Abstract：
BACKGROUND:Epigenetic silencing by promoter methylation and chromatin remodelling affects hundreds of genes and is a causal event for lung cancer. Treatment of patients with low doses of the demethylating agent 5-azacytidine in combination with the histone deacetylase inhibitor entinostat has yielded clinical responses. The subcutaneous dosing route for consecutive days and reduced bioavailability of 5-azacytidine because of inactivation by cytidine deaminase may limit the expansion of epigenetic therapy into Phase III trials. To mitigate these barriers, an aerosol of 5-azacytidine was generated and characterised. METHODS:The effect of aerosol vs systemic delivery of 5-azacytidine on tumour burden and molecular response of engrafted lung tumours in the nude rat was compared. RESULTS:Pharmacokinetics revealed major improvement in the half-life of 5-azacytidine in lung tissue with aerosol delivery. Aerosolised 5-azacytidine significantly reduced lung tumour burden and induced global demethylation of the epigenome at one-third of the comparable effective systemic dose. High commonality for demethylation of genes was seen in tumours sampled throughout lung lobes and across treated animals receiving the aerosolised drug. CONCLUSION:Collectively, these findings show that aerosolised 5-azacytidine targets the lung, effectively reprogrammes the epigenome of tumours, and is a promising approach to combine with other drugs for treating lung cancer.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Reed MD,Tellez CS,Grimes MJ,Picchi MA,Tessema M,Cheng YS,March TH,Kuehl PJ,Belinsky SAdoi
10.1038/bjc.2013.575subject
Has Abstractpub_date
2013-10-01 00:00:00pages
1775-81issue
7eissn
0007-0920issn
1532-1827pii
bjc2013575journal_volume
109pub_type
杂志文章abstract：:The level of expression of the multidrug resistance-associated protein (MRP1) in a panel of human ovarian carcinoma cell lines and their variants with acquired cisplatin resistance was determined using Western blotting. No overexpression of MRP1 was detected in any of the cell lines. In addition, we have transfected t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.461
更新日期：1998-07-01 00:00:00
abstract：:Altered expression and activity of proteases is a key event in cancer, particularly in relation to invasion, modification of the extracellular matrix and metastasis. The transmembrane protease, serine 4 (TMPRSS4) is closely related to other cancer-associated proteases, such as hepsin, TMPRSS2 and matriptase. We review...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/bjc.2014.403
更新日期：2015-01-06 00:00:00
abstract：BACKGROUND:Non-epithelial gonadal tumours largely comprise sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Specific somatic mutations in DICER1, a microRNA maturation pathway gene, have been identified in these tumours. We conducted a study that aimed to confirm, refine and extend the previous observatio...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.637
更新日期：2013-11-12 00:00:00
abstract：:The growth inhibitory effects of interferons, IFN-alpha and IFN-gamma on human lung cancer cell lines were studied using both a tetrazolium (MTT) colorimetric assay and direct cell counting. Significant discrepancies between the two assays were observed, the MTT assay consistently underestimating the growth inhibitory...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.306
更新日期：1989-10-01 00:00:00
abstract：BACKGROUND:The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS:Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605196
更新日期：2009-08-18 00:00:00
abstract：:We assessed the feasibility and pharmacokinetics of high-dose infusional paclitaxel in combination with doxorubicin, cyclophosphamide, and peripheral blood progenitor cell rescue. Between October 1995 and June 1998, 63 patients with high-risk primary [stage II with >or= 10 axillary nodes involved, stage IIIA or stage ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1054/bjoc.2001.1835
更新日期：2001-06-15 00:00:00
abstract：:We cytogenetically investigated six osteoid osteomas, one osteoblastoma and one aggressive osteoblastoma, and observed clonal structural changes in one osteoid osteoma and in the aggressive osteoblastoma. Clonal chromosome changes had not been reported previously in osteoid osteoma, whereas the only reported chromosom...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.496
更新日期：1998-08-01 00:00:00
abstract：:A crude membrane fraction isolated from mouse tumour cells was treated with various chemicals. The effects on the immunogenicity of the membrane sample were tested in syngeneic mice for tumour protection, using a challenge dose of 10(5) viable tumour cells. Best protection was obtained after immunization of mice with ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.236
更新日期：1978-10-01 00:00:00
abstract：BACKGROUND:CXC chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) have important roles in promoting tumour growth and metastasis. Therefore, targeting CXCR4 could be a promising strategy for treatment of human cancer. METHODS:To achieve this goal, we developed a h...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.1
更新日期：2014-03-04 00:00:00
abstract：:A retrospective seroepidemiologic study was performed to examine the association between human papillomaviruses (HPV) 16 infection and carcinomas of the oropharynx, the oesophagus, penis and vagina. Sera were selected from the serum bank from the Antoni van Leeuwenhoek Hospital (Netherlands Cancer Institute) and the S...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600870
更新日期：2003-04-07 00:00:00
abstract：:In the years 1979-1982, 83 patients with malignant teratoma of the testis who had retroperitoneal adenopathy at presentation or after a period of surveillance were treated. Complete radiological resolution of disease was obtained in 34 patients and a residual mass remained in 26, the remainder having progression of th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.105
更新日期：1986-05-01 00:00:00
