Abstract：
BACKGROUND:Alternative treatments are needed for elderly patients with acute myeloid leukaemia, as the disease prognosis is poor and the current treatment is unsuitable for many patients. METHODS:In this study, we investigated whether combining the nucleoside analogue sapacitabine with histone deacetylase (HDAC) inhibitors could be an effective treatment. Synergy and mode-of-action analysis were studied in cultured cell lines and the efficacy of the combination was confirmed in a xenograft model. RESULTS:CNDAC (1-(2-C-cyano-2-deoxy-β-D-arabino-pentofuranosyl)-cytosine), the active component of sapacitabine, synergised with vorinostat in cell lines derived from a range of tumour types. Synergy was not dependent on a specific sequence of drug administration and was also observed when CNDAC was combined with an alternative HDAC inhibitor, valproate. Flow cytometry and western blot analysis confirmed that the combination induced a significant increase in apoptosis. Mode-of-action analysis detected changes in Bcl-xl, Mcl-1, Noxa, Bid and Bim, which are all regulators of the apoptotic process. The sapacitabine/vorinostat combination demonstrated significant benefit compared with the single-agent treatments in an MV4-11 xenograft, in the absence of any observed toxicity. CONCLUSION:Sapacitabine and HDAC inhibitors are an effective drug combination that is worthy of clinical exploration.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Green SR,Choudhary AK,Fleming INdoi
10.1038/sj.bjc.6605922subject
Has Abstractpub_date
2010-10-26 00:00:00pages
1391-9issue
9eissn
0007-0920issn
1532-1827pii
6605922journal_volume
103pub_type
杂志文章abstract：:Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes, by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10(-7)--10(-5)M) of the specific beta3-adrenoceptor antagonist SR59230A. Lipid mobilizing factor (250 nM) produced c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600086
更新日期：2002-02-01 00:00:00
abstract：:In a longitudinal study of the evolution of serum beta 2-microglobulin (beta 2-m) levels in 37 patients with myelomatosis, those patients with a level of < 4 mg/l at first presentation had a median survival of 46 months, whereas those with an initial level of > mg/l had a median survival of 15 months. THe beta 2-m app...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1980.273
更新日期：1980-10-01 00:00:00
abstract：BACKGROUND:There are currently two million cancer survivors in the United Kingdom, and in recent years this number has grown by 3% per annum. The aim of this paper is to provide long-term projections of cancer prevalence in the United Kingdom. METHODS:National cancer registry data for England were used to estimate can...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.366
更新日期：2012-09-25 00:00:00
abstract：:Nuclear polyploidization in the livers of CF-1 mice, exposed to dieldrin (0, 1, 5 and 10 ppm in the diet), was studied up to the median time of liver tumour development (ranging from 15 to 27 months) in the respective treatment groups. In untreated controls nuclear polyploidization is characterized by a linear increas...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.160
更新日期：1988-07-01 00:00:00
abstract：BACKGROUND:While lung adenocarcinoma patients can somewhat benefit from anti-angiogenic therapies, patients with squamous cell lung carcinoma (SQLC) cannot. The reasons for this discrepancy remain largely unknown. Soluble VEGF receptor-1, namely sVEGFR1-i13, is a truncated splice variant of the cell membrane-spanning V...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-018-0128-4
更新日期：2018-06-01 00:00:00
abstract：:The clinical formulation of the anti-tumour agent Taxol involves the use of a mixture of ethanol and Cremophor EL. Gel electrophoresis and density-gradient ultracentrifugation were used to detect effects of Taxol infusions on serum lipoproteins. Use of the Cremophor vehicle results in a decrease in the electrophoretic...
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
abstract：:An analysis of the occurrence of breast cancer in this long-term prospective cohort study shows a significant relative risk (RR) in women who have ever used oral contraceptives (OC) of 3.33 in women age 30 to 34 years at diagnosis and an RR of 5.88 (P = 0.0011) in women who were parity 1 at the time of diagnosis. In w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.285
更新日期：1988-11-01 00:00:00
abstract：:Oestrogen receptor alpha (ER-alpha) gene has two specific promoters, distal (P0) and proximal (P1), which induce almost identical transcripts in size due to different splicing. We examined the methylation at both promoter regions of the ER-alpha gene using HpaII, a methylation-sensitive restriction enzyme, prior to po...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690631
更新日期：1999-08-01 00:00:00
abstract：:Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602611
更新日期：2005-06-06 00:00:00
abstract：:Dendritic cells (DC) are professional antigen-presenting cells (APC) of the immune system, uniquely able to prime naive T-cell responses. They are the focus of a range of novel strategies for the immunotherapy of cancer, a proportion of which include treating DC with ionising radiation to high dose. The effects of rad...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602518
更新日期：2005-04-25 00:00:00
abstract：:Cimetidine has been shown to have beneficial effects in colorectal cancer patients. In this study, a total of 64 colorectal cancer patients who received curative operation were examined for the effects of cimetidine treatment on survival and recurrence. The cimetidine group was given 800 mg day(-1) of cimetidine orall...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1038/sj.bjc.6600048
更新日期：2002-01-21 00:00:00
abstract：:Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m-2 i.v.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-1) starting on day 8. An overall response rate of 40....
