Bone Marrow Transplant; 2002 Aug; 30(3):135-40. PubMed ID: 12189530.
    Abstract:
    Patients with high-risk neuroblastoma (NB) initially respond to aggressive, alkylator-based therapy only to die from recurrent disease that is refractory to chemotherapy, including alkylating agents. We examined the ability of buthionine sulfoximine (BSO)-mediated glutathione (GSH) depletion to modulate melphalan (L-PAM) resistance in five NB cell lines established after progressive disease following myeloablative therapy (high-dose melphalan, carboplatin, etoposide and total body irradiation) supported by autologous hematopoietic stem cell transplant (AHSCT), and in 15 NB cell lines established at diagnosis or after non-myeloablative therapy (pre-AHSCT). Four of five post-AHSCT NB cell lines and 10 of 15 pre-AHSCT NB cell lines were sensitive to single agent BSO (LC(90) <300 microM BSO), while two of five post-AHSCT lines and one of 15 pre-AHSCT lines showed high-level resistance to L-PAM (LC(90)>30 microM). Fixed ratio analysis demonstrated BSO/L-PAM synergy (combination index <1) for all five post-AHSCT and for all 15 pre-AHSCT cell lines tested. Multi-log cytotoxicity (often exceeding four logs of cell kill) was observed in post-AHSCT L-PAM-resistant cell lines (including p53 non-functional lines) only when clinically achievable concentrations of BSO were combined with myeloablative concentrations of L-PAM. We conclude that most neuroblastoma cell lines, including post-AHSCT NB cell lines that are highly resistant to myeloablative levels of L-PAM and lack p53 function, are sensitive to clinically achievable concentrations of L-PAM and BSO. However, some L-PAM-resistant NB cell lines (especially those lacking p53 function) require dose escalation of L-PAM to myeloablative concentrations in order to demonstrate significant synergistic cytotoxicity. Thus, optimal clinical application of BSO/L-PAM may require AHSCT.
    [Abstract] [Full Text] [Related] [New Search]