Abstract:
:TNF-related apoptosis-inducing ligand (TRAIL, also known as Apo-2L) is a promising novel anticancer agent that selectively induces apoptosis in tumour cells and the activity of which can be enhanced by combined treatment with chemo- or radiotherapy. For therapeutic purposes, the use of full-length TRAIL may be favourable to recombinant TRAIL based on its increased tumour cell killing potential, and the delivery of TRAIL at the tumour site by adenovirus vectors may provide an approach to overcome the short half-life of recombinant TRAIL and hepatocyte toxicity in vivo. Here, we constructed an adenoviral vector expressing full-length TRAIL (AdTRAIL) and studied the potential of chemo- and radiotherapy in enhancing AdTRAIL-induced apoptosis in non-small cell lung cancer (NSCLC) H460 cells and normal cells and, in addition, investigated the mechanism of AdTRAIL-induced apoptosis. AdTRAIL effectively killed H460 cells, which we previously showed to have a deficiency in mitochondria-dependent apoptosis by downstream activation of caspase-8 rather than caspase-9. Further analyses revealed that AdTRAIL induces death receptor- and mitochondria-dependent apoptosis that could be partially suppressed by Bcl2 overexpression. Combined treatment with doxorubicin (DOX), cisplatin (CDDP), paclitaxel (PTX) and radiation strongly enhanced AdTRAIL-induced cytotoxicity in a synergistic way. Synergy was accompanied by the cleavage of Bid and an increase in caspase-8 processing that was abolished by Bcl2 overexpression, indicating that the Bid-mitochondrial amplification loop is functional in H460 cells. Moreover, combination treatment did not alter the tumour selectivity of AdTRAIL since normal human fibroblasts (NHFs) remained resistant under these conditions. These findings further indicate that the combined use of chemo/radiotherapy and adenovirus-produced full-length TRAIL may provide a valuable treatment option for NSCLC.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Abou El Hassan MA,Mastenbroek DC,Gerritsen WR,Giaccone G,Kruyt FAdoi
10.1038/sj.bjc.6601910subject
Has Abstractpub_date
2004-07-05 00:00:00pages
171-7issue
1eissn
0007-0920issn
1532-1827pii
6601910journal_volume
91pub_type
杂志文章abstract::Soluble and nuclear oestrogen receptor status was determined in both the central and peripheral portions of tumour for 37 cases of adenocarcinoma of the endometrium. Of these, 29 had functional receptor in the peripheral biopsy, but only 19 retained functional receptor in the centre. Six of the 10 patients whose tumou...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.34
更新日期:1983-02-01 00:00:00
abstract::Pancreatic cancers occurring in carriers of a pathogenic germline alteration in BRCA1/2 (gBRCA1/2) are assumed to demonstrate homologous recombination repair deficiency (HRD), associated with sensitivity to platinum-based chemotherapy and synthetic lethality with PARP inhibitors (PARPi). However, primary and secondary...
