Abstract:
:P-glycoprotein (P-gp) pumps multiple types of drugs out of the cell, using energy generated from ATP, and confers multidrug resistance (MDR) on cancer cells. ZD6474 is an orally active, selective inhibitor of the vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection tyrosine kinases. This study was designed to examine whether ZD6474 reverses P-gp-mediated MDR in cancer cells. Here, we show that clinically achievable levels of ZD6474 reverse P-gp-mediated MDR of the P-gp-overexpressing cell lines derived from breast cancer, MCF-7/adriamycin (ADR), and human oral epidermoid carcinoma, KBV200 to ADR, docetaxel, and vinorelbine. This ability to reverse the P-gp-mediated resistance is comparable to that of another frequently used reversal agent known as verapamil. ZD6474 itself moderately inhibits the proliferation of both MCF-7 and MCF-7/ADR cells with almost equal activity, but its inhibitory effect is not altered by co-incubation with verapamil, suggesting that ZD6474 may not be a substrate of P-gp. In addition, ZD6474 increases the intracellular accumulation of the P-gp substrate, rhodamine-123, and ADR, by enhancing the uptake and/or decreasing the efflux of these compounds in resistant cells. Further studies show that ZD6474 stimulates ATPase activity in a dose-dependent manner, which is required for the proper function of P-gp. In contrast, ZD6474 does not inhibit the expression level of P-gp. Our results suggest that ZD6474 is capable of reversing MDR in cancer cells by directly inhibiting the function of P-gp, a finding that may have clinical implications for ZD6474.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Mi Y,Lou Ldoi
10.1038/sj.bjc.6603985subject
Has Abstractpub_date
2007-10-08 00:00:00pages
934-40issue
7eissn
0007-0920issn
1532-1827pii
6603985journal_volume
97pub_type
杂志文章abstract:BACKGROUND:Most studies use hospital data to calculate postoperative complication rates (PCRs). We report on improving PCR estimates through use of patient-reporting. METHODS:A prospective cohort study of major surgery performed at 10 UK gynaecological cancer centres was undertaken. Hospitals entered the data contempo...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2013.366
更新日期:2013-08-06 00:00:00
abstract:BACKGROUND:Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. METHODS:In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pan...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.355
更新日期:2017-12-05 00:00:00
abstract:INTRODUCTION:This paper reports on an ongoing primary care audit of cancer referrals undertaken in Scotland in 2006-2007 and 2007-2008. METHODS:General practitioners (GPs) in Scotland were asked to review all new cancer diagnoses within their practice during the preceding year. RESULTS:4181 patients were identified i...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605397
更新日期:2009-12-03 00:00:00
abstract::To evaluate current guidelines criteria for inclusion of women in special 'breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at 'less than 'moderate' familial risk'. The Scotti...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6604155
更新日期:2008-02-26 00:00:00
abstract::Magnetic resonance spectroscopy was used to study intracellular pH and compounds which contain phosphorus in normal human brain and primary brain tumours non-invasively. In normal subjects (n = 7) intracellular pH (pHi) of the brain was 7.03 +/- 0.02 (mean +/- s.e.m.). The pHi did not vary between superficial (2 cm, m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.300
更新日期:1989-09-01 00:00:00
abstract::An increasing body of evidence indicates that glutathione S-transferases play a role in the intrinsic and acquired resistance of tumours to anticancer drugs. In view of the wide use of tumour cell lines to understand the factors which confer either sensitivity or resistance to chemotherapeutic agents we have determine...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.280
更新日期:1989-09-01 00:00:00
abstract:BACKGROUND:Melanoma is highly resistant to current modalities of therapy, with the extent of pigmentation playing an important role in therapeutic resistance. Nuclear factor-κB (NF-κB) is constitutively activated in melanoma and can serve as a molecular target for cancer therapy and steroid/secosteroid action. METHODS...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.458
更新日期:2011-12-06 00:00:00
abstract::Seventy-one patients suffering from acute myeloid leukaemia (AML) who were already in complete remission and had already received one further course of cytotoxic drugs as consolidation therapy were randomised to receive maintenance chemotherapy alone or the same maintenance chemotherapy plus immunotherapy with BCG and...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/bjc.1978.1
更新日期:1978-01-01 00:00:00
abstract::Bcl-2 expression in colorectal carcinomas was studied in a series of 224 patients and the relation to p53 expression, stage and survival assessed. Bcl-2 expression was down-regulated compared with normal mucosa in 67% (151) of the cases. In 144 cases staining was positive for p53 (MAB DO7), and 41 of these 144 p53-pos...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.310
更新日期:1998-06-01 00:00:00
abstract::The effect of an antiserum containing antibodies against cell surface components of PyBHK cells on the action of certain anticancer agents has been studied using a colony formation inhibition assay. The effects of x-rays, chlorambucil, CCNU and possibly ICRF 159 are augmented by the antiserum whereas methotrexate and ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.234
更新日期:1975-09-01 00:00:00
abstract::Multiple primary tumours occurring in a three-year population-based series of patients with histopathologically peer-reviewed sarcomas from North West England were ascertained in order to look at the patterns of neoplasms seen. A total of 30 out of the 310 patients entered in the study had additional primary tumours. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.512
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. The present study was conducted to investigate the expression of GOLPH3 and its prognostic significance in renal cell carcinoma (RCC). Meanwhile, the function of GOLPH3 in human RCC was further inves...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.124
更新日期:2014-04-29 00:00:00
