Objective: To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-methylguanine-DNA methyltransferase (MGMT) positive tumorsin vivo. Methods:...Objective: To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-methylguanine-DNA methyltransferase (MGMT) positive tumorsin vivo. Methods: MGMT positive human glioma cell line SF-767 xenografts in nude mice were treated with SarCNU. The antitumor efficacy of SarCNU was compared with the results of 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment with or without 06-benzylguanine (06-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 06-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (P<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than O6-BG plus BCNU treatment (F=51.7,P=0.00036). Conclusion: Since SarCNU enters cells via extraneuronal monoamine transporter (EMT), the enhanced antitumor activity of SarCNU in this MGMT positive human tumor xenograft model may be due to the presence of EMT in SF-767. SarCNU may be used as an alternative treatment for MGMT positive tumors, specifically for tumors expressing EMT.展开更多
Peripheral T-cell lymphoma, not otherwise specified （PTCL-NOS） is a heterogeneous group of aggressive T-ce lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory ca...Peripheral T-cell lymphoma, not otherwise specified （PTCL-NOS） is a heterogeneous group of aggressive T-ce lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory case of PTCL-NOS with widely involvement of subcutaneous tissue, which showed an excellent response to Semustine personal- ized chemotherapy based on the detection finding of positive O6-methylguanine-DNA methyltransferase （MGMT） promoter methylation. This is the first english report to indicate that single nitrosourea agent such as Semustine may have good efficacy and safety for widespread subcutaneous involvement of PTCL-NOS with positive MGMT promoter methylation.展开更多
基金National Natural Science Foundation of China!(No. 39670735)a private donation from Helen and Nicki Lang, Quebec, Canada.
文摘Objective: To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-methylguanine-DNA methyltransferase (MGMT) positive tumorsin vivo. Methods: MGMT positive human glioma cell line SF-767 xenografts in nude mice were treated with SarCNU. The antitumor efficacy of SarCNU was compared with the results of 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment with or without 06-benzylguanine (06-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 06-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (P<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than O6-BG plus BCNU treatment (F=51.7,P=0.00036). Conclusion: Since SarCNU enters cells via extraneuronal monoamine transporter (EMT), the enhanced antitumor activity of SarCNU in this MGMT positive human tumor xenograft model may be due to the presence of EMT in SF-767. SarCNU may be used as an alternative treatment for MGMT positive tumors, specifically for tumors expressing EMT.
文摘Peripheral T-cell lymphoma, not otherwise specified （PTCL-NOS） is a heterogeneous group of aggressive T-ce lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory case of PTCL-NOS with widely involvement of subcutaneous tissue, which showed an excellent response to Semustine personal- ized chemotherapy based on the detection finding of positive O6-methylguanine-DNA methyltransferase （MGMT） promoter methylation. This is the first english report to indicate that single nitrosourea agent such as Semustine may have good efficacy and safety for widespread subcutaneous involvement of PTCL-NOS with positive MGMT promoter methylation.
