Abstract：
BACKGROUND:Tumours are responsive to temozolomide (TMZ) if they are deficient in O(6)-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR) proficient. METHODS:The effect of TMZ on medulloblastoma (MB) cell killing was analysed with clonogenic survival assays. Expression of DNA repair genes and enzymes was investigated using microarrays, western blot, and immunohistochemistry. DNA sequencing and promoter methylation analysis were employed to investigate the cause of loss of the expression of MMR gene MLH1. RESULTS:Temozolomide exhibited potent cytotoxic activity in D425Med (MGMT deficient, MLH1 proficient; IC(50)=1.7 μM), moderate activity against D341Med (MGMT proficient, MLH1 deficient), and DAOY MB cells (MGMT proficient, MLH1 proficient). MGMT inhibitor O(6)-benzylguanine sensitised DAOY, but not D341Med cells to TMZ. Of 12 MB cell lines, D341Med, D283Med, and 1580WÜ cells exhibited MMR deficiency due to MLH1 promoter hypermethylation. DNA sequencing of these cells provided no evidence for somatic genetic alterations in MLH1. Expression analyses of MMR and MGMT in MB revealed that all patient specimens (n=74; expression array, n=61; immunostaining, n=13) are most likely MMR proficient, whereas some tumours had low MGMT expression levels (according to expression array) or were totally MGMT deficient (3 out of 13 according to immunohistochemistry). CONCLUSION:A subset of MB may respond to TMZ as some patient specimens are MGMT deficient, and tumours appear to be MMR proficient.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
von Bueren AO,Bacolod MD,Hagel C,Heinimann K,Fedier A,Kordes U,Pietsch T,Koster J,Grotzer MA,Friedman HS,Marra G,Kool M,Rutkowski Sdoi
10.1038/bjc.2012.403subject
Has Abstractpub_date
2012-10-09 00:00:00pages
1399-408issue
8eissn
0007-0920issn
1532-1827pii
bjc2012403journal_volume
107pub_type
杂志文章abstract：:High-mol.-wt levan injected locally inhibits the growth of Lewis lung carcinoma in C57BL mice. The inhibition is dependent on the number of tumour cells injected and on the dose of levan. The inhibition decreases tumour incidence and size as well as prolonging survival. The polysaccharide is most effective when inject...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.225
更新日期：1979-10-01 00:00:00
abstract：:The management of older patients with aggressive non-Hodgkin's lymphoma presents a challenge to the physician. Age is a poor prognostic indicator, due to reduced ability to tolerate and maintain dose-intensive chemotherapy. Generally, older patients demonstrate a lower response rate, reduced survival and increased tox...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/sj.bjc.6602975
更新日期：2006-03-27 00:00:00
abstract：:The childhood peak of common acute lymphoblastic leukaemia has been proposed as being a rare response to delayed exposure to a common infection. In this context, factors related to the child's immune system are of special interest. Information on such factors was obtained in a recent German case-control study comprisi...
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doi：10.1038/sj.bjc.6690395
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.310
更新日期：1995-07-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.317
更新日期：1994-09-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
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pub_type： 杂志文章,随机对照试验
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doi：10.1038/sj.bjc.6603467
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pub_type： 临床试验,杂志文章
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更新日期：2002-09-23 00:00:00
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pub_type： 杂志文章
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更新日期：2007-10-22 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690301
更新日期：1999-04-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.196
更新日期：1994-06-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.379
更新日期：1992-11-01 00:00:00
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pub_type： 杂志文章,随机对照试验
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pub_type： 杂志文章
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pub_type： 杂志文章
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doi：10.1054/bjoc.2000.1222
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.116
更新日期：1991-04-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.136
更新日期：1996-03-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2003-03-10 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690008
更新日期：1999-01-01 00:00:00
abstract：:This article was originally published under a standard license to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：British journal of cancer
pub_type： 已发布勘误
doi：10.1038/s41416-019-0534-2
更新日期：2019-10-01 00:00:00
