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OBJECTIVE Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in patients receiving hematopoietic cell transplant. It is estimated that 40-70% of engrafted patients surviving the initial transplant eventually develop chronic GVHD (cGVHD), which can persist for months to years and require long-term management from multiple(More)
Loss of p53 function has been shown to cause increased resistance to ionizing radiation in normal murine cells; however, the role of p53 in radioresistance of human tumor cells is less clear. Since wild-type p53 function is required for radiation-induced G1 arrest, we measured G1 arrest in 12 human tumor cell lines that have a wide range of(More)
Loss of DNA mismatch repair because of hypermethylation of the hMLH1 gene promoter occurs at a high frequency in a number of human tumors. A role for loss of mismatch repair (MMR) in resistance to a number of clinically important anticancer drugs has been shown. We have investigated whether the demethylating agent 2'-deoxy-5-azacytidine (DAC) can be used in(More)
BACKGROUND The molecular genetic analysis of invasive breast cancer has identified breast cancer as a genetically complex disease. Ductal carcinoma in situ (DCIS) is thought to represent a preinvasive step in breast cancer progression, yet we know little about its biologic behavior or the genetic alterations present. Because of the increasing diagnosis of(More)
Multiple DNA methylation changes in the cancer methylome are associated with the acquisition of drug resistance; however it remains uncertain how many represent critical DNA methylation drivers of chemoresistance. Using isogenic, cisplatin-sensitive/resistant ovarian cancer cell lines and inducing resensitizaton with demethylating agents, we aimed to(More)
The prognostic impact of p53 immunostaining in a large series of tumours from epithelial ovarian cancer patients in a two-centre study was analysed. The study population (n=476) comprised of a retrospective series of 188 patients (Dutch cohort) and a prospective series of 288 patients (Scottish cohort) enrolled in clinical trials. P53 expression was(More)
Breast cancer is a genetically complex disease. Fluorescence in situ hybridisation can be used to analyse the genetics of breast-cancer progression in interphase cytogenetics. We have analysed the histological distribution of erbB2 and topoll alpha co-amplification in paraffin sections of invasive breast cancer and show that the co-amplified loci share the(More)
We investigated the roles of p53 and Bcl-2 homologues in the induction of apoptosis by cisplatin and paclitaxel in wild-type p53-expressing human ovarian carcinoma cells and cisplatin-resistant derivatives that have lost p53 function. Cisplatin induced apoptosis in parental A2780 but not in cisplatin-resistant A2780/cp70 cells, whereas paclitaxel induced(More)
The role of DNA methylation in the control of mammalian gene expression has been the subject of intensive research in recent years, partly due to the critical role of CpG island methylation in the inactivation of tumour suppressor genes during the development of cancer. However, this research has also helped elucidate the role that DNA methylation plays in(More)
The primary limitations of granulocyte transfusions include low component cell dose and leukocyte incompatibility. Component cell dose improved with granulocyte colony-stimulating factor (G-CSF) mobilization, and the transfusion of G-CSF-mobilized, human leukocyte antigen (HLA)-matched granulocyte components resulted in significant, sustained absolute(More)