abstract::Clinical-pathologic-genetic studies were performed on 3 kindreds showing the familial atypical multiple mole-melanoma syndrome (FAMMM). Findings showed vertical transmission, including father-to-son, of cutaneous malignant melanoma and/or FAMMM moles with no sex predilection. A broad spectrum of clinical signs charact...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.203
更新日期:1980-07-01 00:00:00
abstract::The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690008
更新日期:1999-01-01 00:00:00
abstract::We have studied loss of heterozygosity at the BRCA1 and BRCA2 loci in 992 normal cell clones derived from topographically defined areas of normal tissue in four samples from BRCA1/BRCA2 mutation carriers. The frequency of loss of heterozygosity in the clones was low (1.01%), but it was found in all four samples, wheth...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603298
更新日期:2006-08-21 00:00:00
abstract:BACKGROUND:Treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs) are still limited. We investigated the antitumour activity and safety profile of pazopanib--a multitarget drug with anti-angiogenic activity in patients with metastatic GEP NETs. METHODS:This was a nonran...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.470
更新日期:2013-09-17 00:00:00
abstract:BACKGROUND:Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. METHODS:The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.193
更新日期:2016-07-26 00:00:00
abstract::The binding of ring-labelled and side-chain labelled misonidazole to hypoxic cells in monolayer and spheroid cultures of mammalian cells has been compared. The kinetics and patterns of binding for the two labelled compounds are indistinguishable. This finding has implications for the mechanism of binding and for the d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.33
更新日期:1985-02-01 00:00:00
abstract::Based on observations that for certain cancers, mortality varies according to sun exposure, vitamin D has been proposed to influence on disease progression. This study aims to investigate whether serum levels of 25(OH)D are associated with prognosis in patients with prostate cancer. In total, 160 patients with a serum...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604865
更新日期:2009-02-10 00:00:00
abstract::Forty-one human tumour cell lines were examined for the production of epidermal growth factor (EGF)/transforming growth factor (TGF)-alpha-like activity (EGF/TGF-alpha-LA), immunoreactive (IR-) EGF and IR-TGF-alpha. EGF/TGF-alpha-LA was determined by radioreceptor assay, in which the factors with capacity to bind to E...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.159
更新日期:1989-05-01 00:00:00
abstract::The effect of 6 putative prognostic factors on survival was studied in patients with Stages III and IV malignant teratoma of the testis. Differences between survival curves were tested for statistical significance. A diameter greater than 5 cm in the largest tumour mass, and greater than 8 pulmonary metastases were ad...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.332
更新日期:1980-12-01 00:00:00
abstract::In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnose...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603517
更新日期:2007-01-15 00:00:00
abstract:BACKGROUND:The pathogenesis of lymph node metastases in preinvasive breast cancer – ductal carcinoma in situ (DCIS) – remains controversial. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can assess a whole node and detect clinically relevant metastases. In this retrospective coho...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.168
更新日期:2012-05-08 00:00:00
abstract::Over a 10 year period, between 1974-1984, 257 adult cases of tissue sarcoma have been evaluated in the Department of Medical Oncology, Christie Hospital, Manchester. At registration locally advanced or metastatic diseases was present in 162 (63%). The male/female ratio was 1.5:1 and median age 54 years (range 14-85). ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.43
更新日期:1985-03-01 00:00:00
abstract::In addition to hypoxia, acidic extracellular pH (pH(e)) is recognised as one of the microenvironmental characteristics of solid tumours. A number of studies have examined ways to increase tumour acidity in order to improve tumour-specific targeting of certain drugs and the effectiveness of hyperthermia. However, previ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601766
更新日期:2004-05-04 00:00:00
abstract::The inhibitor of apoptosis protein, XIAP, is frequently overexpressed in chemoresistant human tumours. An antisense oligonucleotide (AEG 35156/GEM 640) that targets XIAP has recently entered phase I trials in the UK. Method validation data are presented on three pharmacodynamic assays that will be utilised during this...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602363
更新日期:2005-02-14 00:00:00
abstract:BACKGROUND:We aimed to analyse clinical and gene expression profiles to predict pathologic complete response and disease-free survival using two consecutive, prospective, preoperative chemotherapy trial cohorts. METHODS:Clinicopathological and gene expression data were evaluated in a cohort from two consecutive phase ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.184
更新日期:2016-08-09 00:00:00
abstract::The growth of s.c. Walker 256 carcinoma was found to be independent of secondary growths induced by i.v. injection. Tumour cells injected i.v. lodged mainly in the lungs, with small clusters of cells in the lymph nodes. The rate of cellular proliferation of these secondary growths of Walker carcinoma was significantly...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.12
更新日期:1978-01-01 00:00:00
abstract::The purpose of the study was to determine the response rates (RR) and duration to second- and third-line chemotherapy programmes in patients with anthracycline-resistant breast cancer, utilizing various definitions of anthracycline resistance. This was a retrospective analysis performed on 1335 patients with metastati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1999.0958
更新日期:2000-02-01 00:00:00
abstract::5-fluorouracil (5FU) is activated intracellularly to cytotoxic 5-fluoronucleotides (FNuct). These were detected non-invasively in rats bearing the Walker carcinosarcoma by 19F-magnetic resonance spectroscopy (MRS) following an i.v. bolus dose of 5FU (50 mg kg-1). Pre-treatment of the rats (3 to 24 h earlier) by methot...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.75
更新日期:1992-03-01 00:00:00