Publications by authors named "Laurens J Lambert"

2 Publications

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Cellular immunotherapy in ovarian cancer: Targeting the stem of recurrence.

Gynecol Oncol 2015 May 26;137(2):335-42. Epub 2015 Feb 26.

Department of Tumor Immunology, Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address:

Ovarian cancer is a devastating disease with a high relapse rate. Due to a mostly asymptomatic early stage and lack of early diagnostic tools, the disease is usually diagnosed in a late stage. Surgery and chemotherapy with taxanes and platinum compounds are very effective in reducing tumor burden. However, relapses occur frequently and there is a lack of credible second-line options. Therefore, new treatment modalities are eagerly awaited. The presence and influx of immune cells in the ovarian cancer tumor microenvironment are correlated with survival. High numbers of infiltrating T cells correlate with improved progression free and overall survival, while the presence of regulatory T cells and expression of T cell inhibitory molecules is correlated with a poor prognosis. These data indicate that immunotherapy, especially cell-based immunotherapy could be a promising novel addition to the treatment of ovarian cancer. Here, we review the available data on the immune contexture surrounding ovarian cancer and discuss novel strategies and targets for immunotherapy in ovarian cancer. In the end the addition of immunotherapy to existing therapeutic options could lead to a great improvement in the outcome of ovarian cancer, especially when targeting cancer stem cells.
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http://dx.doi.org/10.1016/j.ygyno.2015.02.019DOI Listing
May 2015

Etoposide induces nuclear re-localisation of AID.

PLoS One 2013 4;8(12):e82110. Epub 2013 Dec 4.

Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom.

During B cell activation, the DNA lesions that initiate somatic hypermutation and class switch recombination are introduced by activation-induced cytidine deaminase (AID). AID is a highly mutagenic protein that is maintained in the cytoplasm at steady state, however AID is shuttled across the nuclear membrane and the protein transiently present in the nucleus appears sufficient for targeted alteration of immunoglobulin loci. AID has been implicated in epigenetic reprogramming in primordial germ cells and cell fusions and in induced pluripotent stem cells (iPS cells), however AID expression in non-B cells is very low. We hypothesised that epigenetic reprogramming would require a pathway that instigates prolonged nuclear residence of AID. Here we show that AID is completely re-localised to the nucleus during drug withdrawal following etoposide treatment, in the period in which double strand breaks (DSBs) are repaired. Re-localisation occurs 2-6 hours after etoposide treatment, and AID remains in the nucleus for 10 or more hours, during which time cells remain live and motile. Re-localisation is cell-cycle dependent and is only observed in G2. Analysis of DSB dynamics shows that AID is re-localised in response to etoposide treatment, however re-localisation occurs substantially after DSB formation and the levels of re-localisation do not correlate with γH2AX levels. We conclude that DSB formation initiates a slow-acting pathway which allows stable long-term nuclear localisation of AID, and that such a pathway may enable AID-induced DNA demethylation during epigenetic reprogramming.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082110PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852760PMC
September 2014