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; upon light activation the latter induces intracellular release of organelle-bound drug. We investigated whether co-administration of hypericin (photosensitiser) with mitoxantrone (MTZ, chemotherapeutic) plus illumination potentiates cytotoxicity in MDR cancer cells. We mapped the extent of intracellular co-localisation of drug/photosensitiser. We determined whether PCI altered drug-excreting efflux pump P-glycoprotein (Pgp) expression or function in MDR cells. Bladder and breast cancer cells and their Pgp-overexpressing MDR subclones (MGHU1, MGHU1/R, MCF-7, MCF-7/R) were given hypericin/MTZ combinations, with/without blue-light illumination. Pilot experiments determined appropriate sublethal doses for each. Viability was determined by the 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide assay. Intracellular localisation was mapped by confocal microscopy. Pgp expression was detected by immunofluorescence and Pgp function investigated by Rhodamine123 efflux on confocal microscopy. MTZ alone (0.1-0.2 microg ml(-1)) killed up to 89% of drug-sensitive cells; MDR cells exhibited less cytotoxicity (6-28%). Hypericin (0.1-0.2 microM) effects were similar for all cells; light illumination caused none or minimal toxicity. In combination, MTZ /hypericin plus illumination, potentiated MDR cell killing, vs hypericin or MTZ alone. (MGHU1/R: 38.65 and 36.63% increase, P<0.05; MCF-7/R: 80.2 and 46.1% increase, P<0.001). Illumination of combined MTZ/hypericin increased killing by 28.15% (P<0.05 MGHU1/R) compared to dark controls. Intracytoplasmic vesicular co-localisation of MTZ/hypericin was evident before illumination and at serial times post-illumination. MTZ was always found in sensitive cell nuclei, but not in dark resistant cell nuclei. In illuminated resistant cells there was some mobilisation of MTZ into the nucleus. Pgp expression remained unchanged, regardless of drug exposure. Pgp efflux was blocked by the Pgp inhibitor verapamil (positive control) but not impeded by hypericin. The increased killing of MDR cancer cells demonstrated is consistent with PCI. PCI is a promising technique for enhancing treatment efficacy.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Adigbli DK,Wilson DG,Farooqui N,Sousi E,Risley P,Taylor I,Macrobert AJ,Loizidou Mdoi
10.1038/sj.bjc.6603895subject
Has Abstractpub_date
2007-08-20 00:00:00pages
502-12issue
4eissn
0007-0920issn
1532-1827pii
6603895journal_volume
97pub_type
杂志文章abstract::Studies of underground miners occupationally exposed to radon have consistently demonstrated an increased risk of lung cancer in both smokers and non-smokers. Radon exposure also occurs elsewhere, especially in houses, and estimates based on the findings for miners suggest that residential radon is responsible for abo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.506
更新日期:1998-08-01 00:00:00
abstract::The trimodality approach represented by concurrent chemoradiotherapy followed by surgical resection is a highly effective, but potentially toxic therapy for locally advanced non-small-cell lung cancer (NSCLC). In this review, we discuss the current status of this therapy in patients with mediastinal node-positive (N2)...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6603751
更新日期:2007-05-21 00:00:00
abstract:BACKGROUND:Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial. METHODS:In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/bjc.2013.666
更新日期:2013-11-26 00:00:00
abstract:BACKGROUND:The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. METHODS:Forty-six patients were recruited and treated on the basis that MRI scanning had shown poo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605258
更新日期:2009-09-15 00:00:00
abstract::Twenty patients with non-Hodgkin's lymphoma were treated with a combination of cyclophosphamide (750 mg m(-2), day 1), epidoxorubicin (60 mg m(-2), day 1), vincristine (1.4 mg m(-2), day 1) and prednisone (100 mg m(-2), days 1-5) every 14 days. Shortening of intervals was associated with the prophylactic employment of...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1998.578
更新日期:1998-09-01 00:00:00
abstract::Four-hundred-forty-five husbands of women with invasive cervical carcinoma, 165 of women with in situ cervical cancer, and 717 of control women (age range 19-82 years) were interviewed and a sample of exfoliated cells from the penis obtained in seven case-control studies conducted by the International Agency for Resea...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600194
更新日期:2002-03-04 00:00:00
abstract:BACKGROUND:Radio- and chemotherapy (RT/CT) resistance hampers success in combating small and non-small cell lung cancers (SCLC/NSCLC). The underlying molecular mechanisms of RT/CT resistance of LCs are multifactorial and have been understood in part hitherto. miRNAs, key regulators of mRNAs, are well-recognised oncomir...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.382
更新日期:2012-10-09 00:00:00
abstract::A mini-review of the literature concerning epigenetic gene regulation in cancer. ...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1054/bjoc.2000.1549
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas, are malignant tumours displaying smooth muscle differentiation. Althoug...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.280
更新日期:2016-10-11 00:00:00
abstract::The goal of the study was to identify any normal genes that may become inactivated in malignant cells, with associated modifications or loss of gene products. Consequently, attempts were made to identify such products by generating monoclonal antibodies using an immune tolerisation-immunisation procedure. Using such a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.80