journal_title:British journal of cancer
pub_type: 评论,社论
doi:10.1038/s41416-019-0645-9
更新日期:2020-02-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605367
更新日期:2009-12-01 00:00:00
abstract::In a population-based cohort study of all women aged over 50 years with breast cancer in the Swedish Cancer Register in 1961-2003, those diagnosed before 31 December 1987 were regarded as unexposed to tamoxifen, whereas those diagnosed after that date were considered potentially exposed. Crosslinkages within the Cance...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603214
更新日期:2006-07-03 00:00:00
abstract::The 5-year relative survival rates of women diagnosed with breast cancer between 1992 and 1994 were compared among the 99 Health Authorities (1999 boundaries) of England. Substantial variation, with evidence of geographical clustering was observed. Part of this variation was explained by differences in deprivation bet...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601812
更新日期:2004-06-01 00:00:00
abstract::A possible link between protein kinase C (PKC) and P-glycoprotein (P-gp)-mediated-multidrug resistance (MDR) was assumed from studies on MDR cell lines selected in vitro. The functional relevance of PKC for the MDR phenotype remains unclear, and the involvement of a particular PKC isozyme in clinically occurring drug ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.13
更新日期:1998-01-01 00:00:00
abstract::Seventy three children with rhabdomyosarcoma were treated by members of the Children's Solid Tumour Group during the period, 1974-1981. The extent of disease at diagnosis was found to be the major influence affecting outcome. Children with tumours confined to the tissue of origin with no evidence of nodal or metastati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.175
更新日期:1983-08-01 00:00:00
abstract::A standardised, effective systemic therapy for metastatic neuroendocrine tumours (NETs) has not been established to date. We reviewed the management of 15 patients with inoperable, metastatic NET treated systematically with a combination chemotherapy regimen of infusional 5-fluorouracil, folinic acid and streptozocin....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601167
更新日期:2003-08-04 00:00:00
abstract:BACKGROUND:The National Comprehensive Cancer Network (NCCN) guidelines provide recommendations for staging of prostate cancer patients in the objective regarding presence of locoregional lymph node metastases (LNM) and bone metastases. We tested the performance characteristics of these recommendations in a community se...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0323-3
更新日期:2018-12-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.107
更新日期:2012-04-24 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0764-3
更新日期:2020-04-01 00:00:00
abstract::The effects of interferon-alpha (IFN) plus tamoxifen (TMX) in the treatment of advanced breast cancer were assessed. Changes of in vivo biologic determinants including hormone receptors, P24 protein, Ki-67 and growth factor expression were evaluated. Seven patients with advanced, heavily pretreated, breast cancer with...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.339
更新日期:1993-08-01 00:00:00
abstract::Using a recently developed model for studying the biology of locally recurrent (LR) mammary tumours in the 13762NF rat mammary adenocarcinoma system, we examined the sensitivity to polymorphonuclear cell, macrophage and natural killer cell cytolysis. The parental MTF7(T20) cell line; the 'primary' tumours which arose ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.302
更新日期:1988-12-01 00:00:00
abstract::Fluorescence polarization measurement during the progress of fluorochromasia has been used to study the response of human lymphocytes to phytohaemagglutinin (PHA) and to tumour-associated antigens, as a basis for the detection of malignant disease. Polarization (P) values of both stimulated and unstimulated lymphocyte...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.9
更新日期:1980-01-01 00:00:00
abstract::Multidrug resistance (MDR) is the major confounding factor in adjuvant solid tumour chemotherapy. Increasing intracellular amounts of chemotherapeutics to circumvent MDR may be achieved by a novel delivery method, photochemical internalisation (PCI). PCI consists of the co-administration of drug and photosensitiser; u...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603895
更新日期:2007-08-20 00:00:00
abstract:BACKGROUND:Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS:Two cohorts were prospectively enr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.537
更新日期:2014-12-09 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.138
更新日期:1979-07-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604395
更新日期:2008-06-03 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.87
更新日期:1997-01-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.3
更新日期:1985-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjc.6603668
更新日期:2007-04-10 00:00:00
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pub_type: 杂志文章
doi:10.1054/bjoc.2001.1959
更新日期:2001-08-17 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605823
更新日期:2010-08-24 00:00:00
abstract::We have previously reported that supplementation with folic acid (1.2 mg day(-1) for 12 week) elicited a significant improvement in the folate status of 61 healthy volunteers. We have examined effects of this supplement on markers of genomic stability. Little is known about the effect of folate supplementation on DNA ...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.bjc.6603197
更新日期:2006-06-19 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.222
更新日期:2015-07-28 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690827
更新日期:1999-12-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690484
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future resea...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6605388
更新日期:2009-12-03 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in col...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1936
更新日期:2001-08-17 00:00:00
abstract::Van Trommel et al have previously shown that serum human chorionic gonadotropin (hCG) cutoff levels can provide early prediction of resistance to first-line methotrexate (MTX) in patients with persistent trophoblastic disease (PTD). In this study, we validate this approach of prediction of resistance to single-agent c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604849
更新日期:2009-03-24 00:00:00