abstract：:Lysophosphatidic acid (LPA) is a potent lipid mediator that acts on a series of specific G protein-coupled receptors, leading to diverse biological actions. Lysophosphatidic acid induces cell proliferation, survival and migration, which are critically required for tumour formation and metastasis. This bioactive lipid ...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6605588
更新日期：2010-03-16 00:00:00
abstract：:Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways imp...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6603813
更新日期：2007-06-18 00:00:00
abstract：:Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical chang...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603102
更新日期：2006-05-22 00:00:00
abstract：:Cytotoxic antibodies to antigens specific for leukaemic myeloblasts have been sought in the serum of patients with acute myeloblastic leukaemia treated by immunotherapy with irradiated allogeneic myeloblasts and BCG. Assays of complement- and K-cell-mediated activity were used. Cytotoxicity to allogeneic myeloblasts w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.40
更新日期：1977-03-01 00:00:00
abstract：:Metastatic spread of some solid tumours is thought to depend upon the adhesion of tumour cells to the vascular endothelium followed by extravasation into surrounding tissues. We investigated the role of beta 1 integrins in the adhesion of the breast adenocarcinoma cell line MDA-MB-231 and the melanoma cell line RPMI-7...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.627
更新日期：1996-12-01 00:00:00
abstract：:To assess the precise role of IGF1 in benign and malignant breast diseases, we analysed the tissular localisation, characterised, and quantified specific insulin-like growth factor 1 (IGF1) binding sites in these heterogenous tissues, using histo-autoradiographic analysis (HAA). The 125I-IGF1 binding was performed on ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.252
更新日期：1992-08-01 00:00:00
abstract：:The expression of urokinase-type plasminogen activator (uPA) was investigated in squamous cell carcinoma of the human larynx. For this purpose, tissue extracts from 25 matched samples of normal mucosa and neoplastic larynx were compared for the levels of uPA activity as evaluated by a chromogenic PA assay and sodium d...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.512
更新日期：1996-10-01 00:00:00
abstract：BACKGROUND:A major molecular pathway of genetic instability in cancer is DNA mismatch repair deficiency. High-level microsatellite instability (MSI-H) is currently the best predictor of responsiveness towards immune checkpoint blockade. Data about the prevalence of high-level microsatellite instability in cholangiocarc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-018-0199-2
更新日期：2019-01-01 00:00:00
abstract：BACKGROUND:Colorectal cancer (CRC) diagnoses and disease-specific survival (DSS) vary between ethnic groups in the United States. However, few studies have assessed differences among Asian subgroups. METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with invasive CRC...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.97
更新日期：2013-04-16 00:00:00
abstract：BACKGROUND:Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.56
更新日期：2013-03-19 00:00:00
abstract：:The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case-control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1054/bjoc.2000.1121
更新日期：2000-07-01 00:00:00
abstract：BACKGROUND:Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in TECs. Vascular endothe...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.20
更新日期：2011-03-01 00:00:00
abstract：:By using a quantitative RNA-RNA solution hybridisation method, the average number of mdr1 RNA transcripts per cell was measured in total nucleic acid extracts of leukaemic cells from patients with acute leukaemia. The results in different types of leukaemia were (number of patients with detectable mdr1 RNA/total numbe...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.255
更新日期：1992-08-01 00:00:00
abstract：:Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resista...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.339
更新日期：1990-10-01 00:00:00
abstract：:The present study set out to evaluate perceptions of risk, psychological morbidity and health behaviours in women with a family history of breast cancer who have attended genetic counselling and determine how these differ from general population risk women. Data were collected from 62 genetic counselees (cases) attend...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.387
更新日期：1996-08-01 00:00:00
abstract：:The acute toxicity, pharmacokinetics and hypoxic cytotoxicity of RSU-1069 were investigated using the subcutaneous (sc) rat 9L tumour model. The pharmacokinetics were studied after i.p. injection of RSU-1069 (20 mg kg-1 or 100 mg kg-1). For both doses, the elimination of RSU-1069 followed first-order kinetics in both ...
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
abstract：BACKGROUND:Gastroesophageal adenocarcinoma (GOA) has poor clinical outcomes and lacks reliable blood markers. Here we present circulating tumour DNA (ctDNA) as an emerging biomarker. METHODS:Forty patients (17 palliative and 23 curative) were followed by serial plasma monitoring. Primary tumour DNA was analysed by tar...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-1002-8
更新日期：2020-10-01 00:00:00
abstract：BACKGROUND:Several tyrosine kinase inhibitors (TKIs) can decrease docetaxel clearance in patients by an unknown mechanism. We hypothesised that these interactions are mediated by the hepatic uptake transporter OATP1B1. METHODS:The influence of 16 approved TKIs on transport was studied in vitro using HEK293 cells expre...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.811
更新日期：2014-02-18 00:00:00
abstract：:Metastatic variant sublines of the murine large-cell lymphoma cell line RAW117 were tested for their growth and migration properties in vitro in medium conditioned by soluble factors released from syngeneic mouse liver-, lung-, and brain-derived microvessel endothelial cells. Medium conditioned with hepatic sinusoidal...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.269
更新日期：1992-08-01 00:00:00