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND:Thymidine phosphorylase (TP) is often overexpressed in tumours and has a role in tumour aggressiveness and angiogenesis. Here, we determined whether TP increased tumour invasion and whether TP-expressing cancer cells stimulated angiogenesis. METHODS:Angiogenesis was studied by exposing endothelial cells (HU...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.74
更新日期:2011-03-29 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
abstract:BACKGROUND:Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.631
更新日期:2015-02-03 00:00:00
abstract:BACKGROUND:Gamma-glutamyltransferase (GGT) - a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance - is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosi...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2013.323
更新日期:2013-08-06 00:00:00
abstract:BACKGROUND:Glioma stem-like cell (GSC) properties are responsible for gliomagenesis and recurrence. GSCs are invasive but its mechanism remains to be elucidated. Here, we attempted to identify the molecules that promote invasion in GSCs. METHODS:Neurospheres and CD133⁺ cells were collected from glioblastoma (GBM) spec...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.218
更新日期:2013-06-25 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::This phase II study was designed to evaluate the activity and safety of a combination of irinotecan, docetaxel and oxaliplatin in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Forty patients with measurable distant metastasis received irinotecan 150 mg m(-2) and docetaxel 60 mg m(-2) on day 1, ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603917
更新日期:2007-09-03 00:00:00
abstract::The mature epidermal growth factor receptor (EGFR) neither associates with nor requires the molecular chaperone heat-shock protein 90 (Hsp90). Mutations in EGFR exons 18, 19, and 21 confer Hsp90 chaperone dependence. In non-small cell lung cancer (NSCLC), these mutations are associated with enhanced sensitivity to EGF...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603950
更新日期:2007-09-17 00:00:00
abstract:BACKGROUND:Epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial-mesenchymal transition is proposed to occur in various developmental processes and cancer progression. 'Cadherin switch', a process in which cells shift to express d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.415
更新日期:2014-09-23 00:00:00
abstract:BACKGROUND:The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes. METHODS:This was a national, prospective cohort study of DCIS diagnosed during 2003-2012. RESULTS:Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01152-5
更新日期:2020-11-17 00:00:00
abstract::We have investigated the production, growth and inactivation of gastrin-releasing peptide (GRP)-like peptides in human breast cancer cell lines. Radioimmunoassay detected GRP-like immunoreactivity (GRP-LI) in T47D breast cancer cells but not in the conditioned medium, indicating rapid clearance. No GRP-LI was found in...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690036
更新日期:1999-01-01 00:00:00
abstract::When assessing the value of a particular treatment, it is important to consider the impact it may have on the quality of life of those being treated. This is particularly so for cancer patients, whose life expectancy may be short. Patients with advanced colorectal cancer who participated in two international comparati...
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/bjc.1998.420
更新日期:1998-01-01 00:00:00
abstract::Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suita...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604463
更新日期:2008-07-22 00:00:00
abstract::NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6602204
更新日期:2004-11-15 00:00:00
abstract:BACKGROUND:Tumours consist of heterogeneous cancer cells and are likely to contain drug-tolerant cell subpopulations, causing early relapse. However, treatment strategies to eliminate these cells have not been established. METHODS:We established gastric cancer patient-derived cells (PDCs) to examine the contribution o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0600-9
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast can...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.44
更新日期:2011-03-15 00:00:00
abstract:BACKGROUND:Lithium accumulates in the colon and inhibits the enzyme GSK-3β that possesses anti-carcinogenic effects. We therefore examined the association between lithium use and colorectal cancer risk in a nationwide study. METHODS:We used the Danish Cancer Registry to identify all patients diagnosed with incident co...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.10
更新日期:2016-03-01 00:00:00
abstract::C57BL mice were given local irradiation to 2 cm2 of the lower abdomen in the dose range 16--24 Gy. There were some early deaths, but mice dying between 50--240 days predominantly developed invasive adenocarcinomas of the intestine. When the radiosensitizer misonidazole was given in a single dose shortly before irradia...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.240
更新日期:1978-10-01 00:00:00
abstract::Decreased accumulation of the fluorescent dye BCECF [2', 7'-bis-(2-carboxyethyl)-5-(6)- carboxyfluorescein] characterized murine and human multidrug-resistant cell lines overexpressing the multidrug resistance protein (MRP). Indomethacin (10 microM), a known cyclo-oxygenase and glutathione-S-transferase inhibitor as w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.145
更新日期:1997-01-01 00:00:00
abstract::Some cancer cells depend on the function of specific molecules for their growth, survival, and metastatic potential. Targeting of these critical molecules has arguably been the best therapy for cancer as demonstrated by the success of tamoxifen and trastuzumab in breast cancer. This review will evaluate the type I IGF...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6602963
更新日期:2006-02-27 00:00:00