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1996.211
更新日期：1996-05-01 00:00:00
abstract：:To assist in the description of the cellular heterogeneity present in normal and neoplastic urothelium, a panel of monoclonal antibodies (MoAbs) was raised against human transitional cell carcinoma (TCC) of the urinary bladder. All immunizations were carried out using whole cells and membrane preparations from well di...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.220
更新日期：1987-10-01 00:00:00
abstract：:In the present study we have used flow cytometric DNA measurements on synchronised human NHIK 3025 cells to measure cell cycle progression under various conditions of reduced oxygenation. Our data indicate that addition of 0.1 mM deoxycytidine or uridine has no effect on the oxygen-dependent arrest in late G1 or on th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.411
更新日期：1994-11-01 00:00:00
abstract：:This cross-sectional survey aimed to evaluate the prevalence of burnout and estimated psychiatric disorders among haemato-oncology healthcare professionals in Italy. The aspects of work that respondents perceive as stressful and satisfying have also been examined. The assessments were made using the Maslach Burnout In...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/sj.bjc.6604270
更新日期：2008-03-25 00:00:00
abstract：:Multidrug resistance is often associated with the (over)expression of drug efflux transporters of the ATP-binding cassette (ABC) protein family. This minireview discusses the role of one selected ABC-transporter family member, the breast cancer resistance protein (BCRP/ABCG2), in the (pre)clinical efficacy of novel ex...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6604213
更新日期：2008-03-11 00:00:00
abstract：:Sera from 182 newly diagnosed breast cancer patients were assayed for antibodies to p53 using an enzyme-linked immunosorbent assay (ELISA) method, and antibodies were detected in 48 (26%) compared with 1 out of 76 (1.3%) normal control volunteers (P = 0.0001). In breast cancer patients, autoantibodies were found in al...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.219
更新日期：1994-06-01 00:00:00
abstract：:Urethane was found to be uniformly distributed in all the major organs of foetal, young and adult ICR/Jcl mice and then to disappear rapidly as measured by the incorporation of urethane-carbonyl-14C, thus permitting the accurate comparison of tumour susceptibility of cells in various organs of mice at different ages. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.83
更新日期：1976-05-01 00:00:00
abstract：:This study has been designed to verify the specific toxicity of saporin, a type 1 ribosome-inactivating protein (RIP), with the same activity as ricin A chain, targeted by a bispecific monoclonal antibody (bimAb) recognising both the CD25 antigen and the RIP. The CD25 antigen is expressed by lymphoid populations upon ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.233
更新日期：1993-06-01 00:00:00
abstract：:The incidence of ovarian, cervical, lung and prostatic cancer was higher in second-generation Irish living in England and Wales than in all other persons in England and Wales. A higher incidence of ovarian cancer was not found in first-generation Irish. Differences in socioeconomic status did not explain these pattern...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.608
更新日期：1998-10-01 00:00:00
abstract：BACKGROUND:Dysplasia is a marker of cancer risk in Barrett's oesophagus (BO), but this risk is variable and diagnosis is subject to inter-observer variability. Cancer risk in BO is increased when chromosomal instability is present. Nucleotyping (NT) is a new method that uses high-resolution digital images of nuclei to ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.353
更新日期：2011-10-11 00:00:00
abstract：BACKGROUND:Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the prese...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.174
更新日期：2015-06-30 00:00:00
abstract：BACKGROUND:Congenital anomalies have been found more often in children with cancer than in those without. Rib abnormalities (RAs) have been associated with childhood cancer; however, studies have differed in the type of RAs and cancers implicated. METHODS:Rib abnormalities were assessed predominantly by X-ray in a hos...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.366
更新日期：2011-10-25 00:00:00
abstract：:The prodrug N-[4-(daunorubicin-N-carbonyl-oxymethyl)phenyl] O-beta-glucuronyl carbamate (DNR-GA3) was synthesized for specific activation by human beta-glucuronidase, released in necrotic areas of tumour lesions. In vitro, DNR-GA3 was 18 times less toxic than daunorubicin (DNR) and the prodrug was completely activated...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.729
更新日期：1998-12-01 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：:In vivo models of acquired resistance to the platinum-based agents cisplatin (CDDP), carboplatin (CBDCA), iproplatin (CHIP) and tetraplatin have been established using a panel of six parent human ovarian carcinoma lines, two (HX/110 and PXN/87) being derived from previously untreated patients. Resistance has been gene...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.5
更新日期：1993-01-01 00:00:00
abstract：:Although cancer of the cervix is traditionally considered not to be responsive to steroid hormones, an in vitro study has reported that the addition of oestrogen increased cellular proliferation in a cervix cancer cell line that was inhibited by progesterone. We investigated whether the reported in vitro effects of oe...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.97
更新日期：1997-01-01 00:00:00
abstract：:This corrects the article DOI: 10.1038/bjc.2017.327. ...
journal_title：British journal of cancer
pub_type： 杂志文章,已发布勘误
doi：10.1038/bjc.2017.438
更新日期：2018-01-01 00:00:00
abstract：:Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variet...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/bjc.2014.610
更新日期：2015-01-20 00:00:00
abstract：:Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605024
更新日期：2009-05-05 00:00